Optimizing therapy of seizures in women who use oral contraceptives.
There is no evidence that oral contraceptives (OCs) increase seizure activity, and OC use in the setting of antiepileptic drug (AED) treatment provides pregnancy prevention at among the highest rates of any available contraceptive method. One concern, however, is the increased risk for OC failure with the use of cytochrome P450 3A4 enzyme-inducing AEDs, such as phenobarbital, carbamazepine, phenytoin, felbamate, topiramate, and oxcarbazepine. Felbamate induces metabolism of only the progestogenic component, whereas topiramate induces metabolism of only the estrogenic component. There is preliminary evidence that lamotrigine induces the metabolism of a progestin, levonorgestrel. It is unclear whether the estrogenic or the progestogenic component is more clinically important in preventing pregnancy. To ensure maximal pregnancy prevention, it is therefore recommended that women taking enzyme-inducing AEDs should receive OCs containing at least 50 mug of ethinyl estradiol and that low-dose formulations in general should not be used. AEDs that do not induce cytochrome P450 3A4 enzymes, including valproic acid, gabapentin, levetiracetam, tiagabine, vigabatrin, zonisamide, and pregabalin, do not interact with OCs. There are no concerns regarding the treatment of seizures or increased pregnancy risk with the use of OCs and these non-enzyme-inducing AEDs. Lamotrigine levels, however, are reduced by 50% in the setting of OC use. Therefore, women with epilepsy taking lamotrigine need to be monitored carefully for seizures when OCs are started and for toxicity when OCs are discontinued. Dose adjustment to maintain clinical stability may be necessary in these settings. The placebo or pill-free week of the OC regimen may also be a period when clinical toxicity can occur. Even with the considerations discussed in this review, OCs are a reasonable contraceptive option for women with epilepsy taking AEDs.
Harden
Cynthia L
CL
Comprehensive Epilepsy Center, Weill Cornell Medical Center, New York, NY 10021, USA. clharden@med.cornell.edu
Leppik
Ilo
I
D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003276:Contraceptives, Oral / Q000009:adverse effects / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004347:Drug Interactions; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D012640:Seizures / Q000188:drug therapy*; D014227:Triazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D000927:Anticonvulsants; D003276:Contraceptives, Oral; D014227:Triazines; D003577:Cytochrome P-450 Enzyme System; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000077213:Lamotrigine