Drug Interaction Report

MONITOR: Coadministration of glycerol phenylbutyrate may lead to increased concentrations of CYP450 2D6 substrates. The proposed mechanism is inhibition of CYP450 2D6 by phenylbutyrate, the active moiety of glycerol phenylbutyrate, which has been shown to be an in vitro inhibitor of this isoenzyme. In in vitro studies, administration of phenylbutyrate at a concentration of 800 mcg/mL caused greater than 60% reversible inhibition of CYP450 2D6, 2C9, and 3A4/5. The clinical significance of these results has not been established; however, the manufacturer states that a potential interaction with CYP450 2D6 substrates cannot be ruled out.

MANAGEMENT: Caution is recommended if glycerol phenylbutyrate is administered with medicines that are substrates of CYP450 2D6, such as codeine, dextromethorphan, and some beta blockers (including metoprolol, carvedilol, labetalol, propranolol, and nebivolol). Dosage adjustments as well as clinical and laboratory monitoring may be appropriate.

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.