Levetiracetam Does Not Alter the Pharmacokinetics of an Oral Contraceptive in Healthy Women

Abstract

Summary:Purpose: This study was designed to evaluate whether levetiracetam, a novel antiepileptic drug (AED), influences the pharmacokinetics of steroid oral contraceptives.Methods: During a run-in phase, 18 healthy female patients received an oral contraceptive 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 concomitant with the oral contraceptive. Plasma concentrations of ethinyl estradiol and levonorgestrel were measured on days 14 and 15 of the two treatment periods for the evaluation of the 24-h kinetic parameters, and an additional sample was collected on day 21 to determine the trough plasma concentrations. Serum progesterone and luteinizing hormone (LH) levels were determined on days 13, 14, 15, and 21 of each cycle of the treatment phase.Results: The plasma concentration-time curves and pharmacokinetic parameters of ethinyl estradiol and levonorgestrel were not statistically different during concomitant treatment with either levetiracetam or placebo. The ratios of the logtransformed geometric mean areas under the plasma concentration-time curves (AUCs), maximal (C max ) and minimal (C min ) plasma concentrations, and trough concentrations on day 21 (C 21 ) ranged from 99.12 to 99.96% for ethinyl estradiol and from 97.13 to 99.41% for levonorgestrel. The 90% confidence intervals of these ratios were well within the 80 to 125% acceptance range for lack of interaction. Serum progesterone and LH concentrations were fairly constant during the run-in and treatment phases and remained markedly below their respective physiologic levels. Safety and menstrual-bleeding patterns were comparable during levetiracetam and placebo administration.Conclusions: Levetiracetam does not affect the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and levonorgestrel, and on the basis of serum progesterone and LH levels, it does not affect the contraceptive efficacy.

Antiepileptic Drug Interactions - Principles and Clinical Implications

“…Some negative findings regarding other therapeutic classes have, however, been published. No interactions between OCs and gabapentin, levetiracetam, pregabalin, tiagabine, vigabatrin and zonisamide have been reported [68-73]. …”

The Pharmacokinetics and Interactions of New Antiepileptic Drugs

“…4 AEDs can be categorized into 3 groups on the basis of their potential to cause induction-based drug interactions as reflected by their interactions with steroid oral contraceptives (OC). 19 Old AEDs, such as PHT, CBZ, and PB, may reduce steroid OC levels during concomitant administration because of induction of CYP3A and other metabolizing enzymes (UGTs) and increases in OC-binding globulin levels. Both mechanisms may contribute to reduce OC levels during concomitant OC-AED administration.…”

Interactions between hormonal contraception and antiepileptic drugs: Clinical and mechanistic considerations

“…Available data, although sparse, suggest that neither valproate [37], gabapentin [38], levetiracetam [39], zonisamide [40,41], nor lacosamide [42] affect the metabolism of COCs. These AEDs may therefore be regarded as safe with respect to possible contraceptive failure.…”