Antiepileptic Drug Levetiracetam Does Not Interfere With OCP

Laurie Barclay, MD

July 19, 2002

July 22, 2002 — Unlike many antiepileptic drugs (AEDs) that alter the effectiveness of oral contraceptive pills (OCP), primarily through induction of the CYP 3A4 enzyme system, levetiracetam (Keppra) does not, according to the results of a double-blind, randomized trial reported in the July issue of Epilepsia.

"Drug interactions between AEDs and oral contraceptives are a critical concern for women with epilepsy," lead author Isabelle Ragueneau-Majlessi, MD, from the University of Washington School of Pharmacy in Seattle, says in a news release. "To date, few AEDs have been shown not to impede the effect of oral contraceptives."

During the run-in phase of this study, 18 healthy women received an OCP containing ethinyl estradiol, 0.03 mg, and levonorgestrel, 0.15 mg, for the first 21 days of two consecutive menstrual cycles. In a subsequent double-blind, randomized, two-way crossover treatment phase, subjects received either levetiracetam, 500 mg, or placebo twice daily in addition to the OCP.

During concomitant treatment with either levetiracetam or placebo, plasma concentration-time curves and pharmacokinetic parameters of ethinyl estradiol and levonorgestrel were similar, as were safety and menstrual-bleeding patterns. Levetiracetam did not significantly affect plasma levels of ethinyl estradiol and levonorgestrel nor those of serum progesterone or luteinizing hormone levels throughout the cycle, supporting noninterference with the OCP in preventing ovulation.

"When prescribing an antiepileptic drug for a woman of childbearing age, it is important to select a drug that will not compromise the effectiveness of her OCP," says co-author René Levy, PhD, from the University of Washington. "Keppra has been shown to have a low potential to interact with other drugs, and this research shows that Keppra can now be counted as an agent that is unlikely to interact with oral contraceptives."

Keppra was approved by the U.S. Food and Drug Administration in November 1999 for the adjunctive treatment of partial onset seizures in adults with epilepsy. Central nervous system adverse events associated with its use include somnolence, fatigue, coordination difficulties, and behavioral abnormalities. Dosing must be individualized based on renal function, and minor but statistically significant hematological abnormalities may occur.

UCB Pharma Inc. supported this study.

Epilepsia. 2002;43(7):697-702

Reviewed by Gary D. Vogin, MD


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