Drug Interactions between cisplatin and Valproate Sodium

MONITOR: Coadministration with cisplatin may decrease the plasma concentrations and pharmacologic effects of valproic acid. The exact mechanism of interaction is unknown. In one case report, a young woman with a history of epilepsy developed tonic-clonic seizures during antineoplastic therapy with cisplatin and doxorubicin. Anticonvulsant levels were measured during two courses, and lower plasma levels of valproate sodium and carbamazepine were observed after 2 days of antineoplastic therapy. Levels returned to normal 2 to 3 days after the last cisplatin dose. In another report, severe generalized tonic-clonic seizures in association with reduced serum valproate levels developed in a 34-year-old epileptic patient receiving cisplatin-based chemotherapy for the treatment of a testicular tumor. The seizures occurred 7 weeks after the first chemotherapeutic cycle, which consisted of bleomycin and etoposide in addition to cisplatin. Serum valproate concentration was about 50% of what it had been prior to chemotherapy. The patient received the second cycle following recovery of valproate levels and again experienced seizures several days later. Phenytoin 100 mg three times a day was added, but the seizures continued frequently during subsequent cycles in association with markedly reduced serum valproate levels. After four cycles, the chemotherapeutic regimen was changed to paclitaxel, ifosfamide, and cisplatin. However, serum valproate levels remained low, and seizures were observed with each of the two cycles. In contrast, these regimens had no effect on the serum concentrations of phenytoin, which remained in the therapeutic range throughout.

MANAGEMENT: Serum valproate levels should be monitored more closely during therapy with cisplatin. Dosage adjustments may be required.

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