Sign Out
Combinations requiring precautions: Imipramine antidepressant: Imipramine antidepressants may promote generalized convulsions. Clinical monitoring and possibly dosage increase of antiepileptics may be necessary.
Phenobarbital: Increase in plasma phenobarbital concentrations (due to inhibition of liver catabolism), may occur with sedation, most often in children. Clinical monitoring during the first 2 weeks of the combination and immediate phenobarbital dose reduction when signs of sedation develop; if necessary, monitor plasma phenobarbital levels.
Phenytoin: Generally, increases total phenytoin concentrations. In particular, increase in the concentrations of free phenytoin, which may lead to signs of overdosage (valproic displaces phenytoin from its plasma protein binding site and slows its liver catabolism). Clinical monitoring is recommended. If plasma phenytoin are determined, the free form is the most important to consider.
Primidone: Increase in plasma primidone levels with enhancement of its adverse effects (sedation). After prolonged use, this interaction ceases. Clinical monitoring recommended and if necessary, primidone dosage adjustments should be considered, especially at the beginning of the co-administration.
Lamotrigine: Valproate may reduce lamotrigine metabolism necessitating dosage reduction of latter.
Mefloquine: Increases valproic acid metabolism and has a convulsant effect; therefore epileptic seizures may occur in combined therapy.
Miscellaneous: In case of concomitant use of valproate and highly bound protein drugs (like aspirin), free serum levels of valproate may be increased.
The serum levels of valproate may be increased in case of concomitant use with cimetidine or erythromycin.
Close monitoring of prothrombin time should be performed in case of concomitant use of Vitamin K dependent anti-coagulant.
