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Nov.07.2022

Doxylamine; Pyridoxine

Indications/Dosage

Labeled

  • pregnancy-induced nausea/vomiting

Off-Label

    † Off-label indication

    For the treatment of pregnancy-induced nausea/vomiting unresponsive to conservative management

    Oral dosage (delayed-release tablets with doxylamine 10 mg and pyridoxine 10 mg per tablet; e.g., Diclegis)

    Pregnant Adults

    2 tablets PO (on an empty stomach) at bedtime, on day 1; if dose controls symptoms the next day, continue taking 2 tablets PO daily at bedtime. If symptoms persist on the afternoon of day 2, continue 2 tablets PO at bedtime, then take 3 tablets PO starting on day 3 (1 tablet in the morning and 2 tablets at bedtime); if symptoms are controlled, continue regimen. If symptoms persist, on day 4 take 4 tablets PO (1 tablet in the morning, 1 tablet mid-afternoon, and 2 tablets at bedtime). Do not exceed 4 tablets/day PO. Tablets are taken on a daily basis not on an "as needed" basis; reassess continued need for therapy as pregnancy progresses.[54146] Doxylamine; pyridoxine is a first-line pharmacologic agent in the ACOG treatment algorithm for nausea and vomiting due to pregnancy.[66066]

    Pregnant Adolescents

    Safety and efficacy have not been established in pregnant adolescents.[54146]

    Oral dosage (extended-release tablets with doxylamine 20 mg and pyridoxine 20 mg per tablet; e.g., Bonjesta)

    Pregnant Adults

    1 tablet PO (on an empty stomach) at bedtime on day 1; if dose controls symptoms the next day, continue taking 1 tablet PO daily at bedtime only. If symptoms persist on day 2, increase the daily dose to 1 tablet in the morning and 1 tablet at bedtime approximately 12 hours apart. Max: 2 tablets/day PO. Tablets are taken on a daily basis not on an "as needed" basis; reassess continued need for therapy as pregnancy progresses.[61433] Doxylamine; pyridoxine is a first-line pharmacologic agent in the ACOG treatment algorithm for nausea and vomiting due to pregnancy.[66066]

    Pregnant Adolescents

    Safety and efficacy have not been established in pregnant adolescents.[61433]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults

      4 tablets/day PO for delayed-release tablets (e.g., Diclegis); 2 tablets/day PO for extended-release tablets (e.g., Bonjesta).

    • Geriatric

      Safety and efficacy have not been established.

    • Adolescents

      Safety and efficacy have not been established.

    • Children

      Safety and efficacy have not been established.

    • Infants

      Not indicated.

    • Neonates

      Not indicated.

    Patients with Hepatic Impairment Dosing

    Dosage reduction may be warranted for patients with hepatic impairment but no quantitative guidelines are available; doxylamine is extensively metabolized in the liver.

    Patients with Renal Impairment Dosing

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    † Off-label indication
    Revision Date: 11/07/2022, 01:59:56 PM

    References

    54146 - Diclegis (doxylamine; pyridoxine) delayed-release tablets package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.61433 - Diclegis (doxylamine; pyridoxine) package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.66066 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin Number 189: Nausea and vomiting of pregnancy. Obstet Gynecol 2018;131:15-30. Reaffirmed 2019.

    How Supplied

    Doxylamine Succinate, Vitamin B6 (Pyridoxine hydrochloride) Oral tablet, biphasic release

    Bonjesta 20mg-20mg Extended-Release Tablet (55494-0120) (Duchesnay USA, Inc) null

    Doxylamine Succinate, Vitamin B6 (Pyridoxine hydrochloride) Oral tablet, gastro-resistant

    Diclegis 10mg-10mg Delayed-Release Tablet (55494-0100) (Duchesnay USA, Inc) null

    Doxylamine Succinate, Vitamin B6 (Pyridoxine hydrochloride) Oral tablet, gastro-resistant

    Diclegis 10mg-10mg Delayed-Release Tablet (55494-0100) (Duchesnay USA, Inc) (off market)

    Doxylamine Succinate, Vitamin B6 (Pyridoxine hydrochloride) Oral tablet, gastro-resistant

    Doxylamine Succinate and Pyridoxine Hydrochloride 10mg-10mg Delayed-Release Tablet (70505-0100) (Analog Pharma Inc.) null

    Doxylamine Succinate, Vitamin B6 (Pyridoxine hydrochloride) Oral tablet, gastro-resistant

    Doxylamine Succinate and Pyridoxine Hydrochloride 10mg-10mg Delayed-Release Tablet (00378-4615) (Mylan Pharmaceuticals Inc.) null

    Doxylamine Succinate, Vitamin B6 (Pyridoxine hydrochloride) Oral tablet, gastro-resistant

    Doxylamine Succinate and Pyridoxine Hydrochloride 10mg-10mg Delayed-Release Tablet (49884-0186) (Par Pharmaceuticals, an Endo Company) null

    Doxylamine Succinate, Vitamin B6 (Pyridoxine hydrochloride) Oral tablet, gastro-resistant

    Doxylamine Succinate and Pyridoxine Hydrochloride 10mg-10mg Delayed-Release Tablet (00591-2132) (Teva/Actavis US) null

    Description/Classification

    Description

    Doxylamine; Pyridoxine is a combination drug product indicated for the treatment of pregnancy-induced nausea/vomiting (n/v) in women who do not respond to conservative management (i.e., diet and lifestyle modifications).[54146][63316] Doxylamine is a sedating antihistamine (H-1 receptor antagonist) of the ethanolamine class; pyridoxine is also known as vitamin B6. The efficacy and safety of doxylamine; pyridoxine for pregnancy-induced n/v were evaluated in controlled clinical trials. Study subjects (n = 261) were at least 18 years of age and were in their 7 to 14th week of pregnancy. Women were randomized to receive 2 weeks of active treatment or placebo. Women taking doxylamine; pyridoxine experienced greater improvement in n/v compared with those taking placebo. Epidemiological studies have shown no increase risk of teratogenicity with combined use of doxylamine and pyridoxine. Clinical evaluation of doxylamine; pyridoxine was limited to pregnancy within 14 weeks; it is important to reassess continued need for therapy as pregnancy progresses. Doxylamine may cause marked drowsiness or sleepiness. Therefore, women taking doxylamine; pyridoxine should avoid using this product when engaging in activities requiring mental alertness, such as driving or operating heavy machinery, until cleared to do so by their health care provider.[54146][63316] Doxylamine; pyridoxine is a first-line pharmacologic agent to consider in the American College of Obstetrics and Gynecology (ACOG) treatment algorithm for nausea/vomiting due to pregnancy.[66066]

    Classifications

    • Alimentary Tract and Metabolism
      • Antiemetics and Antinauseants
        • Antiemetic and Antinauseant Combinations
          • Miscellaneous Antiemetic and Antinauseant Combinations
    Revision Date: 11/13/2020, 03:53:57 PM

    References

    54146 - Diclegis (doxylamine; pyridoxine) delayed-release tablets package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.63316 - Bonjesta (doxylamine; pyridoxine) extended-release tablets package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.66066 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin Number 189: Nausea and vomiting of pregnancy. Obstet Gynecol 2018;131:15-30. Reaffirmed 2019.

    Administration Information

    General Administration Information

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

    Route-Specific Administration

    Oral Administration

    Oral Solid Formulations

    • The patient should swallow the delayed-release and extended-release tablets whole. Do not crush, break, chew, or split the tablets.
    • Administer on an empty stomach with a glass of water.[54146][61433]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 11/14/2016, 02:13:02 PM

      References

      54146 - Diclegis (doxylamine; pyridoxine) delayed-release tablets package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.61433 - Diclegis (doxylamine; pyridoxine) package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.

