Version May 2024
Note: Qsymia is a fixed-dose combination product of phentermine/topiramate formulated in a 3.75 mg phentermine/23 mg topiramate ratio.
Weight management, chronic:
Note: For use as adjunct therapy with a reduced-calorie diet and increased physical activity in pediatric patients; only use in patients 12 to <18 years of age with an initial BMI in the 95th percentile or higher for age and sex or patients ≥18 years who have a BMI ≥30 kg/m2 or patients with a BMI ≥27 kg/m2 and ≥1 weight-associated comorbidity (eg, dyslipidemia). Pregnancy status must be assessed monthly during therapy. Doses should be administered in the morning to prevent insomnia, which may occur if doses are administered in the evening. Therapeutic monitoring parameters for dosage adjustments vary by age; in patients 12 to <18 years of age, the rate of weight loss and BMI should be used and in patients ≥18 years of age, weight should be used.
Children ≥12 years and Adolescents <18 years: Qsymia:
Initial: Oral: 3.75 mg phentermine/23 mg topiramate once daily for 14 days, then increase to 7.5 mg phentermine/46 mg topiramate once daily; assess BMI after 12 weeks of therapy and adjust dose as appropriate.
Dosage adjustment: Oral:
• If during any point in therapy weight loss is >0.9 kg/week, consider a decrease in current dose.
• After the first 12 weeks of therapy at the 7.5 mg phentermine/46 mg topiramate daily dose, assess BMI.
- If BMI reduced by ≥3% from baseline, continue current dose of 7.5 mg phentermine/46 mg topiramate once daily.
- If BMI reduced by <3% from baseline after 12 weeks of therapy, increase dose to 11.25 mg phentermine/69 mg topiramate once daily for 14 days, then increase to 15 mg phentermine/92 mg topiramate once daily. After 12 weeks at highest dose, reassess patient's BMI. If BMI reduced by ≥5% from baseline, continue current dose. If BMI only reduced by <5%, discontinue therapy, as patient is unlikely to see further efficacy.
Adolescents ≥18 years of age: Qsymia:
Initial: Oral: 3.75 mg phentermine/23 mg topiramate once daily for 14 days, then increase to 7.5 mg phentermine/46 mg topiramate once daily; assess weight after 12 weeks of therapy and adjust dose as appropriate.
Dosage adjustment: Oral:
• After the first 12 weeks of therapy at the 7.5 mg phentermine/46 mg topiramate daily dose, assess weight.
- If weight reduced by ≥3% from baseline, continue current dose of 7.5 mg phentermine/46 mg topiramate once daily.
- If weight reduced by <3% from baseline after 12 weeks of therapy, increase dose to 11.25 mg phentermine/69 mg topiramate once daily for 14 days, then increase to 15 mg phentermine/92 mg topiramate once daily. After 12 weeks at highest dose, reassess patient's weight. If weight reduced by ≥5% from baseline, continue current dose. If weight only reduced by <5%, discontinue therapy, as patient is unlikely to see further efficacy.
Discontinuation of therapy: Children and Adolescents: Qsymia: Oral: Doses should be gradually tapered to prevent possibility of seizure activity; for example, patients on the 15 mg phentermine/92 mg topiramate daily dose should taper to every other day for 1 week prior to discontinuation.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children ≥12 years and Adolescents: Oral:
Note: Kidney function may be estimated using the Cockcroft-Gault formula with actual body weight for dosage adjustment purposes.
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Maximum daily dose: 7.5 mg phentermine/46 mg topiramate once daily.
End-stage kidney disease on dialysis: Avoid use (has not been studied).
Children ≥12 years and Adolescents: Oral:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Maximum daily dose: 7.5 mg phentermine/46 mg topiramate once daily.
Severe impairment (Child-Pugh class C): Avoid use (has not been studied).
(For additional information see "Phentermine and topiramate: Drug information")
Weight management, chronic (alternative agent):
Note: For use as an adjunct to diet and exercise in patients who cannot take preferred agents and who have a BMI ≥30 kg/m2 or patients with a BMI ≥27 kg/m2 and ≥1 weight-associated comorbidity (eg, dyslipidemia). Avoid use in patients with known cardiovascular disease (eg, hypertension or coronary artery disease) (Ref). In females of childbearing potential, perform pregnancy test prior to initiation and monthly thereafter. Phentermine/topiramate is a combination product formulated in a 3.75:23 ratio. Adult dosage recommendations expressed as total mg of phentermine/topiramate.
