Abstracts

Rationale: Pharmacokinetic interactions with oral contraceptives (OC) due to hepatic enzyme induction are well known in several antiepileptic drugs. Oxcarbazepine (OXC) generally tends to show milder induction of hepatic enzymes than carbamazepine, which results in less clinically relevant drug-drug-interactions. However, in two pharmacokinetic studies OXC increased (probably by induction of CYP 3A4) the clearance of the gestagenic compound levenorgestrel (LNG) which is mainly responsible for ovulation inhibition in commonly used combined OCs. This may lead to contraceptive failure. A new OC containing 3mg drospirenone (DRSP) and 30 µg ethinylestradiole (EE) might provide a more reliable contraception in women taking OXC, since DRSP has been shown not to be metabolized by the cytochrom P450 system. Methods: 1) We are currently prospectively evaluating the ovarian function of women with epilepsy on a stable OXC monotherapy who are started on a continous hormonal therapy with an OC containing 3 mg DRSP and 30 µg EE. 2) Parallel to these first clinical experiences a pharmacokinetic study to prove the contraceptive safety of this regimen was initiated. In this monocenter open-label study in healthy women a total of five menstrual cycles (28 days each) are evaluated in each subject. During three initial cycles (1+2 run-in, 3 baseline) the women are treated with an OC containing 3 mg DRSP and 30 µg EE only. During cycle 3 a baseline pharmacokinetic profile over 24 h is gathered at day 21/22. AUCτ, Cmax and Cmin are assessed for DRSP and EE. During cycle 4 OXC is stepwise titrated up to 1200 mg/day. During the last cycle 5, the OC and OXC are co-administered and the pharmacokinetic profile is measured again at day 21. Further parameters evaluated include hormone profiles (LH, FSH, progesterone), clinical assessment of bleeding by diary cards as well as safety measurements. Compliance of subjects is assessed by measuring MHD serum levels. Results: 1) Until now, all 3 patients observed over a period of 2-12 month showed suppressed FSH and LH levels and low endogenous estradiol levels suggesting ovarian suppression and reliable contraception. 2) The pharmacokinetic study (35 subjects recruited so far) is currently ongoing. First interpretable results will be presented.Conclusions: These observational as well as pharmacokinetic study data will help to answer the clinically important question, whether reliable oral contraception is possible in women with epilepsy treated with oxcarbazepine.