      Adverse Reactions

      Mild

      • abdominal pain
      • anxiety
      • asthenia
      • diarrhea
      • dizziness
      • drowsiness
      • fatigue
      • headache
      • hyperhidrosis
      • insomnia
      • irritability
      • maculopapular rash
      • malaise
      • mydriasis
      • nightmares
      • paresthesias
      • pruritus
      • rash
      • restlessness
      • vertigo
      • weakness
      • xerophthalmia
      • xerostomia

      Moderate

      • blurred vision
      • confusion
      • constipation
      • dysarthria
      • dyspnea
      • dysuria
      • hypertension
      • hypotension
      • migraine
      • myasthenia
      • palpitations
      • sinus tachycardia
      • urinary retention

      In safety and efficacy trials, somnolence (drowsiness) was reported in 14.3% of doxylamine; pyridoxine treated women (n = 133) compared to 11.7% of placebo treated women (n = 128).[54146] [61433] CNS depression manifested as drowsiness and/or dizziness can occur during therapy with doxylamine; pyridoxine. Less frequently occurring CNS effects of sedating antihistamines include asthenia/weakness, confusion, dysarthria (slurred speech), myasthenia, fatigue, or headache. There is considerable individual patient response to sedative effects, so patients should be warned of the possible impairment of mental acuity. These side effects may disappear after a few days of medication. Ethanol intake will increase the risk of sedation. If sedation persists or is severe, a dosage reduction may be advisable. The following adverse events have been identified during post-approval use of the doxylamine; pyridoxine combination: disorientation, dizziness, fatigue, headache, malaise, migraine, paresthesias, psychomotor hyperactivity (restlessness), and vertigo.[54146] [61433]

      Doxylamine, like other sedating antihistamines (H1-antagonists) possesses a significant degree of anticholinergic effects [54146] [61433], which can result in thickening of bronchial secretions, xerostomia, urinary retention, insomnia, irritability, nervousness, mydriasis, restlessness, xerophthalmia, and/or blurred vision. Dry mouth (xerostomia) is a common complaint in the use of first-generation antihistamines such as doxylamine. The following adverse events have been identified during post-approval use of the combination of doxylamine; pyridoxine: anxiety, insomnia, irritability, nightmares, blurred vision, visual disturbances, dysuria, and urinary retention.[54146] [61433]

      Doxylamine; pyridoxine contains a sedating antihistamine (H1-antagonist) which may cause adverse GI effects. The following adverse events have been identified during post-approval use of the combination of doxylamine; pyridoxine: abdominal distension, abdominal pain, constipation, diarrhea.[54146] [61433]

      Adverse cardiovascular responses of doxylamine; pyridoxine are likely to be associated with the anticholinergic properties or the quinidine-like anesthetic effects of some antihistamines (H1-antagonists).[54146] [61433] These responses can include sinus tachycardia, extrasystole, palpitations, and/or cardiac arrhythmias. Alpha-adrenergic blockade can lead to symptoms of hypotension. Hypertension can also occur, but is usually not of clinical significance. The following adverse events have been identified during post-approval use of the combination of doxylamine; pyridoxine: chest discomfort, dyspnea, palpitation, and sinus tachycardia.[54146] [61433]

      The following adverse events have been identified during post-approval use of the combination of doxylamine; pyridoxine: hyperhidrosis, hypersensitivity, pruritus, rash (unspecified), and maculopapular rash.[54146] [61433]

      Revision Date: 02/21/2018, 04:07:00 PM

      References

      54146 - Diclegis (doxylamine; pyridoxine) delayed-release tablets package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.61433 - Diclegis (doxylamine; pyridoxine) package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • MAOI therapy
      • anticholinergic medications
      • bladder obstruction
      • breast-feeding
      • closed-angle glaucoma
      • contact lenses
      • driving or operating machinery
      • ethanol ingestion
      • GI obstruction
      • hepatic disease
      • ileus
      • increased intraocular pressure
      • laboratory test interference
      • peptic ulcer disease
      • pregnancy
      • urinary retention

      NOTE: Doxylamine; pyridoxine has not been studied in pregnant women with hyperemesis gravidarum.[54146][61433]

       

      Doxylamine; pyridoxine is contraindicated in patients with known hypersensitivity to doxylamine succinate, other ethanolamine derivative antihistamines, pyridoxine hydrochloride or any inactive ingredient in the formulation.[54146][61433]

      Doxylamine; pyridoxine may cause somnolence due to the anticholinergic properties of doxylamine, a sedating antihistamine. Women should avoid driving or operating machinery while using doxylamine; pyridoxine until cleared to do so by their healthcare provider. In addition, patients using other central nervous system (CNS) depressants including alcohol are at particular risk for severe drowsiness leading to falls or accidents; ethanol ingestion should be avoided during the use of this drug combination, given its use in the pregnant patient and the potential for additive CNS depression.[54146] [61433]

      The anticholinergic effects of doxylamine may be additive with other anticholinergic medications. Also, due to a possible worsening of symptoms, anticholinergic drugs such as doxylamine; pyridoxine should be used with caution in patients with the following conditions: stenosing peptic ulcer disease, GI obstruction (pyloroduodenal obstruction), ileus, urinary bladder obstruction, urinary retention, increased intraocular pressure, and closed-angle glaucoma. Ocular effects resulting from the anticholinergic effects of doxylamine also include dry eyes or blurred vision, which may be of significance in wearers of contact lenses.[54146] [61433]

      No clinical or pharmacokinetic studies have been conducted with this drug combination in patients with hepatic disease. Doxylamine is biotransformed in the liver by N-dealkylation to its principle metabolites N-desmethyldoxylamine and N, N-didesmethyldoxylamine. Pyridoxine is a prodrug primarily metabolized in the liver.[54146] [61433] Therefore, the metabolism of doxylamine; pyridoxine may be reduced in the presence of hepatic impairment.

      This drug combination is intended for use during human pregnancy in women who do not respond to conservative management. No increased risk for congenital malformations has been reported with use in pregnant women. Doxylamine; pyridoxine has been evaluated through epidemiological studies (cohort, case control and meta-analyses) designed to detect possible teratogenicity. A meta-analysis of 16 cohort and 11 case-control studies published between 1963 and 1991 reported no increased risk for malformations from first trimester exposures to doxylamine succinate and pyridoxine hydrochloride, with or without dicyclomine hydrochloride. A second meta-analysis of 12 cohort and 5 case-control studies published between 1963 and 1985 reported no statistically significant relationships between fetal abnormalities and the first trimester use of the combination doxylamine and pyridoxine with or without dicyclomine.[54146] [61433] Doxylamine; pyridoxine is a first-line pharmacologic agent for use following conservative management in the ACOG treatment algorithm for nausea and vomiting due to pregnancy.[66066]

      According to the manufacturer, doxylamine; pyridoxine is not recommended for use during breast-feeding. Data regarding the transfer of doxylamine into human milk are not available; however, the molecular weight of doxylamine suggests that passage into human breast milk is possible. Maternal exposure to antihistamine (H-1 antagonists) has also been reported to induce irritability or sedation in 9.4% of breast-fed infants.[35545] Infants with apnea or other respiratory syndromes may be particularly vulnerable to the sedative effects of doxylamine. Pyridoxine hydrochloride is excreted into breast milk. There have been no reports of adverse events in infants presumably exposed to pyridoxine through breast milk and the use of pyridoxine is compatible with breast-feeding.[27500] [54146] [61433] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.

