Drug Interaction Report

CONTRAINDICATED: Coadministration with valproic acid may diminish the therapeutic effects of sodium benzoate and sodium phenylacetate in the treatment of acute hyperammonemia due to deficiencies in enzymes of the urea cycle. There have been reports that valproic acid can induce hyperammonemia through inhibition of the synthesis of N-acetylglutamate, a co-factor for the urea cycle enzyme carbamyl phosphate synthetase. Hyperammonemic encephalopathy, sometimes fatal, has been reported following initiation of valproate therapy in patients with urea cycle disorders, particularly ornithine transcarbamylase deficiency.

MANAGEMENT: The use of valproic acid is contraindicated in patients with known urea cycle disorders.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.