Drug Interaction Report

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

ADJUST DOSE: In-vivo studies have demonstrated that the absorption of bromfenac is greatly reduced if the drug is taken within three and one-half hours following a high fat meal. The concomitant administration of a high fat meal has led to a 75% reduction in peak plasma concentrations and a 60% reduction in total area under the curve. The mechanism has not been described.

MANAGEMENT: An increased dosage of bromfenac (from 25 to 50 mg) may be needed if a high fat meal is consumed. The clinician may want to warn the patient about subtherapeutic analgesic effects if high fat meals are regularly consumed.