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Morphine

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Nov.06.2023

Morphine

Indications/Dosage

Labeled

  • diarrhea
  • severe pain

General dosing information

  • Individualize dosing for each patient; consider severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse. Use the lowest effective dose for the shortest duration consistent with individual treatment goals.
  • Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours after initiation and dose escalation, and adjust the dosage accordingly. Continually reevaluate patients to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as to monitor for the development of addiction, abuse, or misuse. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the opioid dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
  • There is substantial interpatient variability in the relative potency of different opioid drugs and products. When adjusting morphine dosages or converting from another opioid agonist, it is better to underestimate the patient's daily dose requirements and give rescue doses than to risk an adverse event. If an adverse event occurs, the next dose may be reduced. Refer to the Opioid Agonists Drug Class Overview for approximate equianalgesic doses.
  • When discontinuing morphine therapy in patients who are opioid-dependent, taper the dose gradually by 10% to 25% every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper.[40951][46350][64906]

Off-Label

  • acute myocardial infarction, NSTEMI
  • acute myocardial infarction, STEMI
  • diabetic neuropathy
  • dysautonomia
  • dyspnea
  • neonatal abstinence syndrome
  • procedural sedation
  • rapid-sequence intubation
  • restless legs syndrome (RLS)
  • short bowel syndrome
  • tetanus
  • tetralogy spells
  • unstable angina
† Off-label indication

For the treatment of severe pain where treatment with an opioid is appropriate and for which alternative treatments are inadequate

NOTE: Opioid-tolerant adults are considered as those taking, for 1 week or longer, at least 60 mg/day of morphine, 25 mcg/hour transdermal fentanyl, 30 mg/day of oral oxycodone, 8 mg/day of oral hydromorphone, 25 mg/day oral oxymorphone, 60 mg/day oral hydrocodone, or an equianalgesic dose of another opioid.[40951] [61668]

Oral dosage (immediate-release)

Adults

15 to 30 mg PO every 4 hours as needed, initially. Titrate dose as needed to achieve adequate analgesia.[46350]

Children and Adolescents weighing 50 kg or more

15 to 30 mg PO every 4 hours as needed, initially. Titrate dose as needed to achieve adequate analgesia.[46350] General weight-based dosing for pediatric patients is 0.15 to 0.3 mg/kg/dose PO every 3 to 6 hours as needed.[23625] [43053] [52200] [52207]

Children and Adolescents weighing less than 50 kg†

0.15 to 0.3 mg/kg/dose (Max: 5 mg/dose) PO every 3 to 6 hours as needed, initially. Titrate dose as needed to achieve adequate analgesia.[23625] [43053] [52200] [52207]

Oral dosage (2 mg/mL or 4 mg/mL oral solution)

Adults

10 to 20 mg PO every 4 hours as needed, initially. Titrate dose as needed to achieve adequate analgesia.[43053]

Children and Adolescents 2 to 17 years

0.15 to 0.3 mg/kg/dose (Max: 10 to 20 mg/dose) every 3 to 6 hours as needed, initially. Titrate dose as needed to achieve adequate analgesia.[23625] [43053] [52200] [52207]

Infants and Children 6 to 23 months†

0.15 to 0.3 mg/kg/dose (Max: 5 mg/dose) PO every 3 to 6 hours as needed, initially. Titrate dose as needed to achieve adequate analgesia.[23625] [43053] [52200] [52207]

Oral dosage (20 mg/mL oral solution; for opioid tolerant patients only)

Adults

10 to 20 mg PO every 4 hours as needed, initially. Titrate dose as needed to achieve adequate analgesia.[43053]

Intravenous dosage

Adults

2 to 10 mg IV every 4 hours as needed.[31296] [52190]

Adolescents

0.05 to 0.2 mg/kg/dose IV every 2 to 4 hours as needed; begin at the lower end of dosage range and titrate dose as needed to achieve adequate analgesia. Usual Max: 8 mg/dose; however, dose must be individualized.[23625] [52190]

Children

0.05 to 0.2 mg/kg/dose IV every 2 to 4 hours as needed; begin at the lower end of dosage range and titrate dose as needed to achieve adequate analgesia. Usual Max: 4 mg/dose; however, dose must be individualized.[23625] [52190]

Infants 6 to 11 months

0.05 to 0.2 mg/kg/dose IV every 2 to 4 hours as needed; begin at the lower end of dosage range and titrate dose as needed to achieve adequate analgesia.[23625] [52190]

Infants 1 to 5 months

0.05 to 0.1 mg/kg/dose IV every 3 to 4 hours as needed; begin at the lower end of dosage range and titrate dose as needed to achieve adequate analgesia.[23625] [52218]

Neonates†

0.05 to 0.1 mg/kg/dose IV every 3 to 4 hours as needed; begin at the lower end of dosage range and titrate dose as needed to achieve adequate analgesia.[23625] [52218]

Intramuscular of Subcutaneous dosage

Adults

10 mg IM or subcutaneously every 4 hours as needed; dose may range from 5 to 20 mg IM or subcutaneously every 4 hours depending on response.[52190]

Adolescents

0.05 to 0.2 mg/kg/dose (Usual Max: 8 mg/dose) IM or subcutaneously every 2 to 4 hours as needed; begin at the lower end of dosage range and titrate dose as needed to achieve adequate analgesia.[23625] [52190]

Children

0.05 to 0.2 mg/kg/dose (Usual Max: 4 mg/dose) IM or subcutaneously every 2 to 4 hours as needed; begin at the lower end of dosage range and titrate dose as needed to achieve adequate analgesia.[23625] [52190]

Infants 6 to 11 months

0.05 to 0.2 mg/kg/dose IM or subcutaneously every 2 to 4 hours as needed; begin at the lower end of dosage range and titrate dose as needed to achieve adequate analgesia.[23625] [52190]

Infants 1 to 5 months

0.03 to 0.1 mg/kg/dose IM or subcutaneously every 3 to 4 hours as needed; begin at the lower end of dosage range and titrate dose as needed to achieve adequate analgesia.[23625] [52218]

Neonates†

0.03 to 0.1 mg/kg/dose IM or subcutaneously every 3 to 4 hours as needed; begin at the lower end of dosage range and titrate dose as needed to achieve adequate analgesia.[23625] [52218]

Continuous Intravenous Infusion dosage†

Adults

Administer a loading dose by slow IV infusion at a rate of 2 mg/minute. Loading doses of 15 to 20 mg may be required for adequate analgesia; higher doses may be needed in opioid-tolerant patients. Initial infusion rates of 2 to 5 mg/hour have been used, with usual rates of 2 to 30 mg/hour used in critically ill patients.[57161] [57196] Higher infusion rates may be required in opioid-tolerant patients. Titrate dose to pain relief.

Infants, Children, and Adolescents

A bolus of 0.05 to 0.2 mg/kg IV (or 5 to 10 mg IV for patients weighing more than 60 kg) followed by a continuous infusion. Initial infusion rates of 0.01 to 0.03 mg/kg/hour are common, but initial doses up to 0.06 mg/kg/hour may be appropriate for some patients. Alternatively, rates of 0.8 to 3 mg/hour IV may be used for patients over 60 kg. [44860] [52200] [52221] Higher maintenance infusion rates up to 0.2 mg/kg/hour have been used in patients with sickle cell disease.[25111] Titrate to pain relief.

Neonates

0.01 to 0.03 mg/kg/hour continuous IV infusion. Adjust dose as needed to achieve target pain assessment score.[52218]

Continuous Subcutaneous Infusion dosage†

Adults

Initial infusion rates of 2 to 5 mg/hour subcutaneously may be used, with usual rates of 2 to 30 mg/hour subcutaneously used in critically ill patients.[57161] [57196] Morphine's dose conversion ratio is 1 mg subcutaneous = 1 mg IV. Higher infusion rates may be required in opioid-tolerant patients. Titrate dose to pain relief. Subcutaneous tissue can absorb up to 3 mL/hour.[57164]

Infants, Children, and Adolescents

An initial infusion rate of 0.03 mg/kg/hour subcutaneously has been recommended; however, an initial dose of 0.01 mg/kg/hour is also reasonable.[52198] The mean infusion rate was 0.0175 mg/kg/hour over the first 24 hours after surgery in 60 patients (aged 7 months to 20 years) and decreased to 0.011 to 0.0133 mg/kg/hour over the next 48 hours.[52199] Higher infusion rates, ranging from 0.025 to 1.79 mg/kg/hour subcutaneously (median: 0.06 mg/kg/hour subcutaneously), were used in 17 patients (aged 22 months to 22 years) with terminal cancer.[52196] Titrate dose to pain relief.

Intravenous dosage (Patient Controlled Analgesia (PCA))

Adults

The starting dose should be based on the patient's recent exposure to opioids. Titrate the regimen to patient response. Larger doses may be needed in opioid-tolerant patients. For OPIOID NAIVE patients, start with a demand dose of 1 mg (range: 0.5 to 2.5 mg) IV and lockout interval of 6 minutes (range: 5 to 10 minutes), with a maximal dosing rate of 10 mg/hour. For OPIOID TOLERANT patients, start with a demand dose of 2 to 5 mg IV and lockout interval of 6 minutes (range: 5 to 10 minutes), with a maximal dosing rate of 30 mg/hour.[33306] [57171]

Children 7 years and older and Adolescents

Various regimens have been reported.[52200] [52207] [52223] [52226] [52227]

The following settings have been used in pediatric patients; titrate regimen to patient response.

Demand dose: 0.01 to 0.025 mg/kg IV (max: 1 mg/dose)

Lockout interval: 5 to 10 minutes

Doses per hour: 5

Basal rate (optional): 0.004 to 0.015 mg/kg/hour IV initially

4-hour limit (optional): 0.24 to 0.375 mg/kg

Epidural dosage (morphine sulfate injection)

Adults

Initially, inject 5 mg epidurally in the lumbar region and assess the patient in 1 hour; if pain relief is not adequate at that time, administer incremental doses of 1 to 2 mg, with sufficient time between injections to appropriately assess for efficacy. The manufacturer recommends a maximum of 10 mg per 24 hours. For continuous epidural infusion, initiate at 2 to 4 mg per 24 hours, with additional doses of 1 to 2 mg given if pain relief is not initially achieved. The incidence of early and late respiratory depression is dramatically increased with thoracic administration. Use preservative-free formulations only.[48405]

Infants†, Children†, and Adolescents†

Various regimens have been reported including single preoperative and postoperative doses of 0.03 to 0.1 mg/kg epidurally, postoperative doses of 0.02 to 0.03 mg/kg/dose epidurally every 8 hours, and postoperative continuous infusions of 0.004 to 0.01 mg/kg/hour.[52228] [52229] [52230] Use preservative-free formulations only.

Intrathecal dosage (morphine sulfate injection)

Adults

0.2 to 1 mg in the lumbar area as a single dose or to establish dosage for continuous intrathecal infusion; repeated injections are not recommended. Intrathecal doses more than 20 mg/day increase the development of tolerance and serious toxicity including myoclonic spasms. Intrathecal dosage is usually one-tenth the epidural dosage. Use preservative-free formulations only.[48405]

Infants†, Children†, and Adolescents†

Single preoperative doses of 0.002 to 0.02 mg/kg intrathecally have been reported.[52228] Use preservative free formulations only.

Rectal dosage

Adults

10 to 20 mg rectally every 4 hours, as needed.[48404]

Infants†, Children†, and Adolescents†

0.2 mg/kg/dose rectally every 4 hours or 0.3 mg/kg/dose rectally every 6 hours as needed have been recommended.[52200] Do not exceed the usual adult dose of 10 to 20 mg/dose.

for the treatment of persistent, severe pain that requires an extended treatment period with a daily opioid and for which alternative treatments are inadequate

Oral dosage (extended-release tablets) in opioid non-tolerant adults

Adults

15 mg PO every 8 to 12 hours, initially. Titrate dose every 1 to 2 days as needed to achieve adequate analgesia. To discontinue, gradually decrease the dose by 25% to 50% every 2 to 4 days to prevent withdrawal.[40951] [60209] [61668]

Oral dosage (extended-release capsules) in opioid non-tolerant adults

Adults

30 mg PO every 24 hours, initially. Titrate dose every 1 to 4 days as needed to achieve adequate analgesia. To discontinue, gradually decrease the dose by 25% to 50% every 2 to 4 days to prevent withdrawal.[31637] [35890]

Oral dosage [extended-release tablets (Arymo ER, Morphabond, MS Contin) or capsules (Kadian, Avinza)] in adults receiving other opioid agonist therapy

Adults

Discontinue all other around-the-clock opioids. To convert from other morphine formulations, calculate the morphine 24-hour oral requirement; in general, the 24-hour oral requirement is 3 times the 24-hour parenteral requirement. Initiate dosing, using the 24-hour oral requirement (round down to the closest available tablet/capsule strength), for: Arymo ER, Morphabond, or MS Contin at one-half of the requirement every 12 hours or one-third every 8 hours; Avinza at the total requirement once every 24 hours; and Kadian at one-half every 12 hours or the total once every 24 hours. When initiating extended-release morphine, anticipate and treat breakthrough pain with adequate doses of immediate-release morphine as needed. When converting from other opioids, established conversion ratios to extended-release formulations have not been defined by clinical trials. Initiate dosing for: Arymo ER, Morphabond, or MS Contin at 15 mg PO every 8 or 12 hours; and Avinza or Kadian at 30 mg PO every 24 hours. Alternatively, initiate with one-half of the calculated morphine 24-hour oral requirement estimate, anticipating breakthrough pain and providing adequate doses of immediate-release morphine as needed. When converting from methadone, potency ratios to convert to other opioids can vary widely, warranting extreme caution during conversion to extended-release morphine to avoid overdosage. With the exception of Avinza, adjust dosage every 1 to 2 days based on total daily morphine requirements (extended-release dose plus breakthrough doses). Adjust Avinza dose every 3 to 4 days. Monitor frequently for respiratory depression, especially 24 to 72 hours after initiation or dose escalation. To discontinue, taper the dose by 25% to 50% every 2 to 4 days.[31637] [35890] [40951] [60209] [61668]

Oral dosage [extended-release tablets (MS Contin)] in pediatric patients

Children† and Adolescents†

Although FDA-approved product labeling provides adult dosing for both opioid-naive and opioid-tolerant patients, it would be prudent to limit pediatric use to opioid-tolerant patients. Limited data are available, and there is wide variability in dosage needs. Doses of 0.2 to 2.3 mg/kg/dose PO every 12 hours have been used in patients with various types of cancer and sickle cell disease.[52206] [52207] [52215] [52217] Begin at the lower end of the dosage range, and titrate to pain relief. Do not exceed recommended adult doses; the initial adult dosage recommendation is 15 mg PO every 8 to 12 hours, with the longer interval used in opioid-naive patients.[40951] Many experts recommend beginning with an immediate-release product to titrate to an appropriate daily dose and then switch to an extended-release formulation and divide the patient's total daily dose into 2 or 3 equal doses.[52207] Monitor patients frequently for respiratory depression, particularly during the first 24 to 72 hours after initiation or dose escalation.[40951] Extended-release morphine should not be used for as needed analgesia and is only appropriate for a select group of children; only clinicians highly experienced in pediatric pain management should prescribe extended-release formulations.

For the management of dyspnea†

in patients with end-stage cancer or pulmonary disease†

Intravenous dosage

Adults

1 to 5 mg IV at frequent intervals (as often as every 5 minutes) until the desired response is achieved. Doses are given in addition to other opiate pain medications. In terminal patients with persistent dyspnea, 25% of the equivalent 4-hour dose of morphine may be sufficient to reduce both dyspnea and tachypnea for 4 hours.

Oral inhalation dosage (nebulized intravenous solution for injection)†

Adults

Reported doses include 20 mg in 5 mL saline via nebulizer every 4 hours.

for the adjuvant treatment of acute pulmonary edema†

Intravenous dosage

Adults

1 to 3 mg IV at frequent intervals (as often as every 5 minutes) until the desired response is achieved, or, a dose sufficient to provide relief without producing respiratory depression.

For the treatment of diarrhea

for the treatment of noninfectious diarrhea

Oral dosage (Deodorized Opium Tincture Solution 10 mg/mL concentration ONLY)

Adults

6 mg PO 4 times daily. When using deodorized opium tincture 10 mg/mL, 6 mg = 0.6 mL.[56971] Use caution in geriatric patients due to the potential for adverse CNS effects; and consider alternative drugs for treatment.[56971] [56991]

Adolescents, Children, Infants, and Neonates

Deodorized opium tincture 10 mg/mL solution is not recommended for use in pediatric patients.[56971]

Oral dosage (Camphorated Opium Tincture Solution [Paregoric, USP; contains 0.4 mg/mL anhydrous morphine])

Adults

2 to 4 mg PO 1 to 4 times daily. NOTE: Dosage is expressed in mg/kg dosing units of morphine. When using opium tincture 2 mg/5 mL concentration (Paregoric, USP), 2 to 4 mg = 5 to 10 mL.[56972] Use caution in geriatric patients due to the potential for adverse CNS effects; consider alternative drugs for treatment.[56972] [56991]

Adolescents and Children

0.1 to 0.2 mg/kg/dose PO 1 to 4 times daily (Maximum: 4 mg/dose). NOTE: Dosage is expressed in mg/kg dosing units of morphine. When using opium tincture 2 mg/5 mL concentration (Paregoric, USP), 0.1 to 0.2 mg/kg = 0.25 to 0.5 mL/kg.[56972]

for control of diarrhea† secondary to AIDS-associated enteropathy

Oral dosage

Adults

Although no published studies exist on the effectiveness of nonspecific antimotility agents in treating AIDS-associated diarrhea, opioid agonists may be effective.[57033] Morphine doses of 10 to 30 mg/day PO have been recommended.[24292]

For procedural sedation† before short diagnostic procedures or endoscopy

NOTE: Morphine should be administered as an inducing agent only by those trained in anesthesia.

Intravenous dosage

Adults

2 mg IV.[32456] Premedication with a benzodiazepine may potentiate the response to morphine; a reduced morphine dose may be needed.

For sedation during rapid-sequence intubation†

Intravenous dosage

Adolescents, Children, and Infants

0.1 to 0.2 mg/kg IV has been recommended. Onset of action is typically 2 to 5 minutes.[44771]

Neonates

0.05 to 0.2 mg/kg IV has been recommended. Use the lower end of the range for opioid-naive neonates. Onset is typically 5 minutes.[44771] [44872] Use a preservative-free formulation.

For the treatment of painful diabetic neuropathy†

Oral dosage (extended-release formulations)

Adults

30 mg PO twice daily initially using extended-release tablets (e.g., MS Contin). Use an initial dosage of 15 mg PO twice daily in those who are not opioid tolerant, and consider this lower dose in geriatric patients or those weighing less than 60 kg.[40951] For Kadian, Avinza, and equivalent generic dose forms that may be given once daily, the highest starting dose for patients who are not opioid tolerant is 30 mg PO every 24 hours. Kadian is administered at a frequency of either once daily or twice daily; Avinza is administered at a frequency of once daily.[35890] Titrate as tolerated to a maximum dosage of 120 mg/day PO.[58583] [58281] In one clinical trial, the maximum dosage in patients less than 60 years of age or weighing less than 60 kg was 60 mg/day PO.[58583] Guidelines classify morphine as probably effective for the treatment of painful diabetic neuropathy.[58281]

For the treatment of neonatal abstinence syndrome†

Oral dosage

Neonates

Initially, 0.03 to 0.1 mg/kg/dose PO every 3 to 4 hours. Increase by 20% of the initial dose every 8 hours until symptoms are controlled to a maximum of 0.2 mg/kg/dose. Once the patient is on a stable dose, individualize weaning based on the patient's symptoms. Reductions of 10% to 20% of the initial dose every 1 to 2 days have been suggested.[51390] [52132]

For the treatment of dysautonomia† due to tetanus†

Intravenous dosage

Adults

0.5 to 1 mg/kg/hour continuous IV infusion.[64489] [64492]

Infants, Children, and Adolescents

0.02 to 0.05 mg/kg/hour continuous IV infusion.[64509]

For the treatment of refractory restless legs syndrome (RLS)†

Oral dosage (extended-release)

Adults

15 mg/day PO once daily, initially. Titrate based on efficacy and adverse effects. Usual dose: 15 to 45 mg/day. Longer-acting and controlled-release drugs are preferred, especially at night.[64831]

For the treatment of hypercyanotic episodes associated with tetralogy of fallot (i.e. tetralogy spells†)

Intravenous or Intramuscular dosage

Infants and Children

0.05 to 0.1 mg/kg/dose IV or IM; may repeat dose as needed until desired response is achieved.[32485] [44772]

For the treatment of ischemic chest pain in acute myocardial infarction, STEMI† and non-ST-elevation acute coronary syndromes†, including acute myocardial infarction, NSTEMI† and unstable angina†

Intravenous dosage

Adults

4 to 8 mg IV once, then 1 to 8 mg IV every 5 to 30 minutes as needed. Morphine can alleviate pain and work of breathing, decrease anxiety, produce venodilation, and reduce heart rate and systolic blood pressure.[55688] [58787]

For the treatment of short bowel syndrome†

Oral dosage (opium tincture 10 mg/mL)

Adults

3 to 20 mg PO 4 times daily. Start at a low dose and increase the dose every 2 to 5 days if inadequate response and depending on tolerability.[69771] [69772]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    Immediate-release formulations, extended-release tablets, extended-release capsules (Kadian ONLY), injectable solution (NOT DepoDur): With appropriate dosage titration, there is no maximum dose.

    Extended-release capsules (Avinza ONLY): 1600 mg/day PO due to the high concentrations of fumaric acid in the formulation.

    DepoDur liposome injection: 15 mg/dose epidurally.

    Deodorized opium tincture (10 mg/mL concentration ONLY): 6 mg/dose PO and 24 mg/day PO total.

    Camphorated opium tincture (0.4 mg/mL concentration ONLY): 4 mg/dose PO and 16 mg/day PO total.

  • Geriatric

    Immediate-release formulations, extended-release tablets, extended-release capsules (Kadian ONLY), injectable solution (NOT DepoDur): With appropriate dosage titration, there is no maximum dose.

    Extended-release capsules (Avinza ONLY): 1600 mg/day PO due to the high concentrations of fumaric acid in the formulation.

    DepoDur liposome injection: 15 mg/dose epidurally.

    Deodorized opium tincture (10 mg/mL concentration ONLY): 6 mg/dose PO and 24 mg/day PO total.

    Camphorated opium tincture (0.4 mg/mL concentration ONLY): 4 mg/dose PO and 16 mg/day PO total.

  • Adolescents

    Immediate-release formulations, extended-release tablets (MS Contin ONLY), injectable solution (NOT DepoDur): With appropriate dosage titration, there is no maximum dose.

    Extended-release capsules, extended-release tablets (Arymo ER or Morphabond), DepoDur liposome injection: Safety and efficacy have not been established.

    Deodorized opium tincture (10 mg/mL concentration ONLY): Safety and efficacy have not been established.

    Camphorated opium tincture (0.4 mg/mL concentration ONLY): 0.2 mg/kg/dose PO (Max: 4 mg/dose) and 0.8 mg/kg/day PO (Max: 16 mg/day).

  • Children

    Immediate-release formulations, extended-release tablets (MS Contin ONLY), injectable solution (NOT DepoDur): With appropriate dosage titration, there is no maximum dose.

    Extended-release capsules, extended-release tablets (Arymo ER or Morphabond), DepoDur liposome injection: Safety and efficacy have not been established.

    Deodorized opium tincture (10 mg/mL concentration ONLY): Safety and efficacy have not been established.

    Camphorated opium tincture (0.4 mg/mL concentration ONLY): 0.2 mg/kg/dose PO (Max: 4 mg/dose) and 0.8 mg/kg/day PO (Max: 16 mg/day).

  • Infants

    Immediate-release formulations, injectable solution (NOT DepoDur): With appropriate dosage titration, there is no maximum dose.

    Extended-release formulations, DepoDur liposome injection: Safety and efficacy have not been established.

    Deodorized opium tincture (10 mg/mL concentration ONLY): Safety and efficacy have not been established.

    Camphorated opium tincture (0.4 mg/mL concentration ONLY): Safety and efficacy have not been established.

  • Neonates

    Immediate-release formulations, injectable solution (NOT DepoDur): With appropriate dosage titration, there is no maximum dose.

    Extended-release formulations, DepoDur liposome injection: Safety and efficacy have not been established.

    Deodorized opium tincture (10 mg/mL concentration ONLY): Safety and efficacy have not been established.

    Camphorated opium tincture (0.4 mg/mL concentration ONLY): Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

With the exception of morphine sulfate extended-release liposome injection, which is only used as a single epidural dose, morphine dosage should be modified depending on clinical response and degree of hepatic impairment. Begin treatment with a lower than usual initial dosage, and titrate slowly while monitoring for sedation, respiratory depression, and hypotension.

Patients with Renal Impairment Dosing

The 6-glucuronide and 3-glucuronide metabolites are renally eliminated. With the exception of morphine sulfate extended-release liposome injection, which is only used as a single epidural dose, morphine dosage should be modified to prevent accumulation of the metabolite and excessive side effects. Begin treatment with a lower than usual initial dosage, and titrate slowly while monitoring for sedation, respiratory depression, and hypotension.

† Off-label indication
Revision Date: 11/06/2023, 10:47:19 AM

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Pediatric critical care. 4th ed. Philadelphia: Elsevier; 2011:1654-81.44872 - Kumar P, Denson SE, Mancuso TJ. Clinical report-premedication for nonemergency endotracheal intubation in the neonate. Pediatrics 2010;125:608-15.46350 - Morphine sulfate tablet package insert. Berkley Heights, NJ: Hikma Pharmaceuticals Corp; 2021 Jun.48404 - Morphine sulfate rectal suppositories package insert. Minneapolis, MN: Perrigo.; 2019 Mar.48405 - Astramorph PF (morphine sulfate inj solution) package insert. Schaumburg, IL: APP Pharmaceuticals, LLC; 2008 Jun.51390 - Hudak ML, Tan RC, Committee On Drugs, Committee On Fetus And Newborn, American Academy of Pediatrics. Neonatal drug withdrawal. Pediatrics 2012;129(2):e540-e560. Epub 2012 Jan 30.52132 - Burgos AE, Burke BL, Jr. Neonatal abstinence syndrome. Neoreviews 2009;10:e222-e229.52190 - Morphine injection package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2011 May.52196 - Miser AW, Davis DM, Hughes CS, et al. Continuous subcutaneous infusion of morphine in children with cancer. Am J Dis Child 1983;137:383-5.52198 - World Health Organization. Cancer pain relief and palliative care in children. Geneva, Switzerland: World Health Organization, 1998.52199 - McNicol R. Postoperative analgesia in children using continuous SC morphine. Br J Anaesth 1993;71:752-6.52200 - Kart T, Christrup LL, Rasmussen M. Recommended use of morphine in neonates, infants, and children based on literature review: part 2-clinical use. Paediatr Anaesth 1997;7:93-101.52206 - Jacobson SJ, Kopecky EA, Joshi P, et al. Randomised trial of oral morphine for painful episodes of sickle-cell disease in children. Lancet 1997;350:1358-61.52207 - Zernikow B, Michel E, Craig F, et al. Pediatric palliative care: use of opioids for the management of pain. Pediatr Drugs 2009;11:129-51.52215 - Goldman A, Bowman A. The role of oral controlled-release morphine for pain relief in children with cancer. Palliat Med 1990;4:279-85.52217 - Hunt A, Joel S, Dick G, et al. Population pharmacokinetics of oral morphine and its glucuronides in children receiving morphine as immediate-release liquid or sustained-release tablets for cancer pain. J Pediatr 1999;135:47-55.52218 - Anand KJ, International Evidence-Based Group for Neonatal Pain. Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med 2001;155:173-80.52221 - Playfor S, Jenkins I, Boyles C, et al. Consensus guidelines on sedation and analgesia in critically ill children. Intensive Care Med 2006;32:1125-36.52223 - Berde CB, Lehn BM, Yee JD, et al. Patient-controlled analgesia in children and adolescents: a randomized prospective comparison with intramuscular administration of morphine for postoperative analgesia. J Pediatr 1991;118:460-6.52226 - Karl HW, Tyler DC, Miser AW. Controlled trial of morphine vs hydromorphone for patient-controlled analgesia in children with postoperative pain. Pain Med 2012. Epub ahead of print, doi: 10.1111/j.1526-4637.2012.01496.x.52227 - Doyle E, Mottart KJ, Marshall C, et al. Comparison of different bolus doses of morphine for patient-controlled analgesia in children. Br J Anaesth 1994;72:160-3.52228 - Duedahl TH, Hansen EH. A qualitative systematic review of morphine treatment in children with postoperative pain. Pediatr Anesth 2007;17:756-74.52229 - Reinoso-Barbero F, Saavedra B, Hervilla S, et al. Lidocaine with fentanyl, compared to morphine, marginally improves postoperative epidural analgesia in children. Can J Anesth 2002;49:67-71.52230 - Kart T, Walther-Larsen S, Svejborg TF, et al. Comparison of continuous epidural infusion of fentanyl and bupivacaine with intermittent epidural administration of morphine for postoperative pain management in children. Acta Anaesthesiol Scand 1997;41:461-5.55688 - O'Gara P, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013;127:e362-e425.56971 - Opium Tincture 10 mg/mL oral solution package insert. Baudette, MN: ANI Pharmaceuticals, Inc.; 2021 Feb.56972 - Opium Tincture 2 mg/5 mL oral solution package insert. Amityville, NY: Hi-Tech Pharmacal Co, Inc.; 2013 Oct.56973 - Dallas S, Holquist C, Phillips J. Drug errors associated with opium tincture and paregoric. Drug Topics 2003;147:62.56991 - Zarowitz BJ. Pharmacologic consideration of commonly used gastrointestinal drugs in the elderly. Gastroenterol Clin N Am 2009;38:547-562.57033 - Nwachukwu CE, Okebe JU. Antimotility agents for chronic diarrhea in people with HIV/AIDS. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No CD005644. DOI 10.1002/14651858.CD005644.pub2.57161 - Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013;41:263-306.57164 - End of Life/Palliative Education Resource Center. Subcutaneous opioid infusions, 2nd ed. Fast Fact and Concepts #28: 2008. Retrieved from the World Wide Web May 9, 2014. http://www.eperc.mcw.edu/FileLibrary/User/jrehm/fastfactpdfs/Concept028.pdf.57171 - Morphine sulfate injection (for PCA) package insert. Lake Forest, IL: Hospira, Inc.; 2006 Apr.57196 - Cohen MR, Timko J. Morphine infusion protocol. Hosp Pharm 1981;16:296-297.58281 - Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy. Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2011;76:1758-1765.58583 - Gilron I, Bailey JM, Tu D, et al. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005;352:1324-1334.58787 - Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;130:e344-e426.60209 - Morphabond ER (morphine sulfate extended-release tablets) package insert. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2019 Oct.61668 - Arymo ER (morphine sulfate extended-release tablets) package insert. Wayne, PA: Egalet US Inc.; 2019 Oct.64489 - Hodowanec A, Bleck TP. Tetanus (Clostridium tetani). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 8th ed. New York: Churchill Livingstone; 2015:2757-62.64492 - Brook I. Current concepts in the management of Clostridium tetani infection. Expert Rev Anti-infect Ther. 2008;6:327-36.64509 - Angurana SK, Jayashree M, Bansal A, et al. Post-neonatal tetanus in a PICU of a developing economy: intensive care needs, outcome and predictors of mortality. J Trop Pediatr 2018;64:15-23.64831 - Silber MH, Becker PM, Buchfuhrer MJ, et al. The appropriate use of opioids in the treatment of refractory restless legs syndrome. Mayo Clin Proc 2018;93:59-67.64906 - HHS Guide for Clinicians on the Appropriate Dosage Reduction or Discontinuation of Long-Term Opioid Analgesics. Available on the World Wide Web at https://www.hhs.gov/opioids/sites/default/files/2019-10/Dosage_Reduction_Discontinuation.pdf. Accessed December 27, 2019.69771 - Kumpf VJ, Parrish CR. The clinician’s toolkit for the adult short bowel patient part II: pharmacologic interventions. Practical Gastroenterology. 2022;46:12-31.69772 - Iyer K, DiBaise JK, Rubio-Tapia A. AGA clinical practice update on management of short bowel syndrome: expert review. Clin Gastroenterol Hepatol. 2022;20:2185-2194.e2.

