Elsevier Logo

English (United States)

ThisiscontentfromElsevier'sDrugInformation

TRANSFORM HOW YOU USE DRUG INFORMATION

Learn more about Elsevier's Drug Information today! Get the drug data and decision support you need, including TRUE Daily Updates™ including every day including weekends and holidays.

Jan.24.2020View related content

Phentermine; Topiramate

Indications/Dosage

Labeled

  • obesity
  • weight management

Off-Label

    † Off-label indication

    For the treatment of obesity and for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity

    Oral dosage (phentermine and topiramate extended-release capsules, e.g., Qsymia)

    Adults

    Initially, 3.75 mg/23 mg (phentermine/topiramate extended-release) PO once daily in the morning (avoid evening dosing) for 14 days. Increase to the recommended dose of 7.5 mg/46 mg PO once daily after 14 days. Evaluate weight loss at recommended dose after 12 weeks; if the patient has not lost at least 3% of baseline weight, discontinue therapy OR increase the dose to 11.25 mg/69 mg PO once daily for 14 days, followed by a final increase to 15 mg/92 mg PO once daily. Evaluate weight loss at 12 weeks at the higher dose; if the patient has not lost at least 5% of baseline weight, discontinue as the patient is not likely to achieve and sustain meaningful weight loss with continued treatment. Use the 3.75 mg/23 mg and 11.25 mg/69 mg dosage strengths for titration purposes only.[51256] Guidelines recommend an initial dose of 3.75 mg/23 mg per day and a low maintenance dose of 7.5 mg/46 mg per day in obese patients with depression or an anxiety disorder.[62881] INTENDED USE: For those with an initial body mass index (BMI) of 30 kg/m2 or more, or those with a BMI of 27 kg/m2 or more in the presence of at least 1 weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes). The effect of this product on cardiovascular morbidity/mortality has not been determined. Safety and efficacy are not established for use with other products intended for weight loss, including prescription drugs, over-the-counter drugs, and dietary supplements/herbal preparations.[51256] DISCONTINUATION: Discontinue the 15 mg/92 mg dose gradually by dosing every other day for at least 1 week before stopping treatment altogether, to avoid precipitating a seizure.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, pharmacotherapy should be offered as chronic treatment along with lifestyle modifications to patients with obesity when the potential benefits outweigh the risks. Short-term pharmacotherapy has not been shown to produce longer-term health benefits and cannot be generally recommended. A generalized hierarchy for medication preferences that would apply to all obese patients cannot currently be scientifically justified. Individualized weight loss pharmacotherapy is recommended, based upon factors such as the specific characteristics of each weight loss medication, the presence of weight-related complications, and the medical history of the patient. Combination therapy should only occur when such therapy is approved by the FDA or when sufficient safety and efficacy data assure a favorable benefit-to-risk ratio.[62881]

    Adolescents† 16 years and older

    Safety and efficacy have not been established; not FDA-approved.[51256] However, guidelines recommend that this product be used clinically in the same manner as with adults, using the same dosage titrations.[58571] [62881] [63035] The adult dose regimen is: 3.75 mg/23 mg (phentermine/topiramate extended-release) PO once daily in the morning (avoid evening dosing) for 14 days. Increase to the recommended dose of 7.5 mg/46 mg PO once daily after 14 days. Evaluate weight loss after 12 weeks; if the patient has not lost at least 3% of baseline weight, discontinue therapy OR increase the dose to 11.25 mg/69 mg PO once daily for 14 days, followed by a final increase to 15 mg/92 mg PO once daily. Evaluate weight loss after 12 weeks at higher dose; if the patient has not lost at least 5% of baseline weight, discontinue as the patient is not likely to achieve and sustain meaningful weight loss with continued treatment. Use the 3.75 mg/23 mg and 11.25 mg/69 mg dosage strengths for titration purposes only.[51256] DISCONTINUATION: Discontinue the 15 mg/92 mg dose gradually by dosing every other day for at least 1 week before stopping treatment altogether, to avoid precipitating a seizure.[51256]

    Therapeutic Drug Monitoring

    Maximum Dosage Limits

    • Adults <p>15 mg phentermine/92 mg topiramate extended-release PO daily.</p>
    • Geriatric <p>15 mg phentermine/92 mg topiramate extended-release PO daily.</p>
    • Adolescents <p><em>16 years and older:</em> 15 mg phentermine/92 mg topiramate extended-release PO daily is suggested in off-label use guidelines.</p> <p><em>13 to 15 years:</em> Safety and efficacy have not been established.</p>
    • Children <p>Safety and efficacy have not been established.</p>
    • Infants <p>Do not use.</p>
    • Neonates <p>Do not use.</p>

    Patients with Hepatic Impairment Dosing

    Mild hepatic impairment (Child Pugh Class A): No dose adjustment required.

    Moderate hepatic impairment (Child Pugh Class B): Do not exceed 7.5 mg/46 mg PO once daily.

    Severe hepatic impairment (Child Pugh Class C): Avoid use.[51256]

    Patients with Renal Impairment Dosing

    CrCl 50 mL/minute or greater: No dose adjustment required.

    CrCl less than 50 mL/minute: Do not exceed 7.5 mg/46 mg PO once daily.[51256]

     

    Intermittent hemodialysis

    Avoid use in patients with end-stage renal disease on dialysis.[51256]

    † Off-label indication
    Revision Date: 01/24/2020, 04:56:24 PM

    References

    51256 - Qsymia (phentermine and topiramate extended-release) package insert. Mountain View, CA: Vivus, Inc.; 2020 Sept.58571 - Styne DM, Arslanian SA, Connor EL, et al. Pediatric Obesity-Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102:709-757.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 Suppl 3:1-203.63035 - Greydanus DE, Agana M, Kamboj MK, et al. Pediatric obesity: Current concepts. Dis Mon. 2018;64:98-156. Foreword on p. 97 by Leikin JB.

    How Supplied

    Phentermine Hydrochloride, Topiramate Oral capsule, extended release

    Qsymia 3.75mg-23mg Extended Release Capsule (62541-0201) (Vivus Inc) null

    Phentermine Hydrochloride, Topiramate Oral capsule, extended release

    Qsymia 7.5mg-46mg Extended Release Capsule (62541-0202) (Vivus Inc) null

    Phentermine Hydrochloride, Topiramate Oral capsule, extended release

    Qsymia 11.25mg-69mg Extended Release Capsule (62541-0203) (Vivus Inc) null

    Phentermine Hydrochloride, Topiramate Oral capsule, extended release

    Qsymia 15mg-92mg Extended Release Capsule (62541-0204) (Vivus Inc) null

    Description/Classification

    Description

    Phentermine; topiramate is a combination product containing an anorectic sympathomimetic amine (phentermine) with topiramate, an antiepileptic drug with weak carbonic anhydrase inhibitor activity whose precise role in weight reduction is not known. The combination is used as an adjunct to lifestyle modifications for weight loss and chronic weight management in obese adults or overweight adults with at least 1 weight-related comorbid condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia). Long-term use of this combination product has been associated with an average weight loss of about 8% to 11%.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications should be offered as chronic treatment along with lifestyle modifications to obese patients when the potential benefits outweigh the risks. Short-term pharmacotherapy has not been shown to produce longer-term health benefits and cannot be generally recommended. A generalized hierarchy for medication preferences that would apply to all obese patients cannot currently be scientifically justified. Individualized weight loss pharmacotherapy is recommended, based on factors such as the specific characteristics of each weight loss medication, the presence of weight-related complications, and the medical history of the patient.[62881] Phentermine; topiramate may cause fetal harm (i.e., an increased risk of oral clefts) and therefore the drug is only available via the Qsymia REMs program. Females of reproductive potential require pregnancy testing before initiation of treatment and routinely during treatment. Visit www.QsymiaREMS.com for more information.[51256]

     

    NOTE: On March 22, 2020, the U.S. Food and Drug Administration, as part of the FDA's ongoing efforts to address the coronavirus pandemic (COVID-19), issued updated guidance to sponsors and health care providers regarding certain Risk Evaluation and Mitigation Strategy (REMS)-required testing during this time. The FDA recognizes that during the COVID-19 public health emergency (PHE), completion of REMS-required laboratory testing or imaging studies may be difficult because patients may need to avoid public places and patients suspected of having COVID-19 may be self-isolating and/or subject to quarantine. Under these circumstances, undergoing laboratory testing or imaging studies in order to obtain a drug subject to a REMS can put patients and others at risk for transmission of the coronavirus. For those drugs subject to REMS with laboratory testing or imaging requirements, such as phentermine; topiramate, health care providers prescribing and/or dispensing these drugs should consider whether there are compelling reasons not to complete these tests or imaging studies during this PHE and use their best medical judgment in weighing the benefits and risks of continuing treatment in the absence of such testing. Health care providers and those dispensing these drugs should communicate with their patients regarding these judgments including their benefits and risks. While all REMS requirements remain in effect, the FDA does not intend to take enforcement action against sponsors or others for the duration of the PHE for failing to adhere to REMS requirements or for accommodations that are made regarding laboratory testing or imaging study requirements, as long as the accommodations are based on the judgment of a health care professional. The FDA may require REMS for certain drugs if the agency determines that it is necessary to ensure that the benefits of the drug outweigh its risks.[65154]

    Classifications

    • Alimentary Tract and Metabolism
      • Antiobesity Agents, Excluding Dietetics
        • Centrally-Acting Antiobesity Agents
    Revision Date: 03/26/2020, 02:10:09 PM

    References

    51256 - Qsymia (phentermine and topiramate extended-release) package insert. Mountain View, CA: Vivus, Inc.; 2020 Sept.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 Suppl 3:1-203.65154 - U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER). FDA Guidance for Industry and Health Care Professionals. Policy for Certain REMS Requirements During the COVID-19 Public Health Emergency. Contains non-binding recommendations. Retrieved March 23, 2020. Available at: https://www.fda.gov/media/136317/download

    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

    Extended-release capsules (e.g., Qsymia)

    • Consistent with good practices, do not open, crush, cut, or chew the extended-release capsules or the capsule contents.
    • Administer the capsules once daily in the morning with or without food.
    • Avoid late evening administration because of the possibility of insomnia.[51256]

    Clinical Pharmaceutics Information

    From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
      Revision Date: 12/28/2018, 06:18:04 PM

      References

      51256 - Qsymia (phentermine and topiramate extended-release) package insert. Mountain View, CA: Vivus, Inc.; 2020 Sept.

      Adverse Reactions

      Moderate

      • blurred vision
      • bullous rash
      • chest pain (unspecified)
      • constipation
      • depression
      • euphoria
      • hepatitis
      • hyperammonemia
      • hypertension
      • hypokalemia
      • impaired cognition
      • impotence (erectile dysfunction)
      • memory impairment
      • metabolic acidosis
      • myopia
      • nephrolithiasis
      • palpitations
      • physiological dependence
      • psychological dependence
      • psychosis
      • sinus tachycardia
      • withdrawal

      Mild

      • alopecia
      • anxiety
      • back pain
      • cough
      • diarrhea
      • dizziness
      • dysgeusia
      • dysmenorrhea
      • dyspepsia
      • fatigue
      • gastroesophageal reflux
      • headache
      • hypoesthesia
      • hypothermia
      • infection
      • influenza
      • insomnia
      • irritability
      • libido decrease
      • libido increase
      • metallic taste
      • muscle cramps
      • musculoskeletal pain
      • nasal congestion
      • nausea
      • ocular pain
      • paresthesias
      • pharyngitis
      • rash
      • restlessness
      • sinusitis
      • tremor
      • urticaria
      • xerophthalmia
      • xerostomia

      Severe

      • erythema multiforme
      • hepatic failure
      • ocular hypertension
      • pancreatitis
      • pemphigus
      • Stevens-Johnson syndrome
      • suicidal ideation
      • toxic epidermal necrolysis

      Safety analysis of phentermine; topiramate extended-release included 2318 adult patients with a mean treatment duration of 298 days. Cardiovascular adverse reactions reported for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively) included: chest discomfort (0.4% vs. 2.1%, 0.2%, and 0.9%) and palpitations (0.8% vs. 0.8%, 2.4%, and 1.7%). In addition, phentermine alone has been associated with hypertension and ischemic events, such as chest pain (unspecified) in post-market reports. In clinical evaluation, a greater number of patients receiving phentermine;topiramate extended-release experienced heart rate (sinus tachycardia), with increases from baseline of more than 5, 10, 15, and 20 beats per minute compared to placebo. The clinical significance of a heart rate elevation with treatment is unclear. Periodic measurement of resting heart rate is advised for all patients, especially those at high risk for a cardiovascular event; in addition, monitoring during dose initiation and escalation is recommended for all patients. Patients should be instructed to inform health care providers of palpitations or feelings of a racing heartbeat while at rest. For patients who experience a sustained increase in resting heart rate during therapy, dose reduction or discontinuation should be considered. Of note, the effect of phentermine; topiramate extended-release on cardiovascular morbidity and mortality has not been established.[51256]

      Safety analysis of phentermine; topiramate extended-release included 2318 adult patients with a mean treatment duration of 298 days; commonly reported psychiatric adverse reactions occurring at a rate of >= 5% included insomnia. Adverse reactions reported for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively) included: anxiety (1.9% placebo vs. 2.9%, 1.8%, and 4.1%), depression (2.2% vs. 3.3%, 2.8%, and 4.3%), insomnia (4.7% vs. 5%, 5.8%, and 9.4%), and irritability (0.7% vs. 1.7%, 2.6%, and 3.7%). The majority of mood and sleep disorders first occurred within the initial 12 weeks of drug therapy; however, in some patients, events were reported later in the course of treatments. In the Qsymia clinical trials, the overall prevalence of mood and sleep adverse reactions was approximately twice as great in patients with a history of depression compared to patients without a history of depression; however, the proportion of patients on active treatment versus placebo who reported mood and sleep adverse reactions was similar in these two subgroups. Occurrence of depression-related events was more frequent in patients with a past history of depression across all treatment groups. However, the placebo-adjusted difference in incidence of these events remained constant between groups regardless of previous depression history.[51256] Anticonvulsants, including topiramate, are thought to carry an increased risk of suicidal ideation and behavior. During post-marketing experience with phentermine; topiramate, suicidal ideation and behavior have been reported. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior.[51256] When used alone for weight control, CNS reactions reported with phentermine have included overstimulation, restlessness, insomnia, euphoria, dysphoria, and psychosis.[46595]

      Safety analysis of phentermine; topiramate extended-release included 2318 adult patients with a mean treatment duration of 298 days. Ophthalmic adverse reactions reported for patients receiving placebo compared to increasing doses (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively) included: blurred vision (3.5% vs. 6.3%, 4%, and 5.4%), ocular pain (1.4% vs. 2.1%, 2.2%, and 2.2%), and xerophthalmia (0.8% vs. 0.8%, 1.4%, and 2.5%). Blurred vision was listed among adverse events leading to treatment discontinuation. In addition, topiramate alone has been associated with maculopathy during post marketing surveillance. Further, topiramate alone has been associated with the onset of acute myopia associated with secondary angle closure glaucoma. Symptoms include acute onset of decreased visual acuity and/or ocular pain. Ophthalmologic findings can include myopia, anterior chamber shallowing, ocular hyperemia (redness), and ocular hypertension. Mydriasis may or may not be present. This syndrome may be associated with supraciliary effusion resulting in anterior displacement of the lens and iris, with secondary angle closure glaucoma. Patients with preexisting ocular disease should initiate treatment with extreme caution and monitor for symptoms of increased intraocular pressure. Symptoms typically occur within 1 month of initiating topiramate treatment, but may occur at any time during therapy. The primary treatment to reverse symptoms is immediate discontinuation.[51256]

      Safety analysis of phentermine; topiramate extended-release included 2318 adult patients with a mean treatment duration of 298 days. Musculoskeletal adverse reactions reported for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively) included: back pain (5.1% vs. 5.4%, 5.6%, and 6.6%), muscle cramps (2.2% vs. 2.9%, 2.8%, and 2.9%), musculoskeletal pain (1.2% vs. 0.8%, 3%, and 1.6%), neck pain (1.3% vs. 1.3%, 2.2%, and 1.2%), pain in extremity (2.8% vs. 2.1%, 3%, and 3%).[51256]

      Safety analysis of phentermine; topiramate extended-release included 2318 adult patients with a mean treatment duration of 298 days. Dermatological adverse reactions reported for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively) included: rash (unspecified) (2.2% vs. 1.7%, 2%, and 2.6%) and alopecia (0.7% vs. 2.1%, 2.6%, and 3.7%). Postmarketing, phentermine alone has been associated with urticaria; topiramate alone has been associated with bullous rash (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis) and pemphigus.[51256]

      Phentermine; topiramate extended-release has been associated with metabolic acidosis due to the carbonic anhydrase inhibitor activity of topiramate. In clinical studies, the incidence of persistent treatment-emergent decreases in serum bicarbonate below the normal range (< 21 mEq/L at 2 consecutive visits or at the final visit) for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg) was 2.1% vs. 8.8%, 6.4%, and 12.8%, respectively; the incidence of persistent, markedly low serum bicarbonate values (< 17 mEq/L on 2 consecutive visits or at the final visit) was 0.1% vs. 1.3%, 0.2%, and 0.7%, respectively. Generally, decreases in serum bicarbonate levels were mild (average 1—3 mEq/L) and occurred early in treatment (4-week visit), however severe decreases and decreases later in treatment occurred. A correction of bicarbonate by week 56 was observed in most subjects. It is therefore prudent to measure baseline and periodic serum bicarbonate, along with other serum chemistries during therapy. If persistent metabolic acidosis develops, reduce the dose or taper to discontinue the dose.[51256]

      Safety analysis of phentermine; topiramate extended-release included 2318 adult patients with a mean treatment duration of 298 days. Commonly reported gastrointestinal adverse reactions occurring at a rate of >= 5% included dysgeusia, constipation, and xerostomia. Reports of dysgeusia were characterized as a metallic taste with the majority of events occurring in the first 12 weeks of treatment; however, in some patients, events were reported later. Only phentermine; topiramate-treated patients discontinued treatment due to dysgeusia (0.6%). Adverse reactions reported for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively) included: constipation (6.1% vs. 7.9%, 15.1%, and 16.1%), diarrhea (4.9% vs. 5%, 6.4%, and 5.6%), dysgeusia (1.1% vs. 1.3%, 7.4%, and 9.4%), dyspepsia (1.7% vs. 2.1%, 2.2%, and 2.8%), gastroenteritis (2.2% vs. 0.8%, 2.2%, and 2.5%), gastroesophageal reflux (1.3%, vs. 0.8%, 3.2%, and 2.6%), nausea (4.4% vs. 5.8%, 3.6%, and 7.2%), oral paresthesias (0.3% vs. 0.4%, 0.6%, and 2.2%), and xerostomia (2.8% vs. 6.7%, 13.5%, and 19.1%). Postmarketing, topiramate alone has been associated with pancreatitis, hepatic failure (including fatalities), and hepatitis.[51256]

      Safety analysis of phentermine; topiramate extended-release included 2318 adult patients with a mean treatment duration of 298 days. Commonly reported nervous system adverse reactions occurring at a rate of >= 5% included paraesthesia and dizziness. Reports of paresthesia were characterized as tingling in hands, feet, or face with the majority events occurring in the first 12 weeks of treatment; however, in some patients, events were reported later. Only phentermine; topiramate-treated patients discontinued treatment due to paresthesias (1%). Headache and dizziness were also listed among events leading to discontinuation. Adverse reactions reported for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively) included: disturbance in attention (0.6% vs. 0.4%, 2%, and 3.5%), dizziness (3.4% vs. 2.9%, 7.2%, and 8.6%), headache (9.3% vs. 10.4%, 7%, and 10.6%), hypoesthesia (1.2% vs. 0.8%, 3.6%, and 3.7%), impaired cognition (1.5% vs. 2.1%, 5%, and 7.6%), and paraesthesia (1.9% vs. 4.2%, 13.7%, and 19.9%). Impaired cognition was comprised primarily of reports of problems with attention/concentration, memory impairment, and language (word finding). These events typically began within the first 4 weeks of treatment, had a median duration of approximately 28 days or less, and were reversible upon discontinuation of treatment; however, individual patients did experience events later in treatment, and events of longer duration. Postmarketing, phentermine alone has been associated with tremor.[51256]

      Safety analysis of phentermine; topiramate extended-release included 2318 adult patients with a mean treatment duration of 298 days. Respiratory related adverse reactions reported for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively) included: bronchitis (4.2% vs. 6.7%, 4.4%, and 5.4%), cough (3.5% vs. 3.3%, 3.8%, and 4.8%), influenza (4.4% vs. 7.5%, 4.6%, and 4.4%), nasal congestion (1.4% vs. 1.7%, 1.2%, and 2%), naso-pharyngitis (8% vs. 12.5%, 10.6%, and 9.4%), pharyngolaryngeal pain (2% vs. 2.5%, 1.2%, and 2.3%), sinus congestion (2% vs. 2.5%, 2.6%, and 2%), sinusitis (6.3% vs. 7.5%, 6.8%, and 7.8%), and upper respiratory tract infection (12.8% vs. 15.8%, 12.2%, and 13.5%).[51256]

      Safety analysis of phentermine; topiramate extended-release included 2318 adult patients with a mean treatment duration of 298 days. Genitourinary adverse reactions reported for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively) included: dysmenorrhea (0.2% vs. 2.1%, 0.4%, and 0.8%), nephrolithiasis (0.3% vs. 0.4%, 0.2%, and 1.2%) and urinary tract infection (3.6% vs. 3.3%, 5.2%, and 5.2%). Postmarketing, phentermine alone has been associated with impotence (erectile dysfunction), and changes in libido (libido increase and libido decrease).[51256]

