Drug Interaction Report

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.

Concurrent ingestion of calcium-fortified foods (i.e., cereal, orange juice) may alter the bioavailability of gatifloxacin. The mechanism is chelation of calcium and the quinolone, resulting in decreased bioavailability. In the case of orange juice, inhibition of intestinal transport mechanisms (P-glycoprotein or organic anion-transporting polypeptides) by flavones may also be involved. Data have been conflicting: One study has reported no effect with milk coadministration. Another study reported a modest decrease in gatifloxacin bioavailability (13.5% decrease in Cmax,12% decrease in AUC, 15% increase in total clearance) when taken with 12 ounces of calcium-fortified orange juice instead of water, which could be clinically significant if the infecting organisms have borderline susceptibilities. The manufacturer states that gatifloxacin may be taken without regard to food, milk, or calcium. Clinicians should be aware of the possibility of an interaction if subtherapeutic effects are observed.