Drug Interaction Report

MONITOR: Barbiturates may induce or inhibit the metabolism of phenytoin. Plasma phenytoin concentrations may be decreased or increased. The mechanism are induction of hepatic CYP450 phenytoin metabolism by therapeutic doses of barbiturates, and competitive inhibition of metabolism by large doses. Also, when phenytoin is added to a regimen, the plasma levels of barbiturates may significantly increase via an unknown mechanism.

MANAGEMENT: Close laboratory and clinical observation for altered effects of both agents is recommended when doses of either agent are started, changed, or discontinued. Patients should be advised to notify their physician if they experience loss of seizure control or excessive or prolonged sedative effects. It may be necessary to alter the dosage of one or both of the drugs.

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.