How Supplied

Morphine Sulfate Oral capsule

MSIR 15mg Capsule (00034-1025) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral capsule

MSIR 30mg Capsule (00034-1026) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral capsule, biphasic release

Avinza 30mg Extended-Release Capsule (64365-0505) (Ligand Pharmaceuticals Inc) (off market)

Morphine Sulfate Oral capsule, biphasic release

Avinza 30mg Extended-Release Capsule (60793-0605) (Pfizer Inc.) (off market)

Morphine Sulfate Oral capsule, biphasic release

Morphine Sulfate 30mg Extended-Release Capsule (00228-3090) (Teva/Actavis US) null

Morphine Sulfate Oral capsule, biphasic release

Avinza 45mg Extended-Release Capsule (60793-0603) (Pfizer Inc.) (off market)

Morphine Sulfate Oral capsule, biphasic release

Morphine Sulfate 45mg Extended-Release Capsule (00228-3116) (Teva/Actavis US) null

Morphine Sulfate Oral capsule, biphasic release

Avinza 60mg Extended-Release Capsule (64365-0506) (Ligand Pharmaceuticals Inc) (off market)

Morphine Sulfate Oral capsule, biphasic release

Avinza 60mg Extended-Release Capsule (60793-0606) (Pfizer Inc.) (off market)

Morphine Sulfate Oral capsule, biphasic release

Morphine Sulfate 60mg Extended-Release Capsule (00228-3091) (Teva/Actavis US) null

Morphine Sulfate Oral capsule, biphasic release

Avinza 75mg Extended-Release Capsule (60793-0604) (Pfizer Inc.) (off market)

Morphine Sulfate Oral capsule, biphasic release

Morphine Sulfate 75mg Extended-Release Capsule (00228-3117) (Teva/Actavis US) null

Morphine Sulfate Oral capsule, biphasic release

Avinza 90mg Extended-Release Capsule (64365-0507) (Ligand Pharmaceuticals Inc) (off market)

Morphine Sulfate Oral capsule, biphasic release

Avinza 90mg Extended-Release Capsule (60793-0607) (Pfizer Inc.) (off market)

Morphine Sulfate Oral capsule, biphasic release

Morphine Sulfate 90mg Extended-Release Capsule (00228-3092) (Teva/Actavis US) null

Morphine Sulfate Oral capsule, biphasic release

Avinza 120mg Extended-Release Capsule (64365-0508) (Ligand Pharmaceuticals Inc) (off market)

Morphine Sulfate Oral capsule, biphasic release

Avinza 120mg Extended-Release Capsule (60793-0608) (Pfizer Inc.) (off market)

Morphine Sulfate Oral capsule, biphasic release

Morphine Sulfate 120mg Extended-Release Capsule (00228-3093) (Teva/Actavis US) null

Morphine Sulfate Oral capsule, extended release

Kadian 10mg Extended-Release Capsule (52544-0011) (Allergan USA, Inc.) null

Morphine Sulfate Oral capsule, extended release

Kadian 10mg Extended-Release Capsule (63857-0410) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 10mg Extended-Release Capsule (46987-0410) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 10mg Extended-Release Capsule (63857-0410) (Teva/Alpharma) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 10mg Extended-Release Capsule (00228-3501) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 10mg Extended-Release Capsule (00832-0225) (Upsher-Smith Laboratories, LLC) null

Morphine Sulfate Oral capsule, extended release

Kadian 20mg Extended-Release Capsule (52544-0211) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 20mg Extended-Release Capsule (00023-6012) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 20mg Extended-Release Capsule (63857-0322) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 20mg Extended-Release Capsule (46987-0322) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 20mg Extended-Release Capsule (63857-0322) (Teva/Alpharma) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 20mg Extended-Release Capsule (00115-1277) (Impax Generics, a division of Impax Laboratories, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 20mg Extended-Release Capsule (49884-0665) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 20mg Extended-Release Capsule (49884-0833) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 20mg Extended-Release Capsule (00591-3449) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 20mg Extended-Release Capsule (00228-3502) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

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Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 20mg Extended-Release Capsule (00832-0226) (Upsher-Smith Laboratories, LLC) null

Morphine Sulfate Oral capsule, extended release

Kadian 30mg Extended-Release Capsule (52544-0032) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 30mg Extended-Release Capsule (00023-6013) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 30mg Extended-Release Capsule (63857-0325) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 30mg Extended-Release Capsule (46987-0325) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 30mg Extended-Release Capsule (63857-0325) (Teva/Alpharma) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 30mg Extended-Release Capsule (00115-1278) (Impax Generics, a division of Impax Laboratories, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 30mg Extended-Release Capsule (49884-0666) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 30mg Extended-Release Capsule (49884-0834) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 30mg Extended-Release Capsule (00591-3450) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 30mg Extended-Release Capsule (00228-3503) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 30mg Extended-Release Capsule (00832-0227) (Upsher-Smith Laboratories, LLC) null

Morphine Sulfate Oral capsule, extended release

Kadian 40mg Extended-Release Capsule (52544-0039) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 40mg Extended-Release Capsule (00023-6014) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 40mg Extended-Release Capsule (46987-0327) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 40mg Extended-Release Capsule (00115-1479) (Impax Generics, a division of Impax Laboratories, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 50mg Extended-Release Capsule (52544-0052) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 50mg Extended-Release Capsule (00023-6015) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 50mg Extended-Release Capsule (63857-0323) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 50mg Extended-Release Capsule (46987-0323) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 50mg Extended-Release Capsule (63857-0323) (Teva/Alpharma) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 50mg Extended-Release Capsule (00115-1279) (Impax Generics, a division of Impax Laboratories, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 50mg Extended-Release Capsule (49884-0667) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 50mg Extended-Release Capsule (49884-0835) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 50mg Extended-Release Capsule (00591-3451) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 50mg Extended-Release Capsule (00228-3504) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 50mg Extended-Release Capsule (00228-3504) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 50mg Extended-Release Capsule (00832-0228) (Upsher-Smith Laboratories, LLC) null

Morphine Sulfate Oral capsule, extended release

Kadian 60mg Extended-Release Capsule (52544-0063) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 60mg Extended-Release Capsule (00023-6016) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 60mg Extended-Release Capsule (63857-0326) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 60mg Extended-Release Capsule (46987-0326) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 60mg Extended-Release Capsule (63857-0326) (Teva/Alpharma) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 60mg Extended-Release Capsule (00115-1280) (Impax Generics, a division of Impax Laboratories, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 60mg Extended-Release Capsule (49884-0668) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 60mg Extended-Release Capsule (49884-0836) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 60mg Extended-Release Capsule (00591-3452) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 60mg Extended-Release Capsule (00228-3505) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 60mg Extended-Release Capsule (00832-0229) (Upsher-Smith Laboratories, LLC) null

Morphine Sulfate Oral capsule, extended release

Kadian 70mg Extended-Release Capsule (46987-0328) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 80mg Extended-Release Capsule (52544-0896) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 80mg Extended-Release Capsule (00023-6017) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 80mg Extended-Release Capsule (63857-0412) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 80mg Extended-Release Capsule (46987-0412) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 80mg Extended-Release Capsule (63857-0412) (Teva/Alpharma) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 80mg Extended-Release Capsule (00115-1281) (Impax Generics, a division of Impax Laboratories, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 80mg Extended-Release Capsule (49884-0669) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 80mg Extended-Release Capsule (49884-0837) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 80mg Extended-Release Capsule (00591-3576) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 80mg Extended-Release Capsule (00228-3506) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 80mg Extended-Release Capsule (00228-3506) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 80mg Extended-Release Capsule (00832-0230) (Upsher-Smith Laboratories, LLC) null

Morphine Sulfate Oral capsule, extended release

Kadian 100mg Extended-Release Capsule (52544-0164) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 100mg Extended-Release Capsule (00023-6018) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 100mg Extended-Release Capsule (63857-0324) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 100mg Extended-Release Capsule (46987-0324) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 100mg Extended-Release Capsule (63857-0324) (Teva/Alpharma) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 100mg Extended-Release Capsule (00115-1282) (Impax Generics, a division of Impax Laboratories, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 100mg Extended-Release Capsule (49884-0670) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 100mg Extended-Release Capsule (49884-0838) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 100mg Extended-Release Capsule (00591-3453) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 100mg Extended-Release Capsule (00228-3507) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Morphine Sulfate 100mg Extended-Release Capsule (00832-0233) (Upsher-Smith Laboratories, LLC) null

Morphine Sulfate Oral capsule, extended release

Kadian 130mg Extended-Release Capsule (46987-0329) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 150mg Extended-Release Capsule (46987-0330) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 200mg Extended-Release Capsule (52544-0220) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 200mg Extended-Release Capsule (63857-0377) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 200mg Extended-Release Capsule (46987-0377) (Teva/Actavis US) (off market)

Morphine Sulfate Oral capsule, extended release

Kadian 200mg Extended-Release Capsule (63857-0377) (Teva/Alpharma) (off market)

Morphine Sulfate Oral capsule, extended release

KADIAN 200mg Extended-Release Capsule (00023-6019) (Allergan USA, Inc.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate Concentrated 5mg/0.25mL Solution (58177-0888) (Ethex Corporation) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (60687-0760) (American Health Packaging) nullMorphine Sulfate 10mg/5mL Solution package photo

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (62559-0170) (ANI Pharmaceuticals, Inc.) nullMorphine Sulfate 10mg/5mL Solution package photo

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (00186-1124) (AstraZeneca LP) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (00054-3785) (Hikma Pharmaceuticals USA Inc.) (off market)Morphine Sulfate 10mg/5mL Solution package photo

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (00054-8585) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (00054-8586) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (00054-0237) (Hikma Pharmaceuticals USA Inc.) nullMorphine Sulfate 10mg/5mL Solution package photo

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (60432-0122) (Morton Grove Pharmaceuticals Inc, a subsidiary of Wockhardt, Ltd.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (70408-0358) (Nostrum Laboratories, Inc.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (00121-0904) (Pharmaceutical Associates Inc.) null

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (68094-0001) (Precision Dose, Inc.) null

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/5mL Solution (66689-0032) (Vistapharm Inc) null

Morphine Sulfate Oral solution

Morphine Sulfate Concentrated 10mg/0.5mL Solution (58177-0889) (Ethex Corporation) (off market)

Morphine Sulfate Oral solution

MSIR 10mg/5mL Solution (00034-0521) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/1mL Solution (68094-0755) (Precision Dose, Inc.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/5mL Concentrated Solution (60432-0123) (Morton Grove Pharmaceuticals Inc, a subsidiary of Wockhardt, Ltd.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/5mL Solution (62559-0171) (ANI Pharmaceuticals, Inc.) nullMorphine Sulfate 20mg/5mL Solution package photo

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/5mL Solution (00054-3786) (Hikma Pharmaceuticals USA Inc.) (off market)Morphine Sulfate 20mg/5mL Solution package photo

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/5mL Solution (00054-0238) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/5mL Solution (70408-0359) (Nostrum Laboratories, Inc.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/5mL Solution (66689-0033) (Vistapharm Inc) null

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Concentrated Solution (00186-1123) (AstraZeneca LP) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Concentrated Solution (68462-0349) (Glenmark Pharmaceuticals) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Concentrated Solution (68462-0349) (Glenmark Pharmaceuticals) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Concentrated Solution (00527-1425) (Lannett Company, Inc.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Concentrated Solution (00406-0829) (Mallinckrodt Pharmaceuticals) (off market)Morphine Sulfate 20mg/mL Concentrated Solution package photo

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Concentrated Solution (00406-8003) (Mallinckrodt Pharmaceuticals) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Concentrated Solution (00406-8003) (Mallinckrodt Pharmaceuticals) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Concentrated Solution (60432-0124) (Morton Grove Pharmaceuticals Inc, a subsidiary of Wockhardt, Ltd.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Concentrated Solution (00574-0127) (Paddock Laboratories Inc, a Perrigo Family) null

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Concentrated Solution (60793-0224) (Pfizer Inc.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 20mg/mL Solution (00054-0352) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate Concentrated 20mg/mL Solution (58177-0886) (Ethex Corporation) (off market)Morphine Sulfate Concentrated 20mg/mL Solution package photo

Morphine Sulfate Oral solution

MSIR 20mg/5mL Solution (00034-0522) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral solution

MSIR 20mg/mL Concentrate Solution (00034-0523) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral solution

Roxanol 100 20mg/ml Concentrated Solution (66591-0893) (AAI Pharma Inc) (off market)

Morphine Sulfate Oral solution

Roxanol Concentrated 20mg/ml Solution (00054-3751) (AAI Pharma Inc) (off market)Roxanol Concentrated 20mg/ml Solution package photo

Morphine Sulfate Oral solution

Roxanol Concentrated 20mg/ml Solution (00054-3751) (Hikma Pharmaceuticals USA Inc.) (off market)Roxanol Concentrated 20mg/ml Solution package photo

Morphine Sulfate Oral solution

Roxanol Concentrated 20mg/ml Solution (00054-3751) (Xanodyne Pharmaceuticals, Inc) (off market)Roxanol Concentrated 20mg/ml Solution package photo

Morphine Sulfate Oral solution

Roxanol Concentrated 20mg/ml Solution (66479-0560) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral solution

Roxanol-T Concentrated 20mg/mL Solution (00054-3774) (AAI Pharma Inc) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (63629-2301) (Bryant Ranch Prepack, Inc.) null

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (00054-0404) (Hikma Pharmaceuticals USA Inc.) nullMorphine Sulfate 100mg/5mL Solution package photo

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (00054-0517) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (50383-0965) (Hi-Tech Pharmacal, a subsidiary of Akorn) null

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (00527-1425) (Lannett Company, Inc.) (off market)Morphine Sulfate 100mg/5mL Solution package photo

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (70166-0101) (Lohxa) null

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (00406-8003) (Mallinckrodt Pharmaceuticals) null

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (00574-0153) (Paddock Laboratories Inc, a Perrigo Family) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (00121-0825) (Pharmaceutical Associates Inc.) nullMorphine Sulfate 100mg/5mL Solution package photo

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (27808-0082) (Tris Pharma, Inc.) null

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (Blue Raspberry) (00527-1906) (Lannett Company, Inc.) (off market)

Morphine Sulfate Oral solution

Morphine Sulfate 100mg/5mL Solution (Blue Raspberry) (00527-1906) (Lannett Company, Inc.) null

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/0.5mL Solution (68094-0754) (Precision Dose, Inc.) null

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/0.5mL Solution (68094-0045) (Precision Dose, Inc.) null

Morphine Sulfate Oral solution

Morphine Sulfate 10mg/0.5mL Solution (68094-0056) (Precision Dose, Inc.) null

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Immediate-Release Tablet (58177-0313) (Ethex Corporation) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (60687-0617) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (67877-0670) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) null

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (63629-8459) (Bryant Ranch Prepack, Inc.) null

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (68462-0202) (Glenmark Pharmaceuticals) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (00054-4582) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (00054-8582) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (00054-0235) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (00406-5118) (Mallinckrodt Pharmaceuticals) null

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (00406-5118) (Mallinckrodt Pharmaceuticals) null

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (51862-0615) (Mayne Pharma) nullMorphine Sulfate 15mg Tablet package photo

Morphine Sulfate Oral tablet

Morphine Sulfate 15mg Tablet (00832-0273) (Upsher-Smith Laboratories, LLC) null

Morphine Sulfate Oral tablet

MSIR 15mg Tablet (00034-0518) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Immediate-Release Tablet (58177-0314) (Ethex Corporation) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (67877-0671) (Ascend Laboratories, LLC a Subsidiary of Alkem Laboratories Ltd) null

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (63629-8460) (Bryant Ranch Prepack, Inc.) nullMorphine Sulfate 30mg Tablet package photo

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (68462-0203) (Glenmark Pharmaceuticals) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (00054-4583) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (00054-8583) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (00054-0236) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (00406-5119) (Mallinckrodt Pharmaceuticals) nullMorphine Sulfate 30mg Tablet package photo

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (00406-5119) (Mallinckrodt Pharmaceuticals) nullMorphine Sulfate 30mg Tablet package photo

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (51862-0617) (Mayne Pharma) null

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (55289-0863) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet

Morphine Sulfate 30mg Tablet (00832-0274) (Upsher-Smith Laboratories, LLC) null

Morphine Sulfate Oral tablet

MSIR 30mg Tablet (00034-0519) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral tablet, extended release

Arymo ER 15mg Extended-Release Tablet (69344-0111) (Zyla Life Sciences US Inc) (off market)

Morphine Sulfate Oral tablet, extended release

MorphaBond ER 15mg Extended-Release Tablet (65597-0301) (Daiichi Sankyo Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Controlled-Release Tablet (55289-0682) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Controlled-Release Tablet (00591-3511) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (68084-0403) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (68084-0403) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (68084-0157) (American Health Packaging) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (68084-0403) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (00056-0652) (Bristol Myers Squibb Pharma Co) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (63629-1087) (Bryant Ranch Prepack, Inc.) nullMorphine Sulfate 15mg Extended-Release Tablet package photo

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (71335-0736) (Bryant Ranch Prepack, Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (60951-0652) (Endo Pharmaceuticals Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (58177-0310) (Ethex Corporation) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (43386-0540) (Gavis Pharmaceuticals, LLC, wholly owned subsidiary of Lupin) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (52959-0185) (HJ Harkins Co Inc) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (00904-6557) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (00406-8315) (Mallinckrodt Pharmaceuticals) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (00406-8315) (Mallinckrodt Pharmaceuticals) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (51862-0185) (Mayne Pharma) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (63739-0899) (McKesson Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (00378-2658) (Mylan Pharmaceuticals Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (60951-0652) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (43063-0272) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (43063-0689) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (42858-0801) (Rhodes Pharmaceuticals LP) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (63304-0450) (Sun Pharmaceutical Industries, Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (00172-2162) (Teva Pharmaceuticals USA) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (00591-3740) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (00228-4270) (Teva/Actavis US) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 15mg Extended-Release Tablet (68382-0903) (Zydus Pharmaceuticals (USA) Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 15mg Extended-Release Tablet (00034-0514) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 15mg Extended-Release Tablet (59011-0260) (Purdue Pharma LP) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 15mg Extended-Release Tablet (42858-0515) (Rhodes Pharmaceuticals LP) null

Morphine Sulfate Oral tablet, extended release

Oramorph SR 15mg Sustained-Release Tablet (00054-8790) (AAI Pharma Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 15mg Sustained-Release Tablet (00054-4790) (AAI Pharma Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 15mg Sustained-Release Tablet (00054-4790) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 15mg Sustained-Release Tablet (66591-0841) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 15mg Sustained-Release Tablet (66479-0540) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Arymo ER 30mg Extended-Release Tablet (69344-0211) (Zyla Life Sciences US Inc) (off market)

Morphine Sulfate Oral tablet, extended release

MorphaBond ER 30mg Extended-Release Tablet (65597-0302) (Daiichi Sankyo Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Controlled-Release Tablet (43063-0263) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Controlled-Release Tablet (00591-3512) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (68084-0404) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (68084-0404) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (68084-0158) (American Health Packaging) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (68084-0404) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (00056-0653) (Bristol Myers Squibb Pharma Co) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (63629-1088) (Bryant Ranch Prepack, Inc.) nullMorphine Sulfate 30mg Extended-Release Tablet package photo

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (71335-0676) (Bryant Ranch Prepack, Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (60951-0653) (Endo Pharmaceuticals Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (58177-0320) (Ethex Corporation) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (43386-0541) (Gavis Pharmaceuticals, LLC, wholly owned subsidiary of Lupin) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (00904-6558) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (00406-8330) (Mallinckrodt Pharmaceuticals) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (00406-8330) (Mallinckrodt Pharmaceuticals) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (51862-0186) (Mayne Pharma) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (63739-0726) (McKesson Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (00378-2659) (Mylan Pharmaceuticals Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (60951-0653) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (43063-0274) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (43063-0688) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (42858-0802) (Rhodes Pharmaceuticals LP) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (63304-0451) (Sun Pharmaceutical Industries, Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (00172-2163) (Teva Pharmaceuticals USA) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (00591-3741) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (00228-4271) (Teva/Actavis US) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 30mg Extended-Release Tablet (68382-0904) (Zydus Pharmaceuticals (USA) Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 30mg Extended-Release Tablet (00034-0515) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 30mg Extended-Release Tablet (59011-0261) (Purdue Pharma LP) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 30mg Extended-Release Tablet (42858-0631) (Rhodes Pharmaceuticals LP) null

Morphine Sulfate Oral tablet, extended release

Oramorph SR 30mg Sustained-Release Tablet (00054-8805) (AAI Pharma Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 30mg Sustained-Release Tablet (00054-4805) (AAI Pharma Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 30mg Sustained-Release Tablet (66591-0851) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 30mg Sustained-Release Tablet (00054-4805) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 30mg Sustained-Release Tablet (00054-8805) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 30mg Sustained-Release Tablet (66591-0541) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 30mg Sustained-Release Tablet (66479-0541) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Arymo ER 60mg Extended-Release Tablet (69344-0311) (Zyla Life Sciences US Inc) (off market)

Morphine Sulfate Oral tablet, extended release

MorphaBond ER 60mg Extended-Release Tablet (65597-0303) (Daiichi Sankyo Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Controlled-Release Tablet (55289-0875) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Controlled-Release Tablet (00591-3513) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (68084-0405) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (68084-0159) (American Health Packaging) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (68084-0405) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (00056-0655) (Bristol Myers Squibb Pharma Co) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (71335-0707) (Bryant Ranch Prepack, Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (63629-1089) (Bryant Ranch Prepack, Inc.) nullMorphine Sulfate 60mg Extended-Release Tablet package photo

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (60951-0655) (Endo Pharmaceuticals Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (58177-0330) (Ethex Corporation) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (43386-0542) (Gavis Pharmaceuticals, LLC, wholly owned subsidiary of Lupin) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (00904-6559) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (00406-8380) (Mallinckrodt Pharmaceuticals) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (00406-8380) (Mallinckrodt Pharmaceuticals) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (51862-0187) (Mayne Pharma) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (00378-2660) (Mylan Pharmaceuticals Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (60951-0655) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (43063-0275) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (43063-0684) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (42858-0803) (Rhodes Pharmaceuticals LP) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (63304-0758) (Sun Pharmaceutical Industries, Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (00172-2164) (Teva Pharmaceuticals USA) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (00591-3742) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (00228-4311) (Teva/Actavis US) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 60mg Extended-Release Tablet (68382-0905) (Zydus Pharmaceuticals (USA) Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 60mg Extended-Release Tablet (00034-0516) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 60mg Extended-Release Tablet (59011-0262) (Purdue Pharma LP) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 60mg Extended-Release Tablet (42858-0760) (Rhodes Pharmaceuticals LP) null

Morphine Sulfate Oral tablet, extended release

Oramorph SR 60mg Sustained-Release Tablet (00054-8792) (AAI Pharma Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 60mg Sustained-Release Tablet (00054-4792) (AAI Pharma Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 60mg Sustained-Release Tablet (00054-8792) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 60mg Sustained-Release Tablet (00054-4792) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 60mg Sustained-Release Tablet (66479-0542) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

MorphaBond ER 100mg Extended-Release Tablet (65597-0304) (Daiichi Sankyo Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Controlled-Release Tablet (55289-0684) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Controlled-Release Tablet (00591-3514) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (68084-0406) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (68084-0160) (American Health Packaging) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (68084-0406) (American Health Packaging) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (63629-1090) (Bryant Ranch Prepack, Inc.) nullMorphine Sulfate 100mg Extended-Release Tablet package photo

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (60951-0658) (Endo Pharmaceuticals Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (58177-0340) (Ethex Corporation) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (43386-0543) (Gavis Pharmaceuticals, LLC, wholly owned subsidiary of Lupin) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (00904-6560) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (00406-8390) (Mallinckrodt Pharmaceuticals) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (00406-8390) (Mallinckrodt Pharmaceuticals) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (51862-0188) (Mayne Pharma) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (00378-2661) (Mylan Pharmaceuticals Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (60951-0658) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (43063-0280) (PD-Rx Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (42858-0804) (Rhodes Pharmaceuticals LP) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (63304-0452) (Sun Pharmaceutical Industries, Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (00172-2165) (Teva Pharmaceuticals USA) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (00591-0617) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (52544-0617) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (00591-3743) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (00228-4323) (Teva/Actavis US) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 100mg Extended-Release Tablet (68382-0906) (Zydus Pharmaceuticals (USA) Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 100mg Extended-Release Tablet (00034-0517) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 100mg Extended-Release Tablet (59011-0263) (Purdue Pharma LP) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 100mg Extended-Release Tablet (42858-0799) (Rhodes Pharmaceuticals LP) null

Morphine Sulfate Oral tablet, extended release

Oramorph SR 100mg Sustained-Release Tablet (00054-8793) (AAI Pharma Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 100mg Sustained-Release Tablet (00054-4793) (AAI Pharma Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 100mg Sustained-Release Tablet (00054-4793) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 100mg Sustained-Release Tablet (00054-8793) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 100mg Sustained-Release Tablet (66591-0871) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 100mg Sustained-Release Tablet (66479-0543) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Oramorph SR 100mg Sustained-Release Tablet (66479-0543) (Xanodyne Pharmaceuticals, Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Controlled-Release Tablet (00591-3515) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (63629-1091) (Bryant Ranch Prepack, Inc.) nullMorphine Sulfate 200mg Extended-Release Tablet package photo

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (60951-0659) (Endo Pharmaceuticals Inc) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (58177-0380) (Ethex Corporation) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (43386-0544) (Gavis Pharmaceuticals, LLC, wholly owned subsidiary of Lupin) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (00406-8320) (Mallinckrodt Pharmaceuticals) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (00378-2662) (Mylan Pharmaceuticals Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (60951-0659) (Par Pharmaceuticals, an Endo Company) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (42858-0805) (Rhodes Pharmaceuticals LP) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (63304-0453) (Sun Pharmaceutical Industries, Inc.) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (00172-2166) (Teva Pharmaceuticals USA) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (00591-3744) (Teva/Actavis US) (off market)

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (00228-4347) (Teva/Actavis US) null

Morphine Sulfate Oral tablet, extended release

Morphine Sulfate 200mg Extended-Release Tablet (68382-0907) (Zydus Pharmaceuticals (USA) Inc.) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 200mg Extended-Release Tablet (00034-0513) (Purdue Frederick Co) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 200mg Extended-Release Tablet (59011-0264) (Purdue Pharma LP) (off market)

Morphine Sulfate Oral tablet, extended release

MS Contin 200mg Extended-Release Tablet (42858-0900) (Rhodes Pharmaceuticals LP) null

Morphine Sulfate Rectal suppository

Morphine Sulfate 5mg Rectal Suppository (00713-0193) (Cosette Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Rectal suppository

Morphine Sulfate 5mg Rectal Suppository (00574-7110) (Paddock Laboratories Inc, a Perrigo Family) null

Morphine Sulfate Rectal suppository

RMS 5mg Rectal Suppository (00245-0160) (Upsher-Smith Laboratories, LLC) (off market)

Morphine Sulfate Rectal suppository

Morphine Sulfate 10mg Rectal Suppository (00713-0194) (Cosette Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Rectal suppository

Morphine Sulfate 10mg Rectal Suppository (00574-7112) (Paddock Laboratories Inc, a Perrigo Family) null

Morphine Sulfate Rectal suppository

RMS 10mg Rectal Suppository (00245-0161) (Upsher-Smith Laboratories, LLC) (off market)

Morphine Sulfate Rectal suppository

Morphine Sulfate 20mg Rectal Suppository (00713-0195) (Cosette Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Rectal suppository

Morphine Sulfate 20mg Rectal Suppository (00574-7114) (Paddock Laboratories Inc, a Perrigo Family) null

Morphine Sulfate Rectal suppository

RMS 20mg Rectal Suppository (00245-0162) (Upsher-Smith Laboratories, LLC) (off market)

Morphine Sulfate Rectal suppository

Morphine Sulfate 30mg Rectal Suppository (00713-0196) (Cosette Pharmaceuticals, Inc.) (off market)

Morphine Sulfate Rectal suppository

Morphine Sulfate 30mg Rectal Suppository (00574-7116) (Paddock Laboratories Inc, a Perrigo Family) null

Morphine Sulfate Rectal suppository

RMS 30mg Rectal Suppository (00245-0163) (Upsher-Smith Laboratories, LLC) (off market)

Morphine Sulfate Soluble tablet for injection

Morphine Sulfate 10mg Soluble Tablet for Injection (00002-2549) (Eli Lilly and Co) (off market)

Morphine Sulfate Soluble tablet for injection

Morphine Sulfate 10mg Soluble Tablet for Injection (63304-0706) (Sun Pharmaceutical Industries, Inc.) (off market)

Morphine Sulfate Soluble tablet for injection

Morphine Sulfate 15mg Soluble Tablet for Injection (00002-2550) (Eli Lilly and Co) (off market)

Morphine Sulfate Soluble tablet for injection

Morphine Sulfate 15mg Soluble Tablet for Injection (00002-0707) (Eli Lilly and Co) (off market)

Morphine Sulfate Soluble tablet for injection

Morphine Sulfate 15mg Soluble Tablet for Injection (63304-0707) (Sun Pharmaceutical Industries, Inc.) (off market)

Morphine Sulfate Soluble tablet for injection

Morphine Sulfate 30mg Soluble Tablet for Injection (00002-2551) (Eli Lilly and Co) (off market)

Morphine Sulfate Soluble tablet for injection

Morphine Sulfate 30mg Soluble Tablet for Injection (00002-0708) (Eli Lilly and Co) (off market)

Morphine Sulfate Soluble tablet for injection

Morphine Sulfate 30mg Soluble Tablet for Injection (63304-0708) (Sun Pharmaceutical Industries, Inc.) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 0.5mg/mL Solution for Injection (00186-1150) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 0.5mg/mL Solution for Injection (00186-1152) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 0.5mg/mL Solution for Injection (00186-1159) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 0.5mg/mL Solution for Injection (00186-1159) (Fresenius Kabi USA, LLC ) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 0.5mg/mL Solution for Injection (00186-1150) (Fresenius Kabi USA, LLC ) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 0.5mg/mL Solution for Injection (00186-1152) (Fresenius Kabi USA, LLC ) null

Morphine Sulfate Solution for injection

Astramorph PF 0.5mg/mL Solution for Injection (63323-0291) (Fresenius Kabi USA, LLC ) null

Morphine Sulfate Solution for injection

Astramorph PF 0.5mg/mL Solution for Injection (63323-0291) (Fresenius Kabi USA, LLC ) (off market)

Morphine Sulfate Solution for injection

Duramorph PF 0.5mg/mL Solution for Injection (00641-1112) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Duramorph PF 0.5mg/mL Solution for Injection (60977-0016) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Duramorph PF 0.5mg/mL Solution for Injection (60977-0016) (Hikma Pharmaceuticals USA inc.) (off market)

Morphine Sulfate Solution for injection

Duramorph PF 5mg/10mL Solution for Injection (00641-6020) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Solution for injection

Morphine Sulfate 0.2mg/ml Solution for Injection (00074-6063) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 0.5mg/ml Solution for Injection (00074-3814) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 0.5mg/ml Solution for Injection (00074-2028) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 0.5mg/ml Solution for Injection (00409-4057) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 0.5mg/mL Solution for Injection (00555-1129) (Teva Pharmaceuticals USA) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 0.5mg/mL Solution for Injection (00555-1127) (Teva Pharmaceuticals USA) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/10mL Solution for Injection (00409-3814) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate Preservative Free 0.5mg/ml Solution for Injection (00074-4057) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 1mg/mL Solution for Injection (00186-1151) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 1mg/mL Solution for Injection (00186-1153) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 1mg/mL Solution for Injection (00186-1160) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 1mg/mL Solution for Injection (00186-1160) (Fresenius Kabi USA, LLC ) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 1mg/mL Solution for Injection (00186-1151) (Fresenius Kabi USA, LLC ) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 1mg/mL Solution for Injection (00186-1153) (Fresenius Kabi USA, LLC ) (off market)

Morphine Sulfate Solution for injection

Astramorph PF 1mg/mL Solution for Injection (63323-0292) (Fresenius Kabi USA, LLC ) null

Morphine Sulfate Solution for injection

Astramorph PF 1mg/mL Solution for Injection (63323-0292) (Fresenius Kabi USA, LLC ) null

Morphine Sulfate Solution for injection

Duramorph PF 10mg/10mL Solution for Injection (00641-6019) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Solution for injection

Duramorph PF 1mg/mL Solution for Injection (00641-1114) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Duramorph PF 1mg/mL Solution for Injection (60977-0017) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Duramorph PF 1mg/mL Solution for Injection (60977-0017) (Hikma Pharmaceuticals USA inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/10mL Solution for Injection (00409-3815) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00186-0686) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00186-1120) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00338-2689) (Baxter Medication Delivery) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00338-2686) (Baxter Medication Delivery) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00074-6023) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (61703-0219) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00548-1937) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00548-1911) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00548-2901) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00548-6548) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00548-1931) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00548-1933) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00548-3391) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00548-8450) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (76329-1911) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) null

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/ml Solution for Injection (00406-8700) (Mallinckrodt Pharmaceuticals) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/mL Solution for Injection (00074-3815) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/mL Solution for Injection (00555-1130) (Teva Pharmaceuticals USA) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1mg/mL Solution for Injection (00555-1128) (Teva Pharmaceuticals USA) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate Preservative Free 1mg/ml Solution for Injection (00074-4058) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate Preservative Free 1mg/ml Solution for Injection (00074-2029) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate Preservative Free 1mg/ml Solution for Injection (00409-2029) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate Preservative Free 1mg/mL Solution for Injection (00409-4058) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate Preservative Free 1mg/mL Solution for Injection (76329-1912) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) null

Morphine Sulfate Solution for injection

Morphine Sulfate 2mg/ml Solution for Injection (00338-2687) (Baxter Medication Delivery) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 2mg/ml Solution for Injection (00074-6022) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 2mg/ml Solution for Injection (00074-1762) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 2mg/ml Solution for Injection (00409-1762) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 2mg/ml Solution for Injection (00406-8710) (Mallinckrodt Pharmaceuticals) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 2mg/mL Solution for Injection (63323-0452) (Fresenius Kabi USA, LLC ) null

