JOURNAL OF GYNECOLOGIC SURGERY© Mary Ann Liebert, Inc.

Antibiotics and Oral Contraceptives: Potential Interactions

NEWTON G. OSBORNE, M.D., Ph.D.

OVER THE YEARS, several authors have reported on possible interactions between oral contraceptives andcertain antibiotics.1–4 Antibiotics can have an effect on hormonal contraceptives via two different mech-

anisms. They can alter liver metabolism of estrogen and they can interfere with bacterial breakdown of con-jugated estrogens. The most common estrogenic component of birth control pills is ethinyl estradiol. Ethinylestradiol is metabolized in the liver by cytochrome P450 3A4 and excreted in the bile. Intestinal bacteriabreak down estrogen conjugates to restore free estrogen, which is then reabsorbed via the enterohepatic cir-culation as an active drug.

There are anecdotal reports of women taking birth control pills who have become pregnant as a result ofantibiotic interactions. However, considering the large number of women taking oral contraceptives whohave been treated with antibiotics, the risk of pregnancy as a result of antibiotic-contraceptive interactionmust be low. Regardless of the low risk of failure, the consequences of an unwanted pregnancy could bedevastating and should be taken seriously.

The effects of antibiotic-contraceptive interaction vary not only between drugs, but also between indi-viduals. The most important interactions are with rifampin and griseofulvin. Rifampin and griseofulvin areinducers of cytochrome P450 3A4. Induction of P450 3A4 accelerates elimination of ethinyl estradiol andtherefore lowers contraceptive effectiveness. Rifampin also increases production of sex hormone-bindingglobulin (SHBG). SHBG has a high affinity for progestins. An increase in SHBG can reduce levels of freeprogestin, which contributes further to a loss of contraceptive effectiveness.

Other antibiotics such as penicillins, carbapenems, tetracyclines, et cetera, interfere with intestinal flora.If there is a significant reduction (or even elimination) of organisms capable of releasing estrogen from itsconjugated form, there also could be a reduction in levels of circulating estrogen and in contraceptive ef-fectiveness.

Not all antibiotics cause a reduction in circulating estrogens. Some antibiotics (macrolides5 and azole an-tifungals) inhibit cytochrome P450 3A4, and actually cause an increase in levels of circulating ethinyl estra-diol. However, macrolide antibiotics may also have an adverse effect on cardiac function in women.5,6

It is not possible to predict which women will be at risk of pregnancy as a result of antibiotic-contra-ceptive interaction. It is therefore advisable to instruct women to use an additional contraceptive methodwhile taking antibiotics, and to continue with the back-up method for at least 1 week after completing thecourse of antibiotics. This is especially relevant for women taking rifampin or griseofulvin. These womenshould be advised either to abstain from sexual activity or to use a back-up nonhormonal form of contra-ception (such as diaphragm or condom) during treatment, and for 1 week after completion of antibiotic ther-apy.7

If long-term use of antibiotics is contemplated (i.e., tetracycline for acne), patients should be advised touse a nonhormonal back-up contraceptive for 2 weeks from the start of antibiotic treatment to allow restora-tion of normal intestinal flora and of optimal contraceptive effectiveness. Another alternative is to switchthe patient to a pill with a higher dose of estrogen and progestin for one cycle.

Health care professionals should inform women on hormonal contraception who require antibiotic ther-apy that there is a small risk of drug interaction that may result in contraceptive failure. Women who areunwilling to take this small risk should be provided with a nonhormonal back-up method of contraception.Women taking birth control pills who experience breakthrough bleeding while undergoing antibiotic treat-ment may be at higher risk of contraceptive failure and should be advised to either abstain from sexual ac-

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Department of Obstetrics and Gynecology, Howard University College of Medicine, Washington, DC.

Infectious Diseases

tivity or to use a nonhormonal contraceptive back-up during treatment and for 1 week after completion ofantibiotic therapy.

REFERENCES

1. Ruggiero RJ. Contraception. In: Young LY, Koda-Kimble MA, Kradjan WA, et al. Applied therapeutics: the clin-ical use of drugs, 6th ed. Vancouver, WA: Applied Therapeutics, 1995:43.

2. Carmichael JM, Wieland KA. Contraception and infertility. In: Herfindal ET, Gourley DR, eds. Textbook of thera-peutics: drugs and disease management. 6th ed. Baltimore, MD: Williams & Wilkins, 1996:1752.

3. Ament PW, Bertolino JG, Liszewski JL. Clinically significant drug interactions. Am Fam Physician 2000;61:1745.4. Dickinson BD, Altman RD, Nielsen NH, et al. Drug interactions between oral contraceptives and antibiotics. Ob-

stet Gynecol 2001;