      Use of doxylamine;pyridoxine is contraindicated in women who are currently on monoamine oxidase inhibitors (MAOI therapy). Monoamine oxidase inhibitors (MAOIs) may prolong and intensify the anticholinergic (drying) effects as well as the central nervous system effects of doxylamine.[54146] [61433]

      Administration of doxylamine; pyridoxine may result in laboratory test interference; false positive drug screens for methadone, opiates, and phencyclidine phosphate (PCP) can occur. Confirmatory tests, such as Gas Chromatography Mass Spectrometry (GC-MS), should be used to confirm the identity of the substance in the event of a positive immunoassay result.[61433] [63316]

      Revision Date: 11/02/2022, 04:11:36 PM

      References

      27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.35545 - Ito S, Blajchman A, Stephenson M, et al. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol 1993;168:1393-9.54146 - Diclegis (doxylamine; pyridoxine) delayed-release tablets package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.61433 - Diclegis (doxylamine; pyridoxine) package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.63316 - Bonjesta (doxylamine; pyridoxine) extended-release tablets package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.66066 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin Number 189: Nausea and vomiting of pregnancy. Obstet Gynecol 2018;131:15-30. Reaffirmed 2019.

      Mechanism of Action

      The mechanism of action of doxylamine; pyridoxine for the treatment of pregnancy-induced nausea/vomiting is unknown.[54146]

       

      Doxylamine: Doxylamine does not prevent the release of histamine, but it competes with free histamine for binding at the H1-receptor sites. Like other antihistamines, doxylamine competitively antagonizes the effects of histamine on H1-receptors in the GI tract, uterus, large blood vessels, and bronchial muscle. Blockade of H1-receptors also suppresses the formation of edema, flare, and pruritus that result from histaminic activity. Unlike second generation antihistamines such as loratadine and cetirizine which selectively block peripheral H1-receptors, first generation antihistamines such as doxylamine bind non-selectively to H1-receptors centrally and peripherally. Thus, sedative effects are more likely to occur with first generation antihistamines, especially the ethanolamine group. Doxylamine belongs to the ethanolamine group. Following prolonged use, tolerance can occur, but this may be beneficial, dependent on the indication for drug use, because of reduced sedative effects.



      H1-antagonists are structurally similar to anticholinergic agents and therefore possess anticholinergic properties of varying degrees. Ethanolamine derivatives such as doxylamine have greater anticholinergic activity than do other antihistamines and commonly produce side effects such as dry mouth, blurred vision, constipation and urinary retention. These anticholinergic actions appear to be due to a central antimuscarinic effect which also may be responsible for the antiemetic effects seen with this class, although the exact mechanism is unknown.

       

      Pyridoxine:Vitamin B6 is composed of pyridoxine, pyridoxal, and pyridoxamine, and foods usually contain all three forms. Pyridoxine is converted in erythrocytes to the active moiety, pyridoxal phosphate (requiring riboflavin for the conversion), while pyridoxamine is converted into pyridoxamine phosphate. These active forms act as coenzymes for no fewer than 60 metabolic processes including the metabolism of fat, protein, and carbohydrate. Their role in protein metabolism includes decarboxylation of amino acids, conversion of tryptophan to niacin or serotonin, deamination, and transamination of amino acids. In carbohydrate metabolism, it is necessary for the conversion of glycogen to glucose-1-phosphate. Pyridoxine is essential for synthesis of gamma aminobutyric acid (GABA) in the CNS and synthesis of heme.

      Revision Date: 04/16/2013, 10:49:56 AM

      References

      54146 - Diclegis (doxylamine; pyridoxine) delayed-release tablets package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.

      Pharmacokinetics

      Doxylamine; pyridoxine is administered orally. Pyridoxine is highly protein bound, primarily to albumin. Its main active metabolite, pyridoxal 5'-phosphate (PLP) accounts for at least 60% of circulating vitamin B6 concentrations. Doxylamine is biotransformed in the liver by N-dealkylation to the principle metabolites N-desmethyldoxylamine and N, N-didesmethyldoxylamine. Pyridoxine is a prodrug primarily metabolized in the liver. The principle metabolites of doxylamine are excreted by the kidney. The terminal elimination half-life of doxylamine and pyridoxine are 12.5 hours and 0.5 hours, respectively.[54146]

       

      Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: none

      Route-Specific Pharmacokinetics

      Oral Route

      The pharmacokinetics of doxylamine 10 mg; pyridoxine 10 mg delayed-release tablets have been studied following oral administration of single-dose (2 tablets) and multiple-dose (4 tablets/day). Doxylamine and pyridoxine are absorbed in the gastrointestinal tract, mainly in the jejunum. The time to reach peak concentrations (Tmax) of doxylamine and pyridoxine are within 7.5 and 5.5 hours, respectively. Multiple-dose administration results in increased concentrations of doxylamine (including Cmax and an increased AUC). The time to reach the maximum concentration (Tmax) for doxylamine is not affected by multiple doses. The mean accumulation index is greater than 1 suggesting that doxylamine accumulates following multiple dosing. Although no accumulation was observed for pyridoxine, the mean accumulation index for each metabolite is greater than 1 after multiple-dose administration of the combination product; the Tmax for pyridoxine is not affected by multiple doses.[54146] The pharmacokinetics of a single-dose of doxylamine 20 mg; pyridoxine 20 mg extended-release tablets have been studied in a crossover clinical trial in 48 healthy, premenopausal women under fasting conditions. One doxylamine 20 mg; pyridoxine 20 mg extended-release tablet was bioequivalent to 2 combination tablets of 10 mg doxylamine and 10 mg pyridoxine based on the AUC and Cmax of doxylamine and baseline corrected pyridoxal 5'-phosphate (PLP). In a multiple-dose, crossover clinical trial conducted in 31 healthy, premenopausal women, 1 doxylamine 20 mg; pyridoxine 20 mg extended-release tablet given twice daily for 11 days was bioequivalent to 1 combination tablet of 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride given 3 times daily (1 tablet in the morning, 1 tablet in the afternoon, and 2 tablets at bedtime), based on the AUC and Cmax of doxylamine and baseline corrected PLP.[61433] The administration of food delays the absorption of both doxylamine and pyridoxine.[54146][61433]

      Special Populations

      Hepatic Impairment

      The pharmacokinetic profile of doxylamine; pyridoxine has not been studied in hepatically impaired patients.[54146]

      Renal Impairment

      The pharmacokinetic profile of doxylamine; pyridoxine has not been studied in renally impaired patients.[54146]

      Ethnic Differences

      The effect of ethnic differences on the pharmacokinetic profile of doxylamine; pyridoxine has not been studied.[54146]

      Revision Date: 12/19/2016, 12:45:53 PM

      References

      54146 - Diclegis (doxylamine; pyridoxine) delayed-release tablets package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.61433 - Diclegis (doxylamine; pyridoxine) package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.

      Pregnancy/Breast-feeding

      pregnancy

      This drug combination is intended for use during human pregnancy in women who do not respond to conservative management. No increased risk for congenital malformations has been reported with use in pregnant women. Doxylamine; pyridoxine has been evaluated through epidemiological studies (cohort, case control and meta-analyses) designed to detect possible teratogenicity. A meta-analysis of 16 cohort and 11 case-control studies published between 1963 and 1991 reported no increased risk for malformations from first trimester exposures to doxylamine succinate and pyridoxine hydrochloride, with or without dicyclomine hydrochloride. A second meta-analysis of 12 cohort and 5 case-control studies published between 1963 and 1985 reported no statistically significant relationships between fetal abnormalities and the first trimester use of the combination doxylamine and pyridoxine with or without dicyclomine.[54146] [61433] Doxylamine; pyridoxine is a first-line pharmacologic agent for use following conservative management in the ACOG treatment algorithm for nausea and vomiting due to pregnancy.[66066]

      breast-feeding

      According to the manufacturer, doxylamine; pyridoxine is not recommended for use during breast-feeding. Data regarding the transfer of doxylamine into human milk are not available; however, the molecular weight of doxylamine suggests that passage into human breast milk is possible. Maternal exposure to antihistamine (H-1 antagonists) has also been reported to induce irritability or sedation in 9.4% of breast-fed infants.[35545] Infants with apnea or other respiratory syndromes may be particularly vulnerable to the sedative effects of doxylamine. Pyridoxine hydrochloride is excreted into breast milk. There have been no reports of adverse events in infants presumably exposed to pyridoxine through breast milk and the use of pyridoxine is compatible with breast-feeding.[27500] [54146] [61433] Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, health care providers are encouraged to report the adverse effect to the FDA.