Oral: Initial: Phentermine 3.75 mg/topiramate 23 mg once daily for 14 days. Increase dose as tolerated to phentermine 7.5 mg/topiramate 46 mg once daily for 12 weeks, then evaluate weight loss. If ≥3% of baseline body weight has not been lost, either discontinue therapy with a gradual taper (eg, switch from daily dosing to every other day dosing for at least 1 week before discontinuing) or escalate the dose based on tolerability and patient preference. Dose may be escalated to phentermine 11.25 mg/topiramate 69 mg once daily for 14 days, and then to a maximum dose of phentermine 15 mg/topiramate 92 mg once daily. Evaluate weight loss after 12 weeks on phentermine 15 mg/topiramate 92 mg; if ≥5% of baseline body weight has not been lost, discontinue therapy with a gradual taper (ie, switch from daily dosing to every-other-day dosing for at least 1 week before discontinuing) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Manufacturer's labeling: Note: Kidney function may be estimated using the Cockcroft-Gault formula with actual body weight for dosage adjustment purposes.
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Maximum dose: Phentermine 7.5 mg/topiramate 46 mg once daily.
End-stage kidney disease on dialysis: Avoid use (has not been studied).
Alternate dosing (Ref):
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl 30 to 49 mL/minute: Maximum dose: Phentermine 7.5 mg/topiramate 46 mg once daily.
CrCl <30 mL/minute: Use is not recommended.
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Maximum dose: Phentermine 7.5 mg/topiramate 46 mg once daily
Severe impairment (Child-Pugh class C): Avoid use (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults unless otherwise specified. Also see individual agents.
>10%:
Cardiovascular: Increased heart rate (adolescents and adults: >5 bpm: 70% to 81%; >10 bpm: 50% to 65%; >15 bpm: 33% to 43%; >20 bpm: 14% to 24%)
Endocrine & metabolic: Decreased serum bicarbonate (adolescents: 60% to 70%; adults: 6% to 13%)
Gastrointestinal: Constipation (8% to 16%), xerostomia (7% to 19%)
Nervous system: Headache (10% to 11%), paresthesia (adolescents: 2% to 3%; adults: 4% to 20%), sleep disorder (6% to 11%; including insomnia)
Neuromuscular & skeletal: Decreased bone mineral density (adolescents)
Renal: Increased serum creatinine (≥0.3 mg/dL: [adolescents: 17%, adults: 7% to 8%]; ≥50% over baseline: [adults: 2% to 3%])
Respiratory: Nasopharyngitis (9% to 13%), upper respiratory tract infection (14% to 16%)
1% to 10%:
Cardiovascular: Chest discomfort (1% to 2%), palpitations (2%)
Dermatologic: Alopecia (2% to 4%), skin rash (3%)
Endocrine & metabolic: Decreased serum potassium (<3.5 mEq/L: 4% to 5%; <3 mEq/L: <1%), hypokalemia (1% to 3%), increased thirst (2%)
Gastrointestinal: Decreased appetite (2%), diarrhea (6%), dysgeusia (metallic taste; 7% to 9%), dyspepsia (3%), gastroenteritis (3%), gastroesophageal reflux disease (3%), nausea (6% to 7%), oral paresthesia (1% to 2%), upper abdominal pain (adolescents: 3%)
Genitourinary: Dysmenorrhea (1% to 2%), urinary tract infection (5%)
Infection: Influenza (adolescents and adults: 2% to 8%)
Nervous system: Anxiety (adolescents and adults: 2% to 8%), cognitive dysfunction (including problems with concentration, memory, and language [word finding]: 5% to 8%), depression (adolescents and adults: 2% to 8%), disturbance in attention (2% to 4%), dizziness (adolescents and adults: 2% to 9%), fatigue (adolescents and adults: 3% to 6%), hypoesthesia (4%), irritability (2% to 4%)
Neuromuscular & skeletal: Arthralgia (adolescents: 2% to 4%), back pain (6% to 7%), muscle spasm (3%), musculoskeletal chest pain (adolescents: 3%), musculoskeletal pain (2% to 3%), neck pain (2%)
Ophthalmic: Blurred vision (5% to 6%), dry eye syndrome (3%), eye pain (2%)
Renal: Nephrolithiasis (1%)
Respiratory: Bronchitis (5% to 7%), cough (5%), nasal congestion (2%), paranasal sinus congestion (3%), pharyngolaryngeal pain (3%), sinusitis (7% to 8%)
Miscellaneous: Fever (adolescents: 4%)
