Drug Interaction Report

GENERALLY AVOID: One case series has suggested that benzodiazepines may amplify the teratogenic effects of valproate in the offspring of epileptic women. Both drugs individually have been associated with adverse effects to the fetus. Another study has suggested that valproate may displace diazepam from plasma protein binding sites and inhibit its metabolism; however, the clinical significance has not been established. Other benzodiazepines may interact with valproate in a similar fashion.

MANAGEMENT: Both valproate and benzodiazepines should be avoided during pregnancy unless the potential benefits outweigh the risks to the fetus. In other patients, close observation for clinical evidence of benzodiazepine toxicity (excessive sedation) is recommended if valproate and a benzodiazepine must be used together.

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.

GENERALLY AVOID: Acute ethanol ingestion may potentiate the CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

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