Morphine Sulfate Solution for injection

Morphine Sulfate 2mg/mL Solution for Injection (00409-1890) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 2mg/mL Solution for Injection (00409-1890) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Simplist Morphine Sulfate 2mg/mL Prefilled Syringe Solution for Injection (76045-0004) (BD Rx Inc., a Fresenius Kabi USA Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 4mg/ml Solution for Injection (00074-1258) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 4mg/ml Solution for Injection (00409-1258) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 4mg/ml Solution for Injection (00008-0653) (Wyeth Pharmaceuticals Inc, a subsidiary of Pfizer Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 4mg/mL Solution for Injection (72572-0440) (Civica, Inc.) null

Morphine Sulfate Solution for injection

Morphine Sulfate 4mg/mL Solution for Injection (63323-0454) (Fresenius Kabi USA, LLC ) null

Morphine Sulfate Solution for injection

Morphine Sulfate 4mg/mL Solution for Injection (00641-6125) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Solution for injection

Morphine Sulfate 4mg/mL Solution for Injection (00409-1891) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 4mg/mL Solution for Injection (00409-1891) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Simplist Morphine Sulfate 4mg/mL Prefilled Syringe Solution for Injection (76045-0005) (BD Rx Inc., a Fresenius Kabi USA Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/ml Solution for Injection (00186-0687) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/ml Solution for Injection (10019-0176) (Baxter Anesthesia/Critical Care) (off market)Morphine Sulfate 5mg/ml Solution for Injection package photo

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/ml Solution for Injection (00641-0168) (Baxter Anesthesia/Critical Care) (off market)Morphine Sulfate 5mg/ml Solution for Injection package photo

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/ml Solution for Injection (00338-2690) (Baxter Medication Delivery) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/ml Solution for Injection (10019-0176) (Hikma Pharmaceuticals USA inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/ml Solution for Injection (00641-6073) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/ml Solution for Injection (00074-6028) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/ml Solution for Injection (61703-0221) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/ml Solution for Injection (00409-6028) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/ml Solution for Injection (00409-6028) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 5mg/mL Solution for Injection (63323-0455) (Fresenius Kabi USA, LLC ) null

Morphine Sulfate Solution for injection

Morphine Sulfate Preservative Free 5mg/ml Solution for Injection (10019-0006) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Simplist Morphine Sulfate 5mg/mL Prefilled Syringe Solution for Injection (76045-0006) (BD Rx Inc., a Fresenius Kabi USA Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/ml Solution for Injection (00641-0170) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/ml Solution for Injection (00641-1170) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/ml Solution for Injection (10019-0177) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/ml Solution for Injection (10019-0177) (Hikma Pharmaceuticals USA inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/ml Solution for Injection (00641-6075) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/ml Solution for Injection (00074-1259) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/ml Solution for Injection (00074-1260) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/ml Solution for Injection (00409-1260) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/ml Solution for Injection (00409-1892) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/mL Solution for Injection (63323-0458) (Fresenius Kabi USA, LLC ) null

Morphine Sulfate Solution for injection

Morphine Sulfate 8mg/mL Solution for Injection (00641-6126) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Solution for injection

Simplist Morphine Sulfate 8mg/ml Prefilled Syringe Solution for Injection (76045-0007) (BD Rx Inc., a Fresenius Kabi USA Company) null

Morphine Sulfate Solution for injection

Infumorph PF 10mg/ml Solution for Injection (00641-1131) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Infumorph PF 10mg/ml Solution for Injection (60977-0114) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Infumorph PF 10mg/ml Solution for Injection (60977-0114) (Hikma Pharmaceuticals USA inc.) (off market)

Morphine Sulfate Solution for injection

Infumorph PF 200mg/20ml Solution for Injection (00641-6039) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Solution for injection

MITIGO 200mg/20mL Solution for Injection (66794-0160) (Piramal Critical Care Inc.) null

Morphine Sulfate Solution for injection

Morphine Sulfate 100mg/10ml Solution for Injection (00641-6068) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00186-1139) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00641-0180) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00641-2343) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00641-1180) (Baxter Anesthesia/Critical Care) (off market)Morphine Sulfate 10mg/ml Solution for Injection package photo

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (10019-0178) (Baxter Anesthesia/Critical Care) (off market)Morphine Sulfate 10mg/ml Solution for Injection package photo

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (10019-0178) (Hikma Pharmaceuticals USA inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00641-6070) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00074-6178) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00074-3817) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (61703-0232) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (61703-0231) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00074-1263) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00074-1261) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00409-1261) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (00548-6321) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/ml Solution for Injection (60793-0063) (Pfizer Inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/mL Solution for Injection (63323-0451) (Fresenius Kabi USA, LLC ) null

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/mL Solution for Injection (00641-6127) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/mL Solution for Injection (00409-1893) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 10mg/mL Solution for Injection (00409-1893) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate Preservative Free 10mg/ml Solution for Injection (10019-0007) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Simplist Morphine Sulfate 10mg/mL Prefilled Syringe Solution for Injection (76045-0008) (BD Rx Inc., a Fresenius Kabi USA Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (00186-1158) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (00641-0190) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (00641-1190) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (00641-2345) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (10019-0179) (Baxter Anesthesia/Critical Care) (off market)Morphine Sulfate 15mg/ml Solution for Injection package photo

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (00002-1637) (Eli Lilly and Co) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (10019-0179) (Hikma Pharmaceuticals USA inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (00641-6071) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (00074-3819) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (00074-1262) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (00074-1264) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/ml Solution for Injection (00409-1264) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 15mg/mL Solution for Injection (00409-1894) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 300mg/20ml Solution for Injection (00641-6072) (Hikma Pharmaceuticals USA Inc.) (off market)

Morphine Sulfate Solution for injection

Infumorph PF 25mg/ml Solution for Injection (00641-1132) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Infumorph PF 25mg/ml Solution for Injection (60977-0115) (Baxter Anesthesia/Critical Care) (off market)

Morphine Sulfate Solution for injection

Infumorph PF 25mg/ml Solution for Injection (60977-0115) (Hikma Pharmaceuticals USA inc.) (off market)

Morphine Sulfate Solution for injection

Infumorph PF 500mg/20ml Solution for Injection (00641-6040) (Hikma Pharmaceuticals USA Inc.) null

Morphine Sulfate Solution for injection

MITIGO 500mg/20mL Solution for Injection (66794-0162) (Piramal Critical Care Inc.) null

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Conc P-F Solution for Injection (00074-1135) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Conc P-F Solution for Injection (00409-1135) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00186-1135) (AstraZeneca LP) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00074-6177) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00074-6179) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00074-1133) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (61703-0224) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (61703-0223) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00409-6177) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00409-6179) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00548-6025) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00548-6026) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00548-6043) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00548-6042) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00548-6044) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00548-6328) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00548-6351) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 25mg/ml Solution for Injection (00548-6045) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 1,000mg/20mL Solution for Injection (00409-1896) (Hospira Worldwide, Inc., a Pfizer Company) nullMorphine Sulfate 1,000mg/20mL Solution for Injection package photo

Morphine Sulfate Solution for injection

Morphine Sulfate 50mg/ml Conc Solution for Injection (00074-1134) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 50mg/ml Conc Solution for Injection (00409-1134) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine Sulfate Solution for injection

Morphine Sulfate 50mg/ml Solution for Injection (61703-0226) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 50mg/ml Solution for Injection (61703-0225) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 50mg/ml Solution for Injection (00548-6023) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 50mg/ml Solution for Injection (00548-6039) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 50mg/ml Solution for Injection (00548-6040) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 50mg/ml Solution for Injection (00548-6041) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Solution for injection

Morphine Sulfate 50mg/ml Solution for Injection (00548-6356) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)

Morphine Sulfate Suspension for injection

DepoDur 10mg/ml Extended-Release Suspension for Injection (65250-0020) (EKR Therapeutics) (off market)

Morphine Sulfate Suspension for injection

DepoDur 10mg/ml Extended-Release Suspension for Injection (24477-0020) (EKR Therapeutics) (off market)

Morphine Sulfate Suspension for injection

DepoDur 10mg/ml Extended-Release Suspension for Injection (63481-0110) (Endo Pharmaceuticals Inc) (off market)

Morphine Sulfate Suspension for injection

DepoDur 15mg/1.5ml Extended-Release Suspension for Injection (65250-0020) (EKR Therapeutics) (off market)

Morphine Sulfate Suspension for injection

DepoDur 15mg/1.5ml Extended-Release Suspension for Injection (24477-0020) (EKR Therapeutics) (off market)

Morphine Sulfate Suspension for injection

DepoDur 15mg/1.5ml Extended-Release Suspension for Injection (63481-0115) (Endo Pharmaceuticals Inc) (off market)

Morphine Sulfate Suspension for injection

DepoDur 20mg/2ml Extended-Release Suspension for Injection (63481-0120) (Endo Pharmaceuticals Inc) (off market)

Morphine Sulfate, Dextrose Solution for injection

Morphine Sulfate 1mg/ml in Dextrose 5% Solution for Injection (00074-6062) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Morphine Sulfate, Dextrose Solution for injection

Morphine Sulfate 1mg/ml in Dextrose 5% Solution for Injection (00409-6062) (Hospira Worldwide, Inc., a Pfizer Company) null

Morphine, Anhydrous Oral solution

Opium Tincture (Paregoric) 2% Solution (50383-0855) (Hi-Tech Pharmacal, a subsidiary of Akorn) (off market)

Morphine, Anhydrous Oral solution

Paregoric 2mg/5mL Liquid (50383-0855) (Hi-Tech Pharmacal, a subsidiary of Akorn) (off market)

Morphine, Anhydrous Oral solution

Paregoric 2mg/5mL Liquid (50383-0855) (Hi-Tech Pharmacal, a subsidiary of Akorn) (off market)

Morphine, Anhydrous Oral solution

Paregoric 2mg/5mL Liquid (50383-0855) (Hi-Tech Pharmacal, a subsidiary of Akorn) (off market)

Morphine, Anhydrous Oral solution

Paregoric 2mg/5mL Solution (00556-0257) (HR Cenci Laboratories Inc) (off market)

Morphine, Anhydrous Oral solution

Paregoric 2mg/5mL Solution (00904-0802) (Major Pharmaceuticals Inc, a Harvard Drug Group Company) (off market)

Morphine, Anhydrous Oral solution

Paregoric 2mg/5mL Solution (60432-0457) (Morton Grove Pharmaceuticals Inc, a subsidiary of Wockhardt, Ltd.) (off market)Paregoric 2mg/5mL Solution package photo

Morphine, Anhydrous Oral solution

Paregoric 2mg/5mL Solution (00781-6130) (Sandoz Inc. a Novartis Company) (off market)

Morphine, Anhydrous Oral solution

Paregoric 2mg/5mL Solution (00472-0802) (Teva/Actavis US) (off market)Paregoric 2mg/5mL Solution package photo

Morphine, Anhydrous Oral solution

Paregoric 2mg/5mL Solution (00472-0802) (Teva/Actavis US) (off market)Paregoric 2mg/5mL Solution package photo

Morphine, Anhydrous Oral solution

Opium Tincture 10mg/ml Solution (62559-0153) (ANI Pharmaceuticals, Inc.) null

Morphine, Anhydrous Oral solution

Opium Tincture 10mg/ml Solution (42799-0217) (Edenbridge Pharmaceuticals, LLC) null

Morphine, Anhydrous Oral solution

Opium Tincture 10mg/ml Solution (00002-2606) (Eli Lilly and Co) (off market)

Morphine, Anhydrous Oral solution

Opium Tincture 10mg/ml Solution (00002-0203) (Eli Lilly and Co) (off market)

Morphine, Anhydrous Oral solution

Opium Tincture 10mg/ml Solution (42998-0203) (Marathon Pharmaceuticals LLC) (off market)Opium Tincture 10mg/ml Solution package photo

Morphine, Anhydrous Oral solution

Opium Tincture 10mg/ml Solution (00574-0159) (Paddock Laboratories Inc, a Perrigo Family) (off market)

Morphine, Anhydrous Oral solution

Opium Tincture 10mg/ml Solution (63304-0203) (Sun Pharmaceutical Industries, Inc.) (off market)Opium Tincture 10mg/ml Solution package photo

Morphine, Anhydrous Oral solution

Opium Tincture 10mg/mL Solution (42998-0203) (Bausch Health US, LLC) (off market)

Morphine, Anhydrous Oral solution

Opium Tincture 10mg/mL Solution (00187-4203) (Bausch Health US, LLC) (off market)

Description/Classification

Description

Morphine is the principal alkaloid obtained from the unripened seed capsules of the opium poppy, Papaver somniferum. It was first isolated in 1803 and is the prototype of the opiate agonists. Today, the poppy is still the source of the drug because synthesis of morphine is difficult. Morphine is a strong analgesic that has been used for the relief of moderate to severe acute and chronic pain, for preoperative sedation, and as a supplement to anesthesia; the drug has also been used for analgesia during labor. Morphine is the drug of choice for pain associated with myocardial infarction and cancer. Many different formulations of morphine are available including both extended-release and immediate-release injectable and oral dosage forms, rectal suppositories, and bulk powder for compounding. Morphine was initially marketed before 1962, which is when Congress passed the amended Federal Food, Drug, and Cosmetic Act requiring that the FDA establish both safety and efficacy for all subsequently approved drugs. Many products were approved under current regulations; however, some manufacturers of morphine have not submitted their products for formal evaluation by the FDA. On March 31st 2009, the FDA issued a Warning Letter to specific manufacturers to halt the production and distribution of the unapproved products. Based on this action, all single ingredient morphine products marketed after July 1, 2009 must be FDA approved. Two formulations of opium tincture, deodorized opium tincture and camphorated opium tincture, contain anhydrous morphine and may be useful for the treatment of non-infectious diarrhea. Opium tinctures have not been found to be safe and effective by the FDA, and they are considered unapproved drugs.[56971][56972][57034] Serious medication errors have resulted from confusion between the products, as the deodorized tincture is 25-times more concentrated than the camphorated tincture.[56973]

Classifications

  • Alimentary Tract and Metabolism
    • Antidiarrheals, Intestinal Antiinflammatories/Antiinfective Agents
      • Antipropulsives
  • Central Nervous System
    • Analgesics
      • Opiate Agonists and Related Agents
        • Opioid Agonists
Revision Date: 04/23/2014, 03:26:15 PM

References

56971 - Opium Tincture 10 mg/mL oral solution package insert. Baudette, MN: ANI Pharmaceuticals, Inc.; 2021 Feb.56972 - Opium Tincture 2 mg/5 mL oral solution package insert. Amityville, NY: Hi-Tech Pharmacal Co, Inc.; 2013 Oct.56973 - Dallas S, Holquist C, Phillips J. Drug errors associated with opium tincture and paregoric. Drug Topics 2003;147:62.57034 - International Journal of Pharmaceutical Compounding. Unapproved drugs. Retrieved from the World Wide Web April 18, 2014. https://www.ijpc.com/Patient_Info/Unapproved_Drugs.pdf.

Administration Information

General Administration Information

For storage information, see the specific product information within the How Supplied section.

 

NOTE: If Duramorph or Infumorph gets on the skin, remove any contaminated clothing and rinse the affected area with water.

Route-Specific Administration

Oral Administration

  • When initiating therapy, begin with an immediate-release preparation and titrate to the appropriate analgesic dose and then convert the patient to an extended-release product if appropriate.[52207]
  • Storage: Store morphine securely in a location not accessible by others.
  • Disposal: Flush unused morphine down the toilet when it is no longer needed if a drug take-back option is not readily available.[40951]

Oral Solid Formulations

Immediate-release Tablets

  • Administer without regard to meals; may be given with food or milk to minimize gastrointestinal irritation.[46350]

 

Immediate-release Capsules

  • May be swallowed whole, or opened and the contents sprinkled on cool food such as pudding or applesauce.
  • Capsule contents may be added to juice and administered immediately or delivered via gastric or nasogastric tube by either adding to or following with liquid.

 

Extended-release Tablets (e.g., Arymo ER, MS Contin, Morphabond)

  • Swallow whole; do not cut, crush, break, dissolve, or chew. Swallow Arymo tablets 1 at a time immediately after placing in the mouth. Do not pre-soak, lick, or otherwise wet Arymo tablets prior to placing in the mouth; the tablet may become sticky leading to difficulty in swallowing, choking, gagging, or regurgitation.
  • Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of therapy initiation or dose escalation.
  • MS Contin 100 and 200 mg tablets or Morphabond 100 mg tablets are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Limit use of a single dose of extended-release tablets more than 60 mg or a total daily dose more than 120 mg to opioid-tolerant patients.[40951] [60209] [61668]
  • Morphabond ER: The biologically inert components of this tablet may remain intact and appear as a tablet in the stool.[60209]

 

Extended-release Capsules (e.g., Avinza, Kadian)

  • Swallow whole; do not chew, crush, or dissolve.
  • Capsules may be opened and the contents sprinkled on applesauce (at room temperature or cooler) immediately prior to ingestion; no other food has been tested. Do not chew, crush, or dissolve the pellets/beads inside the capsule. The applesauce needs to be swallowed without chewing. If the pellets/beads are chewed, an immediate release of a potentially fatal morphine dose may be delivered. Rinse mouth to ensure all the pellets/beads have been swallowed. Do not separate applesauce into separate doses; the entire portion should be taken. Discard any unused portion of the capsules after the contents have been sprinkled on the applesauce.
  • Kadian capsules may be administered through a 16 French gastrostomy tube. Flush the tube with water, and sprinkle the capsule contents into 10 mL of water. Using a funnel and a swirling motion, pour the pellets and water into the tube. Rinse the beaker with 10 mL of water, and pour the water into the funnel. Repeat until no pellets remain in the beaker. Do not administer Avinza tablets through a gastrostomy tube. Do not administer Avinza or Kadian through a nasogastric tube.
  • Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of therapy initiation or dose escalation.
  • Avoid concurrent administration of Avinza or Kadian with prescription or non-prescription medications that contain alcohol. Consumption of alcohol while taking the extended-release capsules may result in the rapid release and absorption of a potentially fatal dose of morphine.
  • Avinza 90 and 120 mg capsules or Kadian 100 and 200 mg capsules are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Limit use of a single dose of extended-release capsules more than 60 mg or a total daily dose more than 120 mg to opioid-tolerant patients.[31637] [35890]

Oral Liquid Formulations

Oral Solution

  • Carefully check dose prior to dispensing medication as many concentrations of morphine oral solution are available. Limit the use of the 20 mg/mL concentration to opioid-tolerant adult patients.
  • Always use an appropriately calibrated measuring device (e.g., syringe, dosing cup) with metric units of measure.[43053]

 

Opium Tincture (10 mg/mL or 0.4 mg/mL formulations)

  • Shake well before using.
  • Dispense in unit-dose packaging.
  • Protect from light and excessive heat. The product may deposit sediment if exposed to low temperatures. Filter if necessary.[56972]
  • Serious overdosage may result if product selection is improper. Place poison labels on all containers of opium tincture as well as label the strength of morphine per mL. Include a warning regarding improper substitution of camphorated opium tincture (0.4 mg/mL) with deodorized opium tincture (10 mg/mL).[57035]

Extemporaneous Compounding-Oral

Extemporaneous 0.4 mg/mL Morphine Oral Solution Preparation

  • Measure 10 mL (20 mg) of ethanol-free oral morphine 2 mg/mL solution (commercially-available from Roxane).
  • Transfer to an appropriate-sized plastic amber bottle.
  • Measure 40 mL of Sterile Water for Irrigation in a syringe or graduated cylinder.
  • Transfer to the plastic amber bottle containing morphine.
  • Shake to mix.
  • Storage: The solution is stable for 60 days when stored in a light protected container at room temperature (20 to 25 degrees C).[59313]

Injectable Administration

  • Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
  • Resuscitative medications, including naloxone, and size-appropriate equipment for bag/valve/mask ventilation and intubation must be readily available.[52190]

Intravenous Administration

Intermittent IV Injection

  • Inject directly into a vein or into the tubing of a freely flowing IV solution over 4 to 5 minutes. Rapid IV injection of morphine may result in an increased frequency of adverse effects.[52190]

 

Continuous IV Infusion

  • Dilute in 5% Dextrose Injection, 10% Dextrose Injection, 0.9% Sodium Chloride Injection, 0.45% Sodium Chloride Injection, or Lactated Ringer's Injection.
  • Common concentrations range from 0.5 to 1 mg/mL. Maximum concentrations of 5 mg/mL have been used.[52234]
  • ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 1 mg/mL or 5 mg/mL (for those with high dosage requirements).[64020]
  • ASHP Recommended Standard Concentrations for Pediatric Continuous Infusions: 0.04 mg/mL, 0.5 mg/mL, or 1 mg/mL.[66173]
  • Administer using a controlled-infusion device.
  • Adjust dose and rate based on patient response.

 

Patient-Controlled Analgesia (PCA)

  • A compatible patient-controlled infusion device must be used.
  • Adjust dose and rate based on patient response. Consult the patient-controlled infusion device operator's manual for directions on administering the drug at the desired rate of infusion.

Intramuscular Administration

  • Inject into a large muscle mass (e.g., anterolateral thigh or deltoid [adults, adolescents, and children only]).[64690]

Subcutaneous Administration

  • Inject subcutaneously taking care not to inject intradermally.

 

Continuous Subcutaneous Infusion

  • Morphine is not FDA-approved for continuous subcutaneous administration.
  • Dilute to an appropriate concentration in 5% Dextrose Injection, and administer using a portable, controlled, subcutaneous infusion device. Adjust rate based on patient response and tolerance.
  • Maximum subcutaneous rate of infusion is 2 mL/hour/site.

Intrathecal Administration

  • Use ONLY preservative-free injectable solutions.
  • Intrathecal administration should only be used by specially trained healthcare professionals.
  • Intrathecal dose is approximately one-tenth of the epidural dose.
  • If the product is supplied in a glass vial, filter the drug through a 5 micron or smaller microfilter.[31296] [51758]

 

Intermittent Intrathecal Injection (morphine sulfate solution)

  • After ensuring proper placement of the needle or catheter, inject appropriate dose intrathecally.
  • Monitor patient in a fully equipped and staffed environment for at least 24 hours after each dose. Both early and late respiratory depression has occurred more frequently after intrathecal administration than epidural administration.[31296]

 

Continuous Intrathecal Infusion (morphine sulfate injection)

  • A controlled-infusion device must be used. For highly concentrated injections, an implantable controlled-microinfusion device is used. Monitor patients in a fully equipped and staffed environment for several days after implantation of the device.
  • If dilution of the injection is necessary, 0.9% Sodium Chloride Injection is recommended.
  • Filling of the infusion device reservoir should only be done by fully trained and qualified healthcare professionals. Strict aseptic technique must be used. Ensure proper placement of the needle when filling the reservoir to avoid accidental overdosage.
  • To avoid exacerbation of severe pain and/or reflux of CSF into the reservoir, avoid depletion of the reservoir.[51758]

Other Injectable Administration

Epidural Administration

  • Use ONLY preservative-free injectable solutions.
  • Epidural administration should only be used by specially trained healthcare professionals.
  • May be given as intermittent bolus, continuous infusion, or as patient-controlled epidural analgesia.
  • If the product is supplied in a glass vial, filter the drug through a 5 micron or smaller microfilter.
  • Storage: For single use only. Protect from light; discard any unused portion.[31296] [51758]

 

Intermittent Epidural Injection (morphine sulfate solution)

  • After ensuring proper placement of the needle or catheter, inject appropriate dose into the epidural space.
  • Monitor patient in a fully equipped and staffed environment for at least 24 hours after each dose. Both early and late respiratory depression has occurred more frequently after intrathecal administration than epidural administration.[31296]

 

Continuous Epidural Infusion (morphine sulfate solution)

  • A controlled-infusion device must be used. For highly concentrated injections, an implantable controlled-microinfusion device is used. Monitor patients in a fully equipped and staffed environment for several days after implantation of the device.
  • If dilution of the injection is necessary, 0.9% Sodium Chloride Injection is recommended.
  • Filling of the infusion device reservoir should only be done by fully trained and qualified healthcare professionals. Strict aseptic technique must be used. Ensure proper placement of the needle when filling the reservoir to avoid accidental overdosage.
  • To avoid exacerbation of severe pain and/or reflux of CSF into the reservoir, avoid depletion of the reservoir.[51758]

Rectal Administration

  • Instruct patient or caregiver on proper use of suppository.
  • Moisten the suppository with water prior to insertion. If suppository is too soft because of storage in a warm place, chill in the refrigerator for 30 minutes or run cold water over it before removing the wrapper.