<1%: Nervous system: Suicidal ideation (adolescents), suicidal tendencies (adolescents)
Frequency not defined: Neuromuscular & skeletal: Linear skeletal growth rate below expectation (reduction in height velocity)
Postmarketing:
Endocrine & metabolic: Hyperchloremic metabolic acidosis (nonanion gap)
Ophthalmic: Acute angle-closure glaucoma, increased intraocular pressure
Hypersensitivity to phentermine, topiramate, or any component of the formulation or idiosyncrasy to sympathomimetic amines; hyperthyroidism; glaucoma; use during or within 14 days following monoamine oxidase inhibitor therapy; pregnancy.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Cardiovascular effects: Can increase resting heart rate; monitor closely when starting or increasing dosage, and in patients with cardiac or cerebrovascular disease. Reduce dose or discontinue use with a sustained increase in resting heart rate.
• CNS effects: Cognitive dysfunction and psychiatric disturbances (mood disorders including anxiety, depression or insomnia) may occur with use; incidence of cognitive events (including attention, language, or memory difficulties) may be related to rapid titration and higher doses; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Risk may be increased in patients with a history of depression; dose reduction or discontinuation may be necessary.
• Dermatologic effects: Severe dermatologic reactions, including toxic epidermal necrolysis and Stevens-Johnson syndrome, have been reported with topiramate therapy; discontinue therapy if signs and symptoms occur.
• Hyperthermia: Topiramate may be associated (rarely) with severe oligohidrosis and hyperthermia; use caution and monitor closely during strenuous exercise, during exposure to high environmental temperature, or in patients receiving other carbonic anhydrase inhibitors and drugs with anticholinergic activity.
• Hypokalemia: Can cause hypokalemia; use caution with concurrent use of hydrochlorothiazide or furosemide as risk of hypokalemia may be increased; monitor potassium closely.
• Hypotension: In hypertensive patients, weight loss in conjunction with antihypertensive therapy may increase the risk of hypotension; monitor blood pressure prior to and during treatment; adjust antihypertensive treatment as necessary.
• Metabolic acidosis (hyperchloremic, nonanion gap): May decrease serum bicarbonate concentrations, due to inhibition of carbonic anhydrase and increased renal bicarbonate loss. Risk may be increased in patients with conditions that predispose to acidosis (eg, diarrhea, ketogenic diet, renal disease, severe respiratory disorders, status epilepticus, surgery) or concurrent treatment with other carbonic anhydrase inhibitors. Monitor serum electrolytes and bicarbonate prior to and during treatment. Reduce dose or discontinue use if persistent metabolic acidosis develops.
• Ocular effects: Topiramate has been associated with acute myopia and secondary angle-closure glaucoma in adults and children, typically within 1 month of initiation but may occur at any time; discontinue in patients with acute onset of decreased visual acuity or ocular pain. Topiramate is also associated with visual field effects, which may occur without elevation of intraocular pressure; most effects were reversible with discontinuation.
• Renal calculus: Use is associated with kidney stone formation. Topiramate exhibits weak carbonic anhydrase inhibitory properties and may increase the risk of kidney stones. The risk of stones may be increased in patients on a ketogenic diet or concurrent treatment with other carbonic anhydrase inhibitors; risk of stones may be reduced by increasing fluid intake.
• Renal effects: May increase serum creatinine; peak increases from baseline were observed after 4 to 8 weeks of treatment. Changes in serum creatinine (and GFR) with short-term use appear reversible with discontinuation; effects of long-term treatment on renal function are not known. Monitor serum creatinine prior to and during treatment. For persistent elevations, dose reduction or discontinuation may be necessary.
• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Avoid use in patients with history of suicide attempts or current suicidal ideation. Monitor all patients for notable changes in depression, suicidal thoughts or behavior; discontinue use in patients who experience suicidal thoughts or behavior.
Disease-related concerns:
• Diabetes: Use with caution in patients with type 2 diabetes mellitus; antidiabetic agent requirements (eg, insulin or oral hypoglycemic agents) may be decreased with weight loss, anorexigens and concomitant dietary restrictions. Monitor blood glucose levels prior to and during treatment.
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment may be required. Avoid use in patients with severe hepatic impairment (Child-Pugh class C).
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be required. Avoid use in patients with end-stage renal disease on dialysis.
Dosage form specific issues:
• Tartrazine: May contain FD&C Yellow No. 5 (tartrazine), which may cause allergic reactions, including bronchial asthma in susceptible individuals, especially in patients with aspirin hypersensitivity.
Other warnings/precautions:
• Abuse potential: Phentermine is pharmacologically related to the amphetamines, which have a high abuse potential; prolonged use may lead to dependency. Prescriptions should be written for the smallest quantity consistent with good patient care to minimize the possibility of overdose.
• Withdrawal: Antiseizure medications (including topiramate) should not be discontinued abruptly because of the possibility of increasing seizure frequency. Therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, extended release, oral:
Qsymia: 3.75/23: Phentermine 3.75 mg [immediate release] and topiramate 23 mg [extended release] [contains tartrazine]
Qsymia: 7.5/46: Phentermine 7.5 mg [immediate release] and topiramate 46 mg [extended release] [contains tartrazine]
Qsymia: 11.25/69: Phentermine 11.25 mg [immediate release] and topiramate 69 mg [extended release] [contains tartrazine]
Qsymia: 15/92: Phentermine 15 mg [immediate release] and topiramate 92 mg [extended release] [contains tartrazine]
Capsule ER 24 Hour Therapy Pack (Qsymia Oral)
3.75-23 mg (per each): $7.64
7.5-46 mg (per each): $7.89
11.25-69 mg (per each): $8.46
15-92 mg (per each): $8.46
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
C-IV
Oral: Administer in the morning without regard to food; avoid late evening administration (potential for insomnia).
Oral: Administer in the morning without regard to meals; avoid late evening administration (potential for insomnia).
Bariatric surgery: Capsule, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. ER capsule should be swallowed whole. Do not open, crush, chew, or divide. No alternative formulations are available. Individual components of phentermine and topiramate are available as IR tablets. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, careful evaluation of GI status (gastric emptying and small bowel transit), nutritional intake, and behavioral habits is strongly advised before administering anorexiant agents after bariatric surgery.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022580s023lbl.pdf#page=44, must be dispensed with this medication.
Adjunct treatment for chronic weight management along with a reduced-calorie diet and increased physical activity in pediatric patients with an initial BMI in the ≥95th percentile standardized for age and sex (FDA approved in pediatric patients ≥12 years of age); adjunct treatment for chronic weight management along with a reduced-calorie diet and increased physical activity in patients with either an initial BMI of ≥30 kg/m2 or an initial BMI of ≥27 kg/m2 and at least one weight-related comorbid condition (eg, dyslipidemia, type 2 diabetes, hypertension) (FDA approved in adults).