      Safety analysis of phentermine; topiramate extended-release included 2318 adult patients with a mean treatment duration of 298 days. General adverse reactions reported for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg, respectively) included: decreased appetite (0.6% vs. 2.1%, 1.8%, and 1.5%), fatigue (4.3% vs. 5%, 4.4%, and 5.9%), procedural pain (1.7% vs. 2.1%, 2.4%, and 1.9%), and thirst (0.7% vs. 2.1%, 1.8%, and 2%). Postmarketing, topiramate alone has been associated with hyperammonemia and hypothermia. In addition, phentermine; topiramate can cause an increase in serum creatinine. Peak increases in serum creatinine were observed after 4 to 8 weeks of treatment. On average, serum creatinine gradually declined but remained elevated over baseline creatinine values. Elevations in serum creatinine often signify a decrease in renal function, but the cause for treatment-associated changes in serum creatinine has not been definitively established. Therefore, measurement of serum creatinine prior to starting therapy and during treatment is recommended. If persistent elevations in creatinine occur, reduce the dose or discontinue.[51256]

      Phentermine; topiramate extended-release has been associated with hypokalemia. In clinical studies, the incidence of persistent low serum potassium values (< 3.5 mEq/L at two consecutive visits or at the final visit) for patients receiving placebo compared to increasing doses of phentermine; topiramate (3.75 mg/23 mg, 7.5 mg/46 mg, and 15 mg/92 mg) was 1.1% vs. 0.4%, 3.6%, and 4.9%, respectively; the incidence of markedly low serum potassium (< 3 mEq/L, and a reduction from pre-treatment of > 0.5 mEq/L) at any time during the trial was 0% vs. 0%, 0.2%, and 0.7%, respectively; persistent markedly low serum potassium (< 3 mEq/L, and a reduction from pre-treatment of > 0.5 mEq/L at two consecutive visits or at the final visit) occurred in 0% vs. 0%, 0.2%, and 0.1%. Of the subjects who experienced persistent low serum potassium, 88% were receiving treatment with a non-potassium-sparing diuretic.[51256]

      Phentermine; topiramate extended-release (Qsymia) has not been systematically studied for its potential to produce dependence. Phentermine is related chemically and pharmacologically to the amphetamines, and these stimulant drugs have been extensively abused and the possibility of abuse of phentermine should be kept in mind when evaluating the desirability of including this drug product as part of a weight reduction program. Abuse of amphetamines and related drugs (e.g., phentermine) may be associated with intense psychological dependence and severe social dysfunction.[46595] [51256] There are reports of patients who have increased the dosage of these drugs to many times than recommended. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use. Phentermine; topiramate extended-release has not been systematically studied for physical dependence potential.[51256] Physical dependence (physiological dependence) manifests by drug-class-specific withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Limited data are available for the individual components. For topiramate, abrupt discontinuation has been associated with seizures in patients without a history of seizures or epilepsy. For phentermine, abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on a sleep electroencephalogram. Thus, in situations where rapid withdrawal is required, appropriate medical monitoring is recommended.[51256] Evidence-based data from the literature are relatively limited, and some experts suggest that long-term phentermine pharmacotherapy for obesity does not induce abuse or psychological dependence (addiction), drug craving, and that abrupt treatment cessation within the normal prescription dose range does not induce amphetamine-like withdrawal.[57587] More data are needed to confirm the dependence potential of phentermine-containing obesity products.

      Revision Date: 12/02/2015, 02:03:50 PM

      References

      46595 - Phentermine hydrochloride package insert. Newtown, PA: KVK-Tech Inc; 2018 Dec.51256 - Qsymia (phentermine and topiramate extended-release) package insert. Mountain View, CA: Vivus, Inc.; 2020 Sept.57587 - Hendricks EJ, Srisurapanont M, Schmidt SL, et al. Addiction potential of phentermine prescribed during long-term treatment of obesity. Int J Obes (Lond). 2014;38:292-298.

      Contraindications/Precautions

      Absolute contraindications are italicized.

      • glaucoma
      • hyperthyroidism
      • MAOI therapy
      • pregnancy
      • abrupt discontinuation
      • alcoholism
      • ambient temperature increase
      • anorexia nervosa
      • anticholinergic medications
      • anxiety
      • bariatric surgery
      • behavioral changes
      • breast-feeding
      • bulimia nervosa
      • cardiac arrhythmias
      • cardiac disease
      • children
      • chronic obstructive pulmonary disease (COPD)
      • coadministration with other CNS depressants
      • contraception requirements
      • coronary artery disease
      • depression
      • diabetes mellitus
      • dialysis
      • diarrhea
      • driving or operating machinery
      • emphysema
      • ethanol ingestion
      • geriatric
      • heart failure
      • hepatic disease
      • hyperthermia
      • hypokalemia
      • increased intraocular pressure
      • infants
      • insomnia
      • labor
      • metabolic acidosis
      • myocardial infarction
      • nephrolithiasis
      • obstetric delivery
      • pregnancy testing
      • renal disease
      • renal failure
      • renal impairment
      • reproductive risk
      • schizophrenia
      • seizures
      • status asthmaticus
      • status epilepticus
      • strenuous exercise
      • stroke
      • substance abuse
      • suicidal ideation
      • surgery
      • thyroid disease

      Phentermine; Topiramate is contraindicated in any person with a known hypersensitivity or idiosyncrasy to sympathomimetic amines.[51256]

      Because of the risk of hypertensive crisis due to the interaction between monoamine oxidase inhibitors (MAOIs) and sympathomimetic amines such as phentermine, the use of phentermine; topiramate is contraindicated during or within 14 days of MAOI therapy.[51256]

      Phentermine; topiramate products are federally controlled substances because they contain phentermine and can be abused or lead to drug dependence. Patients should be advised to keep this product in a safe place, to protect it from theft and to never give the drug product to anyone else, because it may cause death or harm them. Selling or giving away this medicine is against the law. It is advisable to use phentermine-containing agents with caution in patients with a known history of substance abuse. Phentermine is related chemically and pharmacologically to amphetamines. The possibility of abuse of phentermine should be kept in mind when evaluating the desirability of including a drug as part of a weight reduction program. However, the abuse and dependence potential of phentermine; topiramate has not been systematically evaluated. As with most controlled substances, the least amount reasonable should be prescribed or dispensed at one time to limit the potential for overuse or drug diversion.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, other weight loss medications should be considered first in patients with a substance abuse disorder. There are insufficient data on the use of phentermine; topiramate in patients with obesity and alcoholism; however, topiramate might exert therapeutic benefits in patients with alcohol use disorder.[62881]

      Phentermine; topiramate can cause an increase in resting heart rate. In clinical evaluation, a higher number of patients receiving phentermine; topiramate experienced heart rate increases from baseline of more than 5, 10, 15, and 20 beats per minute compared to placebo. The clinical significance of a heart rate elevation with treatment is unclear, but may be of concern primarily for those with cardiac disease or cerebrovascular disease (e.g., patients with a history of sinus tachycardia, acute myocardial infarction or stroke in the previous 6 months, life-threatening cardiac arrhythmias, or congestive heart failure). Periodic measurement of resting heart rate is advised for all patients, especially those at high risk for a cardiovascular event; in addition, monitoring during treatment initiation and dose escalation is recommended for all patients. Clinicians should instruct their patients to inform health care providers of palpitations or feelings of a racing heartbeat while at rest. For patients who experience a sustained increase in resting heart rate during therapy, dose reduction or discontinuation should be considered. Of note, the effect of phentermine; topiramate on cardiovascular morbidity and mortality has not been established.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, phentermine; topiramate is a preferred weight loss medication in obese patients with existing hypertension, with careful monitoring of heart rate. Phentermine; topiramate is not a preferred weight loss medication in patients with an established atherosclerotic coronary artery disease or a history or risk of cardiac arrhythmias, but is reasonable to use with caution if weight loss goals are met, with careful monitoring of blood pressure and heart rate. Heart rhythm should also be monitored in those with a history or risk of arrhythmias. The AACE/ACE Obesity Guidelines state that data are insufficient regarding the benefits of the use of phentermine; topiramate in obese patients with heart failure and the use of this product in this population should be avoided.[62881]

      Phentermine; topiramate is contraindicated in patients with glaucoma. A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in patients treated with topiramate. Symptoms include acute onset of decreased visual acuity and/or ocular pain. Ophthalmologic findings can include myopia, anterior chamber shallowing, ocular hyperemia (redness), and increased intraocular pressure. Mydriasis may or may not be present. This syndrome may be associated with supraciliary effusion resulting in anterior displacement of the lens and iris, with secondary angle closure glaucoma. Symptoms typically occur within 1 month of initiating treatment with topiramate but may occur at any time during therapy. The primary treatment to reverse symptoms is immediate discontinuation of phentermine; topiramate. Elevated intraocular pressure of any etiology, if left untreated, can lead to serious adverse events including permanent loss of vision.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, other weight loss medications (i.e., orlistat, lorcaserin, and liraglutide) are preferred treatment options for patients with glaucoma; the use of phentermine; topiramate is contraindicated.[62881]

      Phentermine; topiramate is contraindicated in patients with hyperthyroidism since sympathomimetics like phentermine can exacerbate these conditions. This product should also be used with caution in patients with thyroid disease.[51256]

      Phentermine; topiramate can cause mood disorders, including depression, and anxiety, as well as insomnia. Patients with a history of depression may be at increased risk of recurrent depression or other mood disorders while taking Qsymia. The majority of these mood and sleep disorders resolved spontaneously or resolved upon discontinuation of dosing. For clinically significant or persistent symptoms consider dose reduction or withdrawal of this obesity treatment. If patients have symptoms of suicidal ideation or behavior, discontinue phentermine; topiramate.[51256] Avoid phentermine; topiramate use in patients with a history of suicidal attempts or active suicidal ideation. Antiepileptic drugs (AEDs), including topiramate, a component of Qsymia, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Monitor patients for the emergence or worsening of depression, suicidal thoughts or behavior, and any unusual changes in mood or behavior during treatment. Discontinue phentermine; topiramate in patients who experience suicidal thoughts or behavioral changes.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, phentermine; topiramate may be considered in obese patients with depression, using low initial and maintenance doses; avoid maximum dosing. The maximum daily dose should also be avoided if possible in patients with a comorbid anxiety disorder. All patients undergoing weight loss therapy should be monitored for mood disorders, depression, and suicidal ideation. Evidence assessing safety and efficacy of weight loss medications in patients with a psychotic disorder (e.g., schizophrenia) is insufficient, and the AACE/ACE Obesity Guidelines recommend avoidance of phentermine; topiramate in these patients. The AACE/ACE Obesity Guidelines recommend that patients receiving an antipsychotic be treated with structured lifestyle modifications to promote weight loss and weight gain prevention; metformin may be beneficial for modest weight loss and metabolic improvements in patients receiving an antipsychotic.[62881]

      Phentermine; topiramate can cause cognitive dysfunction (e.g., impairment of concentration/attention, difficulty with memory, and speech or language problems, particularly word-finding difficulties). Rapid titration or high initial doses may be associated with higher rates of cognitive events such as attention, memory, and language/word-finding difficulties. Since this treatment has the potential to impair cognitive function, patients should be cautioned about driving or operating machinery or performing other tasks that require mental alertness until they are aware of how therapy will affect their mental and motor performance. If cognitive impairment persists, consider dose reduction; consider a withdrawal of therapy for symptoms that are moderate to severe, bothersome, or those which fail to resolve with dose reduction.[51256] Alcohol may aggravate these effects, so advise patients to avoid ethanol ingestion while taking phentermine; topiramate. Coadministration with other CNS depressants may potentiate CNS depression or other centrally mediated effects of these agents, such as dizziness, cognitive adverse reactions, drowsiness, light-headedness, impaired coordination, and somnolence.[51256]

      Use phentermine; topiramate with caution in any patients with renal disease. Phentermine; topiramate can cause an increase in serum creatinine that reflects a decrease in renal function as noted by a decrease in glomerular filtration rate (GFR). On average, the serum creatinine gradually declines but remains elevated over baseline values. Following discontinuation of short-term treatment with phentermine; topiramate, the changes in serum creatinine and GFR appear reversible although the effect of chronic treatment on renal function or renal disease is not known. Therefore, assessment of serum creatinine before treatment initiation is recommended. If persistent elevations in serum creatinine occur during treatment with phentermine; topiramate, reduce the dose or discontinue the drug. Both phentermine and topiramate are cleared by renal excretion and exposure to phentermine; topiramate is increased in patients with moderate (CrCl 30 to less than 50 mL/minute) and severe (CrCl less than 30 mL/minute) renal impairment; therefore, a lower maximum daily dose is recommended in these populations. The use of this product has not been studied in patients with renal failure on dialysis; avoid use in this patient population.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, phentermine; topiramate can be used with appropriate caution in obese patients with mild renal impairment (i.e., CrCl 50 to 79 mL/minute). A dose of 7.5 mg/46 mg per day should not be exceeded in patients with moderate renal impairment (i.e., CrCl 30 to 49 mL/minute). Accumulation of phentermine; topiramate occurs in severe renal impairment (i.e., CrCl less than 30 mL/min) and use of the drug should be avoided in this population. Phentermine; topiramate should not be used in patients with end-stage renal failure.[62881]

      Phentermine; topiramate should be used with caution in patients with a history of kidney stones (nephrolithiasis). Topiramate is a carbonic anhydrase inhibitor and promotes kidney stone formation by reducing urinary citrate excretion and by increasing urinary pH. During clinical trials of topiramate for epilepsy, 1.3% to 1.5% of topiramate-treated patients developed kidney stones; this incidence is about 2 to 4 times that expected in a similar, untreated population and was higher in men.[31428] The concomitant use of topiramate with other carbonic anhydrase inhibitors or in patients on a ketogenic diet may create a physiological environment that increases the risk of kidney stone formation, and should, therefore, be avoided. Patients who are receiving phentermine; topiramate, especially those who have a history of kidney stones, should be instructed to maintain adequate fluid intake to reduce the formation of nephrolithiasis.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, phentermine; topiramate should be avoided in patients with recent nephrolithiasis as calcium phosphate stone formation is possible. Caution should be exercised when using phentermine; topiramate in patients with a history of nephrolithiasis.[62881]

      Use phentermine; topiramate with caution in patients with hepatic disease. Exposure to phentermine was higher in patients with mild or moderate (Child-Pugh Class A and B) hepatic impairment. A 7.5 mg/46 mg daily dose should not be exceeded in patients with moderate hepatic impairment. Phentermine; topiramate has not been studied in patients with severe hepatic disease (Child-Pugh Class C); avoid use in this patient population.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, all weight loss medications should be used cautiously in patients with hepatic impairment and should be avoided in severe liver impairment (i.e., Child-Pugh score greater than 9). In patients with moderate hepatic impairment, the AACE/ACE guidelines recommend that the dose of phentermine; topiramate not exceed 7.5 mg/46 mg per day. Close monitoring for cholelithiasis is recommended in any obese patients undergoing weight loss therapy, regardless of modality, due to a proven association between these conditions.[62881]

      Phentermine; topiramate has been associated with metabolic acidosis. Topiramate is a carbonic anhydrase inhibitor that can promote metabolic acidosis and also hypokalemia. Conditions that may predispose patients to acidosis [i.e., diarrhea, ketogenic diet, severe pulmonary disease (chronic obstructive pulmonary disease (COPD), emphysema, status asthmaticus), surgery, status epilepticus or administration with other bicarbonate-lowering drugs] may have an additive risk for this complication. Measurement of baseline and periodic serum bicarbonate, along with other serum chemistries, is recommended during therapy. In clinical trials, the peak reduction in serum bicarbonate occurred by week 4, and in most subjects there was a correction of bicarbonate by week 56, without any change to study drug. However, if persistent metabolic acidosis develops, reduce the dose or taper to discontinue the dose. Hypokalemia risk may be aggravated by the use of diuretic therapy.[51256]

      Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and insulin secretagogues (e.g., sulfonylureas). Phentermine; topiramate has not been studied in combination with insulin. Blood glucose monitoring is warranted in patients with type 2 diabetes before starting and during phentermine; topiramate treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust the anti-diabetic drug regimen accordingly.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications such as phentermine; topiramate should be considered as an adjunct to lifestyle therapy in all patients with type 2 diabetes as needed for weight loss sufficient to improve glycemic control, lipids, and blood pressure. During controlled trial evaluation of phentermine; topiramate as an adjunct to lifestyle therapy versus lifestyle therapy alone for diabetes prevention, a more significant weight loss and more profound reductions in incident diabetes occurred with medication plus lifestyle therapy than lifestyle therapy alone.[62881]

      Topiramate has been associated with oligohidrosis and hyperthermia, infrequently resulting in hospitalization. Decreased sweating and an elevation in body temperature above normal characterized these cases. Some of the cases have been reported with topiramate after exposure to elevated environmental temperatures. Therefore, patients taking phentermine; topiramate should be instructed to limit exposure to ambient temperature increase (i.e., elevated environmental temperature) or other temperature extremes that might aggravate temperature regulation. Proper hydration to help prevent oligohidrosis and hyperthermia is suggested before and during strenuous exercise or exposure to warm temperatures. Use caution when prescribing with other drugs that predispose patients to heat-related disorders, such as anticholinergic medications and other carbonic anhydrase inhibitors.[51256]

      Similar to other weight loss products,  phentermine; topiramate use is not likely to be appropriate in patients with eating disorders such as anorexia nervosa or bulimia nervosa. The AACE/ACE) Obesity Clinical Practice Guidelines state that there are insufficient data on the use of phentermine; topiramate in overweight or obese patients with binge eating disorder (BED); however, there is a possible benefit in BED based on studies with topiramate, and approved medications containing topiramate may be considered along with non-medication interventions (i.e., behavioral/lifestyle program, psychotherapy). The AACE/ACE Obesity Guidelines state that there are limited data available on the benefits of the use of phentermine; topiramate in patients following bariatric surgery.[62881]

      Abrupt discontinuation of phentermine; topiramate, particularly at a dose of 15 mg/92 mg once daily, should be avoided since the withdrawal of topiramate has been associated with seizures, even in individuals without a history of seizures or epilepsy. If immediate discontinuation is medically necessary in any patient, careful monitoring and symptom management is warranted. Patients discontinuing higher-dose therapy due to a lack of efficacy should follow recommended tapering (e.g., every other day dosing for 1 week) to avoid precipitating a seizure.[51256]

      Clinical studies of phentermine; topiramate did not include sufficient numbers of elderly subjects to determine whether they respond differently from younger subjects. In those studied, no age-related differences were observed. Nevertheless, use caution when selecting a dose for a geriatric patient, given their propensity to have concurrent disease states that may influence drug tolerability, usually starting at the low end of the dosing range.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, there are limited data on the use of phentermine; topiramate for weight reduction in the elderly and extra caution is advisable in this population. Elderly patients selected for weight loss therapy should have structured lifestyle interventions including reduced calorie meal plans and exercise, clear health-related goals including blood pressure reduction, diabetes prevention in high risk patients with pre-diabetes, and improvements in osteoarthritis, mobility, and physical functioning. Overweight or obese elderly patients being considered for a weight loss medication should be evaluated for osteopenia and sarcopenia.[62881]

      Phentermine; topiramate is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. Further, data from pregnancy registries and epidemiology studies indicate increased reproductive risk with the use of topiramate; a risk in oral clefts (cleft lip with or without cleft palate) with first-trimester exposure to topiramate is noted. Females of reproductive potential should have negative pregnancy testing before starting therapy and then monthly after that. Females of reproductive potential should be advised of the contraception requirements to use adequate contraception during therapy. If phentermine; topiramate is inadvertently used during pregnancy, or if a patient becomes pregnant while on therapy, discontinue treatment immediately and inform the patient of the potential hazard to the fetus. The Qsymia Pregnancy Surveillance Program is a maternal-fetal outcomes program which monitors pregnancies that occur during therapy; healthcare professional and patients are encouraged to report pregnancies to the program by calling 1-888-998-4887. The effect of phentermine; topiramate on labor and obstetric delivery in humans is unknown. However, metabolic acidosis has been reported in patients treated with phentermine; topiramate and metabolic acidosis in pregnancy can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the ability of the fetus to tolerate labor.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, phentermine; topiramate must not be used during pregnancy. Women of childbearing potential should use contraception and discontinue the drug if pregnancy occurs. Monthly pregnancy testing is necessary during treatment to identify early pregnancy due to the risk of cleft lip/palate.[62881]

      Both topiramate and amphetamines (phentermine has pharmacologic activity and a chemical structure similar to amphetamines) are excreted in human milk. A decision should be made whether to discontinue breast-feeding or to discontinue phentermine; topiramate, taking into account the importance of therapy to the mother.[51256] During lactation, first line weight loss strategies include a healthy diet and exercise, if appropriate. Sufficient calories and nutrition are important for proper lactation. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, the use of phentermine; topiramate in breast-feeding women is not recommended.[62881]

      The manufacturer does not recommend use in children or adolescents. The safety and effectiveness of phentermine; topiramate have not been established in pediatric patients below the age of 18 years. Serious adverse reactions seen in pediatric patients using topiramate include acute angle glaucoma, oligohidrosis and hyperthermia, metabolic acidosis, cognitive and neuropsychiatric reactions, hyperammonemia and encephalopathy, and nephrolithiasis. There is no known indication for the use of obesity drugs in infants.[51256] Clinical guidelines have suggested that phentermine; topiramate use may be acceptable for older adolescents (16 years and older), who meet the same indications as adults for use based on BMI and/or obesity-related comorbidities. In such cases, management by healthcare providers with expertise in weight management is recommended. For younger adolescents or older children, use of obesity medications off-label should be performed in the context of a clinical trial.[58571] [62880] [62881] [63035]

      Revision Date: 01/10/2019, 09:02:45 PM

      References

      31428 - Garris SS, Oles KS. Impact of topiramate on serum bicarbonate concentrations in adults. Ann Pharmacother 2005;39:424-6.51256 - Qsymia (phentermine and topiramate extended-release) package insert. Mountain View, CA: Vivus, Inc.; 2020 Sept.58571 - Styne DM, Arslanian SA, Connor EL, et al. Pediatric Obesity-Assessment, Treatment, and Prevention: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2017;102:709-757.62880 - Apovian CM, Aronne LJ, Bessesen DH, et al. Endocrine Society. Pharmacological management of obesity: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100:342-362. Epub 2015 Jan 15. Erratum in: J Clin Endocrinol Metab. 2015;100:2135-2136.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 Suppl 3:1-203.63035 - Greydanus DE, Agana M, Kamboj MK, et al. Pediatric obesity: Current concepts. Dis Mon. 2018;64:98-156. Foreword on p. 97 by Leikin JB.