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database

Morphine sulfate

pH Range
pH 2.5 to 6.5 (USP range) pH 3.5 to 7 (Duramorph)
ReferencesAnon. The United States Pharmacopeia. Rockville, Maryland: The United States Pharmacopeial Convention. Current edition.
ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
Osmolality/Osmolarity
Morphine sulfate intrathecal injections compounded from powder at concentrations of 5 and 50 mg/mL in sodium chloride 0.9% had osmolalities of 310 and 401 mOsm/kg, respectively. Concentrations of 5 and 50 mg/mL in sterile water for injection were hypotonic having osmolalities of 7 and 104 mOsm/kg, respectively. Schneider et al. reported that commercial morphine sulfate from David Bull Laboratories mixed at a concentration of 7.5 mg/mL in sodium chloride 0.9% was mildly hypotonic having a measured osmolality of 236 mOsm/kg.
ReferencesSchneider JJ, Wilson KM, Ravenscroft PJ. A study of the osmolality and pH of subcutaneous drug infusion solutions. Austral J Hosp Pharm. 1997; 27
ReferencesTrissel LA. Drug information- osmolalities. Data on file.
Stability
Morphine sulfate injection in intact containers stored as directed by the manufacturer is stable until the labeled expiration date. Morphine sulfate is stable in solution. A number of studies have reported the stability of the repackaged undiluted injection and also dilutions for varying periods. Nahata et al. reported that morphine sulfate 1 mg/mL in bacteriostatic water for injection in glass vials was stable by HPLC analysis for at least 91 days at room temperature and refrigerated. Duafala et al. reported that morphine sulfate 2 and 15 mg/mL in sterile water for injection in polyvinyl chloride (PVC) bags was stable by HPLC analysis with no loss in 15 days at room temperature and refrigerated. Walker et al. reported that Allen & Hanburys morphine sulfate 10 mg/mL transferred to glass vials and to PVC bags was stable with HPLC analysis finding no loss in 30 days. A number of studies have evaluated the storage of undiluted morphine sulfate at higher concentrations and also dilutions to concentrations as low as 0.2 mg/mL with storage at body temperature of 37 degree C in simulated implantable pump delivery. Studies by Hildebrand et al., Sadjak et al, and Sitaram et al. reported that morphine sulfate was physically and chemically stable for periods ranging from 30 days to 8 weeks. Medtronic reported that morphine sulfate in the Synchromed implantable pump was stable for up to 90 days at room and body temperature. The manufacturers state in the labeling that morphine sulfate products should not be heat sterilized. Infusion Solutions: Numerous studies of the stability of morphine salts have appeared reporting that morphine sulfate and hydrochloride are stable in common infusion solutions. Study periods have ranged from 36 hours to 3 months at room temperature in dextrose 5% and sodium chloride 0.9% and up to 60 days in sodium chloride 0.9% at 32 degree C. Refrigerated storage in these solutions extended to 57 days in dextrose 5% and 87 days in sodium chloride 0.9% with acceptable drug concentrations being retained. Nguyen-Xuan et al. evaluated the long-term stability of morphine sulfate 1 mg/mL in sodium chloride 0.9% packaged in 100-mL polypropylene infusion bags (Polimoon Langeskov). The solutions were autoclaved at 121 degree C for 20 minutes for sterilization. The solutions were evaluated over 36 months stored at room temperature of 25 degree C and over 6 months at temperatures of 30 and 40 degree C. No visible precipitation appeared in any sample, and electronic particulate evaluation found subvisible particulates remained within compendial limits throughout the study. Little or no loss of moisture or change in pH occurred in any of the samples. Stability-indicating HPLC analysis found no loss of morphine sulfate in any of the solutions and little formation of degradation products throughout the respective study periods. The authors demonstrated that unlike PVC bags that cannot be autoclaved and exhibit excessive loss water through evaporation, polypropylene bags can be successfully used for compounding bags of morphine sulfate solutions with long-term (3-year) stability for use in patient-controlled analgesia. Packaged in Syringes: Morphine sulfate is stable for extended periods when packaged in glass and polypropylene syringes. A number of studies have reported that morphine sulfate undiluted or diluted in sterile water for injection, dextrose 5%, or sodium chloride 0.9% is stable stored at room temperature and refrigerated when protected from exposure to light for study periods ranging up to 12 weeks. Bray et al. reported that morphine 0.1 to 1 mg/mL (salt form was not cited) diluted in sodium chloride 0.9% in polypropylene syringes was stable for 36 hours at room temperature. Duafala et al. reported that morphine sulfate 15 mg/mL (undiluted) and 2 mg/mL in sterile water for injection in Hypod glass syringes was stable for 12 days at room temperature and refrigerated. Grassby and Hutchings reported that morphine sulfate 2 mg/mL in sodium chloride 0.9% in Sherwood and Becton-Dickinson polypropylene syringes was stable for 6 weeks at room temperature protected from light with about 5% loss. Trissel et al. reported that morphine sulfate 50 mg/mL in sterile water for injection, and 5 mg/mL in sodium chloride in Becton-Dickinson polypropylene syringes was stable for up to 60 days at room temperature and refrigerated. However, the 50-mg/mL samples stored refrigerated precipitated. Warming at 37 degree C redissolved the visible precipitate but thousands of undissolved microparticulates remained possibly shed by the syringe components. Gove et al. reported morphine sulfate was stable in plastic syringes for 69 days at room temperature. Strong et al. reported that morphine sulfate 1 and 5 mg/mL in dextrose 5% and in sodium chloride 0.9% in Becton-Dickinson Plastipak and Sherwood Monoject polypropylene syringes was stable for 12 weeks at room temperature and refrigerated protected from exposure to light. However, exposure of the room temperature samples to light resulted in unacceptable losses after only a week. Hung et al. reported that morphine sulfate was stable for 12 weeks in plastic syringes stored at room temperature protected from and exposed to light, although a smaller drug loss occurred if protected from light. Sharley and Burgess reported on the stability of morphine sulfate 0.8 mg/mL with alfentanil hydrochloride 55 mcg/mL in sodium chloride 0.9% packaged in Becton Dickinson polypropylene syringes inside black plastic overwraps. No particulate matter was observed, and HPLC analysis found no loss of morphine sulfate or of alfentanil hydrochloride in 182 days at room temperature or refrigerated. Elastomeric Infusers: Lee et al. reported that morphine sulfate 2 mg/mL and 10 mg/mL (diluent unspecified) was physically and chemically stable in Accufuser Plus silicone balloon infusers stored at room temperature of 20 to 23 degree C and refrigerated at 4 degree C. No visible change in color or clarity was observed, and HPLC analysis found little or no loss of morphine sulfate after storage for 40 days at either temperature. Paramedic Vehicles: Valenzuela et al. reported the stability of morphine sulfate injection exposed to temperatures ranging from 26 to 38 degree C under simulated summer conditions in paramedic vehicles over 4 weeks. Gas chromatography coupled with mass spectrometry found no change in the drug over 4 weeks under these simulated use conditions.
ReferencesAnon. Manufacturer's information and labeling. (Package insert).
ReferencesAnon. Drug stability data for Intermate and Infusor portable elastomeric infusion devices. Round Lake, IL: Baxter Healthcare Corporation.. 2008;
ReferencesAnon. Guidelines for the administration of drugs using the Homepump Eclipse and C-Series disposable elastomeric infusion systems. Lake Forest, CA: I-Flow Corporation. 2004;
ReferencesBing CM, Chamallas SN, Filibeck DJ, et al. Extended stability for Parenteral Drugs, 4th ed., Bethesda, MD: American Society of Health-System Pharmacists. 2009;
ReferencesBray RJ, Davies PA, Seviour JA. The stability of preservative-free morphine in plastic syringes. Anaesthesia. 1986; 41
ReferencesDuafala ME, Kleinberg ML, Nacov C, et al. Stability of morphine sulfate in infusion devices and containers for intravenous administration. Am J Hosp Pharm. 1990; 47
ReferencesGove LF, Gordon NH, Miller J, et al. Pre-filled syringes for self-administration of epidural opiates. Pharm J. 1985; 234
ReferencesGrassby PF, Hutchings L. Factors affecting the physical and chemical stability of morphine sulphate solutions stored in syringes. Int J Pharm Pract. 1993; 2
ReferencesGrassby PF. The stability of morphine sulphate in 0.9% sodium chloride. Pharm J. 1991; 248
ReferencesHildebrand KR, Elsberry DD, Hassenbusch SJ. Stability and compatibility of morphine-clonidine admixtures in an implantable infusion pump system. J Pain Sympt Manag. 2003; 25
ReferencesHung CT, Young M, Gupta PK. Stability of morphine sulfate solutions in plastic syringes determined by reverse-phase ion-pair liquid chromatography. J Pharm Sci. 1988; 77
ReferencesLee G, Sabra K, Doyle L, et al. Stability of morphine sulphate in P.C.A.s. Eur J Hosp Pharm. 2003; 8
ReferencesLee G, Sabra K. Stability of morphine sulphate in ANAPA Plus ambulatory infusion device and PEGA infusion sets. Eur J Hosp Pharm Sci. 2006; 12
ReferencesMacias JM, Martin WJ, Lloyd CW. Stability of morphine sulfate and meperidine hydrochloride in a parenteral nutrient formulation. Am J Hosp Pharm. 1985; 42
ReferencesNahata MC, Morosco RS, Hipple TF. Stability of morphine sulfate in bacteriostatic 0.9% sodium chloride injection stored in glass vials at two temperatures. Am J Hosp Pharm. 1992; 49
ReferencesNguyen-Xuan T, Griffiths W, Kern C, et al. Stability of morphine sulfate in polypropylene infusion bags for use in patient-controlled analgesia pumps for postoperative pain management. Int J Pharmaceut Compound. 2006; 10
ReferencesRoos PJ, Glerum JH, Meilink JW. Stability of morphine hydrochloride in a portable pump reservoir. Pharm Weekbl Sci Ed. 1992; 14
ReferencesSadjak A, Wintersteiger R. Compatibility of morphine, baclofen, floxuridine and fluorouracil in an implantable medication pump. Arzneim Forsch. 1995; 45
ReferencesSitaram BR, Tsui M, Rawicki HB, et al. Stability and compatibility of baclofen and morphine admixtures for use in an implantable infusion pump. Int J Pharm. 1995; 118
ReferencesSitaram BR, Tsui M, Rawicki HB, et al. Stability and compatibility of intrathecal admixtures containing baclofen and high concentrations of morphine. Int J Pharm. 1997; 153
ReferencesStrong ML, Schaaf LJ, Pankaskie MC, et al. Shelf-lives and factors affecting the stability of morphine sulphate and meperidine (pethidine) hydrochloride in plastic syringes for use in patient-controlled analgesic devices. J Clin Pharm Ther. 1994; 19
ReferencesTrissel LA, Xu QA, Pham L. Physical and chemical stability of morphine sulfate 5 mg/mL and 50 mg/mL packaged in plastic syringes. Int J Pharmaceut Compound. 2002; 6
ReferencesValenzuela TD, Criss EA, Hammargen WM, et al. Thermal stability of prehospital medications. Ann Emerg Med. 1989; 18
ReferencesWalker SE, Coons C, Matte D, et al. Hydromorphone and morphine sulfate in portable infusion pump cassettes and minibags. Can J Hosp Pharm. 1988; 41
ReferencesWalker SE, Iazzetta J, Lau DWC. Stability of sulfite free high potency morphine sulfate solutions in portable infusion pump casettes. Can J Hosp Pharm. 1989; 42
ReferencesWilliams OA, Middleton M, Henderson P, et al. Stability of morphine and droperidol separately and combined, for use as an infusion. Hosp Pharm Pract. 1992; 2
pH Effects
Morphine (as sulfate) is stable in aqueous solutions having an acidic pH and exhibits maximum stability below pH 4. However, it is unstable at neutral and alkaline pH undergoing degradation accompanied by yellow to brown discoloration. The source of this discoloration is unknown and not related to the formation of the two principal decomposition products. Schmid et al. reported no difference in morphine sulfate stability at a low concentration of 2 mg/mL in an admixture with ketamine hydrochloride in sodium chloride 0.9% with the pH adjusted over a range of pH 5.5 to 7.5 stored at room temperature over 4 days. However, Lau et al. found that at much higher concentrations precipitation of morphine occurred at pH values above pH 6.4. Mixtures of morphine sulfate at about 18 mg/mL and morphine tartrate at about 58 mg/mL admixed with ketamine hydrochloride were adjusted toward neutrality from the initial pH of 4.85 using sodium bicarbonate injection. Up to pH 5.9, the mixtures did not precipitate over 24 hours at 21 degree C. Precipitation occurred within 2 hours when the solution was adjusted to pH 6.2. Precipitation occurred immediately when the solution was adjusted to pH 6.4 and above.
ReferencesConnors KA, Amidon GL, Stella VJ. Chemical stability of pharmaceuticals, A handbook for pharmacists. New York: John Wiley & Sons, 1986. 1986;
ReferencesLau MH, Hackman C, Morgan DJ. Compatibility of ketamine and morphine injections. Pain. 1998; 75
ReferencesSchmid R, Koren G, Klein J, et al. The stability of a ketamine-morphine solution. Anesth Analg. 2002; 94
ReferencesSitaram BR, Tsui M, Rawicki HB, et al. Stability and compatibility of intrathecal admixtures containing baclofen and high concentrations of morphine. Int J Pharm. 1997; 153
ReferencesVermeire A, Remon JP. Stability and compatibility of morphine. Int J Pharm. 1999; 187
Light Exposure
Morphine sulfate exposed to light will darken and discolor. Some stability studies have reported higher rates of morphine decomposition if exposed to light while others have reported only minor differences. The nature, intensity, and duration of the light exposure may play a role in reported differences. Protection from light exposure may be appropriate for longer-term storage but appears to be unnecessary for short-term exposure during preparation and administration.
ReferencesHung CT, Young M, Gupta PK. Stability of morphine sulfate solutions in plastic syringes determined by reverse-phase ion-pair liquid chromatography. J Pharm Sci. 1988; 77
ReferencesJohnson CE, Christen C, Perez MM, et al. Compatibility of bupivacaine hydrochloride and morphine sulfate. Am J Health-Syst Pharm. 1997; 54
ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
ReferencesStrong ML, Schaaf LJ, Pankaskie MC, et al. Shelf-lives and factors affecting the stability of morphine sulphate and meperidine (pethidine) hydrochloride in plastic syringes for use in patient-controlled analgesic devices. J Clin Pharm Ther. 1994; 19
ReferencesTrissel LA, Xu QA, Pham L. Physical and chemical stability of morphine sulfate 5 mg/mL and 50 mg/mL packaged in plastic syringes. Int J Pharmaceut Compound. 2002; 6
Freezing
Morphine sulfate injection in original containers should be protected from freezing during storage. Depiero et al. reported that Lilly morphine (as sulfate) diluted to 1 mg/mL and 2 mg/mL in dextrose 5% and in sodium chloride 0.9% in polyvinyl chloride (PVC) plastic bags was stable frozen at -20 degree C with HPLC analysis finding little or no drug loss over 14 weeks. Trissel et al. reported morphine (as sulfate) 50 mg/mL in sterile water for injection and 5 mg/mL in sodium chloride 0.9% packaged in polypropylene syringes and frozen at -20 degree C precipitated from solution. The precipitate visually appeared to redissolve upon warming at 37 degree C for several hours, but a residual amount of tens of thousands of microparticulates remained undissolved possibly shed by the syringe components during the freeze-thaw process. No loss of morphine sulfate was found by HPLC analysis.
ReferencesAnon. Manufacturer's information and labeling. (Package insert).
ReferencesDepiero D, Rekhi GS, Souney PF, et al. Stability of morphine sulfate solutions frozen in poyvinyl chloride intravenous bags. Pharm Pract News. 1987; 14
ReferencesTrissel LA, Xu QA, Pham L. Physical and chemical stability of morphine sulfate 5 mg/mL and 50 mg/mL packaged in plastic syringes. Int J Pharmaceut Compound. 2002; 6
Filtration
Vermiere and Remon reported that morphine (tested as the hydrochloride) at concentrations of 10 and 50 mg/mL in dextrose 5%, sodium chloride 0.9%, and water did not undergo substantial binding to cellulose acetate filter membranes. Less than 3% loss was observed. Pall reported that acetazolamide sodium 5 mg/mL underwent no loss due to filtration through a Supor membrane filter.
ReferencesAnon. Pall Medical Supor-membrane IV filter device drug-adsorption data. Data on file. 2004; 8
ReferencesVermeire A, Remon JP. The solubility of morphine and the stability of concentrated morphine solutions in glass, polypropylene syringes and PVC containers. Int J Pharm. 1997; 146
Sorption Leaching
Morphine salts have not been found to undergo substantial sorption to polyvinyl chloride (PVC) containers and tubing, polyethylene tubing, Silastic tubing, cellulose propionate burettes, Vygon ambulatory PCA system, polypropylene and polypropylene/polyethylene in syringes, or glass containers, or to silicone rubber and polysulfone reservoirs and elastomeric (balloon) pump reservoirs. In addition, Xu et al. reported no sorption occurred to a polyurethane central catheter from Arrow International as well as no leaching of the chlorhexidine antimicrobial in it.
ReferencesAnon. Drug stability data for Intermate and Infusor portable elastomeric infusion devices. Round Lake, IL: Baxter Healthcare Corporation.. 2008;
ReferencesAnon. Guidelines for the administration of drugs using the Homepump Eclipse and C-Series disposable elastomeric infusion systems. Lake Forest, CA: I-Flow Corporation. 2004;
ReferencesCaute B, Monsarrat B, Lazorthes Y, et al. The stability of morphine in isobaric and hyperbaric solutions in a drug delivery system. J Pharm Pharmacol. 1988; 40
ReferencesKowaluk EA, Roberts MA, Blackburn HD, et al. Interactions between drugs and polyvinyl chloride infusion bags. Am J Hosp Pharm. 1981; 38
ReferencesKowaluk EA, Roberts MS, Polack AE. Interactions between drugs and intravenous delivery systems. Am J Hosp Pharm. 1982; 39
ReferencesLe Hoang MD, Sarbach C, Prognon P, et al. Stabilite du chlorhydrate de morphine en solution dans les systems PCA portables a usage unique:Interaction content-contenu. [Stability of morphine hydrochloride solutions in portable single-use PCA systems. Additives leaching into the morphine solutions]. J Pharm Clin. 1998; 17
ReferencesMacias JM, Martin WJ, Lloyd CW. Stability of morphine sulfate and meperidine hydrochloride in a parenteral nutrient formulation. Am J Hosp Pharm. 1985; 42
ReferencesNyhammar E, Lindberg I. Stabilitet av morfin- och hydromorfonlosningar i Infusor 0,5 ml/h [The stability of morphine and hydromorphone solutions in an Infusor at 0.5 ml/hr]. Sjukhusfarmaci. 1987; 4
ReferencesSharley NA, Burgess NG. Stability and compatibility of alfentanil hydrochloride and morphine sulfate in polypropylene syringes. J Pharm Pract Res. 2003; 33
ReferencesStiles ML, Tu YH, Allen LV Jr. Stability of morphine sulfate in portable pumps reservoirs during storage and simulated administration. Am J Hosp Pharm. 1989; 46
ReferencesTruelle-Hugon B, Tourette G, Couineaux B, et al. Etude de stabilite du chlorhydrate de morphine Lavoisier dans differents systems actifs pour perfusion apres reconstitution dans divers solvents. [Study of Lavoisier morphine hydrochloride in different active perfusion systems after reconstitution.]. Ann Pharm Fr. 1997; 55
ReferencesVecchio M, Walker SE, Iazetta J, et al. The stability of morphine intravenous infusion solutions. Can J Hosp Pharm. 1988; 41
ReferencesVermeire A, Remon JP. Stability and compatibility of morphine. Int J Pharm. 1999; 187
ReferencesWalker SE, Coons C, Matte D, et al. Hydromorphone and morphine sulfate in portable infusion pump cassettes and minibags. Can J Hosp Pharm. 1988; 41
ReferencesWalker SE, Iazzetta J, Lau DWC. Stability of sulfite free high potency morphine sulfate solutions in portable infusion pump casettes. Can J Hosp Pharm. 1989; 42
ReferencesWilliams OA, Middleton M, Henderson P, et al. Stability of morphine and droperidol separately and combined, for use as an infusion. Hosp Pharm Pract. 1992; 2
ReferencesXu QA, Zhang Y, Trissel LA, et al. Adequacy of a new chlorhexidine-bearing polyurethane central catheter for administration of 82 selected parenteral drugs. Ann Pharmacother. 2000; 34
Other Information
Bupivacaine: Trissel et al. reported the stability of (1) bupivacaine hydrochloride 2.5 mg/mL and morphine sulfate 5 mg/mL in sodium chloride 0.9% and (2) bupivacaine hydrochloride 25 mg/mL and morphine sulfate 50 mg/mL in sterile water for injection for 60 days at room temperature and refrigerated and for 2 days at 37 degree C. Slight yellow color formation did not indicated drug decomposition. Although no decomposition occurred upon freezing at -20 degree C, thousands of microparticulates per milliliter were found upon thawing. Clonidine: Clonidine hydrochloride 0.1 mg/mL with morphine sulfate 10 mg/mL mixed in equal amounts remained clear and colorless and HPLC analysis found little or no change in the concentration of either drug in 14 days at room temperature protected from light. Trissel et al. reported similar results for clonidine 0.25 mg/mL with morphine sulfate 5 mg/mL in sodium chloride 0.9% and also clonidine hydrochloride 4 mg/mL with morphine sulfate 50 mg/mL in sterile water for injection with HPLC analysis finding little or no loss of either drug in 60 days at 4 and 23 degree C, and in 2 days at either 37 degree C or frozen at -20 degree C. Precipitation occurred in the frozen samples, but the visible precipitate dissolved upon warming to room temperature. However, microparticulates remained numbering in the thousands/mL. Hildebrand et al. reported that solutions of morphine sulfate 20 mg/mL with clonidine hydrochloride 0.05 mg/mL and also morphine sulfate 2 mg/mL with clonidine hydrochloride 1.84 mg/mL in Medtronic SynchroMed EL implantable pumps were physically compatible and chemically stable and did not interfere with the mechanical functioning of the pumps. Stability-indicating HPLC analysis found that concentrations of both drugs delivered from the pumps were 94 to 99.6% for both drugs over 3 months at 37 degree C. Ketamine: Donnelly evaluated the compatibility and stability of ketamine hydrochloride 2 mg/mL mixed with morphine sulfate 2, 5, or 10 mg/mL in sodium chloride 0.9% and packaged in polypropylene plastic syringes with tip caps. The mixtures were physically and chemically stable for 91 days at room temperature of 23 degree C exposed to light and refrigerated at 5 degree C protected from exposure to light. Stability-indicating HPLC analysis found little or no loss of either drug within the study period. Ziconotide: Morphine sulfate combined with ziconotide acetate has been found to be therapeutically useful in controlling pain. Additionally, morphine sulfate was found to be physically compatible and chemically stable with ziconotide acetate. However, ziconotide acetate was subject to decomposition depending on the morphine sulfate concentrations. Ziconotide concentrations remained at or above 90% at 37 degree C for the indicated time periods for the morphine sulfate concentrations indicated: Morphine sulfate 35 mg/mL- 8 days Morphine sulfate 20 mg/mL- 19 days Morphine sulfate 10 mg/mL- 34 days Multiple Drugs: Nassr et al. reported the stability of a six-drug combination consisting of morphine sulfate (Sabex) 10 mg/mL, octreotide acetate (Sandoz) 0.01 mg/mL, haloperidol lactate (Sabex) 0.5 mg/mL, famotidine (Merck) 0.4 mg/mL, metoclopramide hydrochloride (Sabex) 0.5 mg/mL, and dimenhydrinate 5 mg/mL diluted in sodium chloride 0.9% and packaged in 5-mL polypropylene syringes. The samples were stored refrigerated at 4 degree C and at room temperature of 25 degree C for 96 hours. No visible haze, color change, particulates, or gas evolution was observed. Stability-indicating HPLC analysis found little or no drug loss occurred. Octreotide was below the limit of detection and was not tested. The Magnificent Seven: Christie et al. reported the stability of a seven-drug combination consisting of equal quantities of bupivacaine hydrochloride 1.5 mg/mL, clonidine hydrochloride 0.03 mg/mL, fentanyl citrate 0.01 mg/mL, ketamine hydrochloride 2 mg/mL, lidocaine hydrochloride 2 mg/mL, morphine sulfate 0.2 mg/mL, and tetracaine hydrochloride 2 mg/mL. The combination remained visually clear and analysis found no new decomposition product peaks formed within 1 hour after mixing.
ReferencesAlicino I, Giglio M, Manca F, et al. Intrathecal combination of ziconotide and morphine for refractory cancer pauin: a rapidly acting and effective choice. Pain. 2012; 153
ReferencesDonnelly RF. Physical compatibility and chemical stability of ketamine-morphine mixtures in polypropylene syringes. Can J Hosp Pharm. 2009; 62
ReferencesHildebrand KR, Elsberry DD, Hassenbusch SJ. Stability and compatibility of morphine-clonidine admixtures in an implantable infusion pump system. J Pain Sympt Manag. 2003; 25
ReferencesNassr S, Brunet M, Lavoie P, et al. HPLC-DAD method for studying the stability of solutions containing morphine, dexamethasone, haloperidol, midazolam, famotidine, metoclopramide, and dimenhydrinate. J Liq Chromatog Rel Technol. 2001; 24
ReferencesSchobelock MJ (Medical Affairs, Roxane Laboratories). Personal communication, November 7, 1997. Data on file. 1997; 11
ReferencesShields D, Montenegro R, Ragusa M. Chemical stability of admixtures combining ziconotide with morphine or hydromorphone during simulated intrathecal administration. Neuromodulation. 2005; 4
ReferencesShields DE, Aclan J, Szatkowski A. Chemical stability of admixtures containing ziconotide 25 mcg/mL and morphine sulfate 10 mg/mL or 20 mg/mL during simulated intrathecal administration. Int J Pharmaceut Compound. 2008; 12
ReferencesAlicino I, Giglio M, Manca F, et al. Intrathecal combination of ziconotide and morphine for refractory cancer pauin: a rapidly acting and effective choice. Pain. 2012; 153
ReferencesChristie JM, Jones CW, Markowsky SJ. Chemical compatibility of regional anesthetic drug combinations. Ann Pharmacother. 1992; 26
Stability Max
Maximum reported stability periods: In D5W- 31 days at room temperature and 57 days refrigerated. In NS- 60 days at 32 degree C (near body temperature) and 182 days at room temperature and refrigerated. Also see Stability.
ReferencesAnon. Drug stability data for Intermate and Infusor portable elastomeric infusion devices. Round Lake, IL: Baxter Healthcare Corporation.. 2008;
ReferencesRoos PJ, Glerum JH, Meilink JW. Stability of morphine hydrochloride in a portable pump reservoir. Pharm Weekbl Sci Ed. 1992; 14
ReferencesSharley NA, Burgess NG. Stability and compatibility of alfentanil hydrochloride and morphine sulfate in polypropylene syringes. J Pharm Pract Res. 2003; 33
ReferencesWalker SE, Iazzetta J, Lau DWC. Stability of sulfite free high potency morphine sulfate solutions in portable infusion pump casettes. Can J Hosp Pharm. 1989; 42
Revision Date: 01/20/2021, 01:45:33 PMCopyright 2004-2024 by Lawrence A. Trissel. All Rights Reserved.

References

31296 - Duramorph (morphine sulfate injection) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Oct.31637 - Avinza (morphine sulfate extended-release capsules) package insert. Gainesville, GA: Alkermes Gainesville LLC.; 2014 Apr.35890 - Kadian (morphine sulfate extended-release capsules) package insert. Madison, NJ: Allergan USA, Inc.; 2021 Mar.40951 - MS Contin (morphine sulfate extended-release tablets) package insert. Stamford, CT: Purdue Pharma L.P.; 2023 Dec.43053 - Morphine sulfate oral solution package insert. Berkley, NJ: Hikma Pharmaceuticals USA, Inc.; 2021 Jun.46350 - Morphine sulfate tablet package insert. Berkley Heights, NJ: Hikma Pharmaceuticals Corp; 2021 Jun.51758 - Infumorph (morphine sulfate injection) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Oct.52190 - Morphine injection package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2011 May.52207 - Zernikow B, Michel E, Craig F, et al. Pediatric palliative care: use of opioids for the management of pain. Pediatr Drugs 2009;11:129-51.52234 - Morphine. In: Pediatric Injectable Drugs. Phelps SJ, Hak EB, Crill CM 9th ed., Bethesda, MD: American Society of Health-System Pharmacists; 2010:406-8.56972 - Opium Tincture 2 mg/5 mL oral solution package insert. Amityville, NY: Hi-Tech Pharmacal Co, Inc.; 2013 Oct.57035 - Institute for Safe Medication Practices (ISMP) Medication Safety Alert. Confusion between opium tinctures marks need for community high alert list. May 2006. Available on the World Wide Web at http://www.ismp.org/newsletters/ambulatory/archives/200605_1.asp.59313 - Sauberan J, Ross S, Kim JH. Stability of dilute oral morphine solution for neonatal abstinence syndrome. J Addict Med 2013;7:113-115.60209 - Morphabond ER (morphine sulfate extended-release tablets) package insert. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2019 Oct.61668 - Arymo ER (morphine sulfate extended-release tablets) package insert. Wayne, PA: Egalet US Inc.; 2019 Oct.64020 - American Society of Health-System Pharmacists. Standardize 4 Safety Initiative, IV adult continuous infusion guidelines. Retrieved March 19th, 2019. Available at: https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/s4s-proposed-standard-concentrations-adult-continuous-infusions.ashx64690 - Morphine sulfate injection package insert. Lake Zurich, IL: Fresenius Kabi; 2018 May.66173 - American Society of Health-System Pharmacists. Standardize 4 Safety Initiative, Pediatric Continuous Infusion Standards. Retrieved December 15th, 2020. Available at: https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/Pediatric-Infusion-Standards.ashx

Adverse Reactions

Moderate

  • adrenocortical insufficiency
  • amblyopia
  • amnesia
  • anemia
  • ataxia
  • bladder spasm
  • blurred vision
  • bone pain
  • chest pain (unspecified)
  • confusion
  • conjunctivitis
  • constipation
  • delirium
  • depression
  • dysphagia
  • dysphoria
  • dyspnea
  • dysuria
  • edema
  • euphoria
  • hallucinations
  • hyperalgesia
  • hyperamylasemia
  • hypertension
  • hypoglycemia
  • hyponatremia
  • hypotension
  • hypoventilation
  • hypoxia
  • impotence (erectile dysfunction)
  • infertility
  • leukopenia
  • myoclonia
  • nystagmus
  • orthostatic hypotension
  • palpitations
  • paresis
  • peripheral edema
  • peripheral vasodilation
  • physiological dependence
  • psychological dependence
  • psychosis
  • respiratory depression
  • sinus tachycardia
  • thrombocytopenia
  • tolerance
  • urinary retention
  • withdrawal

Mild

  • abdominal pain
  • agitation
  • amenorrhea
  • anorexia
  • anxiety
  • arthralgia
  • asthenia
  • back pain
  • chills
  • diaphoresis
  • diarrhea
  • diplopia
  • dizziness
  • drowsiness
  • dysgeusia
  • dyspepsia
  • fever
  • flatulence
  • flushing
  • gastroesophageal reflux
  • gonadal suppression
  • gynecomastia
  • headache
  • hiccups
  • hypoesthesia
  • infection
  • insomnia
  • lethargy
  • libido decrease
  • malaise
  • miosis
  • nausea
  • ocular pain
  • pallor
  • paresthesias
  • pruritus
  • rash
  • restlessness
  • rhinitis
  • syncope
  • tremor
  • urticaria
  • vertigo
  • vomiting
  • weakness
  • weight loss
  • xerosis
  • xerostomia

Severe

  • anaphylactoid reactions
  • apnea
  • atrial fibrillation
  • biliary obstruction
  • bradycardia
  • bronchospasm
  • cardiac arrest
  • coma
  • GI obstruction
  • ileus
  • increased intracranial pressure
  • laryngospasm
  • neonatal opioid withdrawal syndrome
  • oliguria
  • pulmonary edema
  • respiratory arrest
  • seizures
  • serotonin syndrome
  • SIADH

Pharmacologic tolerance to the analgesic effects of opiate agonists including morphine has been reported in some patients. Tolerance is the need for increasing opioid doses to maintain initial pain relief. Typically, tolerance presents as a decrease in the duration of analgesia and is managed by increasing the opioid dose or frequency. There is no limit to tolerance; thus, some patients may require very large doses of opiate analgesics to control their pain. When increasing doses of analgesia are required causes may be multi-factorial including tolerance, progression of disease, or psychological distress.[43053] [46350]

Although extremely rare, anaphylactoid reactions including cases of anaphylaxis have been reported. Evidence of histamine release such as urticaria, wheals, and local tissue irritation may occur with parenteral morphine administration.[48405] Urticaria (less than 5%) has also been reported with other formulations. Other dermatologic or allergic adverse events that have been reported with morphine include rash (10% or less), decubitus ulcer (less than 3%), xerosis (less than 5%), and edema (less than 5%).[31637] [35890] [40951]

The most significant adverse effects associated with opiate agonist use are respiratory depression (2% to 5%), respiratory arrest, and apnea.[29159] [31296] This results from a decreased sensitivity to carbon dioxide in the brainstem. Respiratory depression is more common in elderly or debilitated patients, after large initial doses in non-opioid tolerant patients or when opioids are given with other agents that cause CNS depression. Respiratory depression is most significant after IV administration.[31296] The sensitivity of the respiratory center returns to normal within 2 to 3 hours. When morphine is appropriately titrated, the risk of respiratory depression is generally small as tolerance rapidly develops to this effect. Bronchospasm has been reported infrequently in patients receiving extended-release morphine tablets; such an event may pose an additive danger in patients with pre-existing elevations in airway resistance.[40951] Other respiratory adverse events include decreased oxygen saturation (more than 10%), hypoxia (5% to 10%), hypercapnia (2% to 5%), dyspnea (2% to 10%), hiccups (less than 5%), hypoventilation (less than 5%), voice alteration (less than 5%), depressed cough reflex (less than 3%), rhinitis (less than 3%), atelectasis (less than 3%), asthma (less than 3%), and non-cardiogenic pulmonary edema (less than 3%).[29159] [31637] [43053] [35890] Symptomatic respiratory depression should be treated cautiously with an opioid antagonist such as naloxone. Patients may also develop respiratory depression through sub-acute overdose of an opiate agonist in which sedation builds up slowly leading to a decreased respiratory rate and then respiratory failure. The risk of this is more common with methadone but may be seen with other long-acting opioid preparations or in patients with renal or hepatic impairment. This can be managed by holding 1 to 2 doses of the opioid and then restarting the opioid at 25% of the previous dose and slowly increasing the dose once the symptoms have resolved. Rarely, patients receiving epidural or intrathecal morphine may develop dose-dependent delayed respiratory depression due to migration of morphine to the medullary respiration center. PaCO2 values in the high 40s to low 50s may be seen in fully awake and alert patients. The incidence of respiratory depression is higher after intrathecal versus epidural administration. The delayed respiratory depression follows the onset of analgesia in higher dermatomes and the onset of gastrointestinal events. Delayed respiratory depression may be seen up to 24 hours after a single epidural dose of morphine. Most cases of respiratory depression during spinal administration of morphine occur in patients receiving concomitant parenteral opioids or sedatives. If naloxone is used to reverse respiratory depression from morphine, repeat doses may be needed.[29159]

Morphine may cause a variety of effects on the GI system, most commonly nausea (7% to 10%), vomiting (less than 3% to more than 10% depending on the patient population and formulation), and constipation (9% or more).[29159] [31637] [35890] Nausea (17%), vomiting (10%), constipation (6%), and flatulence (5%) were among the most common adverse reactions reported on initiation of morphine in pediatric patients.[43053] Nausea and vomiting is most commonly seen at the initiation of therapy or when switching agents. Opioids affect the vestibular system and may cause more nausea/vomiting in ambulatory patients than bedridden patients. Scheduled treatment with an antiemetic during the first 1 to 2 days, then as needed during opiate therapy will usually control these symptoms until tolerance develops. If nausea/vomiting is associated with continuous infusion morphine, receipt of 0.2 mg naloxone intravenously may be helpful.[31296] If patients have nausea associated with movement, an anti-vertigo agent such as meclizine may be appropriate. Metoclopramide may be helpful in treating the symptoms of early satiety or fullness, but chronic use of metoclopramide should be avoided due to risks of adverse events. Constipation due to decrease GI motility and secretions is common during opioid therapy. In some cases patients can develop ileus or GI obstruction. Tolerance rarely develops to this effect; therefore, patients require a bowel regimen consisting of a stool softener and mild stimulant throughout opioid therapy. If the patient does not have a bowel movement for 3 days, an enema or suppository should be administered to prevent impaction. Other GI adverse events reported with morphine include anorexia (10% or less), dysphagia (less than 5%), dyspepsia (5% or less), diarrhea (10% or less), abdominal pain (10% or less), stomach atony disorder (less than 3%), gastroesophageal reflux (less than 3%), delayed gastric emptying (less than 3%), flatulence (5% to 10%), abdominal distention (2% to 5%), gastroenteritis (less than 5%), abnormal liver function tests (less than 5%), rectal disorder (less than 5%), thirst (less than 5%), dysgeusia (less than 5%), weight loss (less than 5%), laryngospasm, and abdominal cramps.[29159] [31637] [35890]

General adverse events reported with morphine use include asthenia (10% or less), accidental injury (10% or less), fever (less than 3% to more than 10%), interference with thermal regulation, pain (less than 3%), chest pain (unspecified) (less than 3%), chills (less than 3%), flu syndrome (10% or less), rigors (2% to 5%), and peripheral edema (10% or less).[29159] [31637] [35890] [48405]

Morphine is a controlled substance with a high potential for abuse and psychological dependence. Abuse and addiction are separate and distinct from physiological dependence and tolerance, which can develop during chronic opioid therapy. Tolerance is characterized by a reduced response to a drug after repeated administration. Physiological dependence develops as a result of repeated drug use. It manifests with a withdrawal syndrome after abrupt discontinuation or significant dose reduction, or administration of an agent with opioid antagonist activity (e.g., naloxone). Withdrawal is characterized by restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms include irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal. Neonatal opioid withdrawal syndrome may be life-threatening and requires management according to protocols developed by neonatology experts. It presents as irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight.[43053]

Morphine's effect on opioid receptors in the reticular activating system and striatum produces sedation. Patients should be warned that activity requiring mental alertness can be affected since CNS depression, including drowsiness (2% to 19%), confusion (less than 10%), and dizziness (more than 5%) can occur.[29159] [31637] [35890] [40951] Other CNS-related adverse events reported with morphine include headache (4% or more), nervousness (less than 5%), sleep disturbances, dysphoria, euphoria (less than 5%), lightheadedness, alterations of mood (feelings of floating, disorientation, apprehension), anxiety (2% to 6%), restlessness, tremor (less than 5%), malaise (less than 3%), thinking disturbances/abnormal thinking (less than 5%), sedation, abnormal dreams (less than 3%), lethargy (1% to less than 10%), depression (10% or less), loss of concentration (less than 3%), insomnia (10% or less), amnesia (less than 5%), agitation (less than 5%), foot drop (less than 5%), ataxia (less than 5%), hypesthesia/hypoesthesia (less than 5%), slurred speech (less than 3%), apathy (less than 3%), obtunded feeling, non-arousable condition, unresponsiveness, abnormal gait (less than 5%), coma (less than 5%), delirium (less than 5%,) disorientation, weakness, uncoordinated muscle movements, increased intracranial pressure, and vertigo (less than 3%).[29159] [31637] [35890] [40951] [48403] High doses of morphine given intravenously are excitatory due to an increase in circulating catecholamine concentrations. Hallucinations (less than 3%) and seizures (less than 5%) have been reported in patients receiving opioid agonists. Depending upon the individual patient tolerance, hallucinations may be reported in patients undergoing rapid dose escalation.[29159] [31637] [35890] [40951] Dysphoric reactions or toxic psychosis can occur after any dose.[31296] Flushing may also be reported in patients initiating morphine therapy.[29159] [31637] [35890] [40951]

Opioids can cause spasm of the sphincter of Oddi, with morphine producing greater effects than meperidine and meperidine producing greater effects than codeine. Hyperamylasemia, secondary to drug-induced spasm of the sphincter of Oddi, has been associated with various opiate agonists. While serum amylase and lipase concentrations can rise as a result of biliary obstruction or spasm, overt pancreatitis is rare with opiate analgesics. Gastritis and hepatotoxicity are also relatively rare with these agents. Biliary colic (less than 3%), biliary pain (less than 5%), and biliary tract spasm have been reported with the use of morphine.[31637] [35890] [48403]

Morphine and related compounds can cause cardiovascular adverse reactions. These reactions include sinus bradycardia (5% or less), sinus tachycardia (10% or less), atrial fibrillation (less than 3%), pallor (less than 3%), facial flushing (less than 3%), peripheral vasodilation (less than 5%), palpitations (less than 5%), hypertension (5% or less), hypotension (less than 3% to more than 10% depending on the patient population and formulation), orthostatic hypotension, diaphoresis (less than 3%)/sweating (2% to 10%), faintness, presyncope, and syncope (less than 5%). In cases of severe respiratory and/or circulatory depression, shock and cardiac arrest may occur.[29159] [31637] [35890] [40951] [60209] Morphine may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients as a result of peripheral vasodilation. Patients at increased risk for hypotensive effects include those whose ability to maintain blood pressure is already compromised by reduced blood volume or concurrent administration of certain medications (e.g., phenothiazines, general anesthetics).[31637] Monitor patients carefully.

