Valproic acid interaction with other drugs

Wilder BJ, Willmore LJ, Bruni J, Villarreal HJ. Valproic acid interaction with other anticonvulsant drugs. Neurology (1978) 28, 892-6. 

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. 

Less than 3% of a dose is excreted unchanged in the urine or through the feces. The elimination half-life from plasma is 10-15 h when valproic acid is used alone, but interaction with other anticonvulsant drugs can reduce the half-life to 4-10 h. It may be much longer in hepatic-impaired individuals, the elderly, and young children. 

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. 

Drug interactions involving AEDs are shown in Table 52-5. Phenobarbital, phoiytom, primidone and carbamazepine are potent inducers of cytochrome P450 (CYP450), epoxide hydrolase, and uridine diphosphate gjucuronosyltransferase enzyme systems. Valproic acid inhibits many hepatic enzjrme systems and displaces some drugs from plasma albumin. Felbamate and topiramate can act as inducers with some isoforms and inhibitors with others. 

Interactions with the following drugs may increase the risk of hypoglycemia other hypoglycemics, sulfonamides, propranolol, salicylates, clofibrate, probenecid, pentamidine, valproic acid, dicumarol, cimetidine, MAO inhibitors, and alcohol. In addition, co-ingestion of alcohol may occasionally produce a disulfiram-like interaction (see p 186). 

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