Which Hormonal Contraceptive for a Patient Taking Phenytoin?

April 15, 2007

My 32-year-old patient has a seizure disorder that is treated with phenytoin. She wants to use hormonal contraception. Which agents will not interact with phenytoin?

My 32-year-old patient has a seizure disorder that is treated with phenytoin. She wants to use hormonal contraception. Which agents will not interact with phenytoin?

---- Ivanka Vassileva, MD
Lawton, Okla

Phenytoin induces hepatic microsomal enzymes of the P-450 system, which reduce the efficacy of oral contraceptives. The ethinyl estradiol in these agents is metabolized very rapidly, thereby decreasing their effectiveness.1 Thus, oral contraceptives are not the best option for a woman taking phenytoin.

If your patient will not consider other alternatives, prescribe a pill with 50 µg of ethinyl estradiol. This higher dose of estrogen may compensate for the increased metabolism; however, backup contraception is recommended.

Two alternatives to oral contraceptives are more effective in this setting: subcutaneous or intramuscular medroxyprogesterone acetate and a levonorgestrel-releasing intrauterine system. Medroxyprogesterone acetate remains effective in women taking antiepileptic drugs; in addition, it decreases seizure frequency.2

I recommend the levonorgestrel-releasing intrauterine system, however. This is a highly effective, reversible form of contraception that can remain in the uterus and provide protection against unwanted pregnancy for 5 years. Moreover, fertility returns much sooner after removal of this system than it does after cessation of medroxyprogesterone acetate.3,4 The progesterone acts directly on the uterus, causing the endometrium to become thin and the cervical mucus to become highly viscous. Because there is very little systemic absorption of the hormone, the effect of hepatic metabolism is minor. Although the manufacturer states that women should have had at least 1 child before they use the levonorgestrel-releasing intrauterine system, it can be used in nulliparous patients.5

Note that subdermal levonorgestrel implants are ineffective in patients receiving phenytoin.6

---- John Park, MD
Division of Reproductive Endocrinology
Department of Gynecology and Obstetrics
Emory University School of Medicine Atlanta

References:

REFERENCES:


1.

O'Brien M, Guillebaud J. Contraception for women with epilepsy.

Epilepsia

. 2006;47:1419-1422.

2.

Mattson R, Cramer J, Caldwell B, Siconolfi B. Treatment of seizures with medroxyprogesterone acetate: preliminary report.

Neurology

. 1984;34:1255-1258.

3.

Jain J, Dutton C, Nicosia A, et al. Pharmacokinetics, ovulation suppression, and return to ovulation following a lower dose subcutaneous formulation of Depo-Provera.

Contraception

. 2004;70:11-18.

4.

Backman T. Benefit-risk assessment of the levonorgestrel intrauterine releasing system in contraception.

Drug Saf

. 2004;27:1185-1204.

5.

Grimes D. Intrauterine devices. In: Hatcher R, Tressell J, Stewart F, et al, eds.

Contraceptive Technology

. New York: Ardent Media, Inc; 2004:503.

6.

Haukkamaa M. Contraception by Norplant subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment.

Contraception

. 1986;33:559-565.