Morphine and other opiate agonists are known to cause pruritus (less than 3% to more than 10% depending on the formulation).[29159] [35890] A high incidence of pruritus is associated with a single dose of either epidurally or intrathecally administered morphine. The pruritus is dose-related and is not confined to the administration site. Occasionally, pruritus is also associated with continuous administration of epidural or intrathecal morphine; the cause is poorly understood.[48405] Pruritus tends to be a less frequent adverse effect of oral morphine products.[24326] If pruritus is associated with continuous administration of morphine, receipt of 0.2 mg naloxone intravenously may lessen the adverse reaction.[31296] Alternatively, use of H1-blockers or changing to a different opioid may lessen the pruritus.

Some patients may experience anticholinergic side effects with morphine therapy. Patients can experience xerostomia (10% or less), blurred vision (less than 3%), or urinary retention (less than 5%) and urinary hesitancy (less than 3%), which can cause oliguria (2% to 5%).[29159] [31637] [35890] Morphine may induce the release of antidiuretic hormone to produce an antidiuretic effect.[60209] After epidural or intrathecal administration of morphine, the incidence of urinary retention is 40% to 100%. Urinary retention may last for 10 to 20 hours after a single epidural or intrathecal dose and for several days after initiation of a continuous infusion. While this may not be a problem for some post-operative patients who have an indwelling urinary catheter, ambulatory and chronic pain patients may have significant problems. Cholinomimetic medication may be advisable. If urinary retention is associated with continuous infusion morphine, receipt of 0.2 mg naloxone intravenously may be helpful.[31296] Other urinary adverse events associated with morphine use include urinary abnormality (less than 3%), bladder spasm (2% to 5%), and dysuria (less than 5%).[29159] [31637] [35890]

Morphine and its congeners can cause miosis at typical therapeutic doses; miosis may even occur in total darkness.[35890] Severe overdose can cause mydriasis once brain anoxia develops. Therapeutic doses can increase accommodation and sensitivity to light reflex and decrease intraocular tension in both normal and glaucomatous eyes. Other ocular adverse events reported with morphine use include amblyopia (less than 3%), conjunctivitis (less than 3%), diplopia (less than 3%), ocular pain (less than 5%), nystagmus (less than 3%), and visual disturbances.[31637] [35890] [48404]

Opioid agonists can exert adverse effects on the endocrine system by inhibiting the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH), and by stimulating secretion of prolactin, growth hormone (GH), insulin, and glucagon. Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism. A decrease in production of LH and a corresponding decrease in testosterone may result in libido decrease (less than 3%). Women may experience amenorrhea (less than 3%) and infertility, and men may experience abnormal ejaculation (less than 5%) or impotence (erectile dysfunction) (less than 5%). Women may also experience prolonged labor (less than 3%). Hypogonadism (gonadal suppression) and gynecomastia (less than 3%) have also occurred. Other various medical, physical, lifestyle, and psychological stressors may influence gonadal hormone concentrations; these stressors have not been adequately controlled for in clinical studies with opioids. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation. Morphine can inhibit the release of thyrotropin, leading to a decrease in thyroid hormone. Morphine and related compounds can stimulate the release of vasopressin (ADH). Hyponatremia (less than 3%) can occur as a result of SIADH.[31637] [35890] [43053] [60660]

Opioids may interfere with the endocrine system by inhibiting the secretion of adrenocorticotropic hormone (ACTH) and cortisol.[35890] Rarely, adrenocortical insufficiency has been reported in association with opioid use. Patients should seek immediate medical attention if they experience symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or hypotension. If adrenocortical insufficiency is suspected, confirm with diagnostic testing as soon as possible. If diagnosed, the patient should be treated with physiologic replacement doses of corticosteroids, and if appropriate, weaned off of opioid therapy. If the opioid can be discontinued, a follow-up assessment of adrenal function should be performed to determine if corticosteroid treatment can be discontinued. Other opioids may be tried; some cases reported use of a different opioid with no recurrence of adrenocortical insufficiency. It is unclear which, if any, opioids are more likely to cause adrenocortical insufficiency.[60660]

Unusual acceleration of neuraxial morphine requirements can occur in some persons, which may cause concern regarding systemic absorption and the hazards of large doses; these persons may benefit from hospitalization and detoxification. High doses of neuraxial morphine may produce myoclonia events. Myoclonic-like spasm of the lower extremities has been reported in 2 subjects receiving more than 20 mg/day of intrathecal morphine. After detoxification, it might be possible to resume treatment at lower doses, and some persons have been successfully changed from continuous epidural morphine to continuous intrathecal morphine. Repeat detoxification may be indicated at a later date. The upper daily dosage limit during continuing treatment must be individualized.[51758]

Paresthesias (10% or less) have been reported with the use of morphine.[31637] [35890] Non-infectious inflammatory masses, such as granulomas have surrounded catheter tips in patients that received continuous infusions of opioid analgesics by an intrathecal indwelling catheter.[29942] Symptoms that have led to the discovery of an intraspinal mass include loss of analgesic drug effects, spinal cord or cauda equina compression, or a sudden neurologic deficit, such as paresthesias. Serious neurologic impairment, including paralysis, complete paraplegia or paresis has occurred. At least 92 cases of catheter-tip masses have been reported with a mean duration of therapy of 29 months (range, 0.5 to 120). Half of the patients received morphine and another 11 received morphine mixed with other drugs. Of 33 cases that had morphine concentration data available, 28 received a concentration of at least 25 mg/mL. Although the etiology of the masses has not been determined, catheter placement and opioid usage, including drug concentration are possible causes. Placement of the catheter below the conus medullaris may be ideal. The conus medullaris is the lower region of the spinal cord, and the spinal cord usually does not extend beyond the lower margin of the L-2 vertebral body. Thus, injury to the spinal cord from a mass would be prevented by placement of the catheter tip below the conus medullaris. Avoidance of catheter placement in the thoracic region may be desirable, as this region has the narrowest relative space and slow cerebral spinal fluid flow. Some patients with masses that did not fill the spinal canal or cause neurological impairment were treated by stopping or emptying the drug infusion pump or by refilling the pump with preservative-free normal saline. The action either caused mass stabilization or mass regression over several months. In contrast, despite prompt surgical intervention, permanent neurological impairment occurred in some patients with impending paraplegia from a mass that filled the spinal canal.[29942] Patients who receive continual morphine sulfate with or without preservatives by an indwelling intrathecal catheter need to be monitored for new neurologic signs and symptoms.

Musculoskeletal adverse events reported with the use of morphine include back pain (10% or less), bone pain (less than 3%), arthralgia (less than 3%), skeletal muscle rigidity (less than 5%), and decreased bone mineral density.[29159] [31637] [35890] [43053]

Hematologic adverse events that have been reported with morphine therapy include anemia (less than 5%), leukopenia (less than 3%), thrombocytopenia (less than 5%), and decreased hematocrit (2% to 5%).[29159] [31637] [35890]

Infection (unspecified) and urinary tract infection were reported in 5% to 10% of patients during morphine therapy; causality to the drug is unknown.[31637]

Serotonin syndrome has been reported in patients taking opioids at recommended doses. Patients taking opioids concomitantly with a serotonergic medication should seek immediate medical attention if they develop symptoms such as agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea. Symptoms generally present within hours to days of taking an opioid with another serotonergic agent, but may also occur later, particularly after a dosage increase. If serotonin syndrome is suspected, either the opioid and/or the other agent should be discontinued.[60660]

Cases of opioid-induced hyperalgesia (OIH) have been reported, both with short-term and longer-term use of opioids. OIH occurs when an opioid paradoxically causes an increase in pain or an increase in sensitivity to pain. Symptoms of OIH include increased levels of pain upon opioid dosage increase, decreased levels of pain upon opioid dosage decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of underlying disease progression, opioid tolerance, opioid withdrawal, or addictive behavior. Data suggests a strong biologic plausibility between opioids and OIH and allodynia. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation (safely switching to a different opioid).[68838]

Hypoglycemia has been reported during opioid therapy. Most reports occurred in persons with at least 1 predisposing risk factor, such as diabetes.[40951] [46350]

Revision Date: 01/04/2024, 01:19:02 PM

References

24326 - Bergasa NV, Jones EA. Management of the pruritus of cholestasis: potential role of opiate antagonists. Am J Gastroenterol 1991;86:1404-12.29159 - DepoDur (morphine sulfate extended-release liposome injection) package insert. San Diego, CA: Pacira Pharmaceuticals; 2008 Nov.29942 - Yaksh TL, Hassenbusch S, Burchiel K, et al. Inflammatory masses associated with intrathecal drug infusion: a review of preclinical evidence and human data. Pain Med 2002;3:300-12.31296 - Duramorph (morphine sulfate injection) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Oct.31637 - Avinza (morphine sulfate extended-release capsules) package insert. Gainesville, GA: Alkermes Gainesville LLC.; 2014 Apr.35890 - Kadian (morphine sulfate extended-release capsules) package insert. Madison, NJ: Allergan USA, Inc.; 2021 Mar.40951 - MS Contin (morphine sulfate extended-release tablets) package insert. Stamford, CT: Purdue Pharma L.P.; 2023 Dec.43053 - Morphine sulfate oral solution package insert. Berkley, NJ: Hikma Pharmaceuticals USA, Inc.; 2021 Jun.46350 - Morphine sulfate tablet package insert. Berkley Heights, NJ: Hikma Pharmaceuticals Corp; 2021 Jun.48403 - Oramorph SR (morphine sulfate sustained-release tablets) package insert. Newport, KY: Xanodyne Pharmaceuticals, Inc.; 2006 Feb.48404 - Morphine sulfate rectal suppositories package insert. Minneapolis, MN: Perrigo.; 2019 Mar.48405 - Astramorph PF (morphine sulfate inj solution) package insert. Schaumburg, IL: APP Pharmaceuticals, LLC; 2008 Jun.51758 - Infumorph (morphine sulfate injection) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Oct.60209 - Morphabond ER (morphine sulfate extended-release tablets) package insert. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2019 Oct.60660 - Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. http://www.fda.gov/Drugs/DrugSafety/ucm489676.htm Retrieved March 23, 201668838 - Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA updates prescribing information for all opioid pain medicines to provide additional guidance for safe use. https://www.fda.gov/media/167058/download. Retrieved April 13, 2023.

Contraindications/Precautions

Absolute contraindications are italicized.

  • alcoholism
  • children
  • GI obstruction
  • ileus
  • infants
  • MAOI therapy
  • neonates
  • respiratory depression
  • status asthmaticus
  • status epilepticus
  • strychnine toxicity
  • abrupt discontinuation
  • accidental exposure
  • anticoagulant therapy
  • arteriosclerosis
  • asthma
  • biliary tract disease
  • bladder obstruction
  • brain tumor
  • breast-feeding
  • chronic obstructive pulmonary disease (COPD)
  • CNS depression
  • coadministration with other CNS depressants
  • coagulopathy
  • coma
  • cor pulmonale
  • depression
  • diarrhea
  • driving or operating machinery
  • dysphagia
  • emphysema
  • ethanol ingestion
  • ethanol intoxication
  • geriatric
  • head trauma
  • hepatic disease
  • hypovolemia
  • hypoxemia
  • increased intracranial pressure
  • infection
  • infertility
  • intracranial mass
  • intramuscular administration
  • intrathecal administration
  • intravenous administration
  • labor
  • neonatal opioid withdrawal syndrome
  • obesity
  • obstetric delivery
  • oliguria
  • opioid overdose
  • opioid use disorder
  • opioid-naive patients
  • pancreatitis
  • potential for overdose or poisoning
  • pregnancy
  • prostatic hypertrophy
  • pulmonary disease
  • renal disease
  • renal impairment
  • reproductive risk
  • requires a specialized care setting
  • requires an experienced clinician
  • respiratory insufficiency
  • scoliosis
  • seizure disorder
  • seizures
  • shock
  • sleep apnea
  • subcutaneous administration
  • substance abuse
  • urethral stricture
  • urinary retention

Morphine is contraindicated in persons with known morphine hypersensitivity. Anaphylaxis has been reported in persons receiving morphine.[40951]

Morphine is an opioid agonist and therefore has abuse potential and risk of fatal overdose from respiratory failure. Use with caution in patients with a history of substance abuse or alcoholism; the use of morphine rectal suppositories is specifically contraindicated in patients with acute alcoholism or delirium tremens.[48404] Injectable morphine products have been associated with abuse and dependence among health care providers. Special measures to control the products within the hospital or clinic are recommended because of the limited indications, the overdosage risk, and the diversion/abuse risk. Specifically, rigid accounting, rigorous wastage control, and restricted access are recommended.[31296] Addiction may occur in patients who obtain morphine illicitly or in those appropriately prescribed the drug. The risk of addiction in any individual is unknown. However, patients with mental illness (e.g., major depression) or a family history of substance abuse (including alcoholism) have an increased risk of opioid abuse. Assess patients for risks of addiction, abuse, or misuse before drug initiation, and monitor patients who receive opioids routinely for development of these behaviors or conditions. A potential risk of abuse should not preclude appropriate pain management in any patient, but requires more intensive counseling and monitoring. Abuse and addiction are separate and distinct from physical dependence and tolerance; patients with addiction may not exhibit tolerance and symptoms of physical dependence. The misuse of extended-release morphine products by crushing, chewing, snorting, or injecting the dissolved product will result in uncontrolled drug delivery which may produce fatal respiratory depression. To discourage abuse, the smallest appropriate quantity of morphine should be dispensed and proper disposal instructions for unused drug should be given to patients.[31637] [35890] [40951] [60209] [61668] Discuss the availability of naloxone with all patients and consider prescribing it in patients who are at increased risk of opioid overdose, such as patients who are also using other CNS depressants, who have a history of opioid use disorder (OUD), who have experienced a previous opioid overdose, or who have household members, or other close contacts at risk for accidental ingestion or opioid overdose.[65733]

Morphine is contraindicated for use in patients with significant respiratory depression in unmonitored settings or in the absence of resuscitative equipment. Patients with significant respiratory depression in unmonitored settings should generally not receive injectable solution products due to the risk of fatal respiratory depression.[31637] [52190] Additionally, avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; if concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor patients closely for signs or symptoms of respiratory depression or sedation.[61143] [61668] All formulations of morphine, with the exception of opium tincture oral solutions, are contraindicated in acute or severe bronchial asthma (i.e., status asthmaticus) in unmonitored settings or in the absence of resuscitative equipment. Receipt of moderate doses in these patients may significantly decrease pulmonary ventilation. Although opium tincture solutions are not specifically contraindicated in patients with pre-existing respiratory depression or hypoxia, therapeutic doses may decrease respiratory drive to the point of apnea.[56972] Use of morphine immediate-release tablets and oral solution is contraindicated in patients with hypercarbia, while use of injectable suspension (DepoDur) and solution (Duramorph) is contraindicated in patients with upper airway obstruction. Rapid IV administration may result in chest wall rigidity. Respiratory depression, if left untreated, may cause respiratory arrest and death. Symptoms of respiratory depression include a reduced urge to breathe, a decreased respiratory rate, or deep breaths separated by long pauses (a "sighing" breathing pattern). Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Only healthcare professionals who are knowledgeable of the use of opioids for the management of chronic pain should prescribe morphine extended-release capsules and tablets. These extended-release products should be reserved for patients in whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. Do not use extended-release formulations for as-needed analgesics, for acute pain, or if the pain is mild or not expected to persist for an extended period of time.[55881] Proper dosing and titration are essential; patients should be monitored for respiratory depression, particularly after therapy initiation or after a dose increase. Caution should be exercised when converting from a different opioid to morphine, as initial dose overestimation may lead to fatal overdose. In patients with pulmonary disease such as chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, emphysema, hypoxia, hypercapnia, respiratory insufficiency, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to morphine, as even usual therapeutic doses may decrease respiratory drive and cause apnea in these patient populations. Significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention; therefore, it is recommended to avoid the use of morphine extended-release tablets and capsules during a coma or impaired consciousness. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with morphine. Use morphine with caution in patients with obesity as this is a risk factor for obstructive sleep-apnea syndrome and/or decreased respiratory reserve. Respiratory depression or other adverse reactions may persist for a significant period of time after discontinuation of or overdosage of long-acting morphine preparations; patients require close monitoring until their respiratory rate has stabilized. Patients who receive the extended-release liposome injection (DepoDur) may need monitoring beyond 48 hours after a dose. An increased risk of respiratory depression may be present if the surgical procedure is canceled after DepoDur administration. If treatment of respiratory depression in an individual physically dependent on opioids is necessary, administer the opioid antagonist with extreme care; titrate the antagonist dose by using smaller than usual doses. A high level of vigilant monitoring is recommended.[29159] [31296] [31637] [43053] [46350] [48404] [56971] [56972] [60209] [61668]

Improper use of various morphine dosage forms is associated with increased risks; advise patients accordingly. Also, instruct patients who will take extended-release capsules (e.g., Avinza or Kadian) to avoid ethanol ingestion and to not use any medication that contains alcohol; concurrent alcohol receipt may lead to rapid release and absorption of a potentially fatal morphine dose. Kadian and Avinza capsules are to be swallowed whole. Alternatively, the capsule contents may be sprinkled on applesauce and swallowed without chewing. The capsule or the pellets/beads in the capsule must not be chewed, crushed, or dissolved because of the risk of rapid release and absorption of a potentially fatal morphine dose.[31637] [35890] Similarly, instruct patients to swallow extended-release tablets whole. The tablets must not be chewed, crushed, or broken in half because of the risk of rapid release and absorption. Use of an opioid agonist while under the influence of other CNS depressants or ethanol intoxication will increase risk of CNS and respiratory depressant effects.[40951]

Morphine sulfate extended-release liposome injection (DepoDur) is only for epidural infusion at the lumbar level. DepoDur is not intended for intravenous administration, intrathecal administration, intramuscular administration, or subcutaneous administration. If DepoDur is accidentally injected into the intrathecal space, profound and prolonged hypoventilation is expected. Prolonged and serious respiratory depression or apnea has occurred when administration of DepoDur was associated with subarachnoid puncture; respiratory depression occurred within 12 hours of DepoDur administration after apparent recovery from anesthesia. As intrathecal leakage from the epidural space may occur through a breached dural membrane, especially when the epidural drug is administered as a bolus, do NOT administer DepoDur to a patient after a recent dural puncture without vigilant monitoring of respiratory function for at least 48 hours. Observe all patients in a fully equipped and staffed environment for a minimum of 48 hours after administration. Immediate availability of emergency mechanical ventilation and opioid antagonists are also needed.[29159] Duramorph may be given epidurally, intrathecally, or intravenously; it is not for use in continuous microinfusion devices.[31296] Infumorph is only indicated for intrathecal or epidural administration; it is not for single-dose IV, IM, or subcutaneous administration due to the risk of overdose. Infumorph must also not be used for single-dose neuraxial injection because it is too concentrated for accurate delivery of the smaller doses used in this setting.[51758] Administration of morphine via neuraxial routes requires an experienced clinician familiar with administration techniques, proper dosing, and potential patient management problems that may occur with epidural or intrathecal administration. Since single-dose neuraxial administration may result in serious adverse reactions, including acute or delayed respiratory depression, administration requires a specialized care setting where patients can be observed for up to 24 hours following the initial dose, including the initial test dose of Infumorph. The facility must be in fully equipped to monitor patients and resuscitate any patient with severe opioid overdosage. Personnel must be familiar with the use of opioid antagonists. Continue to monitor patients receiving Infumorph during the first several days following catheter implantation. Epidural administration has been associated with less potential for immediate or late adverse reactions (e.g., respiratory depression) than intrathecal administration, and is preferable to the intrathecal route whenever possible. For safety concerns, limit Duramorph administration by the intrathecal or epidural routes to the lumbar area; thoracic administration has been shown to greatly increase the incidence of early and late respiratory depression even at doses of 1 to 2 mg. Similarly, limit Infumorph administration by the intrathecal route to the lumbar area. Improper substitution of Infumorph (10 or 25 mg/mL) for Duramorph (0.5 or 1 mg/mL) is likely to result in serious overdosage. Parenteral administration of other opioids in patients receiving epidural or intrathecal morphine may result in overdosage.[31296] [51758] Use caution when morphine is also given intravenously; because of a delay in maximum CNS effects (30 minutes) with intravenous morphine, rapid administration may result in overdose.[31296] Several factors contraindicate the administration of morphine by the epidural or intrathecal routes. These factors include infection at the injection site, concomitant anticoagulant therapy, uncontrolled coagulopathy, or the presence of any other concomitant therapy or medical condition which would render epidural or intrathecal administration of medication especially hazardous.[31296] [51758]

Morphine is contraindicated in persons with known or suspected GI obstruction, including paralytic ileus. Morphine may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor persons with biliary tract disease, including acute pancreatitis, for worsening symptoms.[46350] Moistened Arymo extended-release tablets may become sticky leading to difficulty in swallowing the tablets. Instruct persons not to pre-soak, lick, or otherwise wet Arymo extended-release tablets prior to placing in the mouth, and to take 1 tablet at a time with enough water to ensure complete swallowing immediately after placing in the mouth. Tablet stickiness and swelling may also predispose persons to intestinal obstruction and exacerbation of diverticulitis. Persons with underlying GI disorders such as esophageal cancer or colon cancer with a small gastrointestinal lumen are at greater risk of developing these complications. Consider use of an alternative analgesic in persons who have dysphagia and persons at risk for underlying GI disorders resulting in a small gastrointestinal lumen.[61668] Deodorized opium tincture (10 mg/mL) and camphorated opium tincture (0.4 mg/mL) are contraindicated for use in diarrhea caused by poisoning until the toxic material is eliminated from the GI tract.[56971] [56972]

Although all forms of morphine have potential for overdose or poisoning, certain formulations are associated with specific risks. This includes morphine oral solutions due to possible concentration and/or dosing errors, long-acting and high-potency morphine products for the increased risk of life-threatening respiratory depression, and Avinza brand morphine for possible renal toxicity if the maximum dose is exceeded. Knowledge and care in product selection is advised. Serious adverse events and deaths have been reported in conjunction with accidental overdose of morphine 100 mg/5 mL oral solutions and other concentrations. Excessive doses may be a result of morphine oral solutions prescribed in milligrams and erroneously interchanged for milliliters of the product.[43052] Improper substitution of Infumorph injectable solution (10 mg/mL or 25 mg/mL) for Duramorph or Astramorph injectable solutions (0.5 mg/mL or 1 mg/mL) may cause serious overdosage.[31296] [48405] [51758] To reduce the risk of life-threatening adverse effects, several formulations of morphine are intended for opioid-tolerant patients only. Do not use the following in opioid-naive patients: 90 or 120 mg morphine biphasic-release capsules (Avinza); 100 or 200 mg morphine extended-release capsules (Kadian); 100 or 200 mg morphine extended-release tablets (MS Contin); 100 mg extended-release tablets (Morphabond); or 100 mg/5 mL morphine oral solution.[31637] [35890] [40951] [43053] [60209] Only use extended-release morphine (e.g., Arymo, Avinza, Kadian, MS Contin, and Morphabond) for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate; these formulations are not intended for as-needed analgesia.[31637] [35890] [40951] [60209] [61668] Limit the total daily dose of Avinza to a maximum of 1,600 mg/day; Avinza doses more than 1,600 mg/day contain a quantity of fumaric acid that has not been demonstrated to be safe and may result in serious renal toxicity. Morphine should be kept out of the reach of pediatric patients and others for whom it was not prescribed, as accidental exposure may cause a fatal overdose.[31637]

Avoid opioid use in persons with CNS depression, impaired consciousness, or coma; opioids may obscure the clinical course in a person with a head trauma injury. Monitor persons who may be susceptible to the intracranial effect of carbon dioxide retention (e.g., those with evidence of increased intracranial pressure, brain tumor, or intracranial mass) for signs of sedation and respiratory depression, particularly when initiating opioid therapy. Opioids may reduce respiratory drive and resultant carbon dioxide retention can further increase intracranial pressure.[46350] Camphorated opium tincture (0.4 mg/mL) is contraindicated in convulsive states, such as those occurring in status epilepticus, tetanus, and strychnine toxicity.[56972] Use opium tincture with caution in persons with cerebral arteriosclerosis.[56971]

Warn persons against performing potentially hazardous activities such as driving or operating machinery unless they are tolerant to the effects of opioids and know how they will react to the medication. Opioids may impair mental or physical abilities required to perform such tasks.[46350]

Opioids may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory persons. There is an increased risk in persons whose ability to maintain blood pressure has already been compromised by hypovolemia or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines, general anesthetics). Monitor these persons for signs of hypotension after initiating or titrating the opioid dosage. Avoid the use of opioids in persons with circulatory shock; it may cause vasodilation that can further reduce cardiac output and blood pressure.[46350]

Monitor persons with a history of seizure disorder for worsened seizure control during opioid therapy. Opioids may increase the frequency of seizures in persons with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures.[46350]

Morphine and other opioid agonists can cause urinary retention and oliguria, due to increasing the tension of the detrusor muscle. Patients more prone to these effects include those with bladder obstruction, prostatic hypertrophy, urethral stricture, pelvic malignancy, or renal disease. Drug accumulation or prolonged duration of action can occur in patients with renal impairment or hepatic disease. In acute situations, patients require close monitoring to avoid excessive toxicity. Patients with chronic liver or renal disease may require less frequent dosing intervals.[40951] Urinary retention may occur with single epidural or intrathecal morphine administration, or during the first several days of hospitalization for the initiation of continuous intrathecal or epidural morphine therapy. Urinary retention may persist for 10 to 20 hours and occurs more frequently in male patients than females. Monitor patients closely for difficulty in urination and treat as clinically indicated; cases have responded to cholinomimetic treatment and/or judicious use of catheters.[31296] [51758]

Opioid agonists may be used in children with moderate to severe pain. However, certain morphine dosage formulations or administration methods may not be appropriate for children; children also require close monitoring during opioid use. The use of deodorized opium tincture (10 mg/mL) is contraindicated for use in neonates, infants, children, and adolescents; safety and efficacy have not been established.[56971] Neonates and infants younger than 6 months of age have highly variable clearance of opioid agonists. Therefore, infants younger than 6 months of age may be given morphine but must be closely monitored for apnea until 24 hours after their last dose. Guidelines suggest close monitoring of children up to 1 year of age.[23625] The safety and efficacy of epidural or intrathecal use of morphine in children have not been established. The safety and efficacy of extended-release morphine formulations have not been established in pediatric patients younger than 18 years.[31637] [35890] [40951] [60209]

Use morphine with caution in geriatric or debilitated adults as these patients are more susceptible to adverse reactions, especially sedation and respiratory depression, probably as a result of the altered distribution of the drug or decreased elimination. Initial doses may need to be reduced, and doses should be carefully titrated, taking into account analgesic effects, adverse reactions, and concomitant conditions and drugs that may increase CNS depression and depress respiration.[40951] According to the Beers Criteria, opiate agonists are considered potentially inappropriate medications (PIMs) in geriatric adults with a history of falls or fractures and should be avoided in these patient populations, except in the setting of severe acute pain, since opiates can produce ataxia, impaired psychomotor function, syncope, and additional falls. If an opiate must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk. In patients receiving palliative care, the balance of benefits and harms of medication management may differ from those of the general population of older adults.[63923]

Use of morphine oral dosage forms, suppositories, and solution for injection is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. Manufacturers of other morphine dosage forms do not recommend the concurrent use of MAOIs or morphine use within 14 days of stopping such treatment. Additive CNS depression, drowsiness, dizziness, or hypotension may occur.[29159] [31296] [31637] [35890] [40951] [43053] [46350] [48404] [56972] [61668]

Published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects. Results for a population-based prospective cohort, including 448 women exposed to morphine at any time during pregnancy and 70 women exposed during the first trimester of pregnancy, indicate no increased risk for congenital malformations; however, risk cannot be excluded due to study methodological limitations. Neural tube defects (i.e., exencephaly and cranioschisis) have been noted when morphine was given subcutaneously to hamsters and mice at 5 and 16 times a human daily dose of 60 mg based on body surface area. Lower fetal body weight and increased abortion incidence were observed at 0.4 times the human daily dose in rabbits, growth retardation at 6 times the human daily dose in rats, and axial skeletal fusion and cryptorchidism at 16 times the human daily dose in mice. Doses of 3 to 4 times the human daily dose given during organogenesis and throughout lactation have produced cyanosis, hypothermia, decreased brain weight or body weight, adverse effects on reproductive tissues, and death in rats. Some long-term neurochemical changes in the brains of rat offspring which correlate with altered behavioral responses that persist through adulthood have been observed with exposures comparable to and less than the human daily dose.[61668] Some experts suggest increased risk if morphine is used for prolonged periods during pregnancy or at high doses near term.[46351] While certain formulations of morphine have been used in the obstetric setting, caution is advised under various circumstances during labor and obstetric delivery. Morphine sulfate extended-release liposome injection (DepoDur) should not be administered to women for vaginal labor and delivery; this formulation is only for pain associated with Caesarian section after delivery and clamping of the umbilical cord.[29159] Morphine sulfate extended-release tablets or capsules are not recommended for use during or immediately prior to labor. Morphine readily crosses the placenta and all other formulations should be used cautiously during pregnancy or obstetric delivery. An opioid antagonist and resuscitative equipment should be readily available. If used during the second stage of labor, the duration of labor can be prolonged by temporarily reducing the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation.[35890] [40951] Further, prolonged maternal use of long-acting opioids, such as morphine, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including rapid breathing, irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.[31637] [35890] [40951]

Use morphine with caution in breast-feeding mothers because it can pass into breast milk. The milk to plasma AUC ratio of morphine is approximately 2.5:1.[46350] In studies of epidural morphine given postcesarean section, morphine passage into colostrum and breast milk is minimal, while higher concentrations are found with intravenous or oral administration.[61697] In a study of 5 breast-feeding women given epidural, IV, or IM morphine postoperatively, the highest morphine concentrations in milk were 82 mcg/L (measured 30 minutes after two, 4 mg epidural doses) vs. 500 mcg/L (measured 45 minutes after 15 mg parenteral dose).[61698] Morphine passage into breast milk was assessed in a study of 5 women who were given a 7.5 mg loading dose of IV morphine following umbilical cord clamping, then 1 to 1.5 mg every 6 minutes via IV patient-controlled analgesia (PCA), then 5 to 30 mg PO every 2 to 3 hours as needed for pain. Average IV morphine consumption in the first 48 hours was approximately 150 mg. Average morphine consumption across the entire study period (96 hours) was approximately 250 mg (IV and oral). Average milk concentrations among all patients were 50 to 65 mcg/L during the first 48 hours; concentrations dropped to approximately 20 mcg/L at 72 to 96 hours postpartum. Using the maximum reported concentration of 65 mcg/L and assuming 30% oral absorption by the infant, an exclusively breast-fed infant would absorb a maximum of approximately 3 mcg/kg/day equal to 0.3% of the IV maternal weight-adjusted daily dose.[61697] [61699] Previous American Academy of Pediatrics recommendations considered morphine usually compatible with breast-feeding, particularly in short-term post-partum use, due to a lack of data regarding symptoms in exposed infants.[27500] However, opioids may cause serious adverse effects in the infant, including drowsiness, CNS depression, and death. If morphine is used during breast-feeding, short durations and low doses are recommended with close infant monitoring. If morphine is used long-term, the importance of continuing breast-feeding should be judged against the potential risk of adverse drug effects in the infant. Withdrawal symptoms may occur in infants whose mothers discontinue chronic opioid therapy.[61668] Advise the mother to report any excessive sleepiness, breathing difficulties, or difficulties breast-feeding to their health care provider immediately.[61697] Other alternative analgesics considered to be usually compatible with breast-feeding include ibuprofen, acetaminophen, and fentanyl.[27500]

Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism (gonadal suppression) and pose a reproductive risk. Although the exact causal role of opioids in the clinical manifestations of hypogonadism is unknown, patients could experience libido decrease, impotence, amenorrhea, or infertility. It is not known whether the effects on fertility are reversible. Monitor patients for symptoms of opioid-induced endocrinopathy. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.[60660] [61668]

Revision Date: 12/20/2023, 01:17:47 PM

References

23625 - Acute Pain Management Guideline Panel. Acute pain management: operative or medical procedures and trauma. Clinical Practice Guideline. AHCPR Pub. No. 92-0032. Rockville, MD. Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services. Feb. 1992.27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.29159 - DepoDur (morphine sulfate extended-release liposome injection) package insert. San Diego, CA: Pacira Pharmaceuticals; 2008 Nov.31296 - Duramorph (morphine sulfate injection) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Oct.31637 - Avinza (morphine sulfate extended-release capsules) package insert. Gainesville, GA: Alkermes Gainesville LLC.; 2014 Apr.35890 - Kadian (morphine sulfate extended-release capsules) package insert. Madison, NJ: Allergan USA, Inc.; 2021 Mar.40951 - MS Contin (morphine sulfate extended-release tablets) package insert. Stamford, CT: Purdue Pharma L.P.; 2023 Dec.43052 - Food and Drug Administration MedWatch. Morphine sulfate oral solutions 100 mg per 5 ml (20mg/ml): Medication use error - reports of accidental overdose. Retrieved Jan 10, 2011. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm239559.htm43053 - Morphine sulfate oral solution package insert. Berkley, NJ: Hikma Pharmaceuticals USA, Inc.; 2021 Jun.46350 - Morphine sulfate tablet package insert. Berkley Heights, NJ: Hikma Pharmaceuticals Corp; 2021 Jun.46351 - Morphine. In: Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Neonatal Risk. Briggs GG, Freeman RK, Yaffe SJ, (eds.) 9th ed., Philadelphia PA: Lippincott Williams and Wilkins; 2011:985-6.48404 - Morphine sulfate rectal suppositories package insert. Minneapolis, MN: Perrigo.; 2019 Mar.48405 - Astramorph PF (morphine sulfate inj solution) package insert. Schaumburg, IL: APP Pharmaceuticals, LLC; 2008 Jun.51758 - Infumorph (morphine sulfate injection) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Oct.52190 - Morphine injection package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2011 May.55881 - US Food and Drug Administration (FDA). FDA News Release: FDA announces safety and labeling changes and postmarket study requirements for extended-release and long-acting opioid analgesics. Retrieved September 11, 2013. Available on the World Wide Web at: https://www.fda.gov/drugs/information-drug-class/new-safety-measures-announced-extended-release-and-long-acting-opioids56971 - Opium Tincture 10 mg/mL oral solution package insert. Baudette, MN: ANI Pharmaceuticals, Inc.; 2021 Feb.56972 - Opium Tincture 2 mg/5 mL oral solution package insert. Amityville, NY: Hi-Tech Pharmacal Co, Inc.; 2013 Oct.60209 - Morphabond ER (morphine sulfate extended-release tablets) package insert. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2019 Oct.60660 - Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. http://www.fda.gov/Drugs/DrugSafety/ucm489676.htm Retrieved March 23, 201661143 - Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. http://www.fda.gov/Drugs/DrugSafety/ucm518473.htm. Retrieved August 31, 2016.61668 - Arymo ER (morphine sulfate extended-release tablets) package insert. Wayne, PA: Egalet US Inc.; 2019 Oct.61697 - National Institutes of Health (NIH). Morphine monograph. LactMed: Drug and Lactation Database. Revised Aug 2016. Available at https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~Tkh1UE:1. Accessed January 23, 2017.61698 - Feilberg VL, Rosenborg D, Broen Christensen C, et al. Excretion of morphine in human breast milk. Acta Anaesthesiol Scand 1989;33:426-428.61699 - Wittels B, Scott DT, Sinatra RS. Exogenous opioids in human breast milk and acute neonatal neurobehavior: a preliminary study. Anesthesiology 1990;73:864-869.63923 - The American Geriatrics Society 2019 Beers Criteria Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2019;00:1-21.65733 - Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA recommends health care professionals discuss naloxone with all patients when prescribing opioid pain relievers or medicines to treat opioid use disorder. https://www.fda.gov/media/140360/download. Retrieved July 23, 2020.