      Revision Date: 10/28/2020, 03:48:57 PM

      References

      27500 - American Academy of Pediatrics (AAP) Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001;108(3):776-789.35545 - Ito S, Blajchman A, Stephenson M, et al. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol 1993;168:1393-9.54146 - Diclegis (doxylamine; pyridoxine) delayed-release tablets package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.61433 - Diclegis (doxylamine; pyridoxine) package insert. Bryn Mawr, PA: Duchesnay USA, Inc.; 2022 Mar.66066 - American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin Number 189: Nausea and vomiting of pregnancy. Obstet Gynecol 2018;131:15-30. Reaffirmed 2019.

      Interactions

      Level 1 (Severe)

      • Calcium, Magnesium, Potassium, Sodium Oxybates
      • Isocarboxazid
      • Monoamine oxidase inhibitors
      • Phenelzine
      • Sodium Oxybate
      • Tranylcypromine

      Level 2 (Major)

      • Acetaminophen; Caffeine; Dihydrocodeine
      • Acetaminophen; Codeine
      • Acetaminophen; Hydrocodone
      • Acetaminophen; Oxycodone
      • Alfentanil
      • Aspirin, ASA; Butalbital; Caffeine; Codeine
      • Aspirin, ASA; Carisoprodol; Codeine
      • Aspirin, ASA; Oxycodone
      • Azelastine
      • Azelastine; Fluticasone
      • Belladonna; Opium
      • Benzhydrocodone; Acetaminophen
      • Buprenorphine
      • Buprenorphine; Naloxone
      • Butalbital; Acetaminophen; Caffeine; Codeine
      • Celecoxib; Tramadol
      • Chlorpheniramine; Codeine
      • Chlorpheniramine; Dihydrocodeine; Phenylephrine
      • Chlorpheniramine; Hydrocodone
      • Codeine
      • Codeine; Guaifenesin
      • Codeine; Guaifenesin; Pseudoephedrine
      • Codeine; Phenylephrine; Promethazine
      • Codeine; Promethazine
      • Ethanol
      • Fentanyl
      • food
      • Guaifenesin; Hydrocodone
      • Guaifenesin; Hydrocodone; Pseudoephedrine
      • Homatropine; Hydrocodone
      • Hydrocodone
      • Hydrocodone; Ibuprofen
      • Hydrocodone; Pseudoephedrine
      • Hydromorphone
      • Ibuprofen; Oxycodone
      • Levorphanol
      • Meclizine
      • Meperidine
      • Meperidine; Promethazine
      • Methadone
      • Morphine
      • Morphine; Naltrexone
      • Oliceridine
      • Opiate Agonists
      • Oxycodone
      • Oxymorphone
      • Pitolisant
      • Remifentanil
      • Rotigotine
      • Sufentanil
      • Tapentadol
      • Thalidomide
      • Tramadol
      • Tramadol; Acetaminophen

      Level 3 (Moderate)

      • Acetaminophen; Dichloralphenazone; Isometheptene
      • Acetaminophen; Pentazocine
      • Aldesleukin, IL-2
      • Alosetron
      • Amantadine
      • Ambenonium Chloride
      • Amobarbital
      • Amoxapine
      • Amphetamine
      • Amphetamine; Dextroamphetamine
      • Amphetamine; Dextroamphetamine Salts
      • Apomorphine
      • Aripiprazole
      • Asenapine
      • Aspirin, ASA; Butalbital; Caffeine
      • Aspirin, ASA; Caffeine; Orphenadrine
      • Aspirin, ASA; Carisoprodol
      • Atropine
      • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
      • Atropine; Difenoxin
      • Atropine; Edrophonium
      • Baclofen
      • Barbiturates
      • Benzodiazepines
      • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
      • Benzphetamine
      • Benztropine
      • Brompheniramine; Carbetapentane; Phenylephrine
      • Budesonide; Glycopyrrolate; Formoterol
      • Butabarbital
      • Butalbital; Acetaminophen
      • Butalbital; Acetaminophen; Caffeine
      • Butorphanol
      • Cannabidiol
      • Capsaicin; Metaxalone
      • Carbetapentane; Chlorpheniramine
      • Carbetapentane; Chlorpheniramine; Phenylephrine
      • Carbetapentane; Diphenhydramine; Phenylephrine
      • Carbetapentane; Guaifenesin
      • Carbetapentane; Guaifenesin; Phenylephrine
      • Carbetapentane; Phenylephrine
      • Carbetapentane; Phenylephrine; Pyrilamine
      • Carbetapentane; Pseudoephedrine
      • Carbetapentane; Pyrilamine
      • Carbidopa; Levodopa; Entacapone
      • Cariprazine
      • Carisoprodol
      • Cenobamate
      • Cetirizine
      • Cetirizine; Pseudoephedrine
      • Chlorpromazine
      • Chlorzoxazone
      • Clobazam
      • Clozapine
      • COMT inhibitors
      • Cyclobenzaprine
      • Dantrolene
      • Deutetrabenazine
      • Dexmedetomidine
      • Dextroamphetamine
      • Dicyclomine
      • Difelikefalin
      • Diphenoxylate; Atropine
      • Disopyramide
      • Donepezil
      • Donepezil; Memantine
      • Dronabinol
      • Droperidol
      • Entacapone
      • Esketamine
      • Eszopiclone
      • Fenfluramine
      • Flavoxate
      • Flibanserin
      • Fluphenazine
      • Gabapentin
      • Galantamine
      • Glycopyrrolate
      • Glycopyrrolate; Formoterol
      • Haloperidol
      • Hyoscyamine
      • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
      • Iloperidone
      • Indacaterol; Glycopyrrolate
      • Lasmiditan
      • Lemborexant
      • Levocetirizine
      • Lofexidine
      • Loxapine
      • Lumateperone
      • Lurasidone
      • Maprotiline
      • Melatonin
      • Meprobamate
      • Metaxalone
      • Methamphetamine
      • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
      • Methocarbamol
      • Methohexital
      • Methscopolamine
      • Metyrapone
      • Metyrosine
      • Mirtazapine
      • Mitotane
      • Molindone
      • Nabilone
      • Nalbuphine
      • Nefazodone
      • Olanzapine
      • Olanzapine; Fluoxetine
      • Olanzapine; Samidorphan
      • Opicapone
      • Orphenadrine
      • Oxybutynin
      • Paliperidone
      • Papaverine
      • Pentazocine
      • Pentazocine; Naloxone
      • Pentobarbital
      • Perampanel
      • Perphenazine
      • Perphenazine; Amitriptyline
      • Phenobarbital
      • Phenobarbital; Hyoscyamine; Atropine; Scopolamine
      • Phentermine; Topiramate
      • Pimozide
      • Pramipexole
      • Pregabalin
      • Primidone
      • Procarbazine
      • Prochlorperazine
      • Promethazine
      • Promethazine; Dextromethorphan
      • Promethazine; Phenylephrine
      • Propantheline
      • Quetiapine
      • Ramelteon
      • Rasagiline
      • Risperidone
      • Rivastigmine
      • Ropinirole
      • Safinamide
      • Scopolamine
      • Secobarbital
      • Selegiline
      • Sincalide
      • Sodium Iodide
      • Solifenacin
      • Stiripentol
      • Suvorexant
      • Tasimelteon
      • Tetrabenazine
      • Thioridazine
      • Thiothixene
      • Tizanidine
      • Tolcapone
      • Topiramate
      • Trazodone
      • Tricyclic antidepressants
      • Trifluoperazine
      • Trihexyphenidyl
      • Trimethobenzamide
      • Trospium
      • Vigabatrin
      • Vilazodone
      • Zaleplon
      • Ziconotide
      • Ziprasidone
      • Zolpidem

