Drug Interactions between clomipramine and phentermine / topiramate

MONITOR CLOSELY: Certain drugs such as carbonic anhydrase inhibitors and drugs with anticholinergic activity (e.g., antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, disopyramide) may potentiate the risk of oligohidrosis and hyperthermia associated occasionally with the use of topiramate, particularly in pediatric patients. These agents may alter electrolyte and fluid balance (carbonic anhydrase inhibition), inhibit peripheral sweating mechanisms (anticholinergic effect), and/or interfere with core body temperature regulation in the hypothalamus (neuroleptics and phenothiazines), resulting in the inability to adjust to temperature changes, especially in hot weather. Also, agents with anticholinergic activity frequently cause drowsiness and other central nervous system-depressant effects, which may be additively or synergistically increased in patients also treated with topiramate.

MANAGEMENT: Caution is advised when topiramate is prescribed with other drugs that predispose patients to heat-related disorders, including carbonic anhydrase inhibitors and drugs with anticholinergic activity. Patients, particularly pediatric patients, should be monitored closely for evidence of decreased sweating and increased body temperature, especially in warm or hot weather. Proper hydration before and during vigorous activities or exposure to warm temperatures is recommended. Patients (or their guardians or caregivers) should contact their physician immediately if they are not sweating as usual, with or without a fever. Ambulatory patients treated with topiramate and agents with anticholinergic activity should also be made aware of the possibility of additive CNS effects (e.g., drowsiness, dizziness, lightheadedness, confusion) and counseled to avoid activities requiring mental alertness until they know how these agents affect them.

MONITOR: The use of tricyclic antidepressants in combination with amphetamines or sympathomimetic appetite suppressants may produce additive cardiovascular effects, increasing the risk of hypertension, cardiac arrhythmias, tachycardia, and fever. The mechanism involves additive pharmacodynamic effects resulting from increased norepinephrine release by sympathomimetic agents and inhibition of norepinephrine reuptake by tricyclic antidepressants. A pharmacokinetic interaction is also possible between tricyclic antidepressants and amphetamines, since many of these agents are metabolized by CYP450 2D6. Increased plasma levels of one or both drugs may occur during coadministration.

MANAGEMENT: Close monitoring of cardiovascular status is recommended for patients receiving this combination. Patients should be advised to promptly report symptoms such as fever, headache, or fast or irregular heartbeats.

MONITOR: Coadministration with topiramate may increase the plasma concentrations of phentermine. The exact mechanism of interaction has not been established. When a single 15 mg dose of phentermine was administered with a 92 mg dose of topiramate, phentermine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 13% and 42%, respectively, compared to phentermine administered alone. No significant changes were observed in the pharmacokinetics of topiramate.

MANAGEMENT: Caution is advised when phentermine is used in combination with topiramate. Patients should be monitored for potentially increased adverse effects of phentermine such as dizziness, restlessness, insomnia, tremor, headache, euphoria, dysphoria, palpitation, tachycardia, and blood pressure elevation.