Mechanism of Action

Morphine is a potent mu-opiate receptor agonist. Opiate receptors include mu, kappa, and delta, which have been reclassified by an International Union of Pharmacology subcommittee as OP1 (delta), OP2 (kappa), and OP3 (mu). These receptors are coupled with G-protein (guanine-nucleotide-binding protein) receptors and function as modulators, both positive and negative, of synaptic transmission via G-proteins that activate effector proteins. Opioid-G-protein systems include adenylyl cyclase-cyclic adenosine monophosphate (cAMP) and phospholipase3 C (PLC)-inositol 1,4,5 triphosphate (Ins(1,4,5) P3)-Ca2).[25308]

 

Opiates do not alter the pain threshold of afferent nerve endings to noxious stimuli, nor do they affect the conductance of impulses along peripheral nerves. Analgesia is mediated through changes in the perception of pain at the spinal cord (mu2-, delta-, kappa-receptors) and higher levels in the CNS (mu1- and kappa3 receptors). There is no ceiling effect of analgesia for opiates. The emotional response to pain is also altered. Opioids close N-type voltage-operated calcium channels (kappa-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (mu and delta receptor agonist) resulting in hyperpolarization and reduced neuronal excitability. Binding of the opiate stimulates the exchange of guanosine triphosphate (GTP) for guanosine diphosphate (GDP) on the G-protein complex. Binding of GTP leads to a release of the G-protein subunit, which acts on the effector system. In this case of opioid-induced analgesia, the effector system is adenylate cyclase and cAMP located at the inner surface of the plasma membrane.[25309] Thus, opioids decrease intracellular cAMP by inhibiting adenylate cyclase that modulates the release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine and norepinephrine. Opioids also modulate the endocrine and immune systems. Opioids inhibit the release of vasopressin, somatostatin, insulin, and glucagon.[25310]

 

The stimulatory effects of opioids are the result of 'disinhibition' as the release of inhibitory neurotransmitters such as GABA and acetylcholine is blocked. The exact mechanism how opioid agonists cause both inhibitory and stimulatory processes is not well understood. Possible mechanisms include differential susceptibility of the opioid receptor to desensitization or activation of more than one G-protein system or subunit (one excitatory and one inhibitory) by an opioid receptor.

 

Clinically, stimulation of mu-receptors produces analgesia, euphoria, respiratory depression, miosis, decreased gastrointestinal motility, sedation, somnolence, and physical dependence.[40951] Morphine enhances tone in the long segments of longitudinal muscle and inhibits propulsive contraction of both circular and longitudinal muscles to decrease GI motility.[56971] Kappa-receptor stimulation also produces analgesia, miosis, respiratory depression, as well as, dysphoria and some psychomimetic effects (i.e., disorientation and/or depersonalization). Miosis is produced by an excitatory action on the autonomic segment of the nucleus of the oculomotor nerve. Respiratory depression is caused by direct action of opiate agonists on respiratory centers in the brain stem. Opiate agonists increase smooth muscle tone in the antral portion of the stomach, the small intestine (especially the duodenum), the large intestine, and the sphincters. Opiate agonists also decrease secretions from the stomach, pancreas, and biliary tract. The combination of effects of opiate agonists on the GI tract results in constipation and delayed digestion. Urinary smooth muscle tone is also increased by opiate agonists. The tone of the bladder detrusor muscle, ureters, and vesical sphincter is increased, which sometimes causes urinary retention.

 

Several other clinical effects occur with opiate agonists including cough suppression, hypotension, histamine release, nausea, and vomiting.[40951] The antitussive effects of opiate agonists are mediated through direct action on receptors in the cough center of the medulla. Cough suppression can be achieved at lower doses than those required to produce analgesia. Hypotension is possibly due to an increase in histamine release and/or depression of the vasomotor center in the medulla. Induction of nausea and vomiting possibly occurs from direct stimulation of the vestibular system and/or the chemoreceptor trigger zone. Morphine may inhibit the secretion of ACTH, cortisol, testosterone, and luteinizing hormone. Morphine may stimulate the secretion of prolactin, growth hormone, insulin, and glucagon.[40951]

Revision Date: 12/07/2016, 04:58:58 PM

References

25308 - Harrison C, Smart D, Lambert DG. Stimulatory effects of opioids. Br J Anaesth 1998;81:20-8.25309 - Weinstein SM. New pharmacological strategies in the management of cancer pain. Cancer Invest 1998;16:94-101.25310 - Sarne Y, Fields A, Keren O, et al. Stimulatory effects of opioids on transmitter release and possible cellular mechanisms: overview and original results. Neurochem Res 1996;21:1353-61.40951 - MS Contin (morphine sulfate extended-release tablets) package insert. Stamford, CT: Purdue Pharma L.P.; 2023 Dec.56971 - Opium Tincture 10 mg/mL oral solution package insert. Baudette, MN: ANI Pharmaceuticals, Inc.; 2021 Feb.

Pharmacokinetics

Morphine sulfate is administered orally, parenterally, intrathecally, epidurally, and rectally. There is no predictable relationship between morphine serum concentrations and analgesic response; however, there is a minimum effective analgesia plasma concentration in a given patient. The minimum effective analgesia plasma concentration of morphine varies from patient to patient. Several factors may affect a patient's response to a given opiate agonist including age, prior opiate therapy, medical condition, and emotions. Also, there is no relationship between morphine concentrations and incidence of adverse events, although higher concentrations are associated with more adverse events than lower concentrations.[46350][48403]

 

Metabolism of morphine occurs primarily through conjugation in the liver. Morphine is also metabolized by P-glycoprotein (P-gp), which is present on the apical side of enterocytes and on the canalicular side of hepatocytes. Lastly, morphine undergoes N-demethylation by cytochrome P450 3A4 enzymes to yield normorphine; however, the pathway contributes less than 4% of the given dose to total urinary excretion of morphine. Morphine is conjugated with glucuronic acid through UDP-glucuronosyltransferases to form 3-glucuronide (50%), 6-glucuronide (5% to 15%), and 3,6-glucuronide and other minor metabolites. Morphine 3-glucuronide has a low affinity for opioid receptors, has no analgesic activity, and may cause hyperalgesia (hyperesthesia), myoclonus, and allodynia. In addition, the 3-glucuronide metabolite may be important in the development of tolerance to morphine. Morphine 3-glucuronide has been shown to stimulate respiration, but the mechanism (either direct stimulation or morphine and morphine 6-glucuronide antagonism) is unclear. Morphine 6-glucuronide has analgesic activity and may significantly contribute to morphine's activity. With chronic dosing of morphine, the systemic exposure of the glucuronide metabolites is greater than that of morphine.[25336] Morphine 6-glucuronide crosses the blood-brain barrier slowly. Thus, prolonged effects may be seen after morphine discontinuation or dialysis to remove morphine 6-glucuronide.

 

Excretion of morphine is largely in the urine and bile as the morphine 3-glucuronide and 6-glucuronide metabolites. Smaller amounts are excreted as secondary conjugates and approximately 10% is eliminated as unchanged drug. Renal clearance of morphine and morphine- 6-glucuronide exceeds creatinine clearance, which suggests that both are actively secreted by the kidney. Within about 24 hours of the last dose, urinary elimination approximates 90%. Between 7% to 10% is excreted in the feces mainly via the bile. Typical morphine clearance in adults is approximately 15 to 20 mL/minute/kg.[46350] The elimination half-life of morphine is about 1.5 to 2 hours; a half-life after IV administration of 2 to 4 hours has been reported. In some studies with longer durations of plasma sampling, a terminal half-life of approximately 15 hours was reported.[40951] Analgesia can be maintained for 3 to 7 hours after immediate release morphine administration.

 

Affected cytochrome P450 isoenzymes and/or drug transporters: P-gp

Morphine is a substrate for P-gp.[34448]

Route-Specific Pharmacokinetics

Oral Route

Morphine is one-third to one-sixth as potent when administered orally compared to intravenous administration due to morphine's significant first-pass metabolism. The oral bioavailability of morphine is approximately 20% to 40%.[40951] Morphine is readily absorbed from the gut and is absorbed even faster after rectal administration. Oral absorption of the immediate release products can be increased by food. Peak analgesia is obtained about 60 minutes after oral administration. Oral sustained-release products have a slower onset of action and at steady state will have a lower maximum serum concentration and higher minimum serum concentration compared to immediate-release oral morphine. After every 24 hour dosing of Kadian, the maximum plasma concentration occurs in about 8 hours. Avinza capsules consist of an immediate release component that rapidly achieves a morphine concentration and an extended release component that maintains the morphine plasma concentrations throughout the 24-hour dosing interval. Steady-state plasma concentrations of morphine are achieved 2 to 3 days after initiation of daily Avinza therapy. Kadian is not bioequivalent to other extended-release morphine preparations. In a crossover study, at steady-state, similar maximum concentrations, time to maximum concentrations, and systemic exposure over time were achieved with Oramorph SR and MS Contin; 30 mg of either product was given every 12 hours for 3 days followed by a 14-day washout period before the other product was given. The mean time to peak concentration after Oramorph SR was 3.75 +/- 1.21 hours and after MS Contin was 3.48 +/- 1.25 hours. The mean peak concentration was 22.61 +/- 5.83 ng/mL for Oramorph SR and 24.28 +/- 5.28 ng/mL for MS Contin, whereas the mean minimum serum concentration was 11.06 +/- 3.64 ng/mL for Oramorph SR and 9.23 +/- 2.94 ng/mL for MS Contin.[33125] When Arymo ER, MS Contin, or Morphabond ER tablets are given as a fixed dosing regimen, steady-state is achieved in about 1 day.[40951] [60209] [61668] Food does not significantly affect the Cmax or overall exposure (AUC) of Arymo ER tablets.[61668] Administration of a single dose of Morphabond ER with a standardized high fat meal resulted in a 33% increase in Cmax and no change in AUC compared to a fasted state.[60209]

Intravenous Route

Peak analgesia is obtained within 20 minutes after IV injection and the duration of analgesia is approximately 3 to 6 hours.[52190]

Intramuscular Route

Peak analgesia is obtained about 30 to 60 minutes after IM injections and the duration of analgesia is approximately 3 to 6 hours.[52190]

Subcutaneous Route

Peak analgesia is obtained about 50 to 90 minutes after subcutaneous injections and the duration of analgesia is approximately 3 to 6 hours.[52190]

Other Route(s)

Rectal Route

Peak analgesia is achieved about 20 to 60 minutes after rectal administration.[48404] The approximate bioavailability of morphine after rectal administration is 30% (range 6% to 99%) in children. Peak serum concentrations are achieved within 30 minutes when morphine is dissolved in propylene glycol and within 60 to 90 minutes when an aqueous morphine solution is mixed with a dry starch hydrogel.[52231]

 

Intrathecal Route

Lower doses of morphine (one-tenth of the dose) are required to produce similar analgesia when administered intrathecally versus epidurally because intrathecal administration circumvents the meningeal diffusion barriers. When morphine is injected into the intrathecal space, it slowly diffuses out into the systemic circulation. The slow rate of elimination accounts for the prolonged duration of action when administered by this route. Intrathecal morphine may produce noticeable effects, both pain relief and adverse effects, for up to 24 hours.[31296]

 

Epidural Route

After epidural administration, morphine is rapidly absorbed systemically with peak plasma concentrations attained in 10 to 15 minutes. Analgesia achieved with epidural morphine is not dependent on systemic morphine concentrations, and the duration of analgesia continues beyond the time during which morphine may be detected in the plasma.[31296]

Special Populations

Hepatic Impairment

The half-life of morphine is significantly prolonged and clearance is decreased in patients with cirrhosis or hepatic disease. The morphine-3 glucuronide and 6-glucuronide to morphine plasma AUC ratios are also decreased, indicating diminished metabolic activity.[40951] Adequate studies of morphine pharmacokinetics have not been conducted in patients with severe hepatic impairment.[46350]

Renal Impairment

In patients with renal dysfunction, morphine AUC is increased and clearance is decreased. The metabolites, morphine-3 glucuronide and morphine-6 glucuronide, may accumulate to much higher plasma concentrations in patients with renal failure.[61668] Adequate studies of morphine pharmacokinetics have not been conducted in patients with severe renal impairment.[46350]

Pediatrics

Infants, Children, and Adolescents

Morphine's estimated half-life and clearance are 2 hours and 23.6 mL/kg/minute, respectively. The pharmacokinetics of morphine in pediatric patients appear to approach adult values around 2 to 6 months of age; however, there is large interpatient variability and a range of 2 weeks to 2.5 years of age has been reported. Some young children may exhibit clearance up to twice that of adults.[25335][52231][52233] In a population pharmacokinetic analysis of 66 patients 2 to 17 years, the geometric mean plasma half-life was up to 1.8 hours and the mean terminal elimination plasma half-life was 18.6 hours. The single dose mean Cmax of both the morphine 3-glucuronide and 6-glucuronide metabolite was not greater than in adults.[43053]

 

Neonates

In premature neonates, the estimated half-life and clearance of morphine are 9 hours and 2.2 mL/kg/minute, respectively; in term neonates, these estimated values are 6.5 hours and 8.1 mL/kg/minute, respectively. Preterm neonates are capable of glucuronidation, but this capability is influenced by gestational and postnatal age and birth weight leading to a lower metabolic capacity and lower elimination rate in preterm and term neonates compared to older pediatric patients.[25335]

Gender Differences

A pharmacokinetic analysis of healthy subjects taking extended-release morphine demonstrated that morphine concentrations were similar in males and females.[60209]

Ethnic Differences

Chinese subjects given intravenous morphine had a higher clearance compared to Caucasian subjects (1,852 +/- 116 mL/minute vs. 1,495 +/- 80 mL/minute).[61668]

Revision Date: 06/15/2021, 01:29:35 PM

References

25335 - Kart T, Christupp LL, Rasmussen M. Recommended use of morphine in neonates, infants and children based on a literature review: part 1 - pharmacokinetics. Paediatr Anaesth 1997;7:5-11.25336 - Christrupp LL. Morphine metabolites. Acta Anaesthesiol Scand 1997;41:116-22.31296 - Duramorph (morphine sulfate injection) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Oct.33125 - Schobelock MJ, Shepard KV, Mosdell KW, et al. Multiple-dose pharmacokinetic evaluation of two formulations of sustained release morphine sulfate tablets. Curr Ther Res 1995;56:1009-21.34448 - Kharasch ED, Hoffer C, Whittington D, et al. Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine. Clin Pharmacol Ther 2003;74:543-54.40951 - MS Contin (morphine sulfate extended-release tablets) package insert. Stamford, CT: Purdue Pharma L.P.; 2023 Dec.43053 - Morphine sulfate oral solution package insert. Berkley, NJ: Hikma Pharmaceuticals USA, Inc.; 2021 Jun.46350 - Morphine sulfate tablet package insert. Berkley Heights, NJ: Hikma Pharmaceuticals Corp; 2021 Jun.48403 - Oramorph SR (morphine sulfate sustained-release tablets) package insert. Newport, KY: Xanodyne Pharmaceuticals, Inc.; 2006 Feb.48404 - Morphine sulfate rectal suppositories package insert. Minneapolis, MN: Perrigo.; 2019 Mar.52190 - Morphine injection package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2011 May.52231 - Olkkola KT, Hamunen K, Maunuksela EL. Clinical pharmacokinetics and pharmacodynamics of opioid analgesics in infants and children. Clin Pharmacokinet 1995;28:385-404.52233 - McRorie TI, Lynn AM, Nespeca MK, et al. The maturation of morphine clearance and metabolism. Am J Dis Child 1992;146:972-6.60209 - Morphabond ER (morphine sulfate extended-release tablets) package insert. Basking Ridge, NJ: Daiichi Sankyo, Inc.; 2019 Oct.61668 - Arymo ER (morphine sulfate extended-release tablets) package insert. Wayne, PA: Egalet US Inc.; 2019 Oct.

Pregnancy/Breast-feeding

labor, neonatal opioid withdrawal syndrome, obstetric delivery, pregnancy

Published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects. Results for a population-based prospective cohort, including 448 women exposed to morphine at any time during pregnancy and 70 women exposed during the first trimester of pregnancy, indicate no increased risk for congenital malformations; however, risk cannot be excluded due to study methodological limitations. Neural tube defects (i.e., exencephaly and cranioschisis) have been noted when morphine was given subcutaneously to hamsters and mice at 5 and 16 times a human daily dose of 60 mg based on body surface area. Lower fetal body weight and increased abortion incidence were observed at 0.4 times the human daily dose in rabbits, growth retardation at 6 times the human daily dose in rats, and axial skeletal fusion and cryptorchidism at 16 times the human daily dose in mice. Doses of 3 to 4 times the human daily dose given during organogenesis and throughout lactation have produced cyanosis, hypothermia, decreased brain weight or body weight, adverse effects on reproductive tissues, and death in rats. Some long-term neurochemical changes in the brains of rat offspring which correlate with altered behavioral responses that persist through adulthood have been observed with exposures comparable to and less than the human daily dose.[61668] Some experts suggest increased risk if morphine is used for prolonged periods during pregnancy or at high doses near term.[46351] While certain formulations of morphine have been used in the obstetric setting, caution is advised under various circumstances during labor and obstetric delivery. Morphine sulfate extended-release liposome injection (DepoDur) should not be administered to women for vaginal labor and delivery; this formulation is only for pain associated with Caesarian section after delivery and clamping of the umbilical cord.[29159] Morphine sulfate extended-release tablets or capsules are not recommended for use during or immediately prior to labor. Morphine readily crosses the placenta and all other formulations should be used cautiously during pregnancy or obstetric delivery. An opioid antagonist and resuscitative equipment should be readily available. If used during the second stage of labor, the duration of labor can be prolonged by temporarily reducing the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation.[35890] [40951] Further, prolonged maternal use of long-acting opioids, such as morphine, during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including rapid breathing, irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn.[31637] [35890] [40951]

breast-feeding

Use morphine with caution in breast-feeding mothers because it can pass into breast milk. The milk to plasma AUC ratio of morphine is approximately 2.5:1.[46350] In studies of epidural morphine given postcesarean section, morphine passage into colostrum and breast milk is minimal, while higher concentrations are found with intravenous or oral administration.[61697] In a study of 5 breast-feeding women given epidural, IV, or IM morphine postoperatively, the highest morphine concentrations in milk were 82 mcg/L (measured 30 minutes after two, 4 mg epidural doses) vs. 500 mcg/L (measured 45 minutes after 15 mg parenteral dose).[61698] Morphine passage into breast milk was assessed in a study of 5 women who were given a 7.5 mg loading dose of IV morphine following umbilical cord clamping, then 1 to 1.5 mg every 6 minutes via IV patient-controlled analgesia (PCA), then 5 to 30 mg PO every 2 to 3 hours as needed for pain. Average IV morphine consumption in the first 48 hours was approximately 150 mg. Average morphine consumption across the entire study period (96 hours) was approximately 250 mg (IV and oral). Average milk concentrations among all patients were 50 to 65 mcg/L during the first 48 hours; concentrations dropped to approximately 20 mcg/L at 72 to 96 hours postpartum. Using the maximum reported concentration of 65 mcg/L and assuming 30% oral absorption by the infant, an exclusively breast-fed infant would absorb a maximum of approximately 3 mcg/kg/day equal to 0.3% of the IV maternal weight-adjusted daily dose.[61697] [61699] Previous American Academy of Pediatrics recommendations considered morphine usually compatible with breast-feeding, particularly in short-term post-partum use, due to a lack of data regarding symptoms in exposed infants.[27500] However, opioids may cause serious adverse effects in the infant, including drowsiness, CNS depression, and death. If morphine is used during breast-feeding, short durations and low doses are recommended with close infant monitoring. If morphine is used long-term, the importance of continuing breast-feeding should be judged against the potential risk of adverse drug effects in the infant. Withdrawal symptoms may occur in infants whose mothers discontinue chronic opioid therapy.[61668] Advise the mother to report any excessive sleepiness, breathing difficulties, or difficulties breast-feeding to their health care provider immediately.[61697] Other alternative analgesics considered to be usually compatible with breast-feeding include ibuprofen, acetaminophen, and fentanyl.[27500]

Revision Date: 04/21/2023, 04:58:25 PM

References

27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.29159 - DepoDur (morphine sulfate extended-release liposome injection) package insert. San Diego, CA: Pacira Pharmaceuticals; 2008 Nov.31637 - Avinza (morphine sulfate extended-release capsules) package insert. Gainesville, GA: Alkermes Gainesville LLC.; 2014 Apr.35890 - Kadian (morphine sulfate extended-release capsules) package insert. Madison, NJ: Allergan USA, Inc.; 2021 Mar.40951 - MS Contin (morphine sulfate extended-release tablets) package insert. Stamford, CT: Purdue Pharma L.P.; 2023 Dec.46350 - Morphine sulfate tablet package insert. Berkley Heights, NJ: Hikma Pharmaceuticals Corp; 2021 Jun.46351 - Morphine. In: Drugs in Pregnancy and Lactation. A Reference Guide to Fetal and Neonatal Risk. Briggs GG, Freeman RK, Yaffe SJ, (eds.) 9th ed., Philadelphia PA: Lippincott Williams and Wilkins; 2011:985-6.61668 - Arymo ER (morphine sulfate extended-release tablets) package insert. Wayne, PA: Egalet US Inc.; 2019 Oct.61697 - National Institutes of Health (NIH). Morphine monograph. LactMed: Drug and Lactation Database. Revised Aug 2016. Available at https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~Tkh1UE:1. Accessed January 23, 2017.61698 - Feilberg VL, Rosenborg D, Broen Christensen C, et al. Excretion of morphine in human breast milk. Acta Anaesthesiol Scand 1989;33:426-428.61699 - Wittels B, Scott DT, Sinatra RS. Exogenous opioids in human breast milk and acute neonatal neurobehavior: a preliminary study. Anesthesiology 1990;73:864-869.

Interactions

Level 1 (Severe)

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Level 2 (Major)

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  • Isoniazid, INH; Rifampin
  • Istradefylline
  • Ivacaftor
  • Ketoconazole
  • Lapatinib
  • Lasmiditan
  • Ledipasvir; Sofosbuvir
  • Lemborexant
  • Lenacapavir
  • Leuprolide; Norethindrone
  • Levoketoconazole
  • Levomilnacipran
  • Levonorgestrel
  • Levonorgestrel; Ethinyl Estradiol
  • Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate
  • Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate
  • Lidocaine
  • Lidocaine; Epinephrine
  • Lidocaine; Prilocaine
  • Lisdexamfetamine
  • Lisinopril; Hydrochlorothiazide, HCTZ
  • Lithium
  • Lofexidine
  • Lonafarnib
  • Loop diuretics
  • Lopinavir; Ritonavir
  • Lorcaserin
  • Losartan; Hydrochlorothiazide, HCTZ
  • Loxapine
  • Lumacaftor; Ivacaftor
  • Lumateperone
  • Lurasidone
  • Maribavir
  • Melatonin
  • Memantine
  • Mepivacaine
  • Meprobamate
  • Methamphetamine
  • Methscopolamine
  • Methyldopa
  • Methylphenidate
  • Methylphenidate Derivatives
  • Metoclopramide
  • Metolazone
  • Metoprolol; Hydrochlorothiazide, HCTZ
  • Metyrosine
  • Milnacipran
  • Mitapivat
  • Molindone
  • Naratriptan
  • Neostigmine; Glycopyrrolate
  • Neratinib
  • Nirmatrelvir; Ritonavir
  • Norethindrone
  • Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate
  • Norethindrone; Ethinyl Estradiol
  • Norethindrone; Ethinyl Estradiol; Ferrous fumarate
  • Norgestimate; Ethinyl Estradiol
  • Norgestrel
  • Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
  • Olmesartan; Hydrochlorothiazide, HCTZ
  • Ondansetron
  • Oral Contraceptives
  • Osimertinib
  • Oxybutynin
  • Pacritinib
  • Paliperidone
  • Palonosetron
  • Paroxetine
  • Pegvisomant
  • Perampanel
  • Perphenazine
  • Pimozide
  • Pirtobrutinib
  • Posaconazole
  • Potassium-sparing diuretics
  • Prasugrel
  • Pretomanid
  • Prilocaine
  • Prilocaine; Epinephrine
  • Procarbazine
  • Propantheline
  • Pseudoephedrine; Triprolidine
  • Quinapril; Hydrochlorothiazide, HCTZ
  • Quinidine
  • Ramelteon
  • Relugolix; Estradiol; Norethindrone acetate
  • Rifampin
  • Risperidone
  • Ritonavir
  • Rizatriptan
  • Ropivacaine
  • Segesterone Acetate; Ethinyl Estradiol
  • Selpercatinib
  • Serdexmethylphenidate; Dexmethylphenidate
  • Serotonin norepinephrine reuptake inhibitors
  • Serotonin-Receptor Agonists
  • Serotonin-Receptor Antagonists
  • Sertraline
  • Sincalide
  • Sodium Phenylbutyrate; Taurursodiol
  • Sofosbuvir; Velpatasvir; Voxilaprevir
  • Solifenacin
  • Sorafenib
  • Sotorasib
  • Sparsentan
  • Spironolactone
  • Spironolactone; Hydrochlorothiazide, HCTZ
  • St. John's Wort, Hypericum perforatum
  • Stiripentol
  • Sufentanil
  • Sumatriptan
  • Sumatriptan; Naproxen
  • Suvorexant
  • Tasimelteon
  • Telmisartan; Hydrochlorothiazide, HCTZ
  • Temsirolimus
  • Tepotinib
  • Tezacaftor; Ivacaftor
  • Thiazide diuretics
  • Thiothixene
  • Ticagrelor
  • Tolterodine
  • Torsemide
  • Trazodone
  • Triamterene
  • Triamterene; Hydrochlorothiazide, HCTZ
  • Trifluoperazine
  • Trihexyphenidyl
  • Trimethobenzamide
  • Triprolidine
  • Trospium
  • Tucatinib
  • Valerian, Valeriana officinalis
  • Valproic Acid, Divalproex Sodium
  • Valsartan; Hydrochlorothiazide, HCTZ
  • Vemurafenib
  • Venlafaxine
  • Vigabatrin
  • Vilazodone
  • Voclosporin
  • Vortioxetine
  • Zaleplon
  • Ziconotide
  • Ziprasidone
  • Zolmitriptan
  • Zolpidem

Level 4 (Minor)