      Mechanism of Action

      Phentermine; topiramate are two medications, that when combined, are used for chronic weight management. The exact mechanism of action responsible for weight reduction with this combination is not known.[51256]

       

      • Phentermine: Phentermine is an analog of methamphetamine. Similar to the amphetamines, phentermine increases the release of norepinephrine and dopamine from nerve terminals and inhibits their reuptake. Thus, phentermine is classified as an indirect sympathomimetic. Other effects include a weak ability to dose-dependently raise serotonin levels, although the effect on serotonin occurs is less potent than that of methamphetamine itself.[57267] The effect of phentermine on chronic weight management is likely mediated by release of catecholamines in the hypothalamus and limbic region, resulting in reduced appetite and decreased food consumption, but other metabolic effects may also be involved. The exact mechanism of action is not known.[51256] Phentermine is an analog of methamphetamine. Similar to the amphetamines, phentermine increases the release of norepinephrine and dopamine from nerve terminals and inhibits their reuptake. Other clinical effects include CNS stimulation and potential elevation of blood pressure. Tolerance to the anorexiant effects of phentermine usually develops within a few weeks of starting therapy. When tolerance develops to the anorexiant effects, it is generally recommended that phentermine be discontinued rather than the dose increased.
      • Topiramate: The mechanism of action of topiramate on chronic weight management is not known. Its effect on obesity may be due to its effects on both appetite suppression and satiety enhancement, induced by a combination of pharmacologic effects including augmenting the activity of the neurotransmitter gamma-aminobutyrate, modulation of voltage-gated ion channels, inhibition of AMPA/kainite excitatory glutamate receptors, or inhibition of carbonic anhydrase.[51256]
      Revision Date: 06/30/2014, 12:31:44 PM

      References

      51256 - Qsymia (phentermine and topiramate extended-release) package insert. Mountain View, CA: Vivus, Inc.; 2020 Sept.57267 - Zolkowska D, Rothman RB, Baumann MH. Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease. J Pharmacol Exp Ther. 2006;318:604-610.

      Pharmacokinetics

      Phentermine; topiramate extended-release is administered orally.[51256]

       

      • Phentermine: Phentermine is 17.5% plasma protein bound. Phentermine has two metabolic pathways, p-hydroxylation on the aromatic ring and N-oxidation on the alipthatic side chain. Although not extensively metabolized, CYP3A4 accounts for the primary mode of metabolism. Approximately 70—80% of the parent drug remains unchanged in the urine. Population pharmacokinetic analysis estimates oral clearance (CL/F) at 8.79 L/h. The mean phentermine terminal half-life is about 20 hours.[51256]
      • Topiramate: Topiramate is 15—41% plasma protein bound over the blood concentration range of 0.5 to 250 mcg/ml; as blood concentration increases, the bound fraction of topiramate decreases. Topiramate is not metabolized to a great extent. Six metabolites have been identified and are formed via hydroxylation, hydrolysis, and glucuronidation. None of these metabolites constitutes more than 5% of an administered dose. About 70% of an administered dose is eliminated as unchanged drug in the urine. Population pharmacokinetic analysis estimates oral clearance CL/F is 1.17 L/h. The mean topiramate terminal half-life is approximately 65 hours.[51256]

      Route-Specific Pharmacokinetics

      Oral Route

      • Phentermine: Following oral administration of a single phentermine; topiramate extended-release (15 mg/92 mg) dose, the Cmax, Tmax, and AUC for phentermine are 49.1 ng/ml, 6 hr, and 1990—2000 ng•h/ml, respectively. A high fat meal does not affect exposure. Phentermine exhibits approximately dose-proportional pharmacokinetics throughout the recommended dosing range. Upon dosing phentermine;topiramate to steady state, the mean phentermine accumulation ratios for AUC and Cmax are both approximately 2.5.[51256]
      • Topiramate: Following oral administration of a single phentermine; topiramate extended-release (15 mg/92 mg) dose, the Cmax, Tmax, and AUC for topiramate are 1020 ng/ml, 9 hr, and 61,600—68,000 ng•h/ml, respectively. A high fat meal does not affect exposure. Topiramate exhibits approximately dose-proportional pharmacokinetics throughout the recommended dosing range. Upon dosing to steady state, the mean topiramate accumulation ratios for AUC and Cmax are both approximately 4.[51256]

      Special Populations

      Hepatic Impairment

      In pharmacokinetic evaluation, phentermine; topiramate extended-release (15 mg/92 mg dose) was studied in patients with varying degrees of hepatic impairment. In patients with mild (Child Pugh Class A) and moderate (Child Pugh Class B) hepatic impairment, phentermine AUC was 37% and 60% higher compared to healthy subjects. Pharmacokinetics of topiramate was not affected in patients with mild and moderate hepatic impairment. Dose adjustments are recommended. The product has not been studied in patients with severe hepatic impairment (Child Pugh Class C).[51256]

      Renal Impairment

      In pharmacokinetic evaluation, phentermine; topiramate extended-release (15 mg/92 mg dose) was studied in patients with varying degrees of chronic renal impairment. Drug exposures (AUCs) increased with severity of renal impairment. Compared to healthy subjects, phentermine AUC was 91%, 45%, and 22% higher in patients with severe, moderate, and mild renal impairment, respectively; phentermine Cmax was 2% to 15% higher. Compared to healthy subjects, topiramate AUC was 126%, 85%, and 25% higher for patients with severe, moderate, and mild renal impairment, respectively; topiramate Cmax was 6% to 17% higher. Dose adjustments based on renal function are recommended. The product has not been studied in patients with end-stage renal disease on dialysis; use in this population is not recommended.[51256]

      Pediatrics

      No data are available for children or adolescents.[51256]

      Geriatric

      In clinical trials for phentermine; topiramate, a total of 254 (7%) of the patients were 65 years of age and older; specific pharmacokinetic data for the elderly have not been reported.[51256]

      Revision Date: 06/30/2014, 12:38:26 PM

      References

      51256 - Qsymia (phentermine and topiramate extended-release) package insert. Mountain View, CA: Vivus, Inc.; 2020 Sept.

      Pregnancy/Breast-feeding

      contraception requirements, labor, obstetric delivery, pregnancy, pregnancy testing, reproductive risk

      Phentermine; topiramate is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. Further, data from pregnancy registries and epidemiology studies indicate increased reproductive risk with the use of topiramate; a risk in oral clefts (cleft lip with or without cleft palate) with first-trimester exposure to topiramate is noted. Females of reproductive potential should have negative pregnancy testing before starting therapy and then monthly after that. Females of reproductive potential should be advised of the contraception requirements to use adequate contraception during therapy. If phentermine; topiramate is inadvertently used during pregnancy, or if a patient becomes pregnant while on therapy, discontinue treatment immediately and inform the patient of the potential hazard to the fetus. The Qsymia Pregnancy Surveillance Program is a maternal-fetal outcomes program which monitors pregnancies that occur during therapy; healthcare professional and patients are encouraged to report pregnancies to the program by calling 1-888-998-4887. The effect of phentermine; topiramate on labor and obstetric delivery in humans is unknown. However, metabolic acidosis has been reported in patients treated with phentermine; topiramate and metabolic acidosis in pregnancy can cause decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the ability of the fetus to tolerate labor.[51256] According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, phentermine; topiramate must not be used during pregnancy. Women of childbearing potential should use contraception and discontinue the drug if pregnancy occurs. Monthly pregnancy testing is necessary during treatment to identify early pregnancy due to the risk of cleft lip/palate.[62881]

      breast-feeding

      Both topiramate and amphetamines (phentermine has pharmacologic activity and a chemical structure similar to amphetamines) are excreted in human milk. A decision should be made whether to discontinue breast-feeding or to discontinue phentermine; topiramate, taking into account the importance of therapy to the mother.[51256] During lactation, first line weight loss strategies include a healthy diet and exercise, if appropriate. Sufficient calories and nutrition are important for proper lactation. According to the American Association of Clinical Endocrinologists and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, the use of phentermine; topiramate in breast-feeding women is not recommended.[62881]

      Revision Date: 01/10/2019, 08:41:00 PM

      References

      51256 - Qsymia (phentermine and topiramate extended-release) package insert. Mountain View, CA: Vivus, Inc.; 2020 Sept.62881 - Garvey WT, Mechanick JI, Brett EM, et al; Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22 Suppl 3:1-203.

      Interactions

      Level 1 (Severe)

      • Calcium, Magnesium, Potassium, Sodium Oxybates
      • Isocarboxazid
      • Monoamine oxidase inhibitors
      • Ozanimod
      • Phendimetrazine
      • Phenelzine
      • Selegiline
      • Sibutramine
      • Sodium Oxybate
      • Tranylcypromine

      Level 2 (Major)

      • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
      • Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
      • Acetaminophen; Dextromethorphan; Doxylamine
      • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
      • Acetaminophen; Dextromethorphan; Phenylephrine
      • Acetaminophen; Diphenhydramine
      • Acetaminophen; Guaifenesin; Phenylephrine
      • Alogliptin; Metformin
      • Ambrisentan
      • Amifampridine
      • Amphetamines
      • Anxiolytics; Sedatives; and Hypnotics
      • Atomoxetine
      • Belladonna Alkaloids; Ergotamine; Phenobarbital
      • Bosentan
      • Brompheniramine; Carbetapentane; Phenylephrine
      • Brompheniramine; Dextromethorphan; Phenylephrine
      • Bupropion
      • Bupropion; Naltrexone
      • Buspirone
      • Caffeine; Ergotamine
      • Canagliflozin; Metformin
      • Carbetapentane; Chlorpheniramine; Phenylephrine
      • Carbetapentane; Diphenhydramine; Phenylephrine
      • Carbetapentane; Guaifenesin; Phenylephrine
      • Carbetapentane; Phenylephrine
      • Carbetapentane; Phenylephrine; Pyrilamine
      • Carbinoxamine; Hydrocodone; Phenylephrine
      • Carbinoxamine; Phenylephrine
      • Carbonic anhydrase inhibitors
      • Cardiac glycosides
      • Cariprazine
      • Chlophedianol; Guaifenesin; Phenylephrine
      • Chlorpheniramine; Dextromethorphan; Phenylephrine
      • Chlorpheniramine; Dihydrocodeine; Phenylephrine
      • Chlorpheniramine; Hydrocodone; Phenylephrine
      • Chlorpheniramine; Phenylephrine
      • Chlorthalidone; Clonidine
      • Clonidine
      • Cocaine
      • Codeine; Phenylephrine; Promethazine
      • Dapagliflozin; Metformin
      • Desflurane
      • Dextromethorphan; Diphenhydramine; Phenylephrine
      • Dextromethorphan; Guaifenesin; Phenylephrine
      • Digitoxin
      • Digoxin
      • Dihydroergotamine
      • Diphenhydramine
      • Diphenhydramine; Hydrocodone; Phenylephrine
      • Diphenhydramine; Ibuprofen
      • Diphenhydramine; Naproxen
      • Diphenhydramine; Phenylephrine
      • Dopamine
      • Doxorubicin
      • Doxylamine
      • Doxylamine; Pyridoxine
      • Dronedarone
      • Droperidol
      • Droxidopa
      • Empagliflozin; Linagliptin
      • Empagliflozin; Linagliptin; Metformin
      • Empagliflozin; Metformin
      • Enflurane
      • Ephedrine
      • Epoprostenol
      • Ergoloid Mesylates
      • Ergonovine
      • Ergot alkaloids
      • Ergotamine
      • Ertugliflozin; Metformin
      • Esketamine
      • Ethanol
      • Ethiodized Oil
      • Flibanserin
      • Glipizide; Metformin
      • Glyburide; Metformin
      • Green Tea
      • Guaifenesin; Phenylephrine
      • Halogenated Anesthetics
      • Halothane
      • Hydrochlorothiazide, HCTZ; Methyldopa
      • Hydrocodone; Phenylephrine
      • Hydroxyzine
      • Iloprost
      • Iobenguane I 131
      • Iodixanol
      • Iohexol
      • Iopamidol
      • Iopromide
      • Ioversol
      • Isoflurane
      • Isosulfan Blue
      • Ivabradine
      • Linagliptin
      • Linagliptin; Metformin
      • Linezolid
      • Lorcaserin
      • Lumateperone
      • Macitentan
      • Mecamylamine
      • Metaproterenol
      • Metformin
      • Metformin; Pioglitazone
      • Metformin; Repaglinide
      • Metformin; Rosiglitazone
      • Metformin; Saxagliptin
      • Metformin; Sitagliptin
      • Methyldopa
      • Methylergonovine
      • Methysergide
      • Midodrine
      • Mirtazapine
      • Nisoldipine
      • Non-Ionic Contrast Media
      • Norepinephrine
      • Pergolide
      • Phenylephrine
      • Phenylephrine; Promethazine
      • Procarbazine
      • Ramelteon
      • Reserpine
      • Riociguat
      • Selexipag
      • Sevoflurane
      • Simeprevir
      • Sofosbuvir; Velpatasvir
      • Sofosbuvir; Velpatasvir; Voxilaprevir
      • St. John's Wort, Hypericum perforatum
      • Tolvaptan
      • Treprostinil
      • Ulipristal
      • Vasopressors
      • Vemurafenib
      • Yohimbine

      Level 3 (Moderate)

      • Abacavir; Dolutegravir; Lamivudine
      • Abciximab
      • Acarbose
      • Acetaminophen; Aspirin, ASA; Caffeine
      • Acetaminophen; Butalbital; Caffeine
      • Acetaminophen; Butalbital; Caffeine; Codeine
      • Acetaminophen; Caffeine
      • Acetaminophen; Caffeine; Dihydrocodeine
      • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
      • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
      • Acetaminophen; Hydrocodone
      • Acetaminophen; Oxycodone
      • Acetaminophen; Tramadol
      • Aclidinium; Formoterol
      • Albiglutide
      • Albuterol
      • Albuterol; Ipratropium
      • Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
      • Aliskiren; Hydrochlorothiazide, HCTZ
      • Alogliptin; Pioglitazone
      • Alpha-blockers
      • Alpha-glucosidase Inhibitors
      • Alprazolam
      • Amiloride; Hydrochlorothiazide, HCTZ
      • Aminosalicylate sodium, Aminosalicylic acid
      • Amitriptyline
      • Amitriptyline; Chlordiazepoxide
      • Amlodipine; Celecoxib
      • Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan
      • Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
      • Amoxapine
      • Amphetamine
      • Amphetamine; Dextroamphetamine
      • Anagrelide
      • Anticholinergics
      • Antithrombin III
      • Apixaban
      • Aprepitant, Fosaprepitant
      • Arformoterol
      • Argatroban
      • Aripiprazole
      • Aspirin, ASA
      • Aspirin, ASA; Butalbital; Caffeine
      • Aspirin, ASA; Butalbital; Caffeine; Codeine
      • Aspirin, ASA; Caffeine; Dihydrocodeine
      • Aspirin, ASA; Caffeine; Orphenadrine
      • Aspirin, ASA; Carisoprodol
      • Aspirin, ASA; Carisoprodol; Codeine
      • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
      • Aspirin, ASA; Dipyridamole
      • Aspirin, ASA; Omeprazole
      • Aspirin, ASA; Oxycodone
      • Aspirin, ASA; Pravastatin
      • Atazanavir
      • Atazanavir; Cobicistat
      • Atenolol; Chlorthalidone
      • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
      • Azilsartan; Chlorthalidone
      • Barbiturates
      • Benazepril; Hydrochlorothiazide, HCTZ
      • Bendroflumethiazide; Nadolol
      • Benzodiazepines
      • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
      • Benzphetamine
      • Bethanechol
      • Bismuth Subsalicylate
      • Bismuth Subsalicylate; Metronidazole; Tetracycline
      • Bisoprolol; Hydrochlorothiazide, HCTZ
      • Bivalirudin
      • Boceprevir
      • Bretylium
      • Brexpiprazole
      • Bromocriptine
      • Brompheniramine; Guaifenesin; Hydrocodone
      • Brompheniramine; Hydrocodone; Pseudoephedrine
      • Budesonide; Formoterol
      • Budesonide; Glycopyrrolate; Formoterol
      • Bumetanide
      • Bupivacaine; Lidocaine
      • Caffeine
      • Canagliflozin
      • Candesartan; Hydrochlorothiazide, HCTZ
      • Captopril; Hydrochlorothiazide, HCTZ
      • Carbamazepine
      • Carbinoxamine; Hydrocodone; Pseudoephedrine
      • Celecoxib
      • Chlordiazepoxide
      • Chlordiazepoxide; Clidinium
      • Chlorothiazide
      • Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
      • Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
      • Chlorpheniramine; Hydrocodone
      • Chlorpheniramine; Hydrocodone; Pseudoephedrine
      • Chlorpromazine
      • Chlorthalidone
      • Choline Salicylate; Magnesium Salicylate
      • Cilostazol
      • Citalopram
      • Clomipramine
      • Clonazepam
      • Clorazepate
      • Cobicistat
      • Cobimetinib
      • Codeine; Promethazine
      • Conjugated Estrogens; Medroxyprogesterone
      • Dabigatran
      • Dapagliflozin
      • Dapagliflozin; Saxagliptin
      • Darunavir
      • Darunavir; Cobicistat
      • Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
      • Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
      • Delavirdine
      • Desipramine
      • Desirudin
      • Desvenlafaxine
      • Dextroamphetamine
      • Dextromethorphan; Promethazine
      • Diazepam
      • Dichlorphenamide
      • Diclofenac
      • Diclofenac; Misoprostol
      • Dienogest; Estradiol valerate
      • Diflunisal
      • Dihydrocodeine; Guaifenesin; Pseudoephedrine
      • Diltiazem
      • Dipeptidyl Peptidase-4 Inhibitors
      • Dipyridamole
      • Dolutegravir
      • Dolutegravir; Lamivudine
      • Dolutegravir; Rilpivirine
      • Doxazosin
      • Doxepin
      • Dronabinol
      • Drospirenone
      • Drospirenone; Estradiol
      • Drospirenone; Ethinyl Estradiol
      • Drospirenone; Ethinyl Estradiol; Levomefolate
      • Dulaglutide
      • Duloxetine
      • Dyphylline
      • Dyphylline; Guaifenesin
      • Edoxaban
      • Elagolix; Estradiol; Norethindrone acetate
      • Elbasvir; Grazoprevir
      • Elvitegravir
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
      • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
      • Empagliflozin
      • Emtricitabine; Rilpivirine; Tenofovir alafenamide
      • Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate
      • Enalapril; Hydrochlorothiazide, HCTZ
      • Eprosartan; Hydrochlorothiazide, HCTZ
      • Eptifibatide
      • Ertugliflozin
      • Ertugliflozin; Sitagliptin
      • Esomeprazole; Naproxen
      • Estazolam
      • Estradiol Cypionate; Medroxyprogesterone
      • Estradiol; Levonorgestrel
      • Estradiol; Norethindrone
      • Estradiol; Norgestimate
      • Estradiol; Progesterone
      • Estrogens
      • Ethacrynic Acid
      • Ethinyl Estradiol; Desogestrel
      • Ethinyl Estradiol; Ethynodiol Diacetate
      • Ethinyl Estradiol; Etonogestrel
      • Ethinyl Estradiol; Levonorgestrel
      • Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate
      • Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
      • Ethinyl Estradiol; Norelgestromin
      • Ethinyl Estradiol; Norethindrone
      • Ethinyl Estradiol; Norethindrone Acetate
      • Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate
      • Ethinyl Estradiol; Norethindrone; Ferrous fumarate
      • Ethinyl Estradiol; Norgestimate
      • Ethinyl Estradiol; Norgestrel
      • Etodolac
      • Etonogestrel
      • Exenatide
      • Ezogabine
      • Famotidine; Ibuprofen
      • Felbamate
      • Fenoprofen
      • Fentanyl
      • Fluoxetine
      • Fluoxetine; Olanzapine
      • Fluphenazine
      • Flurazepam
      • Flurbiprofen
      • Fluticasone; Salmeterol
      • Fluticasone; Umeclidinium; Vilanterol
      • Fluticasone; Vilanterol
      • Fluvoxamine
      • Fondaparinux
      • food
      • Formoterol
      • Formoterol; Mometasone
      • Fosinopril; Hydrochlorothiazide, HCTZ
      • Furosemide
      • Gefitinib
      • Glimepiride; Pioglitazone
      • Glimepiride; Rosiglitazone
      • Glycopyrrolate; Formoterol
      • Guaifenesin; Hydrocodone
      • Guaifenesin; Hydrocodone; Pseudoephedrine
      • Guanabenz
      • Heparin
      • Homatropine; Hydrocodone
      • Hydantoins
      • Hydralazine; Hydrochlorothiazide, HCTZ
      • Hydrochlorothiazide, HCTZ
      • Hydrochlorothiazide, HCTZ; Irbesartan
      • Hydrochlorothiazide, HCTZ; Lisinopril
      • Hydrochlorothiazide, HCTZ; Losartan
      • Hydrochlorothiazide, HCTZ; Metoprolol
      • Hydrochlorothiazide, HCTZ; Moexipril
      • Hydrochlorothiazide, HCTZ; Olmesartan
      • Hydrochlorothiazide, HCTZ; Propranolol
      • Hydrochlorothiazide, HCTZ; Quinapril
      • Hydrochlorothiazide, HCTZ; Spironolactone
      • Hydrochlorothiazide, HCTZ; Telmisartan
      • Hydrochlorothiazide, HCTZ; Triamterene
      • Hydrochlorothiazide, HCTZ; Valsartan
      • Hydrocodone
      • Hydrocodone; Ibuprofen
      • Hydrocodone; Potassium Guaiacolsulfonate
      • Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
      • Hydrocodone; Pseudoephedrine
      • Hydroxychloroquine
      • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
      • Ibuprofen
      • Ibuprofen; Oxycodone
      • Ibuprofen; Pseudoephedrine
      • Imatinib
      • Imipramine
      • Incretin Mimetics
      • Indacaterol
      • Indacaterol; Glycopyrrolate
      • Indapamide
      • Indomethacin
      • Insulin Degludec; Liraglutide
      • Insulin Glargine; Lixisenatide
      • Insulins
      • Isavuconazonium
      • Ketoprofen
      • Ketorolac
      • Lacosamide
      • Lamotrigine
      • Lansoprazole; Naproxen
      • Lepirudin
      • Leuprolide; Norethindrone
      • Levalbuterol
      • Levetiracetam
      • Levomilnacipran
      • Levonorgestrel
      • Levothyroxine
      • Levothyroxine; Liothyronine (Porcine)
      • Levothyroxine; Liothyronine (Synthetic)
      • Lidocaine
      • Lidocaine; Prilocaine
      • Liothyronine
      • Liraglutide
      • Lisdexamfetamine
      • Lithium
      • Lixisenatide
      • Loop diuretics
      • Loperamide
      • Loperamide; Simethicone
      • Lopinavir; Ritonavir
      • Lorazepam
      • Low Molecular Weight Heparins
      • Lurasidone
      • Magnesium Salicylate
      • Maprotiline
      • Meclofenamate Sodium
      • Medroxyprogesterone
      • Mefenamic Acid
      • Mefloquine
      • Meglitinides
      • Meloxicam
      • Meperidine; Promethazine
      • Mesoridazine
      • Mestranol; Norethindrone
      • Methamphetamine
      • Methenamine
      • Methenamine; Sodium Acid Phosphate
      • Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine
      • Methyclothiazide
      • Metolazone
      • Midazolam
      • Miglitol
      • Milnacipran
      • Molindone
      • Nabilone
      • Nabumetone
      • Naproxen
      • Naproxen; Pseudoephedrine
      • Naproxen; Sumatriptan
      • Nitrates
      • Nonsteroidal antiinflammatory drugs
      • Norethindrone
      • Norgestrel
      • Nortriptyline
      • Ombitasvir; Paritaprevir; Ritonavir
      • Orlistat
      • Oxaprozin
      • Oxazepam
      • Oxycodone
      • Paroxetine
      • Pazopanib
      • Pemoline
      • Pentosan
      • Perampanel
      • Perphenazine
      • Perphenazine; Amitriptyline
      • Phenothiazines
      • Phenoxybenzamine
      • Phentolamine
      • Pioglitazone
      • Pirbuterol
      • Piroxicam
      • Pramlintide
      • Prasugrel
      • Prazosin
      • Pregabalin
      • Prochlorperazine
      • Progesterone
      • Progestins
      • Promethazine
      • Protriptyline
      • Quazepam
      • Rasagiline
      • Rilpivirine
      • Ritonavir
      • Rivaroxaban
      • Rofecoxib
      • Romidepsin
      • Rosiglitazone
      • Rufinamide
      • Safinamide
      • Salicylates
      • Salmeterol
      • Salsalate
      • Segesterone Acetate; Ethinyl Estradiol
      • Selective serotonin reuptake inhibitors
      • Semaglutide
      • Serotonin norepinephrine reuptake inhibitors
      • Sertraline
      • SGLT2 Inhibitors
      • Solifenacin
      • Solriamfetol
      • Sufentanil
      • Sulfonylureas
      • Sulindac
      • Tedizolid
      • Telithromycin
      • Temazepam
      • Terazosin
      • Terbinafine
      • Terbutaline
      • Theophylline, Aminophylline
      • Thiazide diuretics
      • Thiazolidinediones
      • Thiethylperazine
      • Thioridazine
      • Thrombin Inhibitors
      • Thyroid hormones
      • Tiagabine
      • Ticagrelor
      • Ticlopidine
      • Tirofiban
      • Tolmetin
      • Tolterodine
      • Torsemide
      • Tramadol
      • Tretinoin, ATRA
      • Triazolam
      • Tricyclic antidepressants
      • Trifluoperazine
      • Trimipramine
      • Trospium
      • Umeclidinium; Vilanterol
      • Valdecoxib
      • Valproic Acid, Divalproex Sodium
      • Vasodilators
      • Venlafaxine
      • Vilazodone
      • Vorapaxar
      • Vortioxetine
      • Warfarin
      • Zonisamide

