Drug Interaction Report

GENERALLY AVOID: Based on in vitro inhibition data, a single topical application of abametapir lotion may increase plasma concentrations of drugs that are substrates of CYP450 3A4, CYP450 2B6, and CYP450 1A2 isoenzymes and increase their systemic concentrations. The proposed mechanism is high and prolonged systemic exposure to the metabolite abametapir carboxyl, which has been shown to be an in vitro inhibitor of CYP450 3A4, CYP450 2B6, and CYP450 1A2. The mean half-life of abametapir carboxyl in adults is estimated to be 71 hours or longer.

MANAGEMENT: Use of CYP450 3A4, CYP450 2B6, and CYP450 1A2 substrates should generally be avoided within 2 weeks after topical application of abametapir lotion. If this is not feasible, the manufacturer recommends avoiding use of abametapir lotion. If abametapir is used, monitor for increased toxicity of the CYP450 3A4, CYP450 2B6, and/or CYP450 1A2 substrate.

ADJUST DOSING INTERVAL: Administration with food increases the plasma concentrations of efavirenz and may increase the frequency of adverse reactions. According to the product labeling, administration of efavirenz capsules (600 mg single dose) with a high-fat/high-caloric meal (894 kcal, 54 g fat, 54% calories from fat) or a reduced-fat/normal-caloric meal (440 kcal, 2 g fat, 4% calories from fat) was associated with mean increases of 39% and 51% in efavirenz peak plasma concentration (Cmax) and 22% and 17% in systemic exposure (AUC), respectively, compared to administration under fasted conditions. For efavirenz tablets, administration of a single 600 mg dose with a high-fat/high-caloric meal (approximately 1000 kcal, 500-600 kcal from fat) resulted in a 79% increase in mean Cmax and a 28% increase in mean AUC of efavirenz relative to administration under fasted conditions.

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of efavirenz. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Efavirenz should be taken on an empty stomach, preferably at bedtime. Dosing at bedtime may improve the tolerability of nervous system symptoms such as dizziness, insomnia, impaired concentration, somnolence, abnormal dreams and hallucinations, although they often resolve on their own after the first 2 to 4 weeks of therapy . Patients should be advised of the potential for additive central nervous system effects when efavirenz is used concomitantly with alcohol or psychoactive drugs, and to avoid driving or operating hazardous machinery until they know how the medication affects them.