In 2015, 1.2% of the US population was estimated to have active epilepsy.1 For neurologists, key goals in the treatment of epilepsy include: controlling seizures, minimizing adverse effects of antiepileptic drugs (AEDs) and optimizing quality of life. For obstetrician-gynecologists, women with epilepsy (WWE) have unique contraceptive, preconception, and obstetric needs that require highly specialized approaches to care. Here, I highlight 5 care points that are important to keep in mind when counseling WWE.
1. Enzyme-inducing AEDs reduce the effectiveness of estrogen-progestin and some progestin contraceptives.
AEDs can induce hepatic enzymes that accelerate steroid hormone metabolism, producing clinically important reductions in bioavailable steroid hormone concentration (TABLE 1). According to Lexicomp, AEDs that are inducers of hepatic enzymes that metabolize steroid hormones include: carbamazepine (Tegretol), eslicarbazepine (Aptiom), felbamate (Felbatol), oxcarbazepine (Trileptal), perampanel (Fycompa), phenobarbital, phenytoin (Dilantin), primidone (Mysoline), rufinamide (Banzel), and topiramate (Topamax) (at dosages >200 mg daily). According to Lexicomp, the following AEDs do not cause clinically significant changes in hepatic enzymes that metabolize steroid hormones: acetazolamide (Diamox), clonazepam (Klonopin), ethosuximide (Zarontin), gabapentin (Neurontin), lacosamide (Vimpat), levetiracetam (Keppra), pregabalin (Lyrica), tiagabine (Gabitril), vigabatrin (Vigadrone), and zonisamide (Zonegran).2,3 In addition, lamotrigine (Lamictal) and valproate (Depakote) do not significantly influence the metabolism of contraceptive steroids,4,5 but contraceptive steroids significantly influence their metabolism (TABLE 2).
For WWE taking an AED that accelerates steroid hormone metabolism, estrogen-progestin contraceptive failure is common. In a survey of 111 WWE taking both an oral contraceptive and an AED, 27 reported becoming pregnant while taking the oral contraceptive.6 Carbamazepine, a strong inducer of hepatic enzymes, was the most frequently used AED in this sample.
Many studies report that carbamazepine accelerates the metabolisms of estrogen and progestins and reduces contraceptive efficacy. For example, in one study 20 healthy women were administered an ethinyl estradiol (20 µg)-levonorgestrel (100 µg) contraceptive, and randomly assigned to either receive carbamazepine 600 mg daily or a placebo pill.7 In this study, based on serum progesterone measurements, 5 of 10 women in the carbamazepine group ovulated, compared with 1 of 10 women in the placebo group. Women taking carbamazepine had integrated serum ethinyl estradiol and levonorgestrel concentrations approximately 45% lower than women taking placebo.7 Other studies also report that carbamazepine accelerates steroid hormone metabolism and reduces the circulating concentration of ethinyl estradiol, norethindrone, and levonorgestrel by about 50%.5,8
WWE taking an AED that induces hepatic enzymes should be counseled to use a copper or levonorgestrel (LNG) intrauterine device (IUD) or depot medroxyprogesterone acetate (DMPA) for contraception.9 WWE taking AEDs that do not induce hepatic enzymes can be offered the full array of contraceptive options, as outlined in Table 1. Occasionally, a WWE taking an AED that is an inducer of hepatic enzymes may strongly prefer to use an estrogen-progestin contraceptive and decline the preferred option of using an IUD or DMPA. If an estrogen-progestin contraceptive is to be prescribed, safeguards to reduce the risk of pregnancy include:
- prescribe a contraceptive with ≥35 µg of ethinyl estradiol
- prescribe a contraceptive with the highest dose of progestin with a long half-life (drospirenone, desogestrel, levonorgestrel)
- consider continuous hormonal contraception rather than 4 or 7 days off hormones and
- recommend use of a barrier contraceptive in addition to the hormonal contraceptive.
The effectiveness of levonorgestrel emergency contraception may also be reduced in WWE taking an enzyme-inducing AED. In these cases, some experts recommend a regimen of two doses of levonorgestrel 1.5 mg, separated by 12 hours.10 The effectiveness of progestin subdermal contraceptives may be reduced in women taking phenytoin. In one study of 9 WWE using a progestin subdermal implant, phenytoin reduced the circulating levonorgestrel level by approximately 40%.11
Continue to: 2. Do not use lamotrigine with cyclic estrogen-progestin contraceptives...