Drug Interaction Report

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.

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.