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acebrophylline: May enhance the stimulatory effect of CNS Stimulants. Risk X: Avoid combination
Alcohol (Ethyl): May enhance the CNS depressant effect of Topiramate. Alcohol (Ethyl) may increase the serum concentration of Topiramate. This applies specifically to use with the extended-release topiramate capsules (Trokendi XR). Also, topiramate concentrations may be subtherapeutic in the later portion of the dosage interval. Management: Concurrent use of alcohol within 6 hours of ingestion of extended-release topiramate (Trokendi XR) is contraindicated. Any use of alcohol with topiramate should be avoided when possible and should only be undertaken with extreme caution. Risk X: Avoid combination
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Alkalinizing Agents: May decrease the excretion of Amphetamines. Management: Consider alternatives to using amphetamines and alkalinizing agents in combination. If these agents must be used together, patients should be monitored closely for excessive amphetamine effects. Risk D: Consider therapy modification
Alpha-/Beta-Agonists (Indirect-Acting): Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Risk C: Monitor therapy
Amantadine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine. Risk C: Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Amitriptyline: Topiramate may enhance the CNS depressant effect of Amitriptyline. Topiramate may increase serum concentrations of the active metabolite(s) of Amitriptyline. Topiramate may increase the serum concentration of Amitriptyline. Risk C: Monitor therapy
Ammonium Chloride: May decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Risk C: Monitor therapy
Amphetamines: Carbonic Anhydrase Inhibitors may decrease the excretion of Amphetamines. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Antihypertensive Agents: Amphetamines may diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Asenapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Benperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
CarBAMazepine: Topiramate may enhance the CNS depressant effect of CarBAMazepine. CarBAMazepine may decrease the serum concentration of Topiramate. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May enhance the adverse/toxic effect of other Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regards to severity of metabolic acidosis. Risk X: Avoid combination
Carbonic Anhydrase Inhibitors: May decrease the excretion of Amphetamines. Risk C: Monitor therapy
Cariprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Clothiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CloZAPine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider therapy modification
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a moderate CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities (including serotonin syndrome) if used with a strong CYP2D6 inhibitor. Initiate amphetamine therapy at lower doses, monitor frequently, and adjust doses as needed. Discontinue amphetamines if serotoinin syndrome occurs. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the hypertensive effect of CNS Stimulants. Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flecainide: Carbonic Anhydrase Inhibitors may decrease the excretion of Flecainide. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Flupentixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of Topiramate. Topiramate may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Gastrointestinal Acidifying Agents: May decrease the serum concentration of Amphetamines. Risk C: Monitor therapy
Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Haloperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Hormonal Contraceptives: Topiramate may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing topiramate to ensure contraceptive reliability. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Iloperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Iobenguane Radiopharmaceutical Products: Amphetamines may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid combination
Iobenguane Radiopharmaceutical Products: CNS Stimulants may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid combination
Ioflupane I 123: Phentermine may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination
Lacosamide: Antiseizure Agents (Sodium Channel Blockers) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
LamoTRIgine: Topiramate may enhance the arrhythmogenic effect of LamoTRIgine. LamoTRIgine may enhance the CNS depressant effect of Topiramate. Management: Consider the risk of serious arrhythmias or death versus any expected benefit of lamotrigine in patients receiving concomitant sodium channel blockers. Additionally, if combined, caution patients that CNS depressant effects may be increased. Risk D: Consider therapy modification
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levothyroxine: May enhance the adverse/toxic effect of Sympathomimetics. Specifically, the risk of coronary insufficiency may be increased in patients with coronary artery disease. Levothyroxine may enhance the therapeutic effect of Sympathomimetics. Sympathomimetics may enhance the therapeutic effect of Levothyroxine. Risk C: Monitor therapy
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lithium: Topiramate may increase the serum concentration of Lithium. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Loop Diuretics: May enhance the hypokalemic effect of Topiramate. Risk C: Monitor therapy
Loxapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lumateperone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lurasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification
Memantine: Carbonic Anhydrase Inhibitors may increase the serum concentration of Memantine. Risk C: Monitor therapy
MetFORMIN: Topiramate may enhance the adverse/toxic effect of MetFORMIN. Specifically, the risk for lactic acidosis may be increased. MetFORMIN may increase the serum concentration of Topiramate. Topiramate may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Methenamine: Carbonic Anhydrase Inhibitors may diminish the therapeutic effect of Methenamine. Management: Consider avoiding the concomitant use of medications that alkalinize the urine, such as carbonic anhydrase inhibitors, and methenamine. Monitor for decreased therapeutic effects of methenamine if used concomitant with a carbonic anhydrase inhibitor. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Molindone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Risk X: Avoid combination