  • Apraclonidine
  • Cabozantinib
  • Eliglustat
  • Lumacaftor; Ivacaftor
  • Minocycline
  • Nitroglycerin
  • Zonisamide
Abrocitinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with abrocitinib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and abrocitinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [67277] Acetaminophen; Aspirin; Diphenhydramine: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [56616] [61143] Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of morphine with dihydrocodeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or dihydrocodeine is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Acetaminophen; Caffeine; Pyrilamine: (Moderate) Concomitant use of opioid agonists with pyrilamine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with pyrilamine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [33656] [61143] Acetaminophen; Chlorpheniramine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Acetaminophen; Codeine: (Major) Concomitant use of morphine with codeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or codeine is recommended; for extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Acetaminophen; Dextromethorphan; Doxylamine: (Major) Reserve concomitant use of opioids and doxylamine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [52061] [61143] Acetaminophen; Diphenhydramine: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [56616] [61143] Acetaminophen; Hydrocodone: (Major) Concomitant use of hydrocodone with morphine may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage. Also, consider a using a lower dose of morphine. Monitor patients for sedation and respiratory depression. [56303] Acetaminophen; Oxycodone: (Major) Concomitant use of oxycodone with morphine may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of oxycodone and/or morphine is recommended; use an initial dose of oxycodone at one-third to one-half the usual dosage. For extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor for sedation and respiratory depression. [31637] [35890] [39926] [40951] Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concomitant use of opioid agonists with pyrilamine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with pyrilamine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [33656] [61143] Acrivastine; Pseudoephedrine: (Major) Avoid coadministration of opioid agonists with acrivastine due to the risk of additive CNS depression. [61143] [63074] Adagrasib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with adagrasib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and adagrasib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [68325] Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as morphine, may decrease adefovir elimination by competing for common renal tubular transport systems, therefore increasing serum concentrations of either adefovir and/or these coadministered drugs. [29168] Alfentanil: (Major) Concomitant use of morphine with alfentanil can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. If alfentanil is used concurrently with morphine, monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Almotriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28800] [35890] [36460] [40951] [43053] [46350] [60209] Alosetron: (Major) Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as opiate agonists, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. [28382] Alprazolam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Alvimopan: (Moderate) Patients should not take alvimopan if they have received therapeutic doses of opiate agonists for more than seven consecutive days immediately before initiation of alvimopan therapy. Patients recently exposed to opioids are expected to be more sensitive to the effects of mu-opioid receptor antagonists and may experience adverse effects localized to the gastrointestinal tract such as abdominal pain, nausea, vomiting, and diarrhea. [34117] [34666] Amide local anesthetics: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Amiloride: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a potassium-sparing diuretic and morphine; increase the dosage of the potassium-sparing diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a potassium-sparing diuretic and morphine; increase the dosage of the potassium-sparing diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Amiodarone: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with amiodarone is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and amiodarone is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [56579] Amitriptyline: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Amobarbital: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Amoxapine: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression. [28558] [35890] [36460] [40951] [46350] [60209] [61143] Amphetamine: (Moderate) If concomitant use of morphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [43053] Amphetamine; Dextroamphetamine: (Moderate) If concomitant use of morphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [43053] Amphetamines: (Moderate) If concomitant use of morphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [43053] Apomorphine: (Major) Concomitant use of opioid agonists with apomorphine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with apomorphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like apomorphine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. [28661] [36460] [40951] [46350] [60209] Apraclonidine: (Minor) Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as opiate agonists. Although no specific drug interactions were identified with systemic agents and apraclonidine during clinical trials, apraclonidine can cause dizziness and somnolence. [29484] Aripiprazole: (Moderate) Concomitant use of opioid agonists with aripiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with aripiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [42845] [46350] [60209] [61143] Articaine; Epinephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Asenapine: (Moderate) Concomitant use of opioid agonists with asenapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with asenapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [36343] [36460] [40951] [46350] [60209] [61143] Aspirin, ASA; Butalbital; Caffeine: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Aspirin, ASA; Caffeine; Orphenadrine: (Major) Concomitant use of morphine with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of morphine with carisoprodol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with carisoprodol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [31110] [35890] [36460] [40951] [46350] [60209] [61143] (Major) Concomitant use of morphine with codeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or codeine is recommended; for extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Aspirin, ASA; Oxycodone: (Major) Concomitant use of oxycodone with morphine may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of oxycodone and/or morphine is recommended; use an initial dose of oxycodone at one-third to one-half the usual dosage. For extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor for sedation and respiratory depression. [31637] [35890] [39926] [40951] Atazanavir; Cobicistat: (Moderate) The plasma concentrations of morphine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while morphine is a P-gp substrate. [34448] [51664] [58000] Atenolol; Chlorthalidone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Atropine: (Major) Reserve concomitant use of morphine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [63228] Atropine; Difenoxin: (Major) Reserve concomitant use of morphine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [63228] (Moderate) Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. [30269] Azelastine: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [43712] [46350] [60209] [61143] [63556] Azelastine; Fluticasone: (Major) Concomitant use of opioid agonists with azelastine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with azelastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [43712] [46350] [60209] [61143] [63556] Azilsartan; Chlorthalidone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Baclofen: (Major) Concomitant use of morphine with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [57272] [60209] [61143] Barbiturates: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Belladonna; Opium: (Major) Concomitant use of morphine with opium can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or opium is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and belladonna use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [57409] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with benzhydrocodone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of benzhydrocodone with opioid agonists to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If benzhydrocodone is initiated in a patient taking morphine, reduce initial dosage and titrate to clinical response. If morphine is prescribed in a patient taking benzhydrocodone, use a lower initial dose of morphine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of benzhydrocodone and morphine because of the potential risk of serotonin syndrome. Discontinue benzhydrocodone if serotonin syndrome is suspected. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [35890] [40951] [61143] [62889] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Contraindicated) Morphine use in patients taking methylene blue or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. [46350] (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and hyoscyamine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [30922] [46350] Benzphetamine: (Moderate) If concomitant use of morphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [43053] Benztropine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and benztropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [31963] [46350] Bethanechol: (Moderate) Bethanechol facilitates intestinal and bladder function via parasympathomimetic actions. Opiate agonists impair the peristaltic activity of the intestine. Thus, these drugs can antagonize the beneficial actions of bethanechol on GI motility. [29831] Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. [6365] [6925] Bismuth Subsalicylate: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. [6365] [6925] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Additive constipation may be seen with concurrent use of opiate agonists and antidiarrheals. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. [6365] [6925] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Brexanolone: (Moderate) Concomitant use of brexanolone with CNS depressants like the opiate agonists may increase the likelihood or severity of adverse reactions related to sedation and additive CNS depression. Monitor for excessive sedation, dizziness, and a potential for loss of consciousness during brexanolone use. [64021] Brexpiprazole: (Major) Concomitant use of opioid agonists with brexpiprazole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with brexpiprazole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [46350] [59949] [60209] [61143] Brigatinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including sedation and respiratory depression, if coadministration with brigatinib is necessary; consider a reduced dose of morphine with frequent monitoring for respiratory depression and sedation. Morphine is a P-glycoprotein (P-gp) substrate. Brigatinib inhibits P-gp in vitro and may have the potential to increase concentrations of P-gp substrates. [34448] [61909] Brimonidine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists. [29281] Brimonidine; Brinzolamide: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists. [29281] Brimonidine; Timolol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists. [29281] Brompheniramine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [47262] [61143] Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [47262] [61143] Brompheniramine; Phenylephrine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [47262] [61143] Brompheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [47262] [61143] Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Concomitant use of opioid agonists with brompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with brompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [47262] [61143] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [57625] Bumetanide: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and morphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] Bupivacaine Liposomal: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Bupivacaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Bupivacaine; Epinephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Bupivacaine; Lidocaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Bupivacaine; Meloxicam: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Buprenorphine: (Major) Avoid concomitant use of morphine and a mixed opioid agonist/antagonist, such as buprenorphine, due to risk for reduced analgesic effect of morphine and/or precipitation of withdrawal symptoms. [40951] [60270] [60833] [61045] Buprenorphine; Naloxone: (Major) Avoid concomitant use of morphine and a mixed opioid agonist/antagonist, such as buprenorphine, due to risk for reduced analgesic effect of morphine and/or precipitation of withdrawal symptoms. [40951] [60270] [60833] [61045] Bupropion: (Moderate) Monitor for seizure activity during concomitant bupropion and morphine use. Bupropion is associated with a dose-related seizure risk and excessive opioid use also increases seizure risk. [28058] Bupropion; Naltrexone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7 to 10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] (Moderate) Monitor for seizure activity during concomitant bupropion and morphine use. Bupropion is associated with a dose-related seizure risk and excessive opioid use also increases seizure risk. [28058] Buspirone: (Moderate) Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of morphine, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of morphine and buspirone is imperative, reduce the dose of one or both drugs. [28501] Butalbital; Acetaminophen: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Butalbital; Acetaminophen; Caffeine: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] (Major) Concomitant use of morphine with codeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or codeine is recommended; for extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] (Major) Concomitant use of morphine with codeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or codeine is recommended; for extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Butorphanol: (Major) Avoid the concomitant use of butorphanol and opiate agonists, such as morphine. Butorphanol is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects. Butorphanol may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of butorphanol with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. [40951] [49512] Cabozantinib: (Minor) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with cabozantinib is necessary; a dose adjustment of morphine may be necessary. Morphine is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [34448] [52506] [60738] Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28528] [29623] [33654] [40951] [43291] [61143] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Cannabidiol: (Moderate) Concomitant use of opioid agonists with cannabidiol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with cannabidiol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor for adverse reactions, including hypotension, sedation, and respiratory depression and decrease the dose of morphine as necessary. In addition, morphine is a P-gp and UGT2B7 substrate and cannabidiol is a P-gp and UGT2B7 inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [30433] [31637] [35890] [40951] [63309] Capmatinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with capmatinib is necessary; decrease the dose of either drug as necessary. Morphine is a P-glycoprotein (P-gp) substrate and capmatinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [65377] Capsaicin; Metaxalone: (Major) Concomitant use of opioid agonists with metaxalone may cause respiratory depression, profound sedation, and death. Limit the use of opioid pain medication with metaxalone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use of metaxalone and opioid agonists increases the risk for serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary. [30830] [35890] [40951] [46350] [61143] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Carbidopa; Levodopa; Entacapone: (Major) Concomitant use of opioid agonists with COMT inhibitors may cause excessive sedation and somnolence. Limit the use of opioid pain medications with COMT inhibitors to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. [28845] [36460] [40951] [42112] [46350] [60209] Carbinoxamine: (Moderate) Concomitant use of opioid agonists with carbinoxamine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with carbinoxamine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [61143] [61797] Cariprazine: (Moderate) Concomitant use of opioid agonists like morphine with cariprazine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cariprazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [35890] [60164] Carisoprodol: (Major) Concomitant use of morphine with carisoprodol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with carisoprodol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [31110] [35890] [36460] [40951] [46350] [60209] [61143] Carvedilol: (Moderate) Increased concentrations of morphine may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and morphine is a P-gp substrate. [32533] [51834] [58220] Celecoxib; Tramadol: (Major) Concomitant use of morphine with tramadol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of morphine with tramadol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Additionally, monitor patients for seizures and/or the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28314] [40951] Cenobamate: (Moderate) Concomitant use of morphine with cenobamate may cause excessive sedation and somnolence. Limit the use of morphine with cenobamate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [46350] [60209] [61143] [64768] Cetirizine: (Major) Reserve concomitant use of opioids and cetirizine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [28874] [40972] [61143] Cetirizine; Pseudoephedrine: (Major) Reserve concomitant use of opioids and cetirizine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [28874] [40972] [61143] Chlophedianol; Dexbrompheniramine: (Moderate) Concomitant use of opioid agonists with dexbrompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexbrompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [61143] [64881] Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with dexchlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexchlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [61143] [63638] [64882] Chlorcyclizine: (Moderate) Concomitant use of opioid agonists with chlorcyclizine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorcyclizine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59612] [61143] Chlordiazepoxide: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Chlordiazepoxide; Amitriptyline: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] Chlordiazepoxide; Clidinium: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Chlorothiazide: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Chlorpheniramine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Chlorpheniramine; Codeine: (Major) Concomitant use of morphine with codeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or codeine is recommended; for extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Chlorpheniramine; Hydrocodone: (Major) Concomitant use of hydrocodone with morphine may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage. Also, consider a using a lower dose of morphine. Monitor patients for sedation and respiratory depression. [56303] (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Chlorpheniramine; Phenylephrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Chlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with chlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with chlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59535] [61143] Chlorpromazine: (Major) Concomitant use of opioid agonists with chlorpromazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with chlorpromazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression. [28997] [35890] [36460] [40951] [46350] [60209] [61143] Chlorthalidone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Chlorzoxazone: (Major) Concomitant use of morphine with chlorzoxazone may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with chlorzoxazone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [51369] [60209] [61143] Cimetidine: (Moderate) Concurrent use of morphine and cimetidine may increase the adverse effects of morphine, especially if a large cimetidine dose is used or if the patient is not young and healthy. One patient undergoing hemodialysis experienced confusion and severe respiratory depression when given morphine and cimetidine concurrently. As determined by data obtained from healthy patients, the mean systemic exposure, half-life, volume of distribution, and plasma clearance of morphine were similar after 4 days of pretreatment with either placebo or cimetidine 300 mg every 6 hours by mouth. In another crossover study, the concurrent receipt of cimetidine 600 mg orally and 10 mg morphine intramuscularly by 8 healthy adults led to a more profound depression of the CO2 response and delay in its recovery as compared with only morphine receipt; cimetidine alone had negligible respiratory effects. Also, concomitant administration of morphine and cimetidine has been reported to precipitate apnea, confusion, and muscle twitching in an isolated report. Monitor patients for increased respiratory and CNS depression when receiving both cimetidine and morphine. [31637] [31758] [40951] Citalopram: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like morphine with serotonergic drugs, such as citalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28269] [40951] Clemastine: (Moderate) Concomitant use of opioid agonists with clemastine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clemastine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [47268] [61143] Clobazam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Clomipramine: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] Clonazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Clonidine: (Major) Concomitant use of opioid agonists with clonidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with clonidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [25449] [25450] [28290] [42062] [42063] Clopidogrel: (Moderate) Coadministration of opioid agonists delay and reduce the absorption of clopidogrel resulting in reduced exposure to active metabolites and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Coadministration of intravenous morphine decreased the Cmax and AUC of clopidogrel's active metabolites by 34%. Time required for maximal inhibition of platelet aggregation (median 3 hours vs. 1.25 hours) was significantly delayed; times up to 5 hours were reported. Inhibition of platelet plug formation was delayed and residual platelet aggregation was significantly greater 1 to 4 hours after morphine administration. [28435] [56576] Clorazepate: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Clozapine: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include clozapine. Prior to concurrent use of morphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Cobicistat: (Moderate) The plasma concentrations of morphine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while morphine is a P-gp substrate. [34448] [51664] [58000] Codeine: (Major) Concomitant use of morphine with codeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or codeine is recommended; for extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Codeine; Guaifenesin: (Major) Concomitant use of morphine with codeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or codeine is recommended; for extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of morphine with codeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or codeine is recommended; for extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of morphine with codeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or codeine is recommended; for extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] (Major) Concomitant use of opioid agonists with promethazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with promethazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce the opioid dose by one-quarter to one-half (for extended-release morphine tablets, start with 15 mg every 12 hours); use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [46350] [60209] [61143] [63555] Codeine; Promethazine: (Major) Concomitant use of morphine with codeine can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or codeine is recommended; for extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] (Major) Concomitant use of opioid agonists with promethazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with promethazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce the opioid dose by one-quarter to one-half (for extended-release morphine tablets, start with 15 mg every 12 hours); use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [46350] [60209] [61143] [63555] COMT inhibitors: (Major) Concomitant use of opioid agonists with COMT inhibitors may cause excessive sedation and somnolence. Limit the use of opioid pain medications with COMT inhibitors to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. [28845] [36460] [40951] [42112] [46350] [60209] Conivaptan: (Moderate) Use caution when administering conivaptan and morphine concurrently. Conivaptan is an inhibitor of P-glycoprotein (P-gp). Co-administration of conivaptan with P-gp substrates, such as morphine, can increase morphine exposure leading to increased or prolonged therapeutic effects and adverse events. [31764] [34448] [56579] Crofelemer: (Moderate) Pharmacodynamic interactions between crofelemer and opiate agonists are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as opiate agonists, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration. [39926] [52766] Cyclobenzaprine: (Major) Concomitant use of morphine with cyclobenzaprine may cause respiratory depression, hypotension, profound sedation, and death and increase the risk for serotonin syndrome and anticholinergic effects. Limit the use of opioid pain medications with cyclobenzaprine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Monitor patients for serotonin syndrome if concomitant use is necessary, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome. Monitor for signs of urinary retention or reduced gastric motility during coadministration. The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [28425] [35890] [40951] [46350] [61143] Cyproheptadine: (Moderate) Concomitant use of opioid agonists with cyproheptadine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with cyproheptadine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [59577] [61143] Daclatasvir: (Moderate) Systemic exposure of morphine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of morphine; monitor patients for potential adverse effects. [34448] [60001] Dantrolene: (Major) Concomitant use of morphine with dantrolene may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with dantrolene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [49509] [60209] [61143] Daridorexant: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with daridorexant is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and daridorexant is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [67248] Darifenacin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when darifenacin, an anticholinergic drug for overactive bladder, is used with opiate agonists. The concomitant use of these drugs together may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Both agents may also cause drowsiness or blurred vision, and patients should use care in driving or performing other hazardous tasks until the effects of the drugs are known. [30711] Darunavir; Cobicistat: (Moderate) The plasma concentrations of morphine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while morphine is a P-gp substrate. [34448] [51664] [58000] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) The plasma concentrations of morphine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while morphine is a P-gp substrate. [34448] [51664] [58000] Desflurane: (Moderate) Concurrent use with opiate agonists can decrease the minimum alveolar concentration (MAC) of desflurane needed to produce anesthesia. [56070] Desipramine: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with water intoxication, hyponatremia, or SIADH including opiate agonists. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia. [5940] Desogestrel; Ethinyl Estradiol: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Desvenlafaxine: (Moderate) If concomitant use of morphine and serotonin norepinephrine reuptake inhibitors is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [40951] Deutetrabenazine: (Major) Concomitant use of opiate agonists with deutetrabenazine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with deutetrabenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking deutetrabenazine, reduced initial dosages are recommended. For extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Use an initial morphine; naltrexone dose of 20 mg/0.8 mg every 24 hours. If deutetrabenazine is prescribed for a patient taking an opiate agonist, use a lower initial dose of deutetrabenazine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [61845] Dexbrompheniramine: (Moderate) Concomitant use of opioid agonists with dexbrompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexbrompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [61143] [64881] Dexbrompheniramine; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with dexbrompheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexbrompheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [61143] [64881] Dexchlorpheniramine: (Moderate) Concomitant use of opioid agonists with dexchlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexchlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [61143] [63638] [64882] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with dexchlorpheniramine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dexchlorpheniramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [61143] [63638] [64882] Dexmedetomidine: (Moderate) Concomitant use of opioid agonists with dexmedetomidine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with dexmedetomidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [29112] [67509] Dexmethylphenidate: (Moderate) If concomitant use of morphine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [60209] Dextroamphetamine: (Moderate) If concomitant use of morphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [43053] Dextromethorphan; Bupropion: (Moderate) Monitor for seizure activity during concomitant bupropion and morphine use. Bupropion is associated with a dose-related seizure risk and excessive opioid use also increases seizure risk. [28058] Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [56616] [61143] Dextromethorphan; Quinidine: (Moderate) Morphine is a substrate for P-glycoprotein (P-gp), and quinidine is a P-gp substrate and inhibitor. Coadministration may lead to increased systemic exposure of morphine and morphine-related side effects. [29376] [34448] [34452] Diazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. If parental diazepam is used with an opiate agonist, reduce the opiate agonist dosage by at least 1/3. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [43931] [61143] [63923] Dicyclomine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and dicyclomine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [30090] [46350] Dienogest; Estradiol valerate: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Difelikefalin: (Major) Avoid concomitant use of opioids and other CNS depressants, such as difelikefalin. Concomitant use can increase the risk of respiratory depression, hypotension, profound sedation, and death. If alternate treatment options are inadequate and coadministration is necessary, limit dosages and durations to the minimum required, monitor patients closely for respiratory depression and sedation, and consider prescribing naloxone for the emergency treatment of opioid overdose. [61143] [66926] Dimenhydrinate: (Moderate) Concomitant use of opioid agonists with dimenhydrinate may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dimenhydrinate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [48650] [61143] Diphenhydramine: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [56616] [61143] Diphenhydramine; Ibuprofen: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [56616] [61143] Diphenhydramine; Naproxen: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [56616] [61143] Diphenhydramine; Phenylephrine: (Major) Reserve concomitant use of opioids and diphenhydramine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [56616] [61143] Diphenoxylate; Atropine: (Major) Reserve concomitant use of morphine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [63228] (Moderate) Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. [30269] Dolasetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor antagonist. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28308] [31266] [31723] [40951] [46350] [49446] [64690] Donepezil; Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as morphine, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or morphine is recommended to assess for needed dosage adjustments. [29168] Doxepin: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] Doxylamine: (Major) Reserve concomitant use of opioids and doxylamine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [52061] [61143] Doxylamine; Pyridoxine: (Major) Reserve concomitant use of opioids and doxylamine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [52061] [61143] Dronabinol: (Moderate) Concomitant use of opioid agonists with dronabinol may cause excessive sedation and somnolence. Limit the use of opioid pain medication with dronabinol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [30431] [60951] [60958] [65809] Droperidol: (Major) Concomitant use of opioid agonists with droperidol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with droperidol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression. [36460] [40951] [46350] [51289] [60209] [61143] Drospirenone: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Drospirenone; Estetrol: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Drospirenone; Estradiol: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Drospirenone; Ethinyl Estradiol: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Duloxetine: (Moderate) If concomitant use of morphine and serotonin norepinephrine reuptake inhibitors is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [40951] Elacestrant: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with elacestrant is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and elacestrant is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [68530] Elagolix; Estradiol; Norethindrone acetate: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Eletriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28800] [35890] [36460] [40951] [43053] [46350] [60209] Elexacaftor; tezacaftor; ivacaftor: (Moderate) Use caution when administering ivacaftor and morphine concurrently. Ivacaftor is an inhibitor of P-glycoprotein (P-gp). Coadministration of ivacaftor with P-gp substrates, such as morphine, can increase morphine exposure leading to increased or prolonged therapeutic effects and adverse events. [48524] Eliglustat: (Minor) Coadministration of morphine and eliglustat may result in increased plasma concentrations of morphine. Monitor patients closely for morphine-related adverse effects including respiratory depression, and consider reducing the morphine dosage and titrating to clinical effect. Morphine is a P-glycoprotein (P-gp) substrate; eliglustat is a P-gp inhibitor. [34448] [57803] Eluxadoline: (Major) Avoid use of eluxadoline with medications that may cause constipation, such as morphine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle within the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Closely monitor for increased side effects if these drugs are administered together. [59741] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of morphine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while morphine is a P-gp substrate. [34448] [51664] [58000] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of morphine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as oversedation, respiratory depression, and hypotension, is recommended during coadministration. Cobicistat is a P-glycoprotein (P-gp) inhibitor, while morphine is a P-gp substrate. [34448] [51664] [58000] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Enasidenib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with enasidenib is necessary; decrease the dose of either drug as necessary. Morphine is a P-gp substrate and enasidenib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [62181] Entacapone: (Major) Concomitant use of opioid agonists with COMT inhibitors may cause excessive sedation and somnolence. Limit the use of opioid pain medications with COMT inhibitors to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. [28845] [36460] [40951] [42112] [46350] [60209] Entecavir: (Moderate) Both entecavir and morphine are secreted by active tubular secretion. In theory, coadministration of entecavir with morphine may increase the serum concentrations of either drug due to competition for the drug elimination pathway. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered. [29168] [31230] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Escitalopram: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like morphine with serotonergic drugs, such as escitalopram. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28270] [40951] Esketamine: (Major) Concomitant use of opioid agonists with esketamine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with esketamine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep. Educate patients about the risks and symptoms of excessive CNS depression. [63989] Esmolol: (Moderate) Morphine increases the steady-state blood concentrations of esmolol by 50%, although morphine blood concentrations are not affected by esmolol. Careful titration of esmolol is prudent when given with morphine. [29967] Estazolam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Estradiol; Levonorgestrel: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Estradiol; Norethindrone: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Estradiol; Norgestimate: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Eszopiclone: (Moderate) Concomitant use of morphine with eszopiclone can potentiate the effects of morphine on respiration, blood pressure, and alertness. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If eszopiclone is used concurrently with morphine, a reduced dosage of morphine and/or eszopiclone is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30571] [31637] [35890] [40951] Ethacrynic Acid: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and morphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] Ethanol: (Major) Advise patients to avoid alcohol consumption while taking opioids. Alcohol consumption may result in additive CNS depression and may increase the risk for opioid overdose. Alcohol may also increase opioid drug exposure and the risk for fatal overdose by disrupting extended- or delayed-release opioid formulations. Consider the patient's use of alcohol when prescribing opioid medications. If the patient is unlikely to be compliant with avoiding alcohol, consider prescribing naloxone especially if additional risk factors for opioid overdose are present. [61143] Ethinyl Estradiol; Norelgestromin: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Ethinyl Estradiol; Norgestrel: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Ethotoin: (Moderate) Additive CNS depression could be seen with the combined use of the ethotoin and morphine. [28022] [40951] Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Etomidate: (Major) Concomitant use of morphine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [28970] [31036] [35890] [36460] [40951] [43431] [46350] [49500] [49614] [60209] [61143] Etonogestrel; Ethinyl Estradiol: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Etravirine: (Moderate) Increased concentrations of morphine may occur if it is coadministered with etravirine; exercise caution. Etravirine is an inhibitor of the efflux transporter P-glycoprotein (P-gp). Morphine is a P-gp substrate. [33718] [34448] Fenfluramine: (Moderate) Concomitant use of opioid agonists with fenfluramine may cause excessive sedation and somnolence. Limit the use of opioid agonists with fenfluramine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [35890] [36460] [40951] [46350] [60209] [60660] [65634] Fentanyl: (Major) Concomitant use of morphine with fentanyl can potentiate the effects of morphine on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or fentanyl is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Fesoterodine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when fesoterodine, an anticholinergic drug for overactive bladder is used with opiate agonists. The concomitant use of these drugs together may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Both agents may also cause drowsiness or blurred vision, and patients should use care in driving or performing other hazardous tasks until the effects of the drugs are known. [34539] Flavoxate: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and flavoxate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [47398] Flibanserin: (Moderate) Concomitant use of opioid agonists with flibanserin may cause excessive sedation and somnolence. Limit the use of opioid pain medication with flibanserin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [60099] Fluoxetine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like morphine with serotonergic drugs, such as fluoxetine. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [32127] [40951] Fluphenazine: (Moderate) Concomitant use of opioid agonists with fluphenazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with fluphenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [43067] [46350] [60209] [61143] Flurazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] Fluvoxamine: (Major) Because of the potential risk and severity of serotonin syndrome, caution and careful monitoring are recommended when administering selective serotonin reuptake inhibitors (SSRIs), such as fluvoxamine, with other drugs that have serotonergic properties such as morphine. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Morphine and fluvoxamine should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated. [40951] [47184] Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions. [67473] Fosamprenavir: (Moderate) Caution is advised when administering morphine with fosamprenavir, as concurrent use may result in reduced morphine plasma concentrations. Morphine is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer. [29012] [34448] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Fostamatinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with fostamatinib is necessary; a dose adjustment of morphine may be necessary. Morphine is a P-glycoprotein (P-gp) substrate. Fostamatinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [34448] [63084] Frovatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28800] [35890] [36460] [40951] [43053] [46350] [60209] Furosemide: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and morphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] Futibatinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with futibatinib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and futibatinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [68013] Gabapentin: (Major) Concomitant use of opioid agonists with gabapentin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with gabapentin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also, coadministration of morphine and gabapentin may increase gabapentin concentrations and may require dosage adjustment. Mean gabapentin AUC increased by 44% when a 60 mg controlled-release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule (n = 12). Morphine pharmacokinetic parameter values were not affected by administration of gabapentin 2 hours after morphine. The magnitude of interaction at other doses is not known. [27986] [35890] [40951] [46350] [60209] [61143] [63923] [64848] General anesthetics: (Major) Concomitant use of morphine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [28970] [31036] [35890] [36460] [40951] [43431] [46350] [49500] [49614] [60209] [61143] Gilteritinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with gilteritinib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and gilteritinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [63787] Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and morphine as coadministration may increase serum concentrations of morphine and increase the risk of adverse effects. Morphine is a substrate of P-glycoprotein (P-gp); glecaprevir is a P-gp inhibitor. [34448] [62201] (Moderate) Caution is advised with the coadministration of pibrentasvir and morphine as coadministration may increase serum concentrations of morphine and increase the risk of adverse effects. Morphine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp. [34448] [62201] Glycopyrrolate: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [57625] Glycopyrrolate; Formoterol: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [57625] Granisetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor antagonist. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28308] [31266] [31723] [40951] [46350] [49446] [64690] Guaifenesin; Hydrocodone: (Major) Concomitant use of hydrocodone with morphine may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage. Also, consider a using a lower dose of morphine. Monitor patients for sedation and respiratory depression. [56303] Guanfacine: (Moderate) Concomitant use of opioid agonists with guanfacine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with guanfacine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [43566] [50446] [65809] Haloperidol: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include haloperidol. Prior to concurrent use of morphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Homatropine; Hydrocodone: (Major) Concomitant use of hydrocodone with morphine may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage. Also, consider a using a lower dose of morphine. Monitor patients for sedation and respiratory depression. [56303] (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and homatropine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [67638] Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Hydrocodone: (Major) Concomitant use of hydrocodone with morphine may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage. Also, consider a using a lower dose of morphine. Monitor patients for sedation and respiratory depression. [56303] Hydrocodone; Ibuprofen: (Major) Concomitant use of hydrocodone with morphine may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage. Also, consider a using a lower dose of morphine. Monitor patients for sedation and respiratory depression. [56303] Hydrocodone; Pseudoephedrine: (Major) Concomitant use of hydrocodone with morphine may lead to hypotension, profound sedation, coma, respiratory depression and death. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Hydrocodone should be used in reduced dosages if used concurrently with a CNS depressant; initiate hydrocodone at 20 to 30% of the usual dosage. Also, consider a using a lower dose of morphine. Monitor patients for sedation and respiratory depression. [56303] Hydromorphone: (Major) Concomitant use of hydromorphone with morphine can potentiate the effects of both drugs and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of hydromorphone and/or morphine is recommended; start with one-third to one-half of the estimated hydromorphone starting dose when using hydromorphone extended-release tablets. For morphine extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. [30376] [30378] [31637] [35890] [39635] [40951] Hydroxyzine: (Major) Concomitant use of opioid agonists with hydroxyzine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with hydroxyzine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [46350] [60209] [61143] Hyoscyamine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and hyoscyamine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [30922] [46350] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Contraindicated) Morphine use in patients taking methylene blue or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. [46350] (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and hyoscyamine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [30922] [46350] Ibuprofen; Oxycodone: (Major) Concomitant use of oxycodone with morphine may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of oxycodone and/or morphine is recommended; use an initial dose of oxycodone at one-third to one-half the usual dosage. For extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor for sedation and respiratory depression. [31637] [35890] [39926] [40951] Iloperidone: (Moderate) Concomitant use of iloperidone with other centrally-acting medications, such as morphine, may increase both the frequency and the intensity of adverse effects including drowsiness, sedation, and dizziness. [36146] Imipramine: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] Indacaterol; Glycopyrrolate: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [57625] Indapamide: (Moderate) Monitor for decreased diuretic efficacy and additive orthostatic hypotension when indapamide is administered with morphine. Adjustments to diuretic therapy may be needed in some patients. The efficacy of diuretics may be reduced due to opioid-induced release of antidiuretic hormone. Morphine may also cause acute urinary retention by causing a spasm of the bladder sphincter; men with enlarged prostates may have a higher risk of this reaction. [40951] Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Isocarboxazid: (Contraindicated) Morphine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of morphine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as morphine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. [29159] [31296] [35890] [43053] [46350] [48404] [51758] [64690] [67417] Isoflurane: (Major) Concomitant use of morphine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [28970] [31036] [35890] [36460] [40951] [43431] [46350] [49500] [49614] [60209] [61143] Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin may induce the metabolism of morphine and lead to loss of analgesia if coadministered. [30435] Isoniazid, INH; Rifampin: (Moderate) Rifampin may induce the metabolism of morphine and lead to loss of analgesia if coadministered. [30435] Istradefylline: (Moderate) Monitor for morphine-related adverse effects if coadministration with istradefylline is necessary as concurrent use may increase morphine exposure. Morphine is a substrate of P-gp and istradefylline is an inhibitor of P-gp. [34448] [64590] Ivacaftor: (Moderate) Use caution when administering ivacaftor and morphine concurrently. Ivacaftor is an inhibitor of P-glycoprotein (P-gp). Coadministration of ivacaftor with P-gp substrates, such as morphine, can increase morphine exposure leading to increased or prolonged therapeutic effects and adverse events. [48524] Ketamine: (Major) Concomitant use of morphine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [28970] [31036] [35890] [36460] [40951] [43431] [46350] [49500] [49614] [60209] [61143] Ketoconazole: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression. If coadministration with ketoconazole is necessary, assess the need for morphine dosage reduction as clinically indicated. Morphine is a P-glycoprotein (P-gp) substrate and ketoconazole is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [27982] [40951] [67231] Lapatinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death, if coadministration with lapatinib is necessary; decrease the dose of morphine as clinically appropriate. Morphine is a P-glycoprotein (P-gp) substrate and lapatinib is a P-gp inhibitor. The concomitant use of P-gp inhibitors can increase the exposure to morphine by about 2-fold. [33192] [34448] Lasmiditan: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with lasmiditan is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and lasmiditan is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [64685] Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of morphine-associated adverse reactions is advised with concomitant administration of ledipasvir. Morphine is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase morphine plasma concentrations. [34448] [58167] Lemborexant: (Moderate) Concomitant use of morphine with lemborexant may cause excessive sedation and somnolence. Limit the use of morphine with lemborexant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [46350] [60209] [61143] [64870] Lenacapavir: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with lenacapavir is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and lenacapavir is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [68383] Leuprolide; Norethindrone: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Levocetirizine: (Major) Reserve concomitant use of opioids and cetirizine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [28874] [40972] [61143] Levoketoconazole: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression. If coadministration with ketoconazole is necessary, assess the need for morphine dosage reduction as clinically indicated. Morphine is a P-glycoprotein (P-gp) substrate and ketoconazole is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [27982] [40951] [67231] Levomilnacipran: (Moderate) If concomitant use of morphine and serotonin norepinephrine reuptake inhibitors is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [40951] Levonorgestrel: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Levonorgestrel; Ethinyl Estradiol: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Lidocaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Lidocaine; Epinephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Lidocaine; Prilocaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Linezolid: (Contraindicated) Morphine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. [46350] Lisdexamfetamine: (Moderate) If concomitant use of morphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [43053] Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Lithium: (Moderate) If concomitant use of morphine and lithium is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [43053] Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and morphine. Lofexidine can potentiate the effects of CNS depressants. [63161] Lonafarnib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with lonafarnib is necessary; decrease the dose of either drug as necessary. Morphine is a P-glycoprotein (P-gp) substrate and lonafarnib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [66129] Loop diuretics: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and morphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] Lopinavir; Ritonavir: (Moderate) Close clinical monitoring is advised when administering morphine with ritonavir due to an increased potential for morphine-related adverse events, including hypotension, respiratory depression, profound sedation, coma, and death. Dosage reductions of morphine and/or ritonavir may be required. Morphine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); ritonavir is an inhibitor of this efflux protein. Coadministration may cause an approximate 2-fold increase in morphine exposure. [28380] [34557] [40951] Lorazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Lorcaserin: (Moderate) If concomitant use of morphine and lorcaserin is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [43053] Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Loxapine: (Moderate) Concomitant use of opioid agonists, such as morphine, with loxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with loxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [35890] [43462] Lumacaftor; Ivacaftor: (Minor) Although the clinical significance of this interaction is unknown, concurrent use of morphine and lumacaftor; ivacaftor may alter morphine exposure; caution and close monitoring are advised if these drugs are used together. Morphine is a substrate of the drug transporter P-glycoprotein (P-gp). In vitro data suggest that lumacaftor; ivacaftor has the potential to both induce and inhibit P-gp. The net effect of lumacaftor; ivacaftor on P-gp transport is not clear, but substrate exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events. [34448] [59891] Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and morphine concurrently. Ivacaftor is an inhibitor of P-glycoprotein (P-gp). Coadministration of ivacaftor with P-gp substrates, such as morphine, can increase morphine exposure leading to increased or prolonged therapeutic effects and adverse events. [48524] (Minor) Although the clinical significance of this interaction is unknown, concurrent use of morphine and lumacaftor; ivacaftor may alter morphine exposure; caution and close monitoring are advised if these drugs are used together. Morphine is a substrate of the drug transporter P-glycoprotein (P-gp). In vitro data suggest that lumacaftor; ivacaftor has the potential to both induce and inhibit P-gp. The net effect of lumacaftor; ivacaftor on P-gp transport is not clear, but substrate exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events. [34448] [59891] Lumateperone: (Moderate) Concomitant use of opioid agonists like morphine with lumateperone may cause excessive sedation and somnolence. Limit the use of opioid pain medication with lumateperone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [35890] [64885] Lurasidone: (Moderate) Concomitant use of opioid agonists like morphine with lurasidone may cause excessive sedation and somnolence. Limit the use of opioid pain medication with lurasidone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [35890] [42227] Maprotiline: (Major) Concomitant use of opioid agonists with maprotiline may cause excessive sedation and somnolence. Limit the use of opioid pain medications with maprotiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [46350] [51740] [60209] [61143] Maribavir: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with maribavir is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and maribavir is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [67137] Melatonin: (Moderate) Concomitant use of opioid agonists with melatonin may cause excessive sedation and somnolence. Limit the use of opioid pain medications with melatonin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [25471] [35890] [40951] [46350] [60032] [60209] [61143] Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as morphine, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or morphine is recommended to assess for needed dosage adjustments. [29168] Mepivacaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Meprobamate: (Moderate) Concomitant use of morphine with meprobamate can potentiate the effects of morphine on respiration, blood pressure, and alertness. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If meprobamate is used concurrently with morphine, a reduced dosage of morphine and/or meprobamate is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30089] [31637] [35890] [40951] Metaxalone: (Major) Concomitant use of opioid agonists with metaxalone may cause respiratory depression, profound sedation, and death. Limit the use of opioid pain medication with metaxalone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use of metaxalone and opioid agonists increases the risk for serotonin syndrome. Avoid concomitant use if possible and monitor for serotonin syndrome if use is necessary. [30830] [35890] [40951] [46350] [61143] Methadone: (Major) Concomitant use of morphine with methadone can potentiate the effects of both drugs on respiration, blood pressure, and alertness. Profound sedation and coma may also occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of morphine and/or methadone is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] [56303] Methamphetamine: (Moderate) If concomitant use of morphine and amphetamines is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [43053] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Contraindicated) Morphine use in patients taking methylene blue or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. [46350] (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and hyoscyamine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [30922] [46350] Methocarbamol: (Major) Concomitant use of morphine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [28314] [28425] [29244] [30830] [31110] [35890] [36460] [40951] [46350] [49509] [51369] [57272] [60209] [61143] Methohexital: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Methscopolamine: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and methscopolamine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [30424] [46350] Methyldopa: (Moderate) Concomitant use of opioid agonists with methyldopa may cause excessive sedation and somnolence. Limit the use of opioid pain medication with methyldopa to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [29252] Methylene Blue: (Contraindicated) Morphine use in patients taking methylene blue or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. [46350] Methylphenidate Derivatives: (Moderate) If concomitant use of morphine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [60209] Methylphenidate: (Moderate) If concomitant use of morphine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [60209] Metoclopramide: (Moderate) The effects of metoclopramide on gastrointestinal motility are antagonized by narcotic analgesics. Concomitant use of opioid agonists with metoclopramide may also cause excessive sedation and somnolence. Limit the use of opioid pain medications with metoclopramide to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [46350] [57877] [60209] [61143] Metolazone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Metyrosine: (Moderate) The concomitant administration of metyrosine with opiate agonists can result in additive sedative effects. [6341] [7000] Midazolam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Milnacipran: (Moderate) If concomitant use of morphine and serotonin norepinephrine reuptake inhibitors is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [40951] Minocycline: (Minor) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as opiate agonists. Caution should be exercised when using these agents concurrently. [30442] [35529] Mirtazapine: (Major) Concomitant use of opioid agonists with mirtazapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with mirtazapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40942] [40951] [46350] [60209] [61143] Mitapivat: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with mitapivat is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and mitapivat is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [67403] Molindone: (Moderate) Concomitant use of opioid agonists like morphine with molindone may cause excessive sedation and somnolence. Limit the use of opioid pain medication with molindone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [28820] [35890] Monoamine oxidase inhibitors: (Contraindicated) Morphine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of morphine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as morphine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. [29159] [31296] [35890] [43053] [46350] [48404] [51758] [64690] [67417] Nabilone: (Major) Avoid coadministration of opioid agonists with nabilone due to the risk of additive CNS depression. [32226] [61143] Nalbuphine: (Major) Avoid the concomitant use of nalbuphine and opiate agonists, such as morphine. Nalbuphine is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of morphine. Nalbuphine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of nalbuphine with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. [40951] [49631] Naltrexone: (Major) When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7 to 10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7 to 10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. [56099] Naratriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28800] [35890] [36460] [40951] [43053] [46350] [60209] Nefazodone: (Major) Concomitant use of opioid agonists with nefazodone may cause excessive sedation and somnolence. Limit the use of opioid pain medications with nefazodone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [30433] [40951] Neostigmine; Glycopyrrolate: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and glycopyrrolate use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [57625] Neratinib: (Moderate) Monitor for an increase in morphine-related adverse reactions including hypotension, sedation, and respiratory depression if coadministration with neratinib is necessary. Decrease the dose of morphine as necessary. Morphine is a P-glycoprotein (P-gp) substrate. Neratinib is a P-gp inhibitor. Concomitant use of P-gp inhibitors can increase morphine exposure by approximately 2-fold. [34448] [62127] Nesiritide, BNP: (Major) The potential for hypotension may be increased when coadministering nesiritide with opiate agonists. [5796] Nirmatrelvir; Ritonavir: (Moderate) Close clinical monitoring is advised when administering morphine with ritonavir due to an increased potential for morphine-related adverse events, including hypotension, respiratory depression, profound sedation, coma, and death. Dosage reductions of morphine and/or ritonavir may be required. Morphine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); ritonavir is an inhibitor of this efflux protein. Coadministration may cause an approximate 2-fold increase in morphine exposure. [28380] [34557] [40951] Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as opiate agonists. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with opiate agonists. [45206] Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Norethindrone: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Norethindrone; Ethinyl Estradiol: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Norgestimate; Ethinyl Estradiol: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Norgestrel: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Nortriptyline: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] Olanzapine: (Major) Concomitant use of opioid agonists with olanzapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with olanzapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28785] [35890] [36460] [40951] [46350] [60209] [61143] Olanzapine; Fluoxetine: (Major) Concomitant use of opioid agonists with olanzapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with olanzapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28785] [35890] [36460] [40951] [46350] [60209] [61143] (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists like morphine with serotonergic drugs, such as fluoxetine. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [32127] [40951] Olanzapine; Samidorphan: (Contraindicated) Salmidorphan is contraindicated in patients who are using opiate agonists or undergoing acute opioid withdrawal. Salmidorphan increases the risk of precipitating acute opioid withdrawal in patients dependent on opioids. Before initiating salmidorphan, there should be at least a 7-day opioid-free interval from the last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids. In emergency situations, if a salmidorphan-treated patient requires opiates for anesthesia or analgesia, discontinue salmidorphan. The opiate agonist should be administered by properly trained individual(s), and the patient properly monitored in a setting equipped and staffed for cardiopulmonary resuscitation. In non-emergency situations, if a salmidorphan-treated patient requires opiate agonist treatment (e.g., for analgesia) discontinue salmidorphan at least 5 days before opioid treatment. Salmidorphan, as an opioid antagonist, may cause opioid treatment to be less effective or ineffective shortly after salmidorphan discontinuation. [66704] (Major) Concomitant use of opioid agonists with olanzapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with olanzapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28785] [35890] [36460] [40951] [46350] [60209] [61143] Oliceridine: (Major) Concomitant use of oliceridine with morphine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of oliceridine with morphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [60209] [65809] Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Ondansetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor antagonist. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28308] [31266] [31723] [40951] [46350] [49446] [64690] Opicapone: (Major) Concomitant use of opioid agonists with COMT inhibitors may cause excessive sedation and somnolence. Limit the use of opioid pain medications with COMT inhibitors to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. [28845] [36460] [40951] [42112] [46350] [60209] Oral Contraceptives: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Orphenadrine: (Major) Concomitant use of morphine with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Osimertinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death, if coadministration with osimertinib is necessary; decrease the dose of morphine as clinically appropriate. Morphine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor. The concomitant use of P-gp inhibitors can increase the exposure to morphine by about 2-fold. [34448] [60297] Oxazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Oxybutynin: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and oxybutynin use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [29796] [46350] Oxycodone: (Major) Concomitant use of oxycodone with morphine may lead to additive respiratory and/or CNS depression. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A reduced dosage of oxycodone and/or morphine is recommended; use an initial dose of oxycodone at one-third to one-half the usual dosage. For extended-release morphine products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor for sedation and respiratory depression. [31637] [35890] [39926] [40951] Oxymorphone: (Major) Concomitant use of oxymorphone with morphine may produce additive CNS depressant effects. Respiratory depression, hypotension, profound sedation, or coma may result from combination therapy. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Oxymorphone should be used in reduced dosages if used concurrently with a CNS depressant; initiate oxymorphone at one-third to one-half the usual dosage in patients that are also receiving morphine. A reduced dosage of morphine may also be necessary. If the patient is receiving an extended-release product, start with the lowest possible dose of morphine. Slowly titrate the dose as necessary for adequate pain relief and monitor for sedation or respiratory depression. [32438] [51201] Ozanimod: (Major) When possible, morphine should not be used in patients taking MAOIs or within 14 days of stopping such treatment. An active metabolite of ozanimod inhibits MAO-B. MAO inhibitor interactions with morphine may manifest as serotonin syndrome, hypertensive crisis, or opioid toxicity (e.g., respiratory depression, coma). If concurrent use is absolutely necessary, use the lowest possible doses of morphine, and monitor blood pressure and for serotonergic symptoms closely. Although a small number of patients treated with ozanimod were concomitantly exposed to opioids, this exposure was not adequate to rule out the possibility of an adverse reaction from coadministration. [40951] [43053] [51758] [64690] [65169] Pacritinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with pacritinib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and pacritinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [67427] Paliperidone: (Moderate) Drugs that can cause CNS depression such as opiate agonists, if used concomitantly with paliperidone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Monitor for signs and symptoms of CNS depression during coadministration of paliperidone and morphine and advise patients to avoid driving or engaging in other activities requiring mental alertness until they know how this combination affects them. [32936] Palonosetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor antagonist. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28308] [31266] [31723] [40951] [46350] [49446] [64690] Paroxetine: (Moderate) If concomitant use of morphine and paroxetine is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28260] [40951] [43053] Pegvisomant: (Moderate) In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown. [7342] Pentazocine: (Major) Avoid the concomitant use of pentazocine and opiate agonists, such as morphine. Pentazocine is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of morphine. Pentazocine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of pentazocine with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. [30219] [40951] Pentazocine; Naloxone: (Major) Avoid the concomitant use of pentazocine and opiate agonists, such as morphine. Pentazocine is a mixed opiate agonist/antagonist that may block the effects of opiate agonists and reduce analgesic effects of morphine. Pentazocine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Concurrent use of pentazocine with other opiate agonists can cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of the opiate agonist used; antagonistic effects are more common at low to moderate doses of the opiate agonist. [30219] [40951] Pentobarbital: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Perampanel: (Moderate) Concomitant use of opioid agonists with perampanel may cause excessive sedation and somnolence. Limit the use of opioid pain medications with perampanel to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [46350] [52140] [60209] [61143] Perphenazine: (Moderate) Concomitant use of opioid agonists with perphenazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with perphenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [43070] [46350] [60209] [61143] Perphenazine; Amitriptyline: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] (Moderate) Concomitant use of opioid agonists with perphenazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with perphenazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [43070] [46350] [60209] [61143] Phenelzine: (Contraindicated) Morphine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of morphine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as morphine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. [29159] [31296] [35890] [43053] [46350] [48404] [51758] [64690] [67417] Phenobarbital: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] (Major) Reserve concomitant use of morphine and atropine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [63228] (Major) Reserve concomitant use of morphine and scopolamine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [30354] [46350] (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and hyoscyamine use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [30922] [46350] Pimozide: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include pimozide. Prior to concurrent use of morphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Pirtobrutinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with pirtobrutinib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and pirtobrutinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [68520] Posaconazole: (Moderate) Posaconazole and morphine should be coadministered with caution due to a potential for altered plasma concentrations of both drugs. Both morphine and posaconazole are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. This interaction may cause alterations in the plasma concentrations of both posaconazole and morphine, ultimately resulting in an increased risk of adverse events. [32723] [34448] Potassium-sparing diuretics: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a potassium-sparing diuretic and morphine; increase the dosage of the potassium-sparing diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] Pramipexole: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. [36460] [40951] [41505] [46350] [60209] [61143] Pramlintide: (Major) Pramlintide slows gastric emptying and the rate of nutrient delivery to the small intestine. Medications with the potential to slow GI motility, such as opiate agonists, should be used with caution, if at all, with pramlintide until more data are available from the manufacturer. Monitor blood glucose. [8010] Prasugrel: (Moderate) Consider the use of a parenteral anti-platelet agent for patients with acute coronary syndrome who require concomitant opioid agonists. Coadministration of opioid agonists with prasugrel delays and reduces the absorption of prasugrel's active metabolite due to slowed gastric emptying. [36055] Pregabalin: (Major) Concomitant use of opioid agonists with pregabalin may cause excessive sedation, somnolence, and respiratory depression. Limit the use of opioid pain medications with pregabalin to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of respiratory depression and sedation. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and respiratory depression. [31493] [35890] [40951] [46350] [60209] [61143] [63923] [64848] Pretomanid: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with pretomanid is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and pretomanid is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [64561] Prilocaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Prilocaine; Epinephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Primidone: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Procarbazine: (Moderate) In theory, monoamine oxidase inhibitors (MAOIs) potentiate the CNS depression and hypotension caused by opiate agonists such as morphine. Procarbazine is a weak inhibitor of MAO; the manufacturers of morphine do not recommend its use within 14 days of an MAO Inhibitor. Caution is advised until more data are available. [28625] [35890] Prochlorperazine: (Major) Concomitant use of opioid agonists with prochlorperazine may cause excessive sedation and somnolence. Concurrent administration of prochlorperazine is contraindicated in patients receiving large doses of opiate agonists. Limit the use of opioid pain medications with prochlorperazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [46350] [60209] [61143] [62305] Promethazine: (Major) Concomitant use of opioid agonists with promethazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with promethazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce the opioid dose by one-quarter to one-half (for extended-release morphine tablets, start with 15 mg every 12 hours); use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [46350] [60209] [61143] [63555] Promethazine; Dextromethorphan: (Major) Concomitant use of opioid agonists with promethazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with promethazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce the opioid dose by one-quarter to one-half (for extended-release morphine tablets, start with 15 mg every 12 hours); use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [46350] [60209] [61143] [63555] Promethazine; Phenylephrine: (Major) Concomitant use of opioid agonists with promethazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with promethazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce the opioid dose by one-quarter to one-half (for extended-release morphine tablets, start with 15 mg every 12 hours); use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [46350] [60209] [61143] [63555] Propantheline: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and propantheline use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [46350] [47396] Propofol: (Major) Concomitant use of morphine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [28970] [31036] [35890] [36460] [40951] [43431] [46350] [49500] [49614] [60209] [61143] Protriptyline: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] Pseudoephedrine; Triprolidine: (Moderate) Concomitant use of opioid agonists with triprolidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with triprolidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [61143] [62170] Quazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Quetiapine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [33360] [35890] [36460] [40951] [46350] [60209] [61143] Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Quinidine: (Moderate) Morphine is a substrate for P-glycoprotein (P-gp), and quinidine is a P-gp substrate and inhibitor. Coadministration may lead to increased systemic exposure of morphine and morphine-related side effects. [29376] [34448] [34452] Ramelteon: (Moderate) Concomitant use of opioid agonists with ramelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with ramelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [31359] [35890] [40951] [46350] [60209] [61143] Rasagiline: (Contraindicated) Rasagiline is contraindicated for use with morphine due to the risk of serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. At least 14 days should elapse between the discontinuation of rasagiline and the initiation of morphine. [40951] Relugolix; Estradiol; Norethindrone acetate: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Remimazolam: (Major) Concomitant use of opioid agonists with remimazolam may cause respiratory depression, hypotension, profound sedation, and death. Titrate the dose of remimazolam to the desired clinical response and continuously monitor sedated patients for hypotension, airway obstruction, hypoventilation, apnea, and oxygen desaturation. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. [35890] [36460] [40951] [46350] [60209] [61143] [65697] Rifampin: (Moderate) Rifampin may induce the metabolism of morphine and lead to loss of analgesia if coadministered. [30435] Risperidone: (Moderate) Concomitant use of morphine with other CNS depressants can potentiate the effects of morphine on respiration, blood pressure, and alertness; examples of other CNS depressants include risperidone. Prior to concurrent use of morphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If a CNS depressant is used concurrently with morphine, a reduced dosage of morphine and/or the CNS depressant is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours, extended-release capsules). Monitor patients for sedation and respiratory depression. [30433] [31637] [35890] [40951] Ritonavir: (Moderate) Close clinical monitoring is advised when administering morphine with ritonavir due to an increased potential for morphine-related adverse events, including hypotension, respiratory depression, profound sedation, coma, and death. Dosage reductions of morphine and/or ritonavir may be required. Morphine is a substrate of the drug efflux transporter P-glycoprotein (P-gp); ritonavir is an inhibitor of this efflux protein. Coadministration may cause an approximate 2-fold increase in morphine exposure. [28380] [34557] [40951] Rizatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28800] [35890] [36460] [40951] [43053] [46350] [60209] Rolapitant: (Major) Use caution if morphine and rolapitant are used concurrently, and monitor for morphine-related adverse effects. Morphine is a P-glycoprotein (P-gp) substrate, where an increase in exposure may significantly increase adverse effects; rolapitant is a P-gp inhibitor. When rolapitant was administered with another P-gp substrate, digoxin, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied. [34448] [60142] Ropinirole: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. [31241] [31637] [40944] [57407] [65809] Ropivacaine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31296] [40951] [46350] [51758] [52330] Rotigotine: (Major) Concomitant use of opioid agonists with rotigotine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with rotigotine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like rotigotine have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. [36460] [40951] [46350] [49557] [60209] [61143] Safinamide: (Contraindicated) Concomitant use of safinamide with opioids is contraindicated due to the risk of serotonin syndrome. Allow at least 14 days between discontinuation of safinamide and initiation of treatment with opioids. [61825] Scopolamine: (Major) Reserve concomitant use of morphine and scopolamine for patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose and monitor for signs of urinary retention or reduced gastric motility. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death as well as urinary retention and/or severe constipation, which may lead to paralytic ileus. [30354] [46350] Secobarbital: (Major) Concomitant use of morphine with a barbiturate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a barbiturate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [35890] [36460] [40951] [46350] [60209] [61143] Segesterone Acetate; Ethinyl Estradiol: (Moderate) Combination oral contraceptives have been shown to decrease plasma concentrations of morphine, due to induction of conjugation. Monitor for decreased efficacy of morphine. [43307] [58441] Selegiline: (Contraindicated) Morphine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If possible, wait 14 days between discontinuation of selegiline and initiation of treatment with morphine. After stopping treatment with morphine, a time period equal to 4 to 5 half-lives of morphine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. [29159] [31296] [35890] [40951] [43053] [46350] [48404] [51758] [64690] Selpercatinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with selpercatinib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and selpercatinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [65387] Serdexmethylphenidate; Dexmethylphenidate: (Moderate) If concomitant use of morphine and methylphenidate derivatives is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [60209] Serotonin norepinephrine reuptake inhibitors: (Moderate) If concomitant use of morphine and serotonin norepinephrine reuptake inhibitors is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [40951] Serotonin-Receptor Agonists: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28800] [35890] [36460] [40951] [43053] [46350] [60209] Serotonin-Receptor Antagonists: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor antagonist. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28308] [31266] [31723] [40951] [46350] [49446] [64690] Sertraline: (Moderate) If concomitant use of morphine and sertraline is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28343] [40951] [43053] Sevoflurane: (Major) Concomitant use of morphine with a general anesthetic may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a general anesthetic to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [28970] [31036] [35890] [36460] [40951] [43431] [46350] [49500] [49614] [60209] [61143] Sincalide: (Moderate) As morphine may cause constriction of the sphincter of Oddi, a direct counteraction to sincalide, concomitant therapy is usually not advisable. However, morphine augmentation may be desirable in place of delayed imaging in cases when acute cholecystitis is suspected. Withhold opioids for 4 hours prior to radiographic study of the hepatobiliary system with sincalide. [32507] Sodium Oxybate: (Major) Concomitant use of opioid agonists with sodium oxybate may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medication with sodium oxybate to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28528] [29623] [33654] [40951] [43291] [61143] Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with taurursodiol is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and taurursodiol is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [68007] Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Plasma concentrations of morphine, a P-glycoprotein (P-gp) substrate, may be increased when administered concurrently with voxilaprevir, a P-gp inhibitor. Monitor patients for increased side effects if these drugs are administered concurrently. [34448] [62131] Solifenacin: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when morphine is used concomitantly with an anticholinergic drug, such as solifenacin. The concomitant use of morphine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. [40951] [54021] Sorafenib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death, if coadministration with sorafenib is necessary; decrease the dose of morphine as clinically appropriate. Morphine is a P-glycoprotein (P-gp) substrate. Sorafenib inhibits P-gp in vitro and may increase the concentrations of concomitantly administered drugs that are P-gp substrates. The concomitant use of P-gp inhibitors can increase the exposure to morphine by about 2-fold. [31832] [33164] Sotorasib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with sotorasib is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and sotorasib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [66700] Sparsentan: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with sparsentan is necessary; decrease the dose of morphine as necessary. Morphine is a P-gp substrate and sparsentan is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [68641] Spironolactone: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a potassium-sparing diuretic and morphine; increase the dosage of the potassium-sparing diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a potassium-sparing diuretic and morphine; increase the dosage of the potassium-sparing diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] St. John's Wort, Hypericum perforatum: (Moderate) If concomitant use of morphine and St. John's Wort is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [40951] [57514] Stiripentol: (Moderate) Concomitant use of opioid agonists with stiripentol may cause excessive sedation and somnolence. Limit the use of opioid pain medications with stiripentol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [36460] [40951] [61143] [63456] Sufentanil: (Moderate) Concomitant use of sufentanil with morphine can potentiate sufentanil-induced CNS and cardiovascular effects and the duration of these effects. A dose reduction of one or both drugs may be warranted. [29159] Sumatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28800] [35890] [36460] [40951] [43053] [46350] [60209] Sumatriptan; Naproxen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28800] [35890] [36460] [40951] [43053] [46350] [60209] Suvorexant: (Moderate) Concomitant use of opioid agonists with suvorexant may cause excessive sedation and somnolence. Limit the use of opioid pain medications with suvorexant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [46350] [57780] [60209] [61143] Tapentadol: (Major) Concomitant use of tapentadol with morphine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of tapentadol with morphine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36077] [36460] [40951] [45480] [46350] [60209] [61143] Tasimelteon: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [46350] [56665] [60209] [61143] Tedizolid: (Contraindicated) Morphine use in patients taking tedizolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. [46350] Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Temazepam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Temsirolimus: (Moderate) Monitor for an increase in morphine-related adverse reactions, including sedation and respiratory depression, if coadministration with temsirolimus is necessary; a morphine dose adjustment may be necessary. Morphine is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [34448] [50586] Tepotinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with tepotinib is necessary; decrease the dose of either drug as necessary. Morphine is a P-gp substrate and tepotinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [66372] Tetrabenazine: (Major) Additive effects are possible when tetrabenazine is combined with other drugs that cause CNS depression. Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as opiate agonists, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension. [34389] Tezacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and morphine concurrently. Ivacaftor is an inhibitor of P-glycoprotein (P-gp). Coadministration of ivacaftor with P-gp substrates, such as morphine, can increase morphine exposure leading to increased or prolonged therapeutic effects and adverse events. [48524] Thalidomide: (Major) Avoid coadministration of opioid agonists with thalidomide due to the risk of additive CNS depression. [33654] [40944] [57407] [60079] [65809] Thiazide diuretics: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Thioridazine: (Major) Concomitant use of opioid agonists with thioridazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with thioridazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression. [28293] [35890] [36460] [40951] [46350] [60209] [61143] Thiothixene: (Moderate) Concomitant use of opioid agonists like morphine with thiothixene may cause excessive sedation and somnolence. Limit the use of opioid pain medication with thiothixene to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [35890] [46957] Ticagrelor: (Moderate) Coadministration of opioid agonists, such as morphine, may delay and reduce the absorption of ticagrelor resulting in reduced exposure and diminished inhibition of platelet aggregation. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring an opioid agonist. Mean ticagrelor exposure decreased up to 36% in ACS patients undergoing PCI when intravenous morphine was administered with a loading dose of ticagrelor; mean platelet aggregation was higher up to 3 hours post loading dose. Similar effects on ticagrelor exposure and platelet inhibition were observed when fentanyl was administered with a ticagrelor loading dose in ACS patients undergoing PCI. Although exposure to ticagrelor was decreased up to 25% in healthy adults administered intravenous morphine with a loading dose of ticagrelor, platelet inhibition was not delayed or decreased in this population. [44951] Tizanidine: (Major) Concomitant use of morphine with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation. [28314] [28425] [29244] [30830] [31110] [35890] [36460] [40951] [46350] [49509] [51369] [57272] [60209] [61143] Tolcapone: (Major) Concomitant use of opioid agonists with COMT inhibitors may cause excessive sedation and somnolence. Limit the use of opioid pain medications with COMT inhibitors to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. [28845] [36460] [40951] [42112] [46350] [60209] Tolterodine: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when morphine is used concomitantly with an anticholinergic drug, such as tolterodine. The concomitant use of morphine and anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. [31112] [46350] Torsemide: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a loop diuretic and morphine; increase the dosage of the loop diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] Tramadol: (Major) Concomitant use of morphine with tramadol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of morphine with tramadol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Additionally, monitor patients for seizures and/or the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28314] [40951] Tramadol; Acetaminophen: (Major) Concomitant use of morphine with tramadol may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of morphine with tramadol to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Additionally, monitor patients for seizures and/or the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [28314] [40951] Tranylcypromine: (Contraindicated) Morphine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of morphine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as morphine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. [29159] [31296] [35890] [43053] [46350] [48404] [51758] [64690] [67417] Trazodone: (Moderate) Because of the potential risk and severity of excessive sedation, somnolence, and serotonin syndrome, caution should be observed when administering morphine with trazodone. Limit the use of opioid pain medications with trazodone to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Inform patients taking this combination of the possible increased risks and monitor for the emergence of excessive CNS depression and serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [35890] [36460] [40951] [43053] [43857] [46350] [60209] [61143] Triamterene: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a potassium-sparing diuretic and morphine; increase the dosage of the potassium-sparing diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a potassium-sparing diuretic and morphine; increase the dosage of the potassium-sparing diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. [40951] (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Triazolam: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less. Use an initial morphine; naltrexone dose of 20 mg/0.8 mg PO every 24 hours. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. [31637] [35890] [36460] [40951] [61143] [63923] Tricyclic antidepressants: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] Trifluoperazine: (Moderate) Concomitant use of opioid agonists with trifluoperazine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with trifluoperazine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [43071] [46350] [60209] [61143] Trihexyphenidyl: (Moderate) Monitor for signs of urinary retention or reduced gastric motility during concomitant morphine and trihexyphenidyl use. Concomitant use may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. [30336] [46350] Trimethobenzamide: (Moderate) The concurrent use of trimethobenzamide with other medications that cause CNS depression, like opiate agonists, may potentiate the effects of either trimethobenzamide or the opiate agonist. [7086] Trimipramine: (Major) Concomitant use of opioid agonists with tricyclic antidepressants may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tricyclic antidepressants to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [35890] [36460] [40951] [46350] [51356] [60209] [61143] Triprolidine: (Moderate) Concomitant use of opioid agonists with triprolidine may cause excessive sedation and somnolence. Limit the use of opioid pain medication with triprolidine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [61143] [62170] Trospium: (Moderate) Monitor patients for signs of urinary retention or reduced gastric motility when trospium, an anticholinergic drug for overactive bladder, is used with opiate agonists. The concomitant use of these drugs together may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Opiates increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Both agents may also cause drowsiness or blurred vision, and patients should use care in driving or performing other hazardous tasks until the effects of the drugs are known. [29236] Tucatinib: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with tucatinib is necessary; decrease the dose of either drug as necessary. Morphine is a P-glycoprotein (P-gp) substrate and tucatinib is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [65295] Valerian, Valeriana officinalis: (Moderate) Concomitant use of opioid agonists with valerian may cause excessive sedation and somnolence. Limit the use of opioid pain medication with valerian to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. [28209] [28832] [28833] [65809] Valproic Acid, Divalproex Sodium: (Moderate) Concomitant use of opioid agonists with valproic acid may cause excessive sedation and somnolence. Limit the use of opioid pain medications with valproic acid to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. [35890] [40951] [44726] [46350] [60209] [61143] Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs of diminished diuresis and/or effects on blood pressure during coadministration of a thiazide diuretic and morphine; increase the dosage of the thiazide diuretic as needed. Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also potentiate orthostatic hypotension when given concomitantly with a thiazide diuretic. [40951] [41355] Vemurafenib: (Moderate) Concomitant use of vemurafenib and morphine may result in increased morphine concentrations. Vemurafenib is a P-glycoprotein (P-gp) inhibitor and morphine is a P-gp substrate. Monitor patients for increased side effects, including CNS or respiratory depression. [34525] [45335] Venlafaxine: (Moderate) If concomitant use of morphine and serotonin norepinephrine reuptake inhibitors is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. [40951] Vigabatrin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists. [36250] Vilazodone: (Moderate) Because of the potential risk and severity of excessive sedation, somnolence, and serotonin syndrome, caution should be observed when administering morphine with vilazodone. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Inform patients taking this combination of the possible increased risks and monitor for the emergence of excessive CNS depression and serotonin syndrome, particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [40951] [43053] [43177] Voclosporin: (Moderate) Monitor for an increase in morphine-related adverse reactions, including hypotension, sedation, and respiratory depression, if coadministration with voclosporin is necessary; decrease the morphine dose if indicated. Morphine is a P-gp substrate and voclosporin is a P-gp inhibitor. Coadministration with P-gp inhibitors can increase morphine exposure by about 2-fold. [40951] [66336] Vortioxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with vortioxetine. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [35890] [36460] [40951] [43053] [46350] [56041] [60209] Zaleplon: (Moderate) Concomitant use of morphine with zaleplon can potentiate the effects of morphine on respiration, blood pressure, and alertness. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If zaleplon is used concurrently with morphine, a reduced dosage of morphine and/or the zaleplon is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). Monitor patients for sedation and respiratory depression. [29887] [31637] [35890] [40951] Ziconotide: (Moderate) Concurrent use of ziconotide and opiate agonists may result in an increased incidence of dizziness and confusion. Ziconotide neither interacts with opiate receptors nor potentiates opiate-induced respiratory depression. However, in animal models, ziconotide did potentiate gastrointestinal motility reduction by opioid agonists. [30603] Ziprasidone: (Moderate) Because of the potential for additive sedation and CNS depression, caution should be observed when administering morphine with ziprasidone. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. There are case reports of serotonin syndrome with use of ziprasidone postmarketing but causality is not established. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28233] [43053] Zolmitriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor agonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. [28800] [35890] [36460] [40951] [43053] [46350] [60209] Zolpidem: (Moderate) Concomitant use of morphine with zolpidem can potentiate the effects of morphine on respiration, blood pressure, and alertness. In addition, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of zolpidem and other CNS depressants than with zolpidem alone. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. If zolpidem is used concurrently with morphine, a reduced dosage of morphine and/or zolpidem is recommended; for extended-release products, start with the lowest possible dose of morphine (i.e., 15 mg PO every 12 hours, extended-release tablets; 30 mg or less PO every 24 hours; extended-release capsules). For Intermezzo brand of sublingual zolpidem tablets, reduce the dose to 1.75 mg/night. Monitor patients for sedation and respiratory depression. [31637] [35890] [40951] [57789] [61143] Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and morphine is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates. [28843] [34448] Zuranolone: (Major) Avoid concomitant use of opioids and other CNS depressants, such as zuranolone. Concomitant use can increase the risk of respiratory depression, hypotension, profound sedation, and death. If alternate treatment options are inadequate and coadministration is necessary, limit dosages and durations to the minimum required, monitor patients closely for respiratory depression and sedation, and consider prescribing naloxone for the emergency treatment of opioid overdose. [61143] [69264]
Revision Date: 02/29/2024, 02:01:00 AM

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Monitoring Parameters

  • serum sodium

US Drug Names

  • ARYMO ER
  • Astramorph PF
  • Avinza
  • DepoDur
  • Duramorph PF
  • Infumorph
  • Kadian
  • MITIGO
  • MORPHABOND
  • MS Contin
  • MSIR
  • Opium Tincture
  • Oramorph SR
  • RMS
  • Roxanol
  • Roxanol-T
;