Optimizing therapy of seizures in women who use oral contraceptives
Optimizing therapy of seizures in women who use oral contraceptives
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DOI：
10.1212/wnl.67.12_suppl_4.s56
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发表时间：
2006-12-26
期刊：
影响因子：
9.9
通讯作者：
Leppik, Ilo
中科院分区：
文献类型：
--
作者：
Harden, Cynthia L.;Leppik, Ilo
没有证据表明口服避孕药（OC）会增加癫痫发作活动，在抗癫痫药物（AED）治疗的背景下使用OC可以在任何可用的避孕方法中提供最高的避孕率。然而，一个值得关注的问题是，使用细胞色素P450 3A4酶诱导的AEDs（如苯巴比妥、卡马西平、苯妥英、非氨酯、托吡酯和奥卡西平）会增加OC失败的风险。非氨酯仅诱导孕激素成分的代谢，而托吡酯仅诱导雌激素成分的代谢。有初步证据表明，拉莫三嗪可诱导左炔诺孕酮的代谢。目前还不清楚是雌激素还是孕激素成分在预防妊娠方面更重要。为了确保最大限度地预防妊娠，因此建议服用酶诱导AED的妇女应接受至少含有50 μ g炔雌醇的OC，一般不应使用低剂量制剂。不诱导细胞色素P450 3A4酶的AED，包括丙戊酸、加巴喷丁、左乙拉西坦、噻加宾、氨己烯酸、唑尼沙胺和普瑞巴林，不与OC相互作用。使用OC和这些非酶诱导AED治疗癫痫发作或增加妊娠风险方面没有问题。然而，拉莫三嗪水平在OC使用的情况下降低了50%。因此，服用拉莫三嗪的女性癫痫患者在开始服用OCs时需要仔细监测癫痫发作，在停用OCs时需要监测毒性。在这些情况下，可能需要调整剂量以维持临床稳定性。OC方案的无安慰剂或无药丸周也可能是可能发生临床毒性的时期。即使考虑到本综述中讨论的因素，口服避孕药仍是服用抗癫痫药物的癫痫女性的合理避孕选择。
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 mu g 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.