Drug Interaction Report

MONITOR: Concomitant use of phenothiazines with barbiturates may reduce the plasma concentrations and therapeutic effects of both agents. The mechanism is unclear but may relate to metabolic induction of CYP450 hepatic enzymes. In addition, coadministration of phenothiazines and barbiturates may lead to a reduction in seizure threshold and additive central nervous system (CNS) and respiratory depressant effects.

MANAGEMENT: Administration of phenothiazines in patients receiving large doses of barbiturates is considered contraindicated by some authorities (US). If coadministration is required, caution as well as clinical and laboratory monitoring should be considered whenever either of these agents is added to or withdrawn from therapy. If chlorpromazine is coadministered with a barbiturate, the manufacturer of chlorpromazine recommends using 1/4 to 1/2 of the usual barbiturate dosage. Patients should be monitored for hypotension, loss of seizure control and the development of adverse effects including CNS and respiratory depression.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

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.