      Level 4 (Minor)

      • Apraclonidine
      • Daratumumab; Hyaluronidase
      • Desloratadine
      • Desloratadine; Pseudoephedrine
      • Etomidate
      • Halogenated Anesthetics
      • Heparin
      • Hyaluronidase
      • Hyaluronidase, Recombinant; Immune Globulin
      • Ketamine
      • Loratadine
      • Loratadine; Pseudoephedrine
      • Metoclopramide
      • Minocycline
      • Pertuzumab; Trastuzumab; Hyaluronidase
      • Propofol
      • Rituximab; Hyaluronidase
      • Trastuzumab; Hyaluronidase
      Acetaminophen; Caffeine; Dihydrocodeine: (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; Codeine: (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; Dichloralphenazone; Isometheptene: (Moderate) Additive CNS depression may occur if dichloralphenazone is used concomitantly with any of the sedating H1 blockers. Use caution with this combination. Dosage reduction of one or both agents may be necessary. [6946] [6948] Acetaminophen; Hydrocodone: (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; Oxycodone: (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; Pentazocine: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with sedating H1-blockers may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. [30029] [30219] Aldesleukin, IL-2: (Moderate) Aldesleukin, IL-2 may affect CNS function significantly. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity. Use with caution. [41853] Alfentanil: (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] Alosetron: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like sedating H1 blockers, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. [5112] Amantadine: (Moderate) Medications with significant anticholinergic activity may potentiate the anticholinergic effects of amantadine, and may increase the risk of antimuscarinic-related side effects. Additive drowsiness may also occur. [28049] [48306] Ambenonium Chloride: (Moderate) The therapeutic benefits of ambenonium may be diminished when coadministered with drugs known to exhibit anticholinergic properties including sedating H1-blockers. When concurrent use cannot be avoided, monitor the patient for reduced ambenonium efficacy. [29597] Amobarbital: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Amoxapine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur. [28558] [48306] [63923] Amphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine. [28488] [60070] Amphetamine; Dextroamphetamine Salts: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine. [28488] [60070] Amphetamine; Dextroamphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine. [28488] [60070] Apomorphine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and doxylamine could result in additive depressant effects. Careful monitoring is recommended during combined use. A dose reduction of one or both drugs may be warranted. [28661] Apraclonidine: (Minor) No specific drug interactions were identified with systemic agents and apraclonidine during clinical trials. Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as the anxiolytics, sedatives, and hypnotics, including barbiturates or benzodiazepines. [6224] Aripiprazole: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and aripiprazole due to the risk for additive CNS depression. [42845] [52061] Asenapine: (Moderate) Using drugs that can cause CNS depression, such as sedating H1-blockers, concomitantly with asenapine may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. [36343] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Aspirin, ASA; Butalbital; Caffeine; Codeine: (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] (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur. [29244] [63923] Aspirin, ASA; Carisoprodol: (Moderate) Carisoprodol is metabolized to meprobamate, a significant CNS depressant. Carisoprodol can cause additive CNS depression if used concomitantly with other CNS depressants. Additive effects of sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness, may occur if carisoprodol is taken with sedating H1-blockers. Utilize appropriate caution if carisoprodol is coadministered with another CNS depressant. [24512] [30880] [31038] [31039] [31110] [33490] Aspirin, ASA; Carisoprodol; Codeine: (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] (Moderate) Carisoprodol is metabolized to meprobamate, a significant CNS depressant. Carisoprodol can cause additive CNS depression if used concomitantly with other CNS depressants. Additive effects of sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness, may occur if carisoprodol is taken with sedating H1-blockers. Utilize appropriate caution if carisoprodol is coadministered with another CNS depressant. [24512] [30880] [31038] [31039] [31110] [33490] Aspirin, ASA; Oxycodone: (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] Atropine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. [56616] [63228] [63923] Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects. [30922] [56616] [63923] (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. [56616] [63228] [63923] Atropine; Difenoxin: (Moderate) An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. [30269] [6568] [7063] (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. [56616] [63228] [63923] Atropine; Edrophonium: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. [56616] [63228] [63923] Azelastine: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. [43711] Azelastine; Fluticasone: (Major) Avoid concomitant use of azelastine and sedating H1-blockers due to risk for additive CNS depression. [43711] Baclofen: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including skeletal muscle relaxants, such as baclofen. [57272] Barbiturates: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Belladonna; Opium: (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] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and belladonna use. Concomitant use may result in additive anticholinergic adverse effects. [56616] [57409] [63923] Benzhydrocodone; Acetaminophen: (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] Benzodiazepines: (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Use caution with this combination. [30414] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects. [30922] [56616] [63923] Benzphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers. This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine. [5218] Benztropine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and benztropine use. Concomitant use may result in additive anticholinergic adverse effects. [31963] [56616] [63923] Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers. [8141] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects. [56616] [57625] [63923] Buprenorphine: (Major) Reserve concomitant prescribing of buprenorphine and doxylamine for use in 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. Gradually tapering a patient off other CNS depressants or decreasing to the lowest effective dose is preferred in most cases of patients being treated for opioid use disorder. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Also monitor for signs of urinary retention or reduced gastric motility during concomitant use. 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. [41235] [41666] [52061] [62320] Buprenorphine; Naloxone: (Major) Reserve concomitant prescribing of buprenorphine and doxylamine for use in 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. Gradually tapering a patient off other CNS depressants or decreasing to the lowest effective dose is preferred in most cases of patients being treated for opioid use disorder. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Also monitor for signs of urinary retention or reduced gastric motility during concomitant use. 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. [41235] [41666] [52061] [62320] Butabarbital: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Butalbital; Acetaminophen: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Butalbital; Acetaminophen; Caffeine: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Butalbital; Acetaminophen; Caffeine; Codeine: (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] (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Butorphanol: (Moderate) Concomitant use of butorphanol with sedating H1-blockers can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a CNS depressant needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol. [29174] [29822] Calcium, Magnesium, Potassium, Sodium Oxybates: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. [5258] Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and sedating H1-blockers. CNS depressants can potentiate the effects of cannabidiol. [63309] Capsaicin; Metaxalone: (Moderate) Concomitant administration of metaxalone with other CNS depressants can potentiate the sedative effects of either agent. [29600] [30414] [30443] [30830] Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers. [8141] Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers. [8141] Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers. [8141] Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers. [8141] Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers. [8141] Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers. [8141] Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers. [8141] Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers. [8141] Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including sedating h1-blockers. [8141] Carbidopa; Levodopa; Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation. 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. