Check choices for women with epilepsy

In reviewing the chart for your next patient, you note that she is a 28-year-old woman with epilepsy. What information do you need to provide her when it comes to contraceptive choices? Many family planning clinicians encounter this scenario. Epilepsy is one of the most common chronic health conditions affecting reproductive-age women.1

Many antiepileptic drugs (AEDs) are teratogenic; women using them require excellent contraception, says Anita Nelson, MD, professor in the obstetrics and gynecology department at the University of California in Los Angeles (UCLA) and medical director of the women’s health care programs at Harbor-UCLA Medical Center in Torrance. In addition, many AEDs interfere with vitamin K synthesis and cause heavier menstrual blood loss, she reports.

"One final caveat is that many of the AEDs increase hepatic cytochrome P450 activity and cause women to metabolize sex steroids more rapidly," Nelson points out. "For that reason, women using oral contraceptives (OCs) should avoid low-dose formulations."

Cytochrome P450-inducing antiepileptic drugs enhance hepatic metabolism of contraceptive steroids and increase binding of steroids to serum proteins, which results in a reduction of the concentration of biologically active steroid hormone.1 Women receiving a liver enzyme-inducing antiepileptic medication have at least a 6% failure rate per year for OCs.2

Agents that induce liver enzymes and may compromise OC efficacy include carbamazepine (Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), phenobarbital (Luminal), phenytoin (Dilantin), primidone (Mysoline), and topiramate (Topamax). In the case of topiramate, check the dosage of the drug, says Susan Wysocki, RNC, NP, president and chief executive officer of the National Association of Nurse Practitioners in Women’s Health.

Labeling for oral contraceptives states that topiramate will decrease the efficacy of OCs; however, in the topiramate label, it says that the dose that decreases the efficacy is 200 mg, she says. This finding is borne out in a 2004 study, which notes that the drug only increases the oral clearance of ethinyl estradiol in an oral contraceptive at high dosages (more than 200 mg/day).3

Women may wish to back up their OC choice with a second form of birth control, such as a diaphragm, spermicidal cream, or condoms, if they are taking one of the cytochrome P450-inducing AEDs.

Agents that do not compromise OC efficacy include gabapentin (Neurontin), levetiracetam (Keppra), tiagabine (Gabitril), valproate (Depakote), and zonisamide (Zonegran).1 One AED, Lamictal, was originally included in this group; however, its manufacturer, GlaxoSmithKline of Research Triangle Park, NC, revised the drug’s label and issued an August 2004 letter to health care providers to add results from an interaction study of an oral contraceptive preparation (30 mcg ethinyl estradiol and 150 mcg levonorgestrel) administered in combination with Lamictal at 300 mg per day.

The study found that Lamictal had a modest effect on levonorgestrel plasma concentrations; the effect on ethinyl estradiol concentrations was minimal.4 An increase in serum FSH (follicle stimulating hormone) and LH (luteinizing hormone) concentrations and a marginal increase in serum estradiol concentrations were observed during the period of coadministration of the oral contraceptive and Lamictal.4 There was no hormonal evidence of ovulation as evidenced by progesterone serum concentrations.4

"The clinical significance of the observed hormonal changes on ovulatory activity is unknown," states the revised label. "However, the possibility of decreased contraceptive efficacy in some patients cannot be excluded; therefore, patients should be instructed to promptly report changes in their menstrual pattern [e.g., breakthrough bleeding]."5

The effect of other hormonal contraceptive preparations or hormone replacement therapy on the pharmacokinetics of lamotrigine has not been evaluated, although the effect may be similar, the company notes.

What contraceptive choices may work best for women with epilepsy? The most effective methods are the levonorgestrel intrauterine system (Mirena, Berlex Laboratories, Montville, NJ) and injectable depot medroxyprogesterone acetate (DMPA, Depo-Provera, Pfizer, New York City), recommends Nelson.

If OCs are used, at least a 35 mcg formulation is generally needed, she advises. Extended-cycle OC use with shortened pill-free intervals are particularly attractive for these women, she notes.

Advise women to check for breakthrough bleeding while on hormonal contraception; such bleeding midcycle may be a sign of ovulation.6 Provide women with condoms or spermicide as backup contraception.6

References

  1. Morrell MJ. Epilepsy in women. Am Fam Physician 2002; 66:1,489-1,494.
  2. Mattson RH, Cramer JA, Darney PD, et al. Use of oral contraceptives by women with epilepsy. JAMA 1986; 256:238-240.
  3. Bialer M, Doose DR, Murthy B, et al. Pharmacokinetic interactions of topiramate. Clin Pharmacokinet 2004; 43:763-780.
  4. GlaxoSmithKline. Dear Healthcare Professional [Letter]. Research Triangle Park, NC; August 2004.
  5. GlaxoSmithKline. Lamictal (lamotrigine) prescribing information. Research Triangle Park, NC; August 2004.
  6. Epilepsy Foundation. Birth Control for Women with Epilepsy. Accessed at: www.epilepsyfoundation.org.