Drug Interaction Report

MONITOR: Salicylates, particularly aspirin, may displace valproate from protein binding sites and inhibit its clearance. Four-fold increases in the free fraction of valproate have been reported in children. Increased therapeutic and toxic effects may be expected to occur. This interaction is more likely with large or prolonged doses of salicylates.

MANAGEMENT: Small single doses of salicylates are unlikely to cause significant effects. However, patients who take large doses of salicylates or over a prolonged period of time should be closely monitored for clinical and laboratory evidence of valproate toxicity and hepatotoxicity. Free fraction of valproate may be particularly helpful in detecting this interaction. Patients should be advised to notify their physician if they experience possible symptoms of toxicity (e.g., malaise, weakness, lethargy, drowsiness, nausea, vomiting, or abdominal pain).

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.