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them. [28845] [42112] [65338] Cariprazine: (Moderate) Due to the CNS effects of cariprazine, caution should be used when cariprazine is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics like doxylamine. [60164] Carisoprodol: (Moderate) Carisoprodol is metabolized to meprobamate, a significant CNS depressant. Carisoprodol can cause additive CNS depression if used concomitantly with other CNS depressants. Additive effects of sedation and dizziness, which can impair the ability to undertake tasks requiring mental alertness, may occur if carisoprodol is taken with sedating H1-blockers. Utilize appropriate caution if carisoprodol is coadministered with another CNS depressant. [24512] [30880] [31038] [31039] [31110] [33490] Celecoxib; Tramadol: (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] Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and sedating H1-blockers. Concurrent use may result in additive CNS depression. [47262] [47268] [48650] [52061] [56616] [59577] [61470] [64768] Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cetirizine and sedating H1-blockers. Concomitant use may result in additive CNS depression or anticholinergic effects. [40967] [56616] Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cetirizine and sedating H1-blockers. Concomitant use may result in additive CNS depression or anticholinergic effects. [40967] [56616] Chlorpheniramine; Codeine: (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] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (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] Chlorpheniramine; Hydrocodone: (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] Chlorpromazine: (Moderate) Additive anticholinergic and sedative effects may be seen when chlorpromazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription motion sickness, allergy, sleep, and cough and cold product labels carefully for additional interacting antihistamines. [43065] [63923] Chlorzoxazone: (Moderate) Additive CNS depression is possible if chlorzoxazone is used concomitantly with other CNS depressants including sedating H1-blockers. Additive effects of sedation and dizziness can occur, which can impair the ability to undertake tasks requiring mental alertness. Dosage adjustments of one or both medications may be necessary. [30389] Clobazam: (Moderate) Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects. Additive drowsiness may occur when clobazam is combined with CNS depressants such as sedating H1-blockers. In addition, caution is recommended when administering clobazam with medications extensively metabolized by CYP2D6 such as diphenhydramine because clobazam has been shown to inhibit CYP2D6 in vivo and may increase concentrations of drugs metabolized by this enzyme. [34522] [34523] [46370] [6568] Clozapine: (Moderate) Clozapine exhibits clinically significant anticholinergic effects and sedation that may be additive with other medications that may cause anticholinergic effects and sedation, including antihistamines such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines and to avoid tasks requiring mental alertness until they are aware of the effects of the combination. [28262] [52061] [63923] Codeine: (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] Codeine; Guaifenesin: (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] Codeine; Guaifenesin; Pseudoephedrine: (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] Codeine; Phenylephrine; Promethazine: (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] (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects. [43930] [63923] Codeine; Promethazine: (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] (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects. [43930] [63923] COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation. 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. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them. [28845] [42112] [65338] Cyclobenzaprine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cyclobenzaprine and doxylamine. Concomitant use may result in additive CNS depression or anticholinergic effects. [28425] [63923] Dantrolene: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect (e.g., drowsiness) may occur when dantrolene is combined with other CNS depressants. [49509] Daratumumab; Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Desloratadine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers. [7530] Desloratadine; Pseudoephedrine: (Minor) Although desloratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of desloratadine with CNS depressants such as other H1-blockers. [7530] Deutetrabenazine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as doxylamine, may have additive effects and worsen drowsiness or sedation. [61845] Dexmedetomidine: (Moderate) Co-administration of dexmedetomidine with sedating antihistamines is likely to lead to an enhancement of CNS depression. [29112] Dextroamphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of some antihistamines, such as the sedating H1-blockers (i.e., diphenhydramine). This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine. [28488] [60070] Dicyclomine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and dicyclomine use. Concomitant use may result in additive anticholinergic adverse effects. [30090] [56616] [63923] Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions. [66926] Diphenoxylate; Atropine: (Moderate) An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. [30269] [6568] [7063] (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. [56616] [63228] [63923] Disopyramide: (Moderate) The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including disopyramide. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. [28228] [59643] [63923] Donepezil: (Moderate) Concurrent use of sedating H1-blockers and donepezil should be avoided if possible. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil. [29640] [34396] Donepezil; Memantine: (Moderate) Concurrent use of sedating H1-blockers and donepezil should be avoided if possible. Donepezil inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil. [29640] [34396] Dronabinol: (Moderate) Use caution if coadministration of dronabinol with antihistamines is necessary. Concurrent use of dronabinol, THC with antihistamines may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity. [30431] [60951] Droperidol: (Moderate) Sedating H1-blockers have additive or potentiating sedative and other CNS effects with droperidol. Following administration of droperidol, lower doses of the other CNS depressant may need to be used. [28737] Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation. 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. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them. [28845] [42112] [65338] Esketamine: (Moderate) Closely monitor patients receiving esketamine and doxylamine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep. [52061] [63989] Eszopiclone: (Moderate) A reduction in the dose of eszopiclone and concomitantly administered CNS depressants, such as sedating H1-blockers, should be considered to minimize additive sedative effects. 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. [30571] Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression. [61143] [62827] Etomidate: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics. [29822] [30143] Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and doxylamine. Concurrent use may result in additive CNS depression. [52061] [65634] Fentanyl: (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] Flavoxate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and flavoxate use. Concomitant use may result in additive anticholinergic adverse effects. [47398] [56616] [63923] Flibanserin: (Moderate) The concomitant use of flibanserin with CNS depressants, such as sedating H1-blockers, may increase the risk of CNS depression (e.g., dizziness, somnolence) compared to the use of flibanserin alone. Patients should avoid activities requiring full alertness (e.g., operating machinery or driving) until at least 6 hours after each dose and until they know how flibanserin affects them. [60099] Fluphenazine: (Moderate) Additive sedative effects may be seen when fluphenazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [52567] [63923] 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] Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of doxylamine and gabapentin. Concurrent use may result in additive CNS depression. [27986] [52061] [64848] Galantamine: (Moderate) Concurrent use of sedating H1-blockers and galantamine should be avoided if possible. Galantamine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of galantamine. [32342] [34396] Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects. [56616] [57625] [63923] Glycopyrrolate; Formoterol: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects. [56616] [57625] [63923] Guaifenesin; Hydrocodone: (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] Guaifenesin; Hydrocodone; Pseudoephedrine: (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] Halogenated Anesthetics: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics. [28970] [31166] [49611] [49614] Haloperidol: (Moderate) Haloperidol can potentiate the actions of other CNS depressants such as the sedating H1-blockers. Additive anticholinergic effects may occur. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or CNS effects may also occur. [28307] Heparin: (Minor) Antihistamines may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not likely of clinical significance since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient. [56872] Homatropine; Hydrocodone: (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] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and homatropine use. Concomitant use may result in additive anticholinergic adverse effects. [30379] [56616] [63923] [67638] Hyaluronidase, Recombinant; Immune Globulin: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Hydrocodone: (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] Hydrocodone; Ibuprofen: (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] Hydrocodone; Pseudoephedrine: (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] Hydromorphone: (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] Hyoscyamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects. [30922] [56616] [63923] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects. [30922] [56616] [63923] Ibuprofen; Oxycodone: (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] Iloperidone: (Moderate) Drugs that can cause CNS depression, if used concomitantly with iloperidone, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when iloperidone is given in combination with other centrally-acting medications, such as sedating H1-blockers. [36146] Indacaterol; Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects. [56616] [57625] [63923] Isocarboxazid: (Contraindicated) Concomitant use of monoamine oxidase inhibitors and sedating H1-blockers is contraindicated due to increased anticholinergic effects. [29656] [53440] Ketamine: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics. [29822] [30143] Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and sedating H1-blockers. Concurrent use may result in additive CNS depression. [64685] Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and sedating antihistamines (H1-blockers). Dosage adjustments of lemborexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with lemborexant. [52061] [62207] [63270] [64870] Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of cetirizine and sedating H1-blockers. Concomitant use may result in additive CNS depression or anticholinergic effects. [40967] [56616] Levorphanol: (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] Lofexidine: (Moderate) Monitor for additive sedation during coadministration of lofexidine and doxylamine. Lofexidine can potentiate the effects of CNS depressants. Patients should be advised to avoid driving or performing any other tasks requiring mental alertness until the effects of the combination are known. [63161] Loratadine: (Minor) Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as other H1-blockers. [30768] Loratadine; Pseudoephedrine: (Minor) Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness during concurrent use of loratadine with CNS depressants such as other H1-blockers. [30768] Loxapine: (Moderate) Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with other drugs having anticholinergic activity and CNS depressant properties such as traditional antipsychotic agents, including loxapine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other CNS effects may also occur. [53320] Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and doxylamine. Concurrent use may result in additive CNS depression. [52061] [54146] [63316] [64885] Lurasidone: (Moderate) Due to the CNS effects of lurasidone, caution should be used when lurasidone is given in combination with other centrally acting medications. Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur. [28293] [42227] Maprotiline: (Moderate) Additive anticholinergic effects may be seen when maprotiline is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including sedating h1-blockers. [28759] Meclizine: (Major) Meclizine is an H1-blocker which exhibits significant anticholinergic effects. The anticholinergic effects of meclizine may be enhanced when combined with other drugs with antimuscarinic activity, including other sedating H1-blockers. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive sedation may also occur. [29597] [29822] [43856] Melatonin: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of melatonin and sedating H1-blockers due to the risk for additive CNS depression. [25471] [56616] [60032] [61470] Meperidine: (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] Meperidine; Promethazine: (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] (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects. [43930] [63923] Meprobamate: (Moderate) The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including sedating H1-blockers. [30089] Metaxalone: (Moderate) Concomitant administration of metaxalone with other CNS depressants can potentiate the sedative effects of either agent. [29600] [30414] [30443] [30830] Methadone: (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] Methamphetamine: (Moderate) Amphetamines may pharmacodynamically counteract the sedative properties of sedating H1-blockers. This effect may be clinically important if a patient is receiving an antihistamine agent for treatment of insomnia. Alternatively, if a patient is receiving an amphetamine for treatment of narcolepsy, the combination with a sedating antihistamine may reverse the action of the amphetamine. Coadminister with caution and monitor for altered response to drug therapy. [28488] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects. [30922] [56616] [63923] Methocarbamol: (Moderate) Methocarbamol may cause additive CNS depression if used concomitantly with other CNS depressants such as sedating H1-blockers. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary. [30831] Methohexital: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Methscopolamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and methscopolamine use. Concomitant use may result in additive anticholinergic adverse effects. [30424] [56616] [63923] Metoclopramide: (Minor) Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation. [5688] Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as sedating H1-blockers, should be used with caution. Additive drowsiness and/or dizziness is possible. [10379] Metyrosine: (Moderate) The concomitant administration of metyrosine with sedating H1-blockers can result in additive sedative effects. [6341] 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 sedating H1-blockers. Caution should be exercised when using these agents concurrently. [30442] [35529] Mirtazapine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and mirtazapine due to the risk for additive CNS depression. [40942] [52061] Mitotane: (Moderate) Mitotane can cause sedation, lethargy, vertigo, and other CNS side effects. Concomitant administration of mitotane and CNS depressants, including sedating h1-blockers, may cause additive CNS effects. [4788] Molindone: (Moderate) An enhanced CNS depressant effect may occur when sedating h1-blockers are combined with other CNS depressants including molindone. [28820] [5553] [6568] Monoamine oxidase inhibitors: (Contraindicated) Concomitant use of monoamine oxidase inhibitors and sedating H1-blockers is contraindicated due to increased anticholinergic effects. [29656] [53440] Morphine: (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] Morphine; Naltrexone: (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] Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants, such as sedating H1-blockers, can potentiate the effects of nabilone on respiratory depression. [32226] Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants, such as sedating H1-blockers, can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation. [59641] Nefazodone: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including nefazodone. [5414] [6568] Olanzapine: (Moderate) Olanzapine exhibits anticholinergic effects that may be clinically significant. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with olanzapine. Some medications exhibit additive anticholinergic effects include sedating H1-blockers. Olanzapine may also cause additive sedation with many of these drugs. [26650] [28785] [29597] Olanzapine; Fluoxetine: (Moderate) Olanzapine exhibits anticholinergic effects that may be clinically significant. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with olanzapine. Some medications exhibit additive anticholinergic effects include sedating H1-blockers. Olanzapine may also cause additive sedation with many of these drugs. [26650] [28785] [29597] Olanzapine; Samidorphan: (Moderate) Olanzapine exhibits anticholinergic effects that may be clinically significant. Clinicians should keep this in mind when using antimuscarinics and other medications with anticholinergic activity in combination with olanzapine. Some medications exhibit additive anticholinergic effects include sedating H1-blockers. Olanzapine may also cause additive sedation with many of these drugs. [26650] [28785] [29597] Oliceridine: (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] Opiate Agonists: (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] Opicapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation. 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. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them. [28845] [42112] [65338] Orphenadrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur. [29244] [63923] Oxybutynin: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and oxybutynin use. Concomitant use may result in additive anticholinergic adverse effects. [29796] [56616] [63923] Oxycodone: (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] Oxymorphone: (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] Paliperidone: (Moderate) Coadministration of drugs with CNS depressant effects, including paliperidone and doxylamine, 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 and advise patients to avoid driving or engaging in other activities requiring mental alertness until they know how this combination affects them. [40936] Papaverine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as doxylamine could lead to enhanced sedation. [6925] Pentazocine: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with sedating H1-blockers may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. [30029] [30219] Pentazocine; Naloxone: (Moderate) Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity. Coadministration of pentazocine with sedating H1-blockers may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. [30029] [30219] Pentobarbital: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as sedating H1-blockers. [52140] Perphenazine: (Moderate) Additive anticholinergic and sedative effects may be seen when perphenazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription allergy, sleep, cough, and cold product labels carefully for additional interacting antihistamines. [43070] [63923] Perphenazine; Amitriptyline: (Moderate) Additive anticholinergic and sedative effects may be seen when perphenazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription allergy, sleep, cough, and cold product labels carefully for additional interacting antihistamines. [43070] [63923] Pertuzumab; Trastuzumab; Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Phenelzine: (Contraindicated) Concomitant use of monoamine oxidase inhibitors and sedating H1-blockers is contraindicated due to increased anticholinergic effects. [29656] [53440] Phenobarbital: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects. [30922] [56616] [63923] (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. [56616] [63228] [63923] (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and scopolamine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. [30354] [56616] [63923] Phentermine; Topiramate: (Moderate) Monitor for increased CNS effects if topiramate is coadministered with doxylamine. Although not specifically studied, coadministration of CNS depressant drugs with topiramate may potentiate CNS depression, such as dizziness or cognitive adverse reactions, or other centrally mediated effects of these agents. [51256] Pimozide: (Moderate) Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including sedating antihistamines. Sedating H1-blockers are associated with anticholinergic effects and sedation; therefore, additive effects may be seen during concurrent use with pimozide. Additive drowsiness or other CNS effects may occur. [43463] Pitolisant: (Major) Avoid coadministration of pitolisant with doxylamine as the effect of pitolisant may be decreased. Pitolisant increases histamine concentrations in the brain; therefore, H1-receptor antagonists like doxylamine, may reduce pitolisant efficacy. [64562] Pramipexole: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole. [29822] [44285] Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of doxylamine and pregabalin. Concurrent use may result in additive CNS depression. [31493] [52061] [64848] Primidone: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Procarbazine: (Moderate) Use procarbazine and sedating H1-blockers together with caution; additive