Board Review

A 27-year-old woman comes to the office to discuss medications 3 days after experiencing a first seizure. MRI evaluation on the day of the seizure showed left mesial temporal sclerosis, and a subsequent electroencephalogram was significant for temporal sharp waves, findings consistent with temporal lobe epilepsy. She has polycystic ovary syndrome and requires a daily estrogen-progestin combination for symptom management and contraception.

Physical examination findings, including vital signs, are normal.

Which of the following antiepileptic drugs is most appropriate?

A) Carbamazepine

B) Lamotrigine

C) Levetiracetam

D) Oxcarbazepine

E) Topiramate

Answer: C - Levetiracetam

Objective: Treat epilepsy in a woman taking oral contraceptives.

Key Point

Levetiracetam has no major drug-to-drug interactions with hormonal contraceptives and thus is appropriate to use in women with epilepsy who take oral contraceptives.

This patient's epilepsy, which is strongly suggested by her MRI and electroencephalographic findings, should be treated with an antiepileptic drug (AED). Of the AEDs listed, levetiracetam is most appropriate for a woman who takes oral contraceptive pills for polycystic ovary syndrome (PCOS) and also relies on them for contraception because it has no significant interactions with synthetic hormones. Most AEDs, particularly older agents, induce hepatic enzymes that alter the metabolism of hormonal contraceptives. This alteration may lead to unpredictable levels of synthetic estrogens and progestin; additionally, when the contraceptives are used to prevent pregnancy, increased failure can occur in women taking AEDs.

Carbamazepine and oxcarbazepine induce cytochrome CYP3A4 and thus affect the metabolism of synthetic estrogens and progestins, which makes many forms of hormonal contraception ineffective. Neither drug is an appropriate treatment for this patient. An intrauterine device (IUD) is the preferred method of contraception for women taking enzyme-inducing AEDs, but an IUD would not address this patient's PCOS symptoms.

Lamotrigine has unique interactions with hormonal contraceptives. Synthetic estrogens induce the clearance of lamotrigine by as much as 50%, which means that higher dosages of lamotrigine have to be administered to patients taking an oral contraceptive and that AED levels will increase during the placebo week of contraceptive therapy. If needed, lamotrigine can be administered with extended-cycle oral contraceptives, but an IUD is the preferred method of contraception for patients taking lamotrigine. Lamotrigine also decreases levels of synthetic progestins by 20%, although the clinical significance of this decrease is unknown.

Topiramate also increases clearance of synthetic estrogens. Although the clinical significance of this effect with lower doses of topiramate is debated, the World Health Organization advises against combining oral contraceptives with any dose of topiramate and recommends an IUD for contraception in patients taking this drug. Furthermore, topiramate is considered a class D drug for pregnancy because of the increased risk of facial clefting in exposed children, Therefore, it should not be used as a first-line agent in women of childbearing age.

Gaffield ME, Culwell KR, Lee CR. The use of hormonal contraception among women taking anticonvulsant therapy. Contraception. 2011 Jan;83(1):16-29. Link Out