      Level 4 (Minor)

      • Acebutolol
      • Aliskiren; Amlodipine
      • Amlodipine
      • Amlodipine; Atorvastatin
      • Amlodipine; Benazepril
      • Amlodipine; Olmesartan
      • Amlodipine; Telmisartan
      • Amlodipine; Valsartan
      • Atenolol
      • Atovaquone; Proguanil
      • Beta-blockers
      • Betaxolol
      • Bisoprolol
      • Brimonidine; Timolol
      • Carteolol
      • Carvedilol
      • Colchicine
      • Colchicine; Probenecid
      • Dapsone
      • Doravirine
      • Doravirine; Lamivudine; Tenofovir disoproxil fumarate
      • Dorzolamide; Timolol
      • Esmolol
      • Glyburide
      • Labetalol
      • Levamlodipine
      • Levobetaxolol
      • Levobunolol
      • Maraviroc
      • Metoprolol
      • Nadolol
      • Nebivolol
      • Nebivolol; Valsartan
      • Penbutolol
      • Perindopril; Amlodipine
      • Pindolol
      • Probenecid
      • Propranolol
      • Sotalol
      • Timolol
      Abacavir; Dolutegravir; Lamivudine: (Moderate) Caution is warranted when dolutegravir is administered with topiramate as there is a potential for decreased dolutegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Dolutegravir is partially metabolized by this isoenzyme. [27489] [55594] Abciximab: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Acarbose: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acebutolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Acetaminophen; Butalbital; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] Acetaminophen; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] (Moderate) Concomitant use of dihydrocodeine with topiramate can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If topiramate is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Topiramate is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. [28378] [30282] [57036] Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Acetaminophen; Dextromethorphan; Doxylamine: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Acetaminophen; Diphenhydramine: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] Acetaminophen; Guaifenesin; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Acetaminophen; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of oxycodone as needed. If topiramate is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [39926] [57036] Acetaminophen; Tramadol: (Moderate) Topiramate may contribute to the CNS depression seen with tramadol; tramadol may also decrease the seizure threshold in some patients and thus, potentially, interfere with the ability of anticonvulsants to control seizures. [28314] [28378] Aclidinium; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28309] Albiglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Albuterol: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28532] Albuterol; Ipratropium: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28532] Aliskiren; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Alogliptin; Metformin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] Alogliptin; Pioglitazone: (Moderate) A decrease in the exposures of pioglitazone and its active metabolites were observed in a clinical trial during concurrent use of topiramate. The clinical significance is unknown; however, results of routine blood glucose monitoring should be carefully followed during coadministration of pioglitazone and topiramate to ensure adequate glucose control. [51256] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Alpha-blockers: (Moderate) Monitor for desired antihypertensive effect of alpha-blockers when administered with phentermine, Sympathomimetics like phentermine can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly. [46595] Alpha-glucosidase Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Alprazolam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Ambrisentan: (Major) Sympathomimetics, such as phentermine, can antagonize the effects of vasodilators such as ambrisentan when administered concomitantly. Patients should be monitored for reduced efficacy if taking ambrisentan with a sympathomimetic. [26181] [29534] [29548] Amifampridine: (Major) Carefully consider the need for concomitant treatment with phentermine and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Phentermine may increase the risk of seizures. [46595] [63790] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Amitriptyline: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Amitriptyline; Chlordiazepoxide: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Amlodipine; Atorvastatin: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Amlodipine; Benazepril: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Amlodipine; Celecoxib: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Amlodipine; Olmesartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Amlodipine; Telmisartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Amlodipine; Valsartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Amoxapine: (Moderate) Use phentermine and amoxapine together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Amoxapine has pharmacologic activity similar to tricylclic antidepressant agents. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with amoxapine. CNS effects, such as dizziness, are also possible. [28558] [46594] [46595] [51256] [61198] Amphetamine: (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established. [46595] Amphetamine; Dextroamphetamine: (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established. [46595] Amphetamines: (Major) Concurrent use of amphetamines and urinary alkalinizers, such as topiramate, should be avoided. Urinary alkalinizers diminish the urinary excretion of amphetamines by increasing the proportion of non-ionized amphetamines, resulting in increased renal tubular reabsorption of these compounds. The half-life and therapeutic actions of amphetamines will be prolonged in the presence of these drugs. In addition, patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary. [27106] [28559] [29332] [60070] (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established. [46595] Anagrelide: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Anticholinergics: (Moderate) Use caution if carbonic anhydrase inhibitors are administered with anticholinergics and monitor for excessive anticholinergic adverse effects. The use of topiramate with agents that may increase the risk for heat-related disorders, such as anticholinergics, may lead to oligohidrosis, hyperthermia and/or heat stroke. [28378] [29796] Antithrombin III: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Anxiolytics; Sedatives; and Hypnotics: (Major) Although not specifically studied, coadministration of CNS depressant drugs (e.g., anxiolytics, sedatives, and hypnotics) with topiramate may potentiate CNS depression such as dizziness or cognitive adverse reactions, or other centrally mediated effects of these agents. Monitor for increased CNS effects if coadministering. [51256] Apixaban: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aprepitant, Fosaprepitant: (Moderate) Use caution if topiramate and aprepitant, fosaprepitant are used concurrently and monitor for a possible decrease in the efficacy of aprepitant for several days after administration of a multi-day aprepitant regimen. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer; aprepitant is a CYP3A4 substrate. When a single dose of aprepitant (375 mg, or 3 times the maximum recommended dose) was administered on day 9 of a 14-day rifampin regimen (a strong CYP3A4 inducer), the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased by 3-fold. The manufacturer of aprepitant recommends avoidance of administration with strong CYP3A4 inducers, but does not provide guidance for weak-to-moderate inducers. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. [28378] [30676] [40027] Arformoterol: (Moderate) Caution and close observation should be used when arformoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [32901] Argatroban: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aripiprazole: (Moderate) Because aripiprazole is partially metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as topiramate may result in decreased plasma concentrations of aripiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in aripiprazole efficacy. An increase in aripiprazole dosage may be clinically warranted in some patients. Avoid concurrent use of Abilify Maintena with a CYP3A4 inducer when the combined treatment period exceeds 14 days because aripiprazole blood concentrations decline and may become suboptimal. There are no dosing recommendations for Aristada or Aristada Initio during use of a mild to moderate CYP3A4 inducer. [27489] [31327] [53394] [60196] [63328] Aspirin, ASA: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] (Moderate) Concomitant use of dihydrocodeine with topiramate can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If topiramate is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Topiramate is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. [28378] [30282] [57036] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aspirin, ASA; Carisoprodol: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aspirin, ASA; Dipyridamole: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aspirin, ASA; Omeprazole: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Aspirin, ASA; Oxycodone: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of oxycodone as needed. If topiramate is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [39926] [57036] Aspirin, ASA; Pravastatin: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Atazanavir: (Moderate) Caution is warranted when atazanavir is administered with topiramate as there is a potential for decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Atazanavir is a substrate of CYP3A4. [27489] [28142] Atazanavir; Cobicistat: (Moderate) Caution is warranted when atazanavir is administered with topiramate as there is a potential for decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Atazanavir is a substrate of CYP3A4. [27489] [28142] (Moderate) Caution is warranted when cobicistat is administered with topiramate as there is a potential for decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Cobicistat is a substrate of CYP3A4. [27489] [58000] Atenolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Atenolol; Chlorthalidone: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Atomoxetine: (Major) Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with drugs with sympathomimetic activity such as phentermine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if sympathomimetics are coadministered with atomoxetine. [28405] Atovaquone; Proguanil: (Minor) Proguanil is metabolized to cycloguanil by CYP2C19. Potential interactions between proguanil or cycloguanil and other drugs that are CYP2C19 inhibitors are unknown. Use caution when combining atovaquone; proguanil with CYP2C19 inhibitors, such as topiramate. [27489] [28001] [28387] Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Carbonic anhydrase inhibiting drugs, such as topiramate (a weak carbonic anhydrase inhibitor) can alkalinize the urine, thereby decreasing the effectiveness of methenamine by inhibiting the conversion of methenamine to formaldehyde. [28294] [49784] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Azilsartan; Chlorthalidone: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Barbiturates: (Moderate) Although topiramate is not extensively metabolized (70% renally eliminated), an interaction with barbiturates via hepatic isoenzyme activity is possible. In patients receiving either phenobarbital or primidone in combination with topiramate, there was a < 10% change in phenobarbital or primidone plasma concentrations; the effects on topiramate plasma concentrations were not evaluated. Barbiturates may cause additive sedation or other CNS depressive effects when used concurrently with topiramate. When topiramate is combined with phentermine for the treatment of obesity, a greater risk of CNS depression exists. Concurrent use of topiramate and drugs that cause thrombocytopenia, such as the barbiturates, may also increase the risk of bleeding; monitor patients appropriately. [28378] Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. [46537] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Bendroflumethiazide; Nadolol: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Benzodiazepines: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Carbonic anhydrase inhibiting drugs, such as topiramate (a weak carbonic anhydrase inhibitor) can alkalinize the urine, thereby decreasing the effectiveness of methenamine by inhibiting the conversion of methenamine to formaldehyde. [28294] [49784] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Benzphetamine: (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established. [46595] Beta-blockers: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Betaxolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects. [29416] [29831] Bismuth Subsalicylate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Bisoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Bivalirudin: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Boceprevir: (Moderate) Close clinical monitoring is advised when administering topiramate with boceprevir due to the potential for boceprevir treatment failure. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of topiramate and boceprevir. Topiramate is a weak inducer of the hepatic isoenzyme CYP3A4; boceprevir is a substrate of this isoenzyme. When used in combination, the plasma concentrations of boceprevir may decrease. [28378] [44314] Bosentan: (Major) Avoid use of sympathomimetic agents with bosentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including bosentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [28496] [29534] [30000] [53320] [58486] [60482] [63622] (Moderate) Bosentan is a significant inducer of CYP2C9 hepatic isoenzymes.Theoretically, bosentan can increase the hepatic clearance of topiramate, a potential CYP2C9 substrate. [5226] Bretylium: (Moderate) Monitor blood pressure closely when sympathomimetics are administered with bretylium. The pressor effects of catecholamines are enhanced by bretylium. [64910] Brexpiprazole: (Moderate) Because brexpiprazole is partially metabolized by CYP3A4, concurrent use of CYP3A4 inducers such as topiramate may result in decreased plasma concentrations of brexpiprazole. If these agents are used in combination, the patient should be carefully monitored for a decrease in brexpiprazole efficacy. An increase in brexpiprazole dosage may be clinically warranted in some patients. Similar precautions apply to combination products containing topiramate such as phentermine; topiramate. [4190] [59949] Brimonidine; Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Bromocriptine: (Moderate) The combination of bromocriptine with phentermine may cause headache, tachycardia, other cardiovascular abnormalities, seizures, and other serious effects. Concurrent use of bromocriptine and phentermine should be approached with caution. [5585] Brompheniramine; Carbetapentane; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Budesonide; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28309] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28309] Bumetanide: (Moderate) Topiramate is a carbonic anhydrase inhibitor. Concurrent use of topiramate with non-potassium sparing diuretics (e.g., loop diuretics) may potentiate the potassium-wasting action of these diuretics. Monitor baseline and periodic potassium concentrations during coadministration. [28378] [51256] Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and topiramate may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; topiramate induces CYP3A4. [28378] [32857] [57036] Bupropion: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, such as phentermine, may be associated with an increased seizure risk; therefore, seizures may be more likely to occur in patients receiving this weight loss aide with bupropion. Patients should be closely monitored if this combination is necessary. Do not combine therapy with phentermine or phentermine-combinations and bupropion; naltrexone due to this risk and the duplication of therapy for weight loss. [28058] [57922] (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Use with caution when topiramate is used for other purposes, as additive CNS reactions may be possible. Pharmacokinetic interactions have not been noted. [27843] [28058] [40993] [41086] [44094] Bupropion; Naltrexone: (Major) Bupropion is associated with a dose-related risk of seizures. Excessive use of psychostimulants, such as phentermine, may be associated with an increased seizure risk; therefore, seizures may be more likely to occur in patients receiving this weight loss aide with bupropion. Patients should be closely monitored if this combination is necessary. Do not combine therapy with phentermine or phentermine-combinations and bupropion; naltrexone due to this risk and the duplication of therapy for weight loss. [28058] [57922] (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Use with caution when topiramate is used for other purposes, as additive CNS reactions may be possible. Pharmacokinetic interactions have not been noted. [27843] [28058] [40993] [41086] [44094] Buspirone: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] Caffeine; Ergotamine: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. [46537] (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [27950] Calcium, Magnesium, Potassium, Sodium Oxybates: (Severe) Because phentermine is a sympathomimetic and anorexic agent, it should not be used in combination with other psychostimulants. [7005] Canagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Canagliflozin; Metformin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Carbamazepine: (Moderate) Although topiramate is not extensively metabolized (70% renally eliminated), hepatic enzyme inducers. such as carbamazepine, have been shown to reduce topiramate serum concentrations. In patients receiving carbamazepine with topiramate, plasma concentrations of topiramate were decreased by 40% with < 10% change in carbamazepine plasma concentrations. Concurrent use of topiramate and drugs that cause thrombocytopenia, such as carbamazepine and oxcarbazepine, may also increase the risk of bleeding; monitor patients appropriately. [28378] [41237] [5107] Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Carbetapentane; Diphenhydramine; Phenylephrine: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Carbetapentane; Guaifenesin; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Carbetapentane; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Carbetapentane; Phenylephrine; Pyrilamine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Carbinoxamine; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Carbonic anhydrase inhibitors: (Major) Avoid concurrent use of acetazolamide or methazolamide with topiramate. Topiramate is a weak carbonic anhydrase inhibitor. Concomitant use of topiramate with acetazolamide or methazolamide may create a physiological environment that increases the risk of renal stone formation associated with topiramate use. Additionally, through an additive effect, the use of topiramate with agents that may increase the risk for heat-related disorders (acetazolamide and methazolamide), may lead to oligohidrosis, hyperthermia and heat stroke. [5107] Cardiac glycosides: (Major) Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics. [28272] [33363] Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Concurrent use of cariprazine with CYP3A4 inducers, such as topiramate, has not been evaluated and is not recommended because the net effect on active drug and metabolites is unclear. [27583] [60164] Carteolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Carvedilol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Celecoxib: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Chlophedianol; Guaifenesin; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Chlordiazepoxide: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Chlordiazepoxide; Clidinium: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Chlorothiazide: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] (Moderate) Topiramate is a carbonic anhydrase inhibitor. Concurrent use of topiramate with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Monitor baseline and periodic potassium concentrations during coadministration. [51256] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] (Moderate) Concomitant use of dihydrocodeine with topiramate can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If topiramate is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Topiramate is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. [28378] [30282] [57036] Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with topiramate can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If topiramate is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Topiramate is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. [28378] [30282] [57036] Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Chlorpheniramine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Chlorpheniramine; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Chlorpromazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Chlorthalidone: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Chlorthalidone; Clonidine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. [29493] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Choline Salicylate; Magnesium Salicylate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Cilostazol: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as cilostazol may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. In addition, cilostazol is metabolized by the cytochrome P450 CYP2C19 hepatic isoenzyme and may interact with medications that are inhibitors of CYP2C19, including topiramate. [28378] Citalopram: (Moderate) The plasma concentration of citalopram, a CYP2C19 substrate, may be increased when administered concurrently with topiramate, a CYP2C19 inhibitor. Because citalopram causes dose-dependent QT prolongation, the maximum daily dose should not exceed 20 mg per day in patients receiving CYP2C19 inhibitors. In addition, concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors (SSRIs) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28269] [28378] Clomipramine: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Clonazepam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Clonidine: (Major) Sympathomimetics can antagonize the antihypertensive effects of clonidine when administered concomitantly. Patients should be monitored for loss of blood pressure control. [29493] Clorazepate: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with topiramate as there is a potential for decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Cobicistat is a substrate of CYP3A4. [27489] [58000] Cobimetinib: (Moderate) If concurrent use of cobimetinib and topiramate is necessary, use caution and monitor for decreased efficacy of cobimetinib. Cobimetinib is a CYP3A substrate in vitro, and topiramate is a weak inducer of CYP3A. The manufacturer of cobimetinib recommends avoiding coadministration of cobimetinib with moderate or strong CYP3A inducers based on simulations demonstrating that cobimetinib exposure would decrease by 73% or 83% when coadministered with a moderate or strong CYP3A inducer, respectively. Guidance is not available regarding concomitant use of cobimetinib with weak CYP3A inducers. [28378] [57036] [60281] Cocaine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration. [63591] [64935] Codeine; Phenylephrine; Promethazine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Codeine; Promethazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine. [8783] Colchicine; Probenecid: (Minor) Probenecid may increase the renal clearance of topiramate resulting in lower topiramate concentrations. Although not evaluated in humans, animal studies using probenecid along with topiramate showed a significant increase in renal clearance of topiramate. This suggests that topiramate may undergo renal tubular reabsorption. Probenecid may block renal tubular reabsorption of topiramate, thus increasing the renal clearance of the drug. [28378] (Minor) The response to sympathomimetics may be enhanced by colchicine. [8783] Conjugated Estrogens; Medroxyprogesterone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Dabigatran: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Dapagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dapagliflozin; Metformin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dapagliflozin; Saxagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dapsone: (Minor) The metabolism of dapsone may be accelerated when administered concurrently with topiramate, a known inducer of CYP3A4. Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia. [34470] [60612] Darunavir: (Moderate) Caution is warranted when darunavir is administered with topiramate as there is a potential for decreased concentrations of darunavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Darunavir is a substrate of CYP3A4. [27489] [32432] Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with topiramate as there is a potential for decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Cobicistat is a substrate of CYP3A4. [27489] [58000] (Moderate) Caution is warranted when darunavir is administered with topiramate as there is a potential for decreased concentrations of darunavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Darunavir is a substrate of CYP3A4. [27489] [32432] Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with topiramate as there is a potential for decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Cobicistat is a substrate of CYP3A4. [27489] [58000] (Moderate) Caution is warranted when darunavir is administered with topiramate as there is a potential for decreased concentrations of darunavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Darunavir is a substrate of CYP3A4. [27489] [32432] Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of topiramate with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in decreased concentrations of dasabuvir, paritaprevir, and ritonavir. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Ritonavir, paritaprevir, and dasabuvir (minor) are all metabolized by this enzyme. Caution and close monitoring are advised if these drugs are administered together. [28378] [57036] [58664] (Moderate) Concurrent administration of topiramate with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in decreased concentrations of dasabuvir, paritaprevir, and ritonavir. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Ritonavir, paritaprevir, and dasabuvir (minor) are all metabolized by this enzyme. Caution and close monitoring are advised if these drugs are administered together. [28378] [57036] [58664] (Moderate) Concurrent administration of topiramate with ritonavir may result in decreased concentrations of ritonavir. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Ritonavir is metabolized by this enzyme. Caution and close monitoring are advised if these drugs are administered together. [28378] [57036] [58664] Delavirdine: (Moderate) Delavirdine is a potent inhibitor of cytochrome P450 2C9 and might decrease topiramate metabolism leading to increased topiramate serum concentrations and a risk of adverse reactions. [5206] Desflurane: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of the sympathomimetics. Because of this, and its effects on blood pressure, phentermine should be discontinued several days prior to surgery. [49611] Desipramine: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Desirudin: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Desvenlafaxine: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report describes adverse reactions with phentermine and fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal therapies. [30253] [46595] [51256] [57267] [57658] [57659] [57660] Dextroamphetamine: (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established. [46595] Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Dextromethorphan; Promethazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Diazepam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Dichlorphenamide: (Moderate) Use dichlorphenamide and topiramate, another carbonic anhydrase inhibitor, together with caution as both drugs can cause metabolic acidosis. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. [31426] [60122] Diclofenac: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Diclofenac; Misoprostol: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Dienogest; Estradiol valerate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Diflunisal: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Digitoxin: (Major) Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics. [28272] [33363] Digoxin: (Major) Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics. [28272] [33363] (Moderate) Serum digoxin AUC was decreased by 12% when coadministered with topiramate. Although the clinical relevance has not been determined, the clinician should be aware that serum digoxin concentrations may be affected when digoxin and topiramate are used concomitantly. [28378] Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of dihydrocodeine with topiramate can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. If coadministration is necessary, monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal; consider increasing the dose of dihydrocodeine as needed. If topiramate is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs or respiratory depression and sedation. Topiramate is a weak inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. [28378] [30282] [57036] Dihydroergotamine: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. [46537] Diltiazem: (Moderate) Coadministrator topiramate with diltiazem with caution. Concomitant administration of diltiazem (240 mg) with topiramate (150 mg/day) resulted in a 10% decrease in Cmax and a 25% decrease in diltiazem AUC, a 27% decrease in Cmax and an 18% decrease in desacetyl diltiazem AUC, and no effect on N-desmethyl diltiazem. Co-administration of topiramate with diltiazem resulted in a 16% increase in Cmax and a 19% increase in AUC of topiramate. Monitor for loss of diltiazem efficacy and or increased adverse events coming from the topiramate component of phentermine;topiramate. [51256] Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Diphenhydramine: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] Diphenhydramine; Hydrocodone; Phenylephrine: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Diphenhydramine; Ibuprofen: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Diphenhydramine; Naproxen: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Diphenhydramine; Phenylephrine: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Dipyridamole: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Dolutegravir: (Moderate) Caution is warranted when dolutegravir is administered with topiramate as there is a potential for decreased dolutegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Dolutegravir is partially metabolized by this isoenzyme. [27489] [55594] Dolutegravir; Lamivudine: (Moderate) Caution is warranted when dolutegravir is administered with topiramate as there is a potential for decreased dolutegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Dolutegravir is partially metabolized by this isoenzyme. [27489] [55594] Dolutegravir; Rilpivirine: (Moderate) Caution is warranted when dolutegravir is administered with topiramate as there is a potential for decreased dolutegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Dolutegravir is partially metabolized by this isoenzyme. [27489] [55594] (Moderate) Close clinical monitoring is advised when administering topiramate with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Topiramate is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response. [44376] Dopamine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Doravirine: (Minor) Concurrent administration of doravirine and topiramate may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; topiramate is a weak CYP3A4 inducer. [28378] [57036] [63484] Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Concurrent administration of doravirine and topiramate may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A4 substrate; topiramate is a weak CYP3A4 inducer. [28378] [57036] [63484] Dorzolamide; Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Doxazosin: (Moderate) Monitor for desired antihypertensive effect of alpha-blockers when administered with phentermine, Sympathomimetics like phentermine can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly. [46595] Doxepin: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Doxorubicin: (Major) Topiramate is a mild CYP3A4 inducer; doxorubicin is a major substrate of CYP3A4. Inducers of CYP3A4 may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy. Avoid coadministration of topiramate and doxorubicin if possible. If not possible, monitor doxorubicin closely for efficacy. [28378] [56361] [57036] Doxylamine: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] Doxylamine; Pyridoxine: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] Dronabinol: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm. [28488] [30431] [33363] (Moderate) Use caution if coadministration of dronabinol with topiramate is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; topiramate is a weak inducer of CYP3A4. Concomitant use may result in decreased plasma concentrations of dronabinol. [28378] [30431] [57036] [60951] Dronedarone: (Major) The concomitant use of dronedarone and CYP3A4 inducers should be avoided. Dronedarone is metabolized by CYP3A. Topiramate induces CYP3A4. Coadministration of CYP3A4 inducers, such as topiramate, with dronedarone may result in reduced plasma concentration and subsequent reduced effectiveness of dronedarone therapy. [36101] Droperidol: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] Drospirenone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Drospirenone; Estradiol: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Drospirenone; Ethinyl Estradiol: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Droxidopa: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Dulaglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Duloxetine: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report describes adverse reactions with phentermine and fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal therapies. [30253] [46595] [51256] [57267] [57658] [57659] [57660] Dyphylline: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias. [30227] Dyphylline; Guaifenesin: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias. [30227] Edoxaban: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Elagolix; Estradiol; Norethindrone acetate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Elbasvir; Grazoprevir: (Moderate) Caution is advised when administering elbasvir with topiramate. Topiramate is a mild CYP3A inducer, while elbasvir is a substrate of CYP3A. Use of these drugs together may decrease the plasma concentrations of elbasvir and could result in decreased virologic response. [28378] [57036] [60523] (Moderate) Caution is advised when administering elbasvir; grazoprevir with topiramate. Topiramate is a mild CYP3A inducer, while grazoprevir is a substrate of CYP3A. Use of these drugs together may decrease the plasma concentrations of grazoprevir and could result in decreased virologic response. [28378] [57036] [60523] Elvitegravir: (Moderate) Caution is warranted when elvitegravir is administered with topiramate as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Elvitegravir is a CYP3A4 substrate. [27489] [60269] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with topiramate as there is a potential for decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Cobicistat is a substrate of CYP3A4. [27489] [58000] (Moderate) Caution is warranted when elvitegravir is administered with topiramate as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Elvitegravir is a CYP3A4 substrate. [27489] [60269] Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with topiramate as there is a potential for decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Cobicistat is a substrate of CYP3A4. [27489] [58000] (Moderate) Caution is warranted when elvitegravir is administered with topiramate as there is a potential for decreased elvitegravir concentrations. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Elvitegravir is a CYP3A4 substrate. [27489] [60269] Empagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Empagliflozin; Linagliptin: (Major) Inducers of CYP3A4 (e.g., topiramate) can decrease exposure to linagliptin to subtherapeutic and likely ineffective concentrations. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended. [31240] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Empagliflozin; Linagliptin; Metformin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] (Major) Inducers of CYP3A4 (e.g., topiramate) can decrease exposure to linagliptin to subtherapeutic and likely ineffective concentrations. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended. [31240] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Empagliflozin; Metformin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Close clinical monitoring is advised when administering topiramate with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Topiramate is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response. [44376] Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Close clinical monitoring is advised when administering topiramate with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Topiramate is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response. [44376] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Enflurane: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of the sympathomimetics. Because of this, and its effects on blood pressure, phentermine should be discontinued several days prior to surgery. [49611] Ephedrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Epoprostenol: (Major) Avoid use of sympathomimetic agents with epoprostenol. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including epoprostenol. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [28168] [29534] [30000] [53320] [58486] [60482] [63622] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Eptifibatide: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Ergoloid Mesylates: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. [46537] Ergonovine: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. [46537] Ergot alkaloids: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. [46537] Ergotamine: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. [46537] Ertugliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Ertugliflozin; Metformin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Ertugliflozin; Sitagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Esketamine: (Major) Closely monitor blood pressure during concomitant use of esketamine and phentermine. Coadministration of psychostimulants, such as phentermine, with esketamine may increase blood pressure. [63989] Esmolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Esomeprazole; Naproxen: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Estazolam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Estradiol Cypionate; Medroxyprogesterone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Estradiol; Levonorgestrel: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Estradiol; Norethindrone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Estradiol; Norgestimate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Estradiol; Progesterone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Estrogens: (Moderate) Topiramate can increase the clearance of estrogens and compromise the efficacy of estrogens used as hormone replacement therapies or contraceptives. Patients taking oral contraceptives, non-oral combination contraceptives, or progestins for contraception or patients taking estrogens or progestins for hormone replacement therapy should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of the products may need adjustment; the manufacturer of topiramate recommends that an oral contraceptive containing 50 mcg of ethinyl estradiol be used. Different or additional forms of contraception may also be needed. [28378] Ethacrynic Acid: (Moderate) Topiramate is a carbonic anhydrase inhibitor. Concurrent use of topiramate with non-potassium sparing diuretics (e.g., loop diuretics) may potentiate the potassium-wasting action of these diuretics. Monitor baseline and periodic potassium concentrations during coadministration. [28378] [51256] Ethanol: (Major) Avoid alcohol with topiramate. Topiramate is a CNS depressant. Concomitant administration of topiramate with alcohol can result in significant CNS depression. Trokendi XR is contraindicated with recent alcohol use (i.e., within 6 hours before and 6 hours after use). In the presence of alcohol, the pattern of topiramate release from Trokendi XR is significantly altered. As a result, plasma concentrations of topiramate may be markedly higher soon after dosing and subtherapeutic later in the day. [28378] [55675] Ethinyl Estradiol; Desogestrel: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Etonogestrel: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Levonorgestrel: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Norelgestromin: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Norethindrone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Norgestimate: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethinyl Estradiol; Norgestrel: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Ethiodized Oil: (Major) Phentermine lowers the seizure threshold and should be discontinued at least 48 hours before and for at least 24 hours after intrathecal use of contrast media. [28963] [30266] [57419] Etodolac: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Etonogestrel: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Exenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Ezogabine: (Moderate) Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant ezogabine, may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (23%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Famotidine; Ibuprofen: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Felbamate: (Moderate) Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant felbamate may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Fenoprofen: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of topiramate is necessary. If topiramate is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A4 inducer like topiramate with fentanyl, a CYP3A4 substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression. [28378] [29623] [29763] [32731] [40943] [57036] Flibanserin: (Major) The concomitant use of flibanserin with CYP3A4 inducers significantly decreases flibanserin exposure compared to the use of flibanserin alone. Therefore, concurrent use of flibanserin and CYP3A4 inducers, such as topiramate is not recommended. [4190] [60099] Fluoxetine: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors (SSRIs) like fluoxetine may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Fluoxetine; Olanzapine: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors (SSRIs) like fluoxetine may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Fluphenazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Flurazepam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Flurbiprofen: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Fluticasone; Salmeterol: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28467] [30000] Fluticasone; Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. [54633] [56564] Fluticasone; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. [54633] [56564] Fluvoxamine: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors (SSRIs) like fluvoxamine may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Fondaparinux: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Food: (Moderate) Topiramate may influence the pharmacokinetic profile of cannabinoids in Marijuana and may also influence the pharmacodynamic profile. This may result in an altered adverse event profile of one or both drugs. Topiramate is an inducer of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (THC). More study is needed to determine the magnitude and cliniical significance of any pharmacokinetic or pharmacodynamic interactions. Additive drowsiness and CNS depression is possible. Monitor for changes in moods or behaviors, or for other CNS effects. [28378] [42135] [42448] Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28309] Formoterol; Mometasone: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28309] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Furosemide: (Moderate) Topiramate is a carbonic anhydrase inhibitor. Concurrent use of topiramate with non-potassium sparing diuretics (e.g., loop diuretics) may potentiate the potassium-wasting action of these diuretics. Monitor baseline and periodic potassium concentrations during coadministration. [28378] [51256] Gefitinib: (Moderate) Monitor for clinical response of gefitinib if used concomitantly with topiramate. Gefitinib is metabolized significantly by CYP3A4 and topiramate is a weak CYP3A4 inducer; coadministration may increase gefitinib metabolism and decrease gefitinib concentrations. This also applies to combination products containing topiramate, such as phentermine; topiramate. While the manufacturer has provided no guidance regarding the use of gefitinib with mild or moderate CYP3A4 inducers, administration of a single 500 mg gefitinib dose with a concurrent strong CYP3A4 inducer (rifampin) resulted in reduced mean AUC of gefitinib by 83%. [28378] [45935] [57036] Glimepiride; Pioglitazone: (Moderate) A decrease in the exposures of pioglitazone and its active metabolites were observed in a clinical trial during concurrent use of topiramate. The clinical significance is unknown; however, results of routine blood glucose monitoring should be carefully followed during coadministration of pioglitazone and topiramate to ensure adequate glucose control. [51256] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Glimepiride; Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Glipizide; Metformin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] Glyburide: (Minor) Coadministration of glyburide with topiramate may decrease systemic exposure to glyburide. A pharmacokinetic drug interaction study evaluated the combination of topiramate and glyburide. Reductions in AUC and Cmax were noted for glyburide and the active metabolites. [43364] Glyburide; Metformin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] (Minor) Coadministration of glyburide with topiramate may decrease systemic exposure to glyburide. A pharmacokinetic drug interaction study evaluated the combination of topiramate and glyburide. Reductions in AUC and Cmax were noted for glyburide and the active metabolites. [43364] Glycopyrrolate; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28309] Green Tea: (Major) Some, but not all, green tea products contain caffeine. Additive CNS stimulant effects are likely to occur when caffeine is coadministered with other CNS stimulants or psychostimulants. Caffeine should be avoided or used cautiously with phentermine. [4666] [4671] Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Guaifenesin; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Guanabenz: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of guanabenz when administered concomitantly. Patients should be monitored for loss of blood pressure control. [26181] [26815] [26816] [29332] [29548] [33263] [33363] [49571] [53320] [60070] [61368] Halogenated Anesthetics: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of the sympathomimetics. Because of this, and its effects on blood pressure, phentermine should be discontinued several days prior to surgery. [49611] Halothane: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of the sympathomimetics. Because of this, and its effects on blood pressure, phentermine should be discontinued several days prior to surgery. [49611] Heparin: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Homatropine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Hydantoins: (Moderate) Although topiramate is not extensively metabolized (70% renally eliminated), hepatic enzyme inducers, such as hydantoins, have been shown to reduce topiramate serum concentrations.Topiramate may increase phenytoin concentrations through its inhibitory effects on CYP2C19. In some patients receiving phenytoin concurrently with topiramate, plasma concentrations of phenytoin were increased by 25% and topiramate plasma concentrations were decreased by 48%. These patients were generally receiving dosage regimens of phenytoin twice-daily. Other patients experienced a change of < 10% in phenytoin plasma concentrations. A similar reaction would be expected with fosphenytoin or ethotoin. Concurrent use of topiramate and drugs that cause thrombocytopenia, such as the hydantoins, may also increase the risk of bleeding; monitor patients appropriately. [28378] [4190] [4741] [5107] [5265] Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Phentermine has vasopressor effects and may limit the benefit of antihypertensive agents particularly sympatholytic agents such as methyldopa. Concomitant use of phentermine with methyldopa may antagonize the antihypertensive effects of these agents. Although leading drug interaction texts differ in the potential for an interaction between phentermine and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications. [46595] (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Concurrent use or topiramate, a carbonic anhydrase inhibitor, with non-potassium sparing diuretics (e.g., thiazide diuretics) may potentiate the potassium-wasting action of these diuretics. Additionally, the addition of HCTZ to topiramate therapy may require a reduction in the topiramate dose. Alternatively, the discontinuation of HCTZ therapy may require a dose increase in topiramate. In a pharmacokinetic drug interaction study, the topiramate Cmax and AUC increased by 27% and 29% when HCTZ was added to topiramate. The clinical significance of this change is unknown. The steady-state pharmacokinetics of HCTZ were not altered to any significant degree. [28378] [51256] (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Hydrocodone; Ibuprofen: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Hydrocodone; Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of hydrocodone as needed. If topiramate is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs or respiratory depression and sedation. Hydrocodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease hydrocodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30379] [56303] [57036] Hydroxychloroquine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as topiramate. Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. [41806] Hydroxyzine: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Carbonic anhydrase inhibiting drugs, such as topiramate (a weak carbonic anhydrase inhibitor) can alkalinize the urine, thereby decreasing the effectiveness of methenamine by inhibiting the conversion of methenamine to formaldehyde. [28294] [49784] (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Ibuprofen: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Ibuprofen; Oxycodone: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of oxycodone as needed. If topiramate is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [39926] [57036] Ibuprofen; Pseudoephedrine: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Iloprost: (Major) Avoid use of sympathomimetic agents with iloprost. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including iloprost. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [29534] [30000] [30774] [53320] [58486] [60482] [63622] Imatinib: (Moderate) Imatinib is a potent inhibitors of cytochrome P450 2C9 and might decrease topiramate metabolism leading to increased topiramate serum concentrations and a risk of adverse reactions. [4966] Imipramine: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Incretin Mimetics: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Indacaterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. [44979] Indacaterol; Glycopyrrolate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. [44979] Indapamide: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. [2843] [5917] [6234] [6275] Indomethacin: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Insulin Degludec; Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Insulin Glargine; Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Insulins: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Iobenguane I 131: (Major) Discontinue sympathomimetics for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart sympathomimetics until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as sympathomimetics, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy. [63402] Iodixanol: (Major) Phentermine lowers the seizure threshold and should be discontinued at least 48 hours before and for at least 24 hours after intrathecal use of contrast media. [28963] [30266] [57419] Iohexol: (Major) Phentermine lowers the seizure threshold and should be discontinued at least 48 hours before and for at least 24 hours after intrathecal use of contrast media. [28963] [30266] [57419] Iopamidol: (Major) Phentermine lowers the seizure threshold and should be discontinued at least 48 hours before and for at least 24 hours after intrathecal use of contrast media. [28963] [30266] [57419] Iopromide: (Major) Phentermine lowers the seizure threshold and should be discontinued at least 48 hours before and for at least 24 hours after intrathecal use of contrast media. [28963] [30266] [57419] Ioversol: (Major) Phentermine lowers the seizure threshold and should be discontinued at least 48 hours before and for at least 24 hours after intrathecal use of contrast media. [28963] [30266] [57419] Isavuconazonium: (Moderate) Caution and close monitoring are warranted when isavuconazonium is administered with topiramate as there is a potential for decreased concentrations of isavuconazonium. Decreased isavuconazonium concentrations may lead to a reduction of antifungal efficacy and the potential for treatment failure. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of this enzyme. [28378] [57036] [59042] Isocarboxazid: (Severe) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. [27957] [28862] [29656] [30438] [61173] [61932] Isoflurane: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of the sympathomimetics. Because of this, and its effects on blood pressure, phentermine should be discontinued several days prior to surgery. [49611] Isosulfan Blue: (Major) Phentermine lowers the seizure threshold and should be discontinued at least 48 hours before and for at least 24 hours after intrathecal use of contrast media. [28963] [30266] [57419] Ivabradine: (Major) Avoid coadministration of ivabradine and topiramate. Ivabradine is primarily metabolized by CYP3A4; topiramte is a weak inducer of CYP3A4. Coadministration may decrease the plasma concentrations of ivabradine resulting in the potential for treatment failure. [28378] [59430] Ketoprofen: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Ketorolac: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Labetalol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Lacosamide: (Moderate) Use lacosamide with caution in patients taking concomitant medications that affect cardiac conduction including those that prolong PR interval, such as sodium channel blocking anticonvulsants (e.g., topiramate), because of the risk of AV block, bradycardia, or ventricular tachyarrhythmia. If use together is necessary, obtain an ECG prior to lacosamide initiation and after treatment has been titrated to steady-state. In addition, monitor patients receiving lacosamide via the intravenous route closely. [34626] [63771] [63772] Lamotrigine: (Moderate) Use caution when coadministering lamotrigine and topiramate. Concurrent use of topiramate and drugs that cause thrombocytopenia, such as lamotrigine, may increase the risk of bleeding. In pediatric patients who underwent craniotomy for epilepsy surgery (n = 84), treatment for confirmed or suspected coagulopathy was required in 5 of 7 patients taking a regimen of topiramate and lamotrigine, approximately one-third of the overall study population requiring blood products. Concurrent use may also result in significant CNS depression. Further, co-administration of topiramate and lamotrigine resulted in a 13% decrease in topiramate concentration; however, the clinical significance of this finding is unknown. Plasma concentrations of lamotrigine do not appear to be affected by the combined use of the drugs. [28378] [28451] [55675] [61243] Lansoprazole; Naproxen: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Lepirudin: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Leuprolide; Norethindrone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Levalbuterol: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28532] Levamlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Levetiracetam: (Moderate) Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant levetiracetam, may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Levobetaxolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Levobunolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Levomilnacipran: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report describes adverse reactions with phentermine and fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal therapies. [30253] [46595] [51256] [57267] [57658] [57659] [57660] Levonorgestrel: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Levothyroxine: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur. [29548] [43942] Levothyroxine; Liothyronine (Porcine): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur. [29548] [43942] Levothyroxine; Liothyronine (Synthetic): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur. [29548] [43942] Lidocaine: (Moderate) Concomitant use of systemic lidocaine and topiramate may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; topiramate induces CYP3A4. [28378] [32857] [57036] Lidocaine; Prilocaine: (Moderate) Concomitant use of systemic lidocaine and topiramate may decrease lidocaine plasma concentrations. Higher lidocaine doses may be required; titrate to effect. Lidocaine is a CYP3A4 and CYP1A2 substrate; topiramate induces CYP3A4. [28378] [32857] [57036] Linagliptin: (Major) Inducers of CYP3A4 (e.g., topiramate) can decrease exposure to linagliptin to subtherapeutic and likely ineffective concentrations. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended. [31240] Linagliptin; Metformin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] (Major) Inducers of CYP3A4 (e.g., topiramate) can decrease exposure to linagliptin to subtherapeutic and likely ineffective concentrations. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended. [31240] Linezolid: (Major) Phentermine should not be administered during or within 14 days following the use of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Drugs that possess MAO-inhibiting activity, such as linezolid, can prolong and intensify the cardiac stimulation and vasopressor effects of phentermine which may invoke a hypertensive reaction. Additonally, phentermine has a weak ability to dose-dependently raise serotonin levels. Linezolid has the potential for interaction with serotonergic agents, which may increase the risk for serotonin syndrome. If coadministration is necessary, closely monitor for increased blood pressure and signs of serotonin syndrome. [28599] [32308] [46537] Liothyronine: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur. [29548] [43942] Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Lisdexamfetamine: (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established. [46595] Lithium: (Moderate) In patients, the pharmacokinetics of lithium were unaffected during treatment with topiramate at doses of 200 mg/day; however, there was an observed increase in systemic exposure of lithium (27% for Cmax and 26% for AUC) following topiramate doses up to 600 mg/day. Lithium levels should be monitored; monitor patients for adequate control of symptoms when phentermine; topiramate is added to lithium therapy. [28378] [51256] Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Loop diuretics: (Moderate) Topiramate is a carbonic anhydrase inhibitor. Concurrent use of topiramate with non-potassium sparing diuretics (e.g., loop diuretics) may potentiate the potassium-wasting action of these diuretics. Monitor baseline and periodic potassium concentrations during coadministration. [28378] [51256] Loperamide: (Moderate) The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with topiramate. Loperamide is metabolized by the hepatic enzyme CYP3A4; topiramate is a mild inducer of this enzyme. [28378] [30106] [57036] Loperamide; Simethicone: (Moderate) The plasma concentration and efficacy of loperamide may be reduced when administered concurrently with topiramate. Loperamide is metabolized by the hepatic enzyme CYP3A4; topiramate is a mild inducer of this enzyme. [28378] [30106] [57036] Lopinavir; Ritonavir: (Moderate) Concurrent administration of topiramate with ritonavir may result in decreased concentrations of ritonavir. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Ritonavir is metabolized by this enzyme. Caution and close monitoring are advised if these drugs are administered together. [28378] [57036] [58664] Lorazepam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Lorcaserin: (Major) The safety and efficacy of coadministration of lorcaserin with other products intended for weight loss including prescription drugs (e.g., phentermine, fenfluramine, dexfenfluramine, orlistat, phendimetrazine, amphetamines), over-the-counter drugs (e.g., orlistat, phenylpropanolamine, ephedrine), and herbal preparations (ephedra, Ma huang) have not been established. Some of these agents (fenfluramine, dexfenfluramine) are known to increase the risk for cardiac valvulopathy and pulmonary hypertension. Coadministration of sibutramine with other serotonergic medications is contraindicated due to the risk for serotonin-related adverse effects, such as serotonin syndrome. [28609] [51065] Low Molecular Weight Heparins: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Lumateperone: (Major) Avoid coadministration of lumateperone and topiramate as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A4 substrate; topiramate is a weak CYP3A4 inducer. [28378] [57036] [64885] Lurasidone: (Moderate) Because lurasidone is primarily metabolized by CYP3A4, decreased plasma concentrations of lurasidone may theoretically occur when the drug is co-administered with inducers of CYP3A4 such as topiramate. [27489] [42227] Macitentan: (Major) Avoid use of sympathomimetic agents with macitentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including macitentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [29534] [30000] [53320] [56260] [58486] [60482] [63622] Magnesium Salicylate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Maprotiline: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy. [28759] (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity. [28759] Maraviroc: (Minor) Use caution if coadministration of maraviroc with topiramate is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate and topiramate is a CYP3A4 inducer. Monitor for a decrease in maraviroc efficacy with concomitant use. [28378] [33473] [57036] Mecamylamine: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by mecamylamine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. [29332] [53320] [60070] Meclofenamate Sodium: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Medroxyprogesterone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Mefenamic Acid: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Mefloquine: (Moderate) Topiramate induces CYP3A4 and may increase the metabolism of mefloquine if coadministered. Use may reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria. Coadministration of mefloquine and anticonvulsants may also result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of drug concentrations (if therapeutic monitoring is advised for the anticonvulsant) is recommended. When topiramate is used for other conditions, monitor for clinical efficacy. Mefloquine may additionally cause CNS side effects that may cause seizures or alter moods or behaviors. [28301] Meglitinides: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Meloxicam: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Meperidine; Promethazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Mesoridazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Mestranol; Norethindrone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Metaproterenol: (Major) Caution and close observation should also be used when metaproterenol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [46792] Metformin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] Metformin; Pioglitazone: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] (Moderate) A decrease in the exposures of pioglitazone and its active metabolites were observed in a clinical trial during concurrent use of topiramate. The clinical significance is unknown; however, results of routine blood glucose monitoring should be carefully followed during coadministration of pioglitazone and topiramate to ensure adequate glucose control. [51256] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Metformin; Repaglinide: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] Metformin; Rosiglitazone: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Metformin; Saxagliptin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] Metformin; Sitagliptin: (Major) Extended-release topiramate is contraindicated in patients with metabolic acidosis who are taking concomitant metformin because topiramate can frequently cause metabolic acidosis, a condition for which metformin use is contraindicated. Consider more frequent monitoring of patients taking immediate-release topiramate with metformin. In healthy volunteers, metformin Cmax and AUC increased by 17% and 25%, respectively, when topiramate was added, and oral plasma clearance of topiramate appears to be reduced when administered with metformin. However, the clinical significance of these pharmacokinetic effects is unclear. [28378] [28550] [55675] Methamphetamine: (Moderate) Concurrent use of phentermine with amphetamines may result in additive cardiovascular and CNS adverse effects. Coadministration is not recommended when amphetamines are used for weight loss as safety and efficacy of phentermine in combination with other weight loss products has not been established. [46595] Methenamine: (Moderate) Carbonic anhydrase inhibiting drugs, such as topiramate (a weak carbonic anhydrase inhibitor) can alkalinize the urine, thereby decreasing the effectiveness of methenamine by inhibiting the conversion of methenamine to formaldehyde. [28294] [49784] Methenamine; Sodium Acid Phosphate: (Moderate) Carbonic anhydrase inhibiting drugs, such as topiramate (a weak carbonic anhydrase inhibitor) can alkalinize the urine, thereby decreasing the effectiveness of methenamine by inhibiting the conversion of methenamine to formaldehyde. [28294] [49784] Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Carbonic anhydrase inhibiting drugs, such as topiramate (a weak carbonic anhydrase inhibitor) can alkalinize the urine, thereby decreasing the effectiveness of methenamine by inhibiting the conversion of methenamine to formaldehyde. [28294] [49784] Methyclothiazide: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Methyldopa: (Major) Phentermine has vasopressor effects and may limit the benefit of antihypertensive agents particularly sympatholytic agents such as methyldopa. Concomitant use of phentermine with methyldopa may antagonize the antihypertensive effects of these agents. Although leading drug interaction texts differ in the potential for an interaction between phentermine and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications. [46595] Methylergonovine: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. [46537] Methysergide: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. [46537] Metolazone: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Metoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Midazolam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Midodrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Miglitol: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Milnacipran: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report describes adverse reactions with phentermine and fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal therapies. [30253] [46595] [51256] [57267] [57658] [57659] [57660] Mirtazapine: (Major) Because of the potential risk and severity of serotonin syndrome, caution should be observed during co-administration of mirtazapine with other drugs that have serotonergic properties. As a drug related to the amphetamines, phentermine has the potential to cause serotonin syndrome when combined with serotonergic agents. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. Mirtazapine should be discontinued if a patient develops a combination of symptoms suggestive of serotonin syndrome. [40942] [46595] Molindone: (Moderate) Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant. [28820] Monoamine oxidase inhibitors: (Severe) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. [27957] [28862] [29656] [30438] [61173] [61932] Nabilone: (Moderate) Concurrent use of nabilone with sympathomimetics (e.g., amphetamine or cocaine) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 to 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm. [32226] Nabumetone: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Nadolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Naproxen: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Naproxen; Pseudoephedrine: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Naproxen; Sumatriptan: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Nebivolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Nebivolol; Valsartan: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Nisoldipine: (Major) Avoid coadministration of nisoldipine with topiramate due to decreased plasma concentrations of nisoldipine. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Coadministration with a strong CYP3A4 inducer lowered nisoldipine plasma concentrations to undetectable levels. [28378] [29088] [57036] Nitrates: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. [26181] [26815] [29493] [29548] [53320] Non-Ionic Contrast Media: (Major) Phentermine lowers the seizure threshold and should be discontinued at least 48 hours before and for at least 24 hours after intrathecal use of contrast media. [28963] [30266] [57419] Nonsteroidal antiinflammatory drugs: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Norepinephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Norethindrone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Norgestrel: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Nortriptyline: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of topiramate with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in decreased concentrations of dasabuvir, paritaprevir, and ritonavir. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Ritonavir, paritaprevir, and dasabuvir (minor) are all metabolized by this enzyme. Caution and close monitoring are advised if these drugs are administered together. [28378] [57036] [58664] (Moderate) Concurrent administration of topiramate with ritonavir may result in decreased concentrations of ritonavir. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Ritonavir is metabolized by this enzyme. Caution and close monitoring are advised if these drugs are administered together. [28378] [57036] [58664] Orlistat: (Moderate) The safety and efficacy of coadministration of phentermine with other products intended for weight loss has not been established. [51256] Oxaprozin: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Oxazepam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of oxycodone as needed. If topiramate is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [39926] [57036] Ozanimod: (Severe) Coadministration of ozanimod with phentermine is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of phentermine. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics such as phentermine may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors. [46595] [65169] Paroxetine: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors (SSRIs) like paroxetine may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Pazopanib: (Moderate) Coadministration of pazopanib and topiramate may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly. Pazopanib is a substrate for CYP3A4. Topiramate in a weak CYP3A4 inducer. [28378] [37098] Pemoline: (Moderate) A reduction in seizure threshold has been reported following concomitant administration of pemoline with anticonvulsant agents. [31583] Penbutolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Pentosan: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Perampanel: (Moderate) During clinical trials, co-administration of topiramate and perampanel to patients led to a 20% decrease in the AUC of perampanel compared to patients not taking enzyme-inducing antiepileptic drugs. Topiramate is an inducer of CYP3A4, while perampanel is a substrate of this enzyme. Patients taking topiramate who begin treatment with perampanel should be closely monitored for adverse effects and receive a higher initial dose of perampanel. Addition or withdrawal of enzyme-inducing antiepileptic drugs may require a perampanel dose adjustment. [52140] Pergolide: (Major) Phentermine, which increases catecholamine release, can increase blood pressure; this effect may be additive with the prolonged vasoconstriction caused by ergot alkaloids. Monitoring for cardiac effects during concurrent use of ergot alkaloids with phentermine may be advisable. [46537] Perindopril; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as topiramate, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased. [28378] [35588] [57036] Perphenazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Perphenazine; Amitriptyline: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Phendimetrazine: (Severe) Phendimetrazine is a phenylalkaline sympathomimetic agent. All sympathomimetics and psychostimulants, including other anorexiants, should be used cautiously or avoided in patients receiving phendimetrazine. The safety of phendimetrazine when used with other anorexiants such as phentermine is controversial and concurrent use should be avoided. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmia. Similarly, phendimetrazine should not be used in combination with OTC preparations and herbal products that may contain ephedra alkaloids or Ma huang. [3490] [3640] [3646] [3666] [6528] [7166] Phenelzine: (Severe) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. [27957] [28862] [29656] [30438] [61173] [61932] Phenothiazines: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Phenoxybenzamine: (Moderate) Monitor for desired antihypertensive effect of alpha-blockers when administered with phentermine, Sympathomimetics like phentermine can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly. [46595] Phentolamine: (Moderate) Monitor for desired antihypertensive effect of alpha-blockers when administered with phentermine, Sympathomimetics like phentermine can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly. [46595] Phenylephrine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Phenylephrine; Promethazine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Pindolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Pioglitazone: (Moderate) A decrease in the exposures of pioglitazone and its active metabolites were observed in a clinical trial during concurrent use of topiramate. The clinical significance is unknown; however, results of routine blood glucose monitoring should be carefully followed during coadministration of pioglitazone and topiramate to ensure adequate glucose control. [51256] (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Pirbuterol: (Moderate) Caution and close observation should also be used when pirbuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28533] Piroxicam: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Pramlintide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Prasugrel: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Prazosin: (Moderate) Monitor for desired antihypertensive effect of alpha-blockers when administered with phentermine, Sympathomimetics like phentermine can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly. [46595] Pregabalin: (Moderate) Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant pregabalin, may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Probenecid: (Minor) Probenecid may increase the renal clearance of topiramate resulting in lower topiramate concentrations. Although not evaluated in humans, animal studies using probenecid along with topiramate showed a significant increase in renal clearance of topiramate. This suggests that topiramate may undergo renal tubular reabsorption. Probenecid may block renal tubular reabsorption of topiramate, thus increasing the renal clearance of the drug. [28378] Procarbazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. [28518] [32121] [32223] [45905] [46595] [60070] Prochlorperazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Progesterone: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Progestins: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Promethazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Propranolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Protriptyline: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Quazepam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Ramelteon: (Major) 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. Monitor for increased CNS effects if coadministering. [51256] Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetics was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and sympathomimetics including stimulants for ADHD and weight loss, non-prescription nasal, oral, and ophthalmic decongestants, and weight loss dietary supplements containing Ephedra. Although sympathomimetics are contraindicated for use with other non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. One case of elevated blood pressure has been reported in a patient during concurrent use of the recommended dose of rasagiline and ophthalmic tetrahydrozoline. One case of hypertensive crisis has been reported in a patient taking the recommended dose of another MAO-B inhibitor, selegiline, in combination with ephedrine. It should be noted that the MAO-B selectivity of rasagiline decreases in a dose-related manner as increases are made above the recommended daily dose and interactions with sympathomimetics may be more likely to occur at these higher doses. [32223] [60070] Reserpine: (Major) Phentermine has vasopressor effects and may limit the benefit of antihypertensive agents particularly sympatholytic agents such as reserpine. Concomitant use of phentermine with reserpine may antagonize the antihypertensive effects of these agents. Although leading drug interaction texts differ in the potential for an interaction between phentermine and this group of antihypertensive agents, these effects are likely to be clinically significant and have been described in hypertensive patients on these medications. [46595] Rilpivirine: (Moderate) Close clinical monitoring is advised when administering topiramate with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Topiramate is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response. [44376] Riociguat: (Major) Avoid use of sympathomimetic agents with riociguat. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including riociguat. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [29534] [30000] [53320] [56096] [58486] [60482] [63622] Ritonavir: (Moderate) Concurrent administration of topiramate with ritonavir may result in decreased concentrations of ritonavir. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Ritonavir is metabolized by this enzyme. Caution and close monitoring are advised if these drugs are administered together. [28378] [57036] [58664] Rivaroxaban: (Moderate) Concurrent use of topiramate and anticoagulants may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. However, coadministration of rivaroxaban and topiramate may result in decreased rivaroxaban exposure and may decrease the efficacy of rivaroxaban. Topiramate is a mild inducer of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs of bleeding or lack of efficacy of rivaroxaban. [44854] [5107] Rofecoxib: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Romidepsin: (Moderate) Romidepsin is a substrate for CYP3A4. Coadministration of a CYP3A4 inducer, like topiramate, may decrease systemic concentrations of romidepsin. Use caution when concomitant administration of these agents is necessary. [37292] Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Rufinamide: (Moderate) Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant rufinamide, may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Safinamide: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as phentermine. If concomitant use of safinamide and phentermine is necessary, monitor for hypertension and hypertensive crisis. [61825] Salicylates: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Salmeterol: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28467] [30000] Salsalate: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Segesterone Acetate; Ethinyl Estradiol: (Moderate) Topiramate may increase the clearance and compromise the efficacy of progestins used in contraception or hormone replacement therapies. In a pharmacokinetic interaction study, a combination oral contraceptive (containing norethindrone and ethinyl estradiol) administered with only topiramate at doses of 50 to 200 mg/day did not result in clinically significant alterations of AUC for either component of the oral contraceptive. Norethindrone pharmacokinetics were not significantly affected. However, pregnancy has been reported in patients who are using hormonal-containing contraceptives and taking hepatic enzyme inducers like topiramate. Patients taking progestin-containing contraceptives or patients taking progestins for hormone replacement therapy (HRT) should report changes in their bleeding patterns to their prescribers. Reduced contraceptive efficacy can occur even in the absence of breakthrough bleeding. Dosages of hormone replacement products may need adjustment. Different or additional forms of contraception may also be needed. [22005] [28378] [33941] [55436] [57046] [57048] [57648] Selective serotonin reuptake inhibitors: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report has been received of adverse reactions with phentermine and fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal co-therapies. [46595] [51256] [57267] [57658] [57659] [57660] Selegiline: (Severe) The product label for phentermine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phentermine should generally not be used concurrently with MAOIs or within 14 days before or after their use. [32026] [32436] [61198] Selexipag: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [29534] [30000] [53320] [56096] [58486] [60482] [63622] Semaglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Serotonin norepinephrine reuptake inhibitors: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report describes adverse reactions with phentermine and fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal therapies. [30253] [46595] [51256] [57267] [57658] [57659] [57660] Sertraline: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as selective serotonin reuptake inhibitors (SSRIs) like topiramate may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Sevoflurane: (Major) Halogenated anesthetics may sensitize the myocardium to the effects of the sympathomimetics. Because of this, and its effects on blood pressure, phentermine should be discontinued several days prior to surgery. [49611] SGLT2 Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Sibutramine: (Severe) Sibutramine is contraindicated in patients taking other centrally-acting appetite suppressant drugs, such as phentermine. In addition, many of these agents enhance central serotonergic activity by various mechanisms. Concurrent use of sibutramine with other serotonergic agents may increase the potential for serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [28609] [46595] Simeprevir: (Major) Avoid concurrent use of simeprevir and topiramate. Induction of CYP3A4 by topiramate may significantly reduce the plasma concentrations of simeprevir, resulting in treatment failure. [27489] [56471] Sodium Oxybate: (Severe) Because phentermine is a sympathomimetic and anorexic agent, it should not be used in combination with other psychostimulants. [7005] Sofosbuvir; Velpatasvir: (Major) Use caution when administering velpatasvir with topiramate. Taking these drugs together may decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; topiramate is a weak inducer of CYP3A4. [28378] [57036] [60911] Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Use caution when administering velpatasvir with topiramate. Taking these drugs together may decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; topiramate is a weak inducer of CYP3A4. [28378] [57036] [60911] Solifenacin: (Moderate) Through an additive effect, the use of topiramate with agents that may increase the risk for heat related disorders, such as solifenacin, may lead to oligohidrosis, hyperthermia, and/or heat stroke. [27578] [28378] Solriamfetol: (Moderate) Monitor blood pressure and heart rate during coadministration of solriamfetol, a norepinephrine and dopamine reuptake inhibitor, and phentermine, a CNS stimulant. Concurrent use of solriamfetol and other medications that increase blood pressure and/or heart rate may increase the risk of such effects. Coadministration of solriamfetol with other drugs that increase blood pressure or heart rate has not been evaluated. [64026] Sotalol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] St. John's Wort, Hypericum perforatum: (Major) St. John's wort (Hypericum perforatum) may reduce the neuronal uptake of monoamines and should be used cautiously with sympathomimetics. [28211] Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if topiramate must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with topiramate is necessary; consider increasing the dose of sufentanil injection as needed. If topiramate is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs or respiratory depression and sedation. Sufentanil is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Concomitant use with CYP3A4 inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence. [28378] [30966] [57036] [63731] Sulfonylureas: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [29413] [29418] [35040] [43364] [44662] [51002] Sulindac: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Tedizolid: (Moderate) Caution is warranted with the concurrent use of tedizolid and phentermine. Tedizolid is an antibiotic that is also a weak reversible, non-selective inhibitor of MAO which could potentially prolong and intensify the cardiac stimulation and vasopressor effects of phentermine. Phentermine should not be administered during or within 14 days following the use of drugs with MAO-inhibiting activity. [46595] [57468] Telithromycin: (Moderate) Caution is warranted when topiramate is administered with telithromycin as there is a potential for decreased telithromycin concentrations and loss of efficacy. Topiramate is not extensively metabolized, but is a mild CYP3A4 inducer. Telithromycin is a substrate of CYP3A4. [28156] [28378] Temazepam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Terazosin: (Moderate) Monitor for desired antihypertensive effect of alpha-blockers when administered with phentermine, Sympathomimetics like phentermine can antagonize the effects of antihypertensives such as alpha-blockers when administered concomitantly. [46595] Terbinafine: (Moderate) Caution is advised when administering terbinafine with topiramate. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may alter the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C19 and CYP3A4; topiramate is an inducer of CYP3A4 and an inhibitor of CYP2C19. Monitor patients for adverse reactions and breakthrough fungal infections if these drugs are coadministered. [37590] [43880] [43881] [56538] Terbutaline: (Moderate) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate. [28467] Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with some sympathomimetics can produce excessive stimulation and effects such as nervousness, irritability, or insomnia. [5241] (Moderate) Concurrent administration of theophylline or aminophylline with some sympathomimetics can produce excessive stimulation and effects such as nervousness, irritability, or insomnia. Seizures or cardiac arrhythmias are also possible. [5241] Thiazide diuretics: (Moderate) Sympathomimetics can antagonize the effects of antihypertensives when administered concomitantly. [46595] Thiazolidinediones: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Thiethylperazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Thioridazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Thrombin Inhibitors: (Moderate) Concurrent use of topiramate and anticoagulants (e.g., warfarin, enoxaparin, dabigatran) may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Thyroid hormones: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur. [29548] [43942] Tiagabine: (Moderate) Concurrent use of topiramate and drugs that cause thrombocytopenia such as the anticonvulsant tiagabine, may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Ticagrelor: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Ticlopidine: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Tirofiban: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as aspirin, ASA and other salicylates or platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2-3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Tolmetin: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Tolterodine: (Moderate) Through an additive effect, the use of topiramate (a weak carbonic anhydrase inhibitor) with agents that may increase the risk for heat-related disorders, such as antimuscarinics, may lead to oligohidrosis, hyperthermia and/or heat stroke. [27578] [28378] Tolvaptan: (Major) Tolvaptan is metabolized by CYP3A4. Topiramate is an inducer of CYP3A4. Coadministration may result in reduced plasma concentration and subsequent reduced effectiveness of tolvaptan therapy and should be avoided. If coadministration is unavoidable, an increase in the tolvaptan dose may be necessary and patients should be monitored for decreased effectiveness of tolvaptan. [35780] Torsemide: (Moderate) Topiramate is a carbonic anhydrase inhibitor. Concurrent use of topiramate with non-potassium sparing diuretics (e.g., loop diuretics) may potentiate the potassium-wasting action of these diuretics. Monitor baseline and periodic potassium concentrations during coadministration. [28378] [51256] Tramadol: (Moderate) Topiramate may contribute to the CNS depression seen with tramadol; tramadol may also decrease the seizure threshold in some patients and thus, potentially, interfere with the ability of anticonvulsants to control seizures. [28314] [28378] Tranylcypromine: (Severe) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. [27957] [28862] [29656] [30438] [61173] [61932] Treprostinil: (Major) Avoid use of sympathomimetic agents with treprostinil. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including treprostinil. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [29534] [30000] [30210] [53320] [58486] [60482] [63622] Tretinoin, ATRA: (Moderate) Topiramate may increase the CYP450 metabolism of tretinoin, ATRA, potentially resulting in decreased plasma concentrations of tretinoin, ATRA. Monitor for decreased clinical effects of tretinoin, ATRA while receiving concomitant therapy. [28568] Triazolam: (Moderate) Topiramate has the potential to cause CNS depression as well as other cognitive and/or neuropsychiatric adverse reactions. The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia (e.g., clonazepam, lorazepam, and clobazam), may also increase the risk of bleeding; monitor patients appropriately during benzodiazepine therapy. [28378] Tricyclic antidepressants: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Trifluoperazine: (Moderate) The phenothiazines, when used concomitantly with anticonvulsants, can lower the seizure threshold. Adequate dosages of anticonvulsants should be continued when a phenothiazine is added. [28817] [29024] Trimipramine: (Moderate) Tricyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold. In addition, during concurrent use of topiramate and amitriptyline the Cmax and AUC of amitriptyline were increased by 12%. Dosage adjustments of amitriptyline may be needed based upon tolerability to the regimen during combined use of amitriptyline and topiramate. [28378] [28557] (Moderate) Use phentermine and tricyclic antidepressants (TCAs) together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with the tricyclic antidepressants. Additive CNS effects (e.g., dizziness) may also occur. [28562] [28566] [41163] [42075] [46594] [46595] [51256] [60083] [61198] Trospium: (Moderate) Oligohidrosis and hyperthermia have been reported in post-marketing experience with topiramate. Use caution when topiramate is prescribed with agents known to predispose patients to similar heat-related disorders such as trospium. [27578] Ulipristal: (Major) Avoid administration of ulipristal with drugs that induce CYP3A4. Ulipristal is a substrate of CYP3A4 and topiramate is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal. [41569] [48201] [50623] Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. [54633] [56564] Valdecoxib: (Moderate) Concurrent use of topiramate and drugs that affect platelet function such as NSAIDs may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (2 to 3%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] Valproic Acid, Divalproex Sodium: (Moderate) Concomitant administration of topiramate and valproic acid has been associated with hyperammonemia with or without encephalopathy in patients who have tolerated either drug alone. In addition, concomitant administration of topiramate and valproic acid has been associated with hypothermia with or without hyperammonemia in patients who have tolerated either drug alone. Assessment of blood ammonia levels may be advisable in patients presenting with symptoms of hypothermia. Concurrent use of topiramate and drugs that cause thrombocytopenia, such as valproic acid, may also increase the risk of bleeding; monitor patients appropriately. In several case reports, children with localized epilepsy have presented with somnolence, seizure exacerbation, behavioral alteration, decline in speech and cognitive abilities, and ataxia while being treated with a combination of valproate and topiramate. Previously, the children tolerated valproic acid with other antiepileptic drugs. Children presented with elevated serum ammonia, normal or elevated LFTs, and generalized slowing of EEG background activity during encephalopathy, which promptly reverted to normal along with clinical improvement following withdrawal of valproate. The possible mechanism is topiramate-induced aggravation of all the known complications of valproic acid monotherapy; it is not due to a pharmacokinetic interaction. This condition is reversible with cessation of either valproic acid or topiramate. [28378] [32148] [32149] [32150] [32151] Vasodilators: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present. [26181] [26815] [26816] [29332] [29548] [33263] [33363] [53320] [60070] Vasopressors: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias. [46595] Vemurafenib: (Major) Concomitant use of vemurafenib and topiramate may result in decreased concentrations of vemurafenib. Vemurafenib is a CYP3A4 substrate and topiramate is a weak CYP3A4 inducer. Use caution and monitor patients for therapeutic effects. [27489] [28378] [45335] Venlafaxine: (Moderate) Use phentermine and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report describes adverse reactions with phentermine and fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal therapies. [30253] [46595] [51256] [57267] [57658] [57659] [57660] Vilazodone: (Moderate) Use phentermine and vilazodone together with caution; use together might be efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report describes adverse reactions with phentermine and the antidepressant fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with extended-release phentermine or extended-release phentermine combinations for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal therapies. [30253] [51256] [57267] [57658] [57659] [57660] Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and topiramate. Decreased serum concentrations of vorapaxar and thus decreased efficacy are possible when vorapaxar, a CYP3A4 substrate, is coadministered with topiramate, a mild inducer of CYP3A4 in vitro. In addition, concurrent use of topiramate and drugs that affect platelet function such as platelet inhibitors may increase the risk of bleeding. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate (4.5%) compared to placebo (23%). In those with severe bleeding events, patients were often taking drugs that cause thrombocytopenia or affect platelet function or coagulation. [28378] [57151] Vortioxetine: (Moderate) Use phentermine and vortioxetine together with caution; use together may be safe and efficacious for some patients based on available data, provided the patient is on a stable antidepressant regimen and receives close clinical monitoring. Regular appointments to assess the efficacy of the weight loss treatment, the emergence of adverse events, and blood pressure monitoring are recommended. Watch for excessive serotonergic effects. Phentermine is related to the amphetamines, and there has been historical concern that phentermine might exhibit potential to cause serotonin syndrome or cardiovascular or pulmonary effects when combined with serotonergic agents. One case report has been received of adverse reactions with phentermine and the antidepressant fluoxetine. However, recent data suggest that phentermine's effect on MAO inhibition and serotonin augmentation is minimal at therapeutic doses, and that phentermine does not additionally increase plasma serotonin levels when combined with other serotonergic agents. In large controlled clinical studies, patients were allowed to start therapy with phentermine or phentermine; topiramate extended-release for obesity along with their antidepressants (e.g., SSRIs or SNRIs, but not MAOIs or TCAs) as long as the antidepressant dose had been stable for at least 3 months prior to the initiation of phentermine, and the patient did not have suicidal ideation or more than 1 episode of major depression documented. In analyses of the results, therapy was generally well tolerated, especially at lower phentermine doses, based on discontinuation rates and reported adverse events. Because depression and obesity often coexist, the study data may be important to providing optimal co-therapies. [51256] [56041] [57267] [57658] [57659] [57660] [7004] Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with topiramate is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy; increased bleeding is also possible with the combination. Topiramate is a weak CYP3A4 inducer and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance. In a pooled analysis of placebo-controlled trials, bleeding was more frequently reported in patients receiving topiramate compared to placebo. In patients with serious bleeding events, conditions that increased the risk for bleeding, including concurrent use of drugs that affect coagulation, were often present. [28378] [28549] Yohimbine: (Major) At high doses, yohimbine may nonselectively inhibit MAO and also, at normal doses, activates the sympathetic nervous system. Traditional MAOIs can cause serious adverse effects when taken concomitantly with sympathomimetics. [29541] [29542] Zonisamide: (Moderate) Monitor for the appearance or worsening of metabolic acidosis if zonisamide is given concomitantly with topiramate. Concomitant use of zonisamide with another carbonic anhydrase inhibitor, like topiramate, may increase the severity of metabolic acidosis and may also increase the risks of hyperammonemia, encephalopathy, and kidney stone formation. Monitor serum ammonia concentrations if signs or symptoms of encephalopathy occur. Hyperammonemia resulting from zonisamide resolves when zonisamide is discontinued and may resolve or decrease in severity with a decrease of the daily dose. [28378] [28843]
      Revision Date: 09/30/2020, 02:27:00 AM

      References

      2843 - Chua SS, Benrimoj SI. Non-prescription sympathomimetic agents and hypertension. Med Toxicol Adverse Drug Exp 1988;3:387-417.3490 - Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-1838.3640 - Karch SB. Ma huang and the Ephedra alkaloids. In: Toxicology and Clinical Pharmacology of Herbal Products, 1st ed. (Cupp MJ ed.) Humana Press. Totowa, New Jersey. 2000, pp. 11-25.3646 - White LM, Gardner SF, Gurley BJ, et al. Pharmacokinetics and cardiovascular effects of Ma-huang (Ephedra sinica) in normotensive adults. J Clin Pharmacol 1997;37:116-122.3666 - US Food and Drug Administration. Adverse events with Ephedra and other botanical dietary supplements. FDA Medical Bulletin; Sept 1994.4190 - Benedetti MS. Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundam Clin Pharmacol 2000;14:301-19.4666 - Cafcit (caffeine citrate) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Dec.4671 - Brown NJ, Ryder D, Branch RA. A pharmacodynamic interaction between caffeine and phenylpropanolamine. Clin Pharmacol Ther 1991;50:363-71.4741 - Peganone (ethotoin) tablets package insert. Lebanon, NJ: Recordati Rare Diseases Inc.; 2017 Feb.4966 - Gleevec (imatinib mesylate) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2014 May.5107 - Topamax (topiramate) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Jun.5206 - Rescriptor (delavirdine) package insert. Research Triangle Park, NC: ViiV Healthcare; 2012 Aug.5226 - Tracleer (bosentan) package insert. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2019 May.5241 - Weinberger M, Bronsky E, Bensch GW, et al. Interaction of ephedrine and theophylline. Clin Pharmacol Ther 1975;17:585-92.5265 - Cerebyx (fosphenytoin sodium) package insert. New York, NY: Pfizer Labs; 2020 Jan.5585 - Cafergot (caffeine; ergotamine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2002 June.5917 - HydroDIURIL (hydrochlorothiazide) package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 1998 Jun.6234 - Epinephrine injection 1:1000 package insert. Shirley, NY: American Regent, Inc.; 2005 Nov.6275 - Bradley JG. Nonprescription drugs and hypertension. Which ones affect blood pressure? Postgrad Med 1991;89:195-7, 201-2.6528 - Naik SD, Freudenberger RS. Ephedra-associated cardiomyopathy. Ann Pharmacother 2004;38:400-3.7004 - Bostwick JM, Brown TM. A toxic reaction from combining fluoxetine and phentermine. J Clin Psychopharmacol 1996;16:189-90.7005 - Fastin® (phentermine) package insert. Philadelphia, PA: Beecham Laboratories; 1987 Oct.7166 - Phendimetrazine tartrate extended-release capsules package insert. Laurelton, NY: Eon Labs Manufacturing, Inc.; 1994 Apr.8783 - Colchicine Tablets, USP package insert. Corona, CA: Watson Laboratories, Inc.; 2001 Jun.22005 - Perucca E. Clinically relevant drug interactions with antiepileptic drugs. Br J Clin Pharmacol 2006;61(3):246-255.24172 - Coates ML, et al. Does pseudoephedrine increase blood pressure in patients with controlled hypertension? J Fam Pract 1995;40:22-6.24656 - Abenhaim L, Moride Y, Brenot F, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. N Engl J Med 1996;335:609-16.26181 - Chua SS, Benrimoj SI. Non-prescription sympathomimetic agents and hypertension. Med Toxicol Adverse Drug Exp 1988;3:387-417.26815 - Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-1838.26816 - Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000;343:1826-1832.27106 - Zagnoni PG, Albano C. Psychostimulants and epilepsy. Epilepsia 2002;43(S2):28-31.27369 - Beck RA, Mercado DL, Seguin SM, et al. Cardiovascular effects of pseudoephedrine in medically controlled hypertensive patients. Arch Intern Med 1992;152:1242-5.27489 - Benedetti MS. Enzyme induction and inhibition by new antiepileptic drugs: a review of human studies. Fundam Clin Pharmacol 2000;14:301-19.27578 - Ben-Zeev B, Watemberg N, Augarten A, et al. Oligohydrosis and hyperthermia: a pilot study of a novel topiramate adverse effect. J Child Neurol 2003;18:254-7.27583 - Mayron D, Gennaro AR. Stability and compatibility of topotecan hydrochloride with selected drugs. Am J Health-Syst Pharm 1999;56:875-81.27843 - Ketter TA, Jenkins JB, Schroeder DH, et al. Carbamazepine but not valproate induces bupropion metabolism. J Clin Psychopharmacol 1995;15:327-33.27950 - Cafcit (caffeine citrate) package insert. Eatontown, NJ: West-Ward Pharmaceuticals; 2019 Dec.27957 - Nardil (phenelzine) tablet package insert. New York, NY: Pfizer; 2009 Feb.28001 - Hansten PD, Horn JR. Cytochrome P450 Enzymes and Drug Interactions, Table of Cytochrome P450 Substrates, Inhibitors, Inducers and P-glycoprotein, with Footnotes. In: The Top 100 Drug Interactions - A guide to Patient Management. 2008 Edition. Freeland, WA: H&H Publications; 2008:142-157.28058 - Wellbutrin XL (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 Nov.28142 - Reyataz (atazanavir) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2020 Sept.28156 - Ketek (telithromycin) package insert. Bridgewater, NJ: Sanofi-Aventis Pharmaceuticals; 2015 Oct.28168 - Flolan (epoprostenol) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2018 Dec,28211 - Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56.28269 - Celexa (citalopram) package insert. Irvine, CA: Allergan USA, Inc.; 2019 Jan.28272 - Lanoxin (digoxin) tablets package insert. St. Michael, Barbados: Concordia Pharmaceuticals Inc.; 2019 Feb.28294 - Methazolamide tablet package insert. Basking Ridge, NJ: Micro Labs USA, Inc.; 2019 Nov.28301 - Mefloquine package insert. Princeton, NJ: Sandoz Inc.; 2013 Jul.28309 - Foradil Aerolizer (formoterol fumarate inhalation powder capsules) package insert. Novartis Pharma AG: 2012 Nov.28314 - Ultram (tramadol immediate-release tablets) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 Oct.28378 - Topamax (topiramate) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Jun.28387 - Malarone (atovaquone, proguanil) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2018 Feb.28405 - Strattera (atomoxetine) package insert. Indianapolis, IN: Eli Lilly and Company; 2020 Feb.28451 - Lamictal (lamotrigine) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.28467 - Serevent Diskus (salmeterol xinafoate inhalation powder) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2019 July.28488 - Dexedrine Spansule (dextroamphetamine sustained-release capsules) package insert. Winchester, KY: Catalent Pharma Solutions; 2019 Jan.28496 - Tracleer (bosentan) package insert. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2019 May.28518 - Ritalin and Ritalin SR (methylphenidate) package insert. East Hanover, NJ: Novartis Pharmaceutical Corp.; 2019 Nov.28532 - Proventil HFA (albuterol sulfate) Inhalational Aerosol package insert. Whitehouse Station, NJ: Merck Sharp & Dohme Corp., a subsidiary of MERCK & CO., INC.; 2017 Sept.28533 - Maxair Autoinhaler (pirbuterol acetate inhalation aerosol) package insert. Northridge, CA: 3M Pharmaceuticals; 2008 Jan.28549 - Coumadin (warfarin tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2017 Aug.28550 - Glucophage and Glucophage XR (metformin HCl tablets and extended-release tablets) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2018 May.28557 - Elavil (amitriptyline) package insert. Birmingham, AL: Thompson Medical Solutions; 2016 Apr.28558 - Amoxapine package insert. Parsippany, NJ: Actavis Pharma, Inc.; 2015 Feb.28559 - Zagnoni PG, Albano C. Psychostimulants and epilepsy. Epilepsia 2002;43 Suppl 2:28-31.28562 - Norpramin (desipramine) package insert. Parsippany, NJ: Validus Pharmaceuticals LLC; 2018 Nov.28566 - Vivactil (protriptyline) package insert. Horsham, NJ: Teva Select Brands; 2014 May28568 - Vesanoid (tretinoin) capsules package insert. Nutley, NJ: Roche Laboratories Inc.; 2004 Oct.28599 - Zyvox (linezolid) package insert. New York, NY: Pharmacia and Upjohn Company; 2020 Aug.28609 - Meridia (sibutramine) package insert. North Chicago, IL: Abbott Laboratories; 2009 Apr.28759 - Maprotiline HCl tablet package insert. Morgantown WV: Mylan Pharmaceuticals Inc; 2014 Dec.28817 - Pisani F, Oteri G, Costa C, et al. Effects of psychotropic drugs on seizure threshold. Drug Saf. 2002;25:91-110.28820 - Moban (Molindone) package insert. Chadds Ford, PA: Endo Pharmaceuticals Inc; 2017 Mar.28843 - Zonegran (zonisamide) package insert. Dublin, Ireland: Concordia Pharmaceuticals, Inc.; 2020 Apr.28862 - Bernstein JG. Chapter 12 - Drug Interactions. In: Drug Therapy in Psychiatry. 3rd ed. St. Louis MO: Mosby-Year Book, Inc.;1995:328-364.28963 - Omnipaque (iohexol) package insert. Marlborough, MA: GE Healthcare, Inc.; 2020 Jul.29024 - Hedges D, Jeppson K, Whitehead P. Antipsychotic medication and seizures: a review. Drugs Today (Barc). 2003;39:551-7.29088 - Sular (nisoldipine) package insert. Atlanta, GA: Shionogi Pharma, Inc.; 2017 Jun.29332 - Adderall XR (amphetamine; dextroamphetamine) package insert. Lexington, MA: Shire US Inc.; 2019 July.29413 - Glucotrol (glipizide) package insert. New York, NY; Pfizer Pharmaceuticals; 2011 Feb.29416 - Bruckner J, Thomas Jr KC, Bikhazi GB, et al. Neuromuscular drug interactions of clinical importance. Anesth Analg 1980;59:678-82.29418 - Diabeta (glyburide) package insert. Bridgewater, NJ: Sanofi-aventis; 2016 July.29493 - Epinephrine injection 1:1000 package insert. Shirley, NY: American Regent, Inc.; 2005 Nov.29534 - Bradley JG. Nonprescription drugs and hypertension. Which ones affect blood pressure? Postgrad Med 1991;89:195-7, 201-2.29541 - Food and Drug Administration (FDA), Center for Food Safety and Applied Nutrition. Illnesses and Injuries Associated with the use of Selected Dietary Supplements. Published 1993. Retrieved July 23, 2004. Available on the World Wide Web at http://www.cfsan.fda.gov/~dms/ds-ill.html.29542 - Grossman E, Rosenthal T, Peleg E, et al. Oral yohimbine increases blood pressure and sympathetic nervous outflow in hypertensive patients. J Cardiovasc Pharmacol 1993;22:22-6.29548 - Hoffman BB, Lefkowitz RJ. Catecholamines and sympathomimetic drugs. Gilman AG, Rall TW, Nies AS, Taylor P, (eds.) In: Goodman and Gilman's Pharmacological Basis of Therapeutics. 8th ed., New York, Pergamon Press. 1990. 187-91.29623 - Duragesic (fentanyl transdermal system) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 Oct.29656 - Parnate (tranylcypromine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals; 2018 Jan.29763 - Actiq (oral transmucosal fentanyl citrate) package insert. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2019 Oct.29796 - Ditropan XL (oxybutynin chloride) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 Sept.29831 - Bethanechol chloride tablet package insert. Parsippany, NJ: Wockhardt USA; 2020 Jun.30000 - Hoffman BB. Catecholamines, sympathomimetic drugs, and adrenergic receptor antagonists. Gilman AG, Hardman JG, Limbird LE, (eds.) In: Goodman and Gilman's The Pharmacological Basis of Therapeutics. 10th ed., New York, McGraw-Hill Companies. 2001:249-58.30106 - Imodium A-D Liquid and Caplets (loperamide HCL) consumer product labels. Fort Washington, PA: Johnson and Johnson Consumer Inc., McNeil Consumer Healthcare Division; 2019.30210 - Remodulin (treprostinil sodium injection) package insert. Research Triangle Park, NC: United Therapeutics Corp.; 2018 Jul.30227 - Dilor (dyphylline) package insert. Melville, NY: Savage Laboratories; 1987 Sep.30253 - Bostwick JM, Brown TM. A toxic reaction from combining fluoxetine and phentermine. J Clin Psychopharmacol 1996;16:189-90.30266 - Fedutes BA, Ansani NT. Seizure potential of concomitant medications and radiographic contrast media agents. Ann Pharmacother 2003;37:1506-10. Review.30282 - Synalgos-DC (aspirin; caffeine; dihydrocodeine) capsules package insert. Atlanta, GA: Mikart, Inc.; 2019 Oct.30379 - Hycodan (hydrocodone bitartrate; homatropine methylbromide) package insert. Malvern, PA: Endo Pharmaceuticals Inc.; 2018 Jun.30431 - Marinol (dronabinol, THC) package insert. Marietta, GA: Unimed Pharmaceuticals, Inc.; 2017 Aug.30438 - Marplan (isocarboxazid) package insert. Parsippany, NJ: Validus Pharmaceuticals; 2018 Nov.30676 - Emend (aprepitant oral products) package insert. Whitehouse Station, NJ: Merck & Co.,Inc.; 2019 Nov.30774 - Ventavis (iloprost) package insert. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2019 Dec.30966 - Sufenta (sufentanil citrate injection) package insert. Lake Forest, IL: Akorn Pharmaceuticals, Inc.; 2019 Oct31240 - Tradjenta (linagliptin) package insert. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc.; 2020 Mar.31327 - Abilify (aripiprazole) tablets, discmelt orally-disintegrating tablets, oral solution, and intramuscular injection. Rockville, MD: Otsuka America Pharmaceutical, Inc.; 2020 Feb.31426 - Groeper K, McCann ME. Topiramate and metabolic acidosis: a case series and review of the literature. Paediatr Anaesth 2005;15:167-70.31583 - Cylert (pemoline) package insert. North Chicago, IL: Abbott Laboratories; 2002 Dec.32026 - Emsam (selegiline) transdermal system package insert. Morgantown, WV: Somerset Pharmaceuticals, Inc.; 2020 May.32121 - Daytrana (methylphenidate transdermal system) package insert. Miami, FL: Noven Therapeutics, LLC; 2019 Oct.32148 - Depakote ER (divalproex sodium extended-release tablets) package insert. North Chicago, IL: AbbVie Inc.; 2020 May.32149 - Panda S, Radhakrishnan K. Two cases of valproate-induced hyperammonemic encephalopathy without hepatic failure. J Assoc Physicians India 2004;52:746-8.32150 - Cheung E, Wong V, Fung CW. Topiramate-valproate-induced hyperammonemic encephalopathy syndrome: case report. J Child Neurol 2005;20:157-60.32151 - Longin E, Teich M, Koelfen W, et al. Topiramate enhances the risk of valproate-associated side effects in three children. Epilepsia 2002;43:451-4.32223 - Azilect (rasagiline mesylate) tablets. Kansas City, MO: Teva Neurosciences, Inc.; 2020 Jun.32226 - Cesamet (nabilone) capsule package insert. Somerset, NJ: Meda Pharmaceuticals; 2020 Mar.32308 - Lawrence KR, Adra M, Gillman PK. Serotonin toxicity associated with the use of linezolid: A review of postmarketing data. Clin Infect Dis 2006;42:1578-83.32432 - Prezista (darunavir) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2019 May.32436 - Zelapar (selegiline orally-disintegrating tablets) package insert. Bridgewater, NJ: Bausch Health U.S., LLC; 2020 Feb.32731 - Fentora (fentanyl buccal tablet) package insert. North Wales, PA: Teva Pharmaceuticals, Inc.; 2019 Oct.32857 - Lidocaine hydrochloride and 5% dextrose injection package insert. Deerfield, IL: Baxter Healthcare Corporation; 2017 Feb.32901 - Brovana (arformoterol tartrate) inhalation solution package insert. Marlborough, MA: Sunovion Pharmaceuticals, Inc..; 2019 May.33263 - Vyvanse (lisdexamfetamine) capsules and chewable tablets package insert. Lexington, MA: Shire US Inc.; 2017 July.33363 - Desoxyn (methamphetamine hydrochloride) package insert. Deerfield, IL: Abbott Pharmaceuticals, Inc.; 2017 May.33473 - Selzentry (maraviroc) package insert. Research Triangle Park, NC: ViiV Healthcare; 2020 Oct.33941 - Doose DR, Wang SS, Padmanabhan M, et al. Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia 2003;44:540-9.34470 - Aczone (dapsone gel 5%) package insert. Irvine CA: Allergan Inc.; 2018 May.34626 - Vimpat (lacosamide) package insert. Smyrna, GA: UCB, Inc.; 2020 Nov.35040 - Amaryl (glimepiride) package insert. Bridgewater, NJ: Sanofi-Aventis; 2016 Dec.35588 - Exforge HCT (amlodipine, valsartan, hydrochlorothiazide) tablets package insert. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2020 Aug.35780 - Samsca (tolvaptan) package insert. Rockville, MD: Otsuka America Pharmaceutical, Inc.; 2018 Apr.36101 - Multaq (dronedarone) package insert. Bridgewater, NJ: Sanofi-aventis; 2014 Mar.37098 - Votrient (pazopanib) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2011 Oct.37292 - Istodax (romidepsin) package insert. Bedford, OH: Ben Venue Laboratories, Inc.; 2018 Nov.37590 - Elewski B, Tavakkol A. Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality. Ther Clin Risk Manag. 2005;1(4):299-306.39926 - OxyContin (oxycodone HCl extended-release) package insert. Stamford, CT: Purdue Pharma L.P.; 2019 Oct.40027 - Emend (fosaprepitant dimeglumine injection) package insert. Whitehouse Station, NJ: Merck & Co.,Inc.; 2019 Nov.40942 - Remeron and RemeronSolTabs (mirtazapine tablets and ODT tablets) package insert. Roseland, NJ: Organon USA, Inc.; 2020 Apr.40943 - Onsolis (fentanyl buccal soluble film) package insert. Raleigh, NC: BioDelivery Sciences, International, Inc.; 2019 Oct.40993 - Wellbutrin SR (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41086 - Wellbutrin (bupropion) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2020 Oct.41163 - Tofranil (imipramine) package insert. Hazelwood, MO; Mallinckrodt Inc.; 2017 April.41237 - Tegretol (carbamazepine) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2018 Mar.41569 - Ella (ulipristal 30 mg tablets) package insert. Paris, France: Laboratoire HRA Pharma; 2018 May.41806 - Plaquenil (hydroxychloroquine) package insert. St. Michael, Barbados: Concordia Pharmaceuticals, Inc.; 2017 Jan.42075 - Anafranil (clomipramine capsules) package insert. Hazelwood, MO: Mallinckrodt, Inc.; 2019 May.42135 - Adams IB, Martin BR: Cannabis: pharmacology and toxicology in animals and humans. Addiction 1996;91(11):1585-1614.42227 - Latuda (lurasidone) package insert. Marlborough, MA: Sunovion Pharmaceuticals, Inc.; 2019 Dec.42448 - Watanabe K, Yamaori S, Funahashi T, et al: Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sciences 2007;80:1415-1419.43364 - Glynase (glyburide) package insert. New York, NY; Pfizer Pharmaceuticals; 2017 Aug.43880 - Lamisil (terbinafine oral granules) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019 Mar.43881 - Lamisil (terbinafine tablet) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019 Mar.43942 - Levothroid (levothyroxine sodium tablet) package insert. Shenandoah, IA: Lloyd Pharmaceutical; 2011 June.44094 - Zyban (bupropion sustained release tablets) package insert. Research Triangle Park, NC: GlaxoSmithKline; 2017 May.44314 - Victrelis (boceprevir) capsule package insert. Whitehouse Station, NJ: Merck and Co, Inc; 2017 Jan.44376 - Edurant (rilpivirine) package insert. Titusville, NJ: Janssen Therapeutics; 2019 May.44662 - Condit FS, Campbell RK, White JR. Diabetes. In: Handbook of Nonprescription Drugs. 12th ed. Washington, DC: American Pharmaceutical Association 2000;285:315-359.44854 - Xarelto (rivaroxaban) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Mar44979 - Arcapta Neohaler (indacaterol inhalation powder) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2019 May.45335 - Zelboraf (vemurafenib) tablet package insert. South San Francisco, CA: Genentech USA, Inc.; 2020 May.45905 - Matulane (procarbazine) package insert. Gaithersburg, MD: Sigma-tau Pharmaceuticals, Inc; 2008 Mar.45935 - Gefitinib (Iressa) package insert. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2018 Aug.46537 - Adipex-P (phentermine hydrochloride tablets and capsules) package insert. Sellersville, PA: Teva Pharmaceuticals; 2013 Jan.46594 - Suprenza (phentermine hydrochloride) package insert. Cranford, NJ: Akrimax Pharmaceuticals; 2011 Oct.46595 - Phentermine hydrochloride package insert. Newtown, PA: KVK-Tech Inc; 2018 Dec.46792 - Metaproterenol tablet package insert. Spring Valley, NY: Par Pharmaceutical Companies, Inc.; 2010 Jul.48201 - US Department of Health and Human Services/Centers for Disease Control and Prevention. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65:1-103.49571 - Guanabenz acetate tablet package insert. Miami, FL: Ivax Pharmaceuticals, Inc.; 2010 Nov.49611 - Halothane package insert. Lake Forest, IL: Hospira, Inc.; 2005 Jun.49784 - Urogesic-Blue (methenamine; sodium acid phosphate; methylene blue; hyoscyamine) package insert. Ripley, Mississippi: Belcher Pharmaceuticals Inc for Edwards Pharmaceutical, Inc.; 2010 Aug.50623 - Ulipristal (Esmya 5 mg tablets) European package insert. London UK; Gedeon Richter (UK) Ltd: 2017 Aug.51002 - Chan JC, Cockram CS, Critchley JA. Drug-induced disorders of glucose metabolism. Mechanisms and management. Drug Saf 1996;15:135—57.51065 - Belviq and Belviq XR (lorcaserin hydrochloride) package insert. Woodcliff Lake, NJ: Eisai Inc.; 2016 Nov.51256 - Qsymia (phentermine and topiramate extended-release) package insert. Mountain View, CA: Vivus, Inc.; 2020 Sept.52140 - Perampanel (Fycompa) tablets and oral suspension package insert. Woodcliff Lake, NJ: Eisai Inc.; 2019 May.53320 - Markowitz JS, Patrick KS. Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder. Clin Pharmacokinet 2001;40:753-72.53394 - Abilify Maintena (aripiprazole) extended-release intramuscular injection package insert. Rockville, MD:Otsuka America Pharmaceutical, Inc.; 2020 Feb.54633 - Breo Ellipta (fluticasone; vilanterol) package insert. Research Triangle Park, NC: GlaxoSmithkline; 2019 Jan.55436 - Patsalos PN, Berry DJ, Bourgeois BF. Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia 2008;49:1239-1276.55594 - Tivicay (dolutegravir) package insert. Research Triangle Park, NC: ViiV Healthcare; 2020 Jun.55675 - Trokendi XR (topiramate extended-release capsules) package insert. Rockville, MD: Supernus Pharmaceuticals; 2020 Nov.56041 - Trintellix (vortioxetine tablets) package insert. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2020 Nov.56096 - Adempas (riociguat) package insert. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2018 Dec.56260 - Opsumit (macitentan) package insert. South San Francisco, CA: Actelion Pharmaceuticals US, Inc; 2019 Apr.56303 - Zohydro ER (hydrocodone extended-release capsules) package insert. Morristown, NJ: Currax Pharmaceuticals LLC; 2019 Oct.56361 - Doxorubicin hydrochloride package insert. New York, NY: Pfizer Labs; 2013 Oct.56471 - Olysio (simeprevir) capsule package insert. Titusville, NJ: Janssen Therapeutics; 2017 Nov.56538 - Vickers AE, Sinclair JR, Zollinger M. Multiple cytochrome P-450s involved in the metabolism of terbinafine suggest a limited potential for drug-drug interactions. Drug Metab Dispos. 1999;27(9):1029-1038.56564 - Anoro Ellipta (umeclidinium; vilanterol) package insert. Research Triangle Park, NC: GlaxoSmithkline; 2019 Jun.57036 - Brodie MJ, Mintzer S, Pack AM, et al. Enzyme induction with antiepileptic drugs: cause for concern? Epilepsia 2013;54:11-27.57046 - Perucca E, Hedges A, Makki KA, et al. A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. Br J Clin Pharmacol 1984;18:401-10.57048 - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Retrieved from the World Wide Web December 27, 2013. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#major57151 - Zontivity (vorapaxar) package insert. Parsippany, NJ: Aralez Pharmaceuticals US Inc.; 2019 Nov.57267 - Zolkowska D, Rothman RB, Baumann MH. Amphetamine analogs increase plasma serotonin: implications for cardiac and pulmonary disease. J Pharmacol Exp Ther. 2006;318:604-610.57419 - Isovue-M (iopamidol) injection package insert. Monroe Township, NJ: Bracco Diagnostics Inc.; 2017 Mar.57468 - Sivextro (tedizolid) prescribing information. Whitehouse Station, NJ: Merck & Co. Inc.; 2020 Oct.57648 - Depo-Provera (medroxyprogesterone acetate 400 mg/ml) injection suspension package insert. New York, NY: Pharmacia & Upjohn Company; 2017 Apr.57658 - Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:1341-1352. Epub 2011 Apr 8. Erratum in: Lancet. 2011;377:1494.57659 - O'Neill PM, Peterson, CA. Weight Loss and Depression in Overweight/Obese Subjects With a History of Depression Receiving Phentermine and Topiramate Extended-Release. Presented at the 166th Annual Meeting of the American Psychiatric Association (APA) San Francisco, CA; 2013 May 20. (unpublished).57660 - Allison DB, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20:330-342.57922 - Contrave (naltrexone HCl and bupropion HCl) extended-release tablets package insert. La Jolla, CA: Nalpropion Pharmaceuticals, Inc.; 2020 Aug.58000 - Tybost (cobicistat) package insert. Foster City, CA: Gilead Sciences, Inc; 2020 Aug.58486 - Taichman DB, Ornelas J, Chung L, et al. Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report. Chest. 2014;146:449-75.58664 - Viekira Pak (ombitasvir; paritaprevir; ritonavir; dasabuvir) tablet package insert. North Chicago, IL: AbbVie, Inc; 2019 Dec.59042 - Cresemba (isavuconazonium) package insert. Northbrook, IL: Astellas Pharma US, Inc; 2019 Dec.59430 - Corlanor (ivabradine) package insert. Thousand Oaks, CA: Amgen Inc.; 2019 Apr.59949 - Rexulti (brexpiprazole) tablets package insert. Rockville, MD: Otsuka Pharmaceutical Co., Ltd.; 2020 Jun.60070 - Evekeo (amphetamine sulfate tablets) package insert. Atlanta, GA: Arbor Pharmaceuticals, LLC: 2015 Apr.60083 - Amitriptyline tablets package insert. Morgantown, WV; Mylan Pharmaceuticals, Inc.: 2014 Dec.60099 - Addyi (flibanserin tablets) package insert. Raleigh, NC: Sprout Pharmaceuticals, Inc.; 2019 Aug.60122 - Keveyis (dichlorphenamide) tablets package insert. Trevose, PA: Strongbridge US Inc.; 2019 Nov.60164 - Vraylar (cariprazine capsules) package insert. Parsippany, NJ:Actavis Pharma, Inc.; 2019 May.60196 - Aristada (aripiprazole lauroxil) extended-release intramuscular suspension package insert. Waltham, MA: Alkermes, Inc.; 2020 Feb.60269 - Genvoya (elvitegravir; cobicistat; emtricitabine; tenofovir alafenamide) package insert. Foster City, CA: Gilead Sciences, Inc; 2019 Feb.60281 - Cotellic (cobimetinib) tablets package insert. San Francisco, CA: Genentech USA, Inc; 2016 June.60482 - Galie N, Corris PA, Frost A, et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol 2013;62:D60-72.60523 - Zepatier (elbasvir; grazoprevir) tablet package insert. Whitehouse Station, NJ: Merck, Inc; 2019 Dec.60612 - Aczone (dapsone gel 7.5%) package insert. Exton, PA: Almirall, LLC; 2019 Sept.60911 - Epclusa (sofosbuvir; velpatasvir) tablet package insert. Foster City, CA: Gilead Sciences, Inc; 2020 Jul.60951 - Syndros (dronabinol) oral solution package insert. Chandler, AZ; Insys Therapeutics, Inc. 2018 Sept.61173 - Livingston MG, Livingston HM. Monoamine oxidase inhibitors: an update on drug interactions. Drug Safety 1996;14:219-27.61198 - Lomaira (phentermine hydrochloride) package insert. Newton, PA: KVK-Tech, Inc.; 2016 Sept.61243 - Manohar C, Avitsian R, Lozano S, et al. The effect of antiepileptic drugs on coagulation and bleeding in the perioperative period of epilepsy surgery: the Cleveland Clinic experience. J Clin Neurosci 2011;18:1180-1184.61368 - Holmes B, Brogden RN, Heel RC, et al. Guanabenz. A review of its pharmacodynamic properties and therapeutic efficacy in hypertension. Drugs 1983;26:212-29.61825 - Xadago (safinamide) package insert. Louisville, KY: US WorldMeds, LLC; 2017 Mar.61932 - Rapaport MH. Dietary restrictions and drug interactions with monoamine oxidase inhibitors: the state of the art. J Clin Psychiatry. 2007;68 Suppl 8:42-46.63328 - Aristada Initio (aripiprazole lauroxil extended-release injectable suspension) package insert. Altham, MA:Alkermes, Inc.; 2020 Feb.63402 - Azedra (iobenguane I-131) injection package insert. New York, NY: Progenics Pharmaceuticals, Inc.; 2018 July.63484 - Pifeltro (doravirine) package insert. Whitehouse Station, NJ: Merck & Co., Inc.; 2019 Oct.63591 - Goprelto (cocaine) nasal solution package insert. Allentown, PA: Genus Lifesciences, Inc.; 2017 Dec.63622 - Wilcox SR, Kabrhel C, Channick RN. Pulmonary Hypertension and Right Ventricular Failure in Emergency Medicine. Ann Emerg Med. 2015;66:619-28.63731 - Dsuvia (sufentanil) sublingual tablets package insert. Redwood City, CA: AcelRx Pharmaceuticals, Inc.; 2019 Oct.63771 - Brodie MJ. Sodium channel blockers in the treatment of epilepsy. CNS Drugs 2017;31:527-534.63772 - Cook AM, Bensalem-Owen MK. Mechanisms of action of antiepileptic drugs. Therapy 2011;8:307-313.63790 - Firdapse (amifampridine) tablets package insert. Coral Gables, FL: Catalyst Pharmaceuticals, Inc.; 2018 Nov.63989 - Spravato (esketamine) nasal spray package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2020 Jul.64026 - Sunosi (solriamfetol tablets) package insert. Palo Alto, CA: Jazz Pharmaceuticals, Inc.; 2019 Jun.64885 - Caplyta (lumateperone) capsules package insert. Hamilton, Bermuda; Intra-Cellular Therapies, Inc.; 2019 Dec.64910 - Bretylium tosylate injection package insert. Baudette, MN; ANI Pharmaceuticals, Inc.: 2019 Dec.64935 - Numbrino (cocaine hydrochloride) nasal solution package insert. Philadelphia, PA: Lannett Company, Inc.; 2020 Aug.65169 - Ozanimod (Zeposia) capsules package insert. Summit, NJ: Celgene Corporation; 2020 Sep.

      Monitoring Parameters

      • blood glucose
      • serum bicarbonate
      • serum creatinine/BUN
      • serum electrolytes
      • weight

      US Drug Names

      • Qsymia