Drug Interaction Report

MONITOR: Coadministration with bosentan may decrease the plasma concentrations of drugs that are substrates of the CYP450 2C9 and/or 3A4 isoenzymes. The mechanism is accelerated clearance due to induction of those isoenzymes by bosentan.

MANAGEMENT: When drugs that are known substrates of CYP450 2C9 and/or 3A4 are coadministered with bosentan, the possibility of a diminished therapeutic response to those drugs should be considered. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs, particularly those with a narrow therapeutic range, whenever bosentan is added to or withdrawn from therapy.

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.