central nervous system depression may occur. [45905] Prochlorperazine: (Moderate) Additive anticholinergic and sedative effects may be seen when prochlorperazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [29498] [63923] Promethazine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects. [43930] [63923] Promethazine; Dextromethorphan: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects. [43930] [63923] Promethazine; Phenylephrine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and promethazine. Concomitant use may result in additive CNS depression or anticholinergic effects. [43930] [63923] Propantheline: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and propantheline use. Concomitant use may result in additive anticholinergic adverse effects. [47396] [56616] [63923] Propofol: (Minor) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when they are combined with general anesthetics. [29822] [30143] Quetiapine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects. [29118] Ramelteon: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as ramelteon. [31359] Rasagiline: (Moderate) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-blockers (sedating antihistamines) may result in additive sedation, anticholinergic effects, or hypotensive reactions. Rasagiline may be less likely to produce these interactions than other MAOIs, due to MAO-B selectivity. However, consider alternatives therapy to antihistamines where possible. If alternative combinations are not available, these medications may be used together with close monitoring. Many non-prescription products for coughs, colds, allergy, hay fever or insomnia contain sedating antihistamines. Patients receiving rasagiline should be counseled that it is essential to consult their healthcare provider or pharmacist prior to the use of any non-prescription products. Patients should also be advised against driving or engaging in other activities requiring mental alertness until they know how this combination affects them. [32223] [59433] [61157] [61172] [61173] Remifentanil: (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] Risperidone: (Moderate) Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including sedating H1-blockers. Additive drowsiness or other CNS effects may occur. [28414] Rituximab; Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Rivastigmine: (Moderate) Concurrent use of sedating H1-blockers and rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Sedating H1-blockers may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine. [34396] [41681] Ropinirole: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole. [31241] Rotigotine: (Major) Concomitant use of rotigotine with other CNS depressants, such as doxylamine, can potentiate the sedation effects of rotigotine. [10179] Safinamide: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of other sedating medications, such as sedating H1-blockers. [61825] Scopolamine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and scopolamine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. [30354] [56616] [63923] Secobarbital: (Moderate) Because doxylamine can cause pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as barbiturates. [5326] [6946] [6948] [7598] [7801] Selegiline: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and selegiline due to the risk for additive CNS depression. [32026] [32436] [52061] Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent medications, including H1-blockers. False study results are possible; thorough patient history is important in the interpretation of procedure results. [9348] [9349] Sodium Iodide: (Moderate) Antihistamines may alter sodium iodide I-131 pharmacokinetics and dynamics for up to 1 week after administration. In addition, medications that decrease salivation increase the time of radiation exposure to salivary glands. Consider discontinuing sedating H1-blockers prior to sodium iodide I-131 administration. [31884] [48920] Sodium Oxybate: (Contraindicated) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. [5258] Solifenacin: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics, such as doxylamine. [29597] [30515] Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and doxylamine. CNS depressants can potentiate the effects of stiripentol. [63456] Sufentanil: (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] Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of suvorexant and sedating antihistamines (H1-blockers). Dosage adjustments of suvorexant and sedating H1-blockers may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants. Patients should generally avoid nonprescription antihistamine products that are marketed as sleep-aids concurrently with suvorexant. [52061] [57780] [62207] [63270] Tapentadol: (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] Tasimelteon: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon. [56665] Tetrabenazine: (Moderate) Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as doxylamine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension. [11246] Thalidomide: (Major) Avoid the concomitant use of thalidomide with opiate agonists; antihistamines; antipsychotics; anxiolytics, sedatives, and hypnotics; and other central nervous system depressants due to the potential for additive sedative effects. [49713] Thioridazine: (Moderate) Additive anticholinergic and sedative effects may be seen when thioridazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [28293] [63923] Thiothixene: (Moderate) Additive anticholinergic effects may be seen when antipsychotics, such as thiothixene, are used concomitantly with other drugs such as sedating H1-blockers. Additive drowsiness or other CNS effects may also occur. [46957] Tizanidine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and tizanidine due to the risk for additive CNS depression. [52061] [52430] Tolcapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including sedating H1-blockers, due to the possibility of additive sedation. 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. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them. [28845] [42112] [65338] Topiramate: (Moderate) Monitor for increased CNS effects if topiramate is coadministered with doxylamine. Although not specifically studied, coadministration of CNS depressant drugs with topiramate may potentiate CNS depression, such as dizziness or cognitive adverse reactions, or other centrally mediated effects of these agents. [51256] Tramadol: (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] Tramadol; Acetaminophen: (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] Tranylcypromine: (Contraindicated) Concomitant use of monoamine oxidase inhibitors and sedating H1-blockers is contraindicated due to increased anticholinergic effects. [29656] [53440] Trastuzumab; Hyaluronidase: (Minor) H1-blockers (antihistamines), when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients receiving these medications may require larger amounts of hyaluronidase for equivalent dispersing effect. [28946] [41365] [41366] Trazodone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of doxylamine and trazodone due to the risk for additive CNS depression. [43857] [52061] Tricyclic antidepressants: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and tricyclic antidepressants. Concomitant use may result in additive CNS depression or anticholinergic effects. [28557] [28562] [28563] [28565] [28566] [41163] [63923] Trifluoperazine: (Moderate) Additive anticholinergic and sedative effects may be seen when trifluoperazine is used with first generation antihistamines, such as doxylamine. Patients should be informed to read non-prescription cough and cold product labels carefully for additional interacting antihistamines. [43071] [63923] Trihexyphenidyl: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant sedating H1-blocker and trihexyphenidyl use. Concomitant use may result in additive anticholinergic adverse effects. [30336] [56616] [63923] Trimethobenzamide: (Moderate) The concurrent use of trimethobenzamide with other medications that cause CNS depression, like the sedating h1-blockers, may potentiate the effects of either trimethobenzamide or the sedating h1-blocker. [7086] Trospium: (Moderate) Additive anticholinergic effects may be seen when trospium is used concomitantly with drugs that are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function and temperature regulation. While CNS-related side effects such as drowsiness and blurred vision are not typically noted with trospium, they may occur in some patients. [59641] 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 sedating H1-blockers. [36250] Vilazodone: (Moderate) Due to the CNS effects of vilazodone, caution should be used when vilazodone is given in combination with other centrally acting medications such as anxiolytics, sedatives, and hypnotics. Also, Cyproheptadine is an antagonist of serotonin in the CNS, a property which may oppose some of the pharmacologic effects of vilazodone. Cyproheptadine has been used for the management of orgasm dysfunction caused by the serotonergic antidepressants and for the adjunctive treatment of serotonin syndrome; however, a reversal of antidepressant effects may occur when cyproheptadine is given in a routine manner along with the antidepressant. Clinically, cyproheptadine reportedly has interfered with the antidepressant and anti-bulimia actions of fluoxetine, but more data are needed to confirm a direct drug-drug interaction. [43177] [5326] [5926] [6259] Zaleplon: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of sedating H1-blockers and zaleplon due to the risk for additive CNS depression and next-day psychomotor impairment; dose adjustments may be necessary. [29887] [56616] [61470] Ziconotide: (Moderate) Sedating H1-blockers are CNS depressant medications that may increase drowsiness, dizziness, and confusion that are associated with ziconotide. [52472] Ziprasidone: (Moderate) Sedating H1-blockers are associated with sedation; therefore, additive effects may be seen during concurrent use with other drugs having CNS depressant properties such as antipsychotics. Additive drowsiness or other CNS effects may occur with ziprasidone. [28233] Zolpidem: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of sedating H1-blockers and zolpidem due to the risk for additive CNS depression and next-day psychomotor impairment; dose adjustments may be necessary. Limit the dose of Intermezzo sublingual tablets to 1.75 mg/day. [46915] [56616] [57789] [61470]
      Revision Date: 12/29/2022, 02:30:00 AM

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      Monitoring Parameters

      • laboratory monitoring not necessary

      US Drug Names

      • BONJESTA
      • Diclegis
      ;