Multivitamins/Fluoride (with ADE): May decrease the serum concentration of Amphetamines. More specifically, the ascorbic acid (vitamin C) in many multivitamins may decrease amphetamine concentrations. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Amphetamines. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Amphetamines. Specifically, vitamin C may impair absorption of amphetamines. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
OLANZapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy
Paliperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: Topiramate may enhance the CNS depressant effect of Perampanel. Topiramate may decrease the serum concentration of Perampanel. Risk C: Monitor therapy
Periciazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Perphenazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Phenytoin: Topiramate may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Topiramate. Risk C: Monitor therapy
Pimozide: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pioglitazone: Topiramate may decrease the serum concentration of Pioglitazone. Risk C: Monitor therapy
Pipamperone [INT]: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pipamperone [INT]. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Promazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
QUEtiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Quinolones: Amphetamines may enhance the cardiotoxic effect of Quinolones. Risk C: Monitor therapy
RisperiDONE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Salicylates: May enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors): Amphetamines may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors). This could result in serotonin syndrome. Selective Serotonin Reuptake Inhibitors (Strong CYP2D6 Inhibitors) may increase the serum concentration of Amphetamines. Management: Monitor for amphetamine toxicities, including serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust dose as needed. Risk C: Monitor therapy
Serotonergic Agents (High Risk): Amphetamines may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability). Initiate amphetamines at lower doses, monitor frequently, and adjust doses as needed. Risk C: Monitor therapy
Sertindole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Sibutramine: May enhance the adverse/toxic effect of Centrally Acting Weight Loss Agents. Risk X: Avoid combination
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy
Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Solriamfetol: CNS Stimulants may enhance the hypertensive effect of Solriamfetol. CNS Stimulants may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy
Sulpiride: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: May enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Topiramate. Risk C: Monitor therapy
Thioridazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Thiothixene: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ulipristal: Topiramate may decrease the serum concentration of Ulipristal. Risk X: Avoid combination
Urinary Acidifying Agents: May decrease the serum concentration of Amphetamines. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valproate Products: Topiramate may enhance the adverse/toxic effect of Valproate Products. Specifically, the risk of hypothermia and hyperammonemia, with or without encephalopathy, may be increased. Valproate Products may decrease the serum concentration of Topiramate. Topiramate may decrease the serum concentration of Valproate Products. Risk C: Monitor therapy
Ziprasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Take in the morning; avoid taking in the late evening. Most effective when combined with a low calorie diet, increased physical activity and behavior modification counseling.
Evaluate pregnancy status prior to use in patients who can become pregnant. Patients who can become pregnant should have a negative pregnancy test prior to and monthly during therapy. Effective contraception should be used during treatment. Irregular bleeding may occur with use of combination oral contraceptives; efficacy of contraception may be dependent upon dose. Consult drug interactions database for more detailed information.
Obesity increases the risk of infertility. Optimal weight control prior to conception improves pregnancy outcomes. However, medications for weight loss are not recommended prior to pregnancy due to safety issues and adverse events. Weight loss medications should be discontinued prior to conception (ACOG 2021; Wharton 2020).
An increased risk in oral clefts (cleft lip with or without cleft palate) has been reported with first trimester exposure to topiramate. An increased risk of small for gestational age has also been reported following in utero exposure to topiramate.
An increased risk of adverse maternal and fetal events is associated with obesity. However, moderate gestational weight gain based on pre-pregnancy BMI is required for positive fetal outcomes in all pregnancies, including patients with overweight or obesity. Therefore, medications for weight loss therapy are not recommended during pregnancy (ACOG 2021; Wharton 2020). Use of this combination product is contraindicated during pregnancy. Refer to individual monographs for additional information.
Data collection to monitor pregnancy and infant outcomes following exposure is ongoing. Health care providers should report all pregnancies exposed to Qsymia in the Qsymia Pregnancy Surveillance Program (1-888-998-4887).
Pregnancy status (baseline, monthly with therapy; must be negative); weight, height, BMI; heart rate (resting); serum bicarbonate, potassium, glucose, and serum creatinine (at baseline and periodically); blood pressure; suicidality or mood disorders; symptoms of secondary angle-closure glaucoma; symptoms of acute acidosis and complications of long-term acidosis (eg, nephrolithiasis); dermatologic reactions.
Phentermine: A sympathomimetic amine with pharmacologic properties similar to amphetamines. The mechanism of action in reducing appetite appears to be secondary to CNS effects, including stimulation of the hypothalamus to release norepinephrine.
Topiramate: Effect on weight management may be due to its effects on appetite suppression and satiety enhancement and based on a combination of potential mechanisms: blocks neuronal voltage-dependent sodium channels, enhances GABA(A) activity, antagonizes AMPA/kainite glutamate receptors, and weakly inhibits carbonic anhydrase.
See individual agents.
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