Valproic acid drug interactions

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Scheyer RD. Valproic acid Drug interactions. In Levy RH, Mattson RH, Meldrum BS, et al, eds. Antiepileptic Drugs, 5th ed. Philadelphia, Lippincott Williams Wilkins, 2002 801-807. 

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Svinarov DA, Pippenger CE. Valproic acid-carbamazepine interaction is valproic acid a selective inhibitor of epoxide hydrolase Ther Drug Mordt (1995) 17, 217-20. 

Tobin JK, Golightly LK, Kick SD, Jones MA. Valproic acid-carbapenem interaction report of six cases and a review of the literature. Drug Metabol Drug Interact 2009 24(2-4) 153-82. 

Carbamazepine may interact with other drugs by inducing their metabolism. Valproic acid increases concentrations ofthe 10,11-epoxide metabolite without affecting the concentration of carbamazepine. The interaction of erythromycin and clarithromycin (CYP3A4 inhibition) with carbamazepine is particularly significant. 

Unlike carbamazepine, valproic acid has few drug interactions, an added benefit for elderly patients. One interaction worthy of mention, however, is that aspirin can increase levels of valproic acid. For this reason, vascular dementia patients taking an aspirin a day may need a lower dose of valproic acid or at least more careful monitoring of blood levels when starting valproic acid. 

Drugs that may interact with acyclovir include hydantoins, probenecid, theophylline, valproic acid, and zidovudine. 

Carbamazepine also can induce the enzymes that metabolize other anticonvulsant drugs, including phenytoin, primidone, phenobarbital, valproic acid, clonazepam, and ethosuximide, and metabolism of other drugs the patient may be taking. Similarly, other drugs may induce metabolism of carbamazepine the end result is the same as for autoinduction, and the dose of carbamazepine must be readjusted. A common drug-drug interaction is between carbamazepine and the macrolide antibiotics erythromycin and trolean-domycin. After a few days of antibiotic therapy, symptoms of carbamazepine toxicity develop this is readily reversible if either the antibiotic or carbamazepine is discontinued. 

Administration of ethosuximide with valproic acid results in a decrease in ethosuximide clearance and higher steady-state concentrations owing to inhibition of metabolism. No other important drug interactions have been reported for the succinimides. 

The interaction between proteins and a drug is governed by the law of mass action, in that the proportion of bound drug remains constant, provided the binding sites are not saturated. With the possible exception of valproic acid and disopyramide, the saturability of binding sites does not occur within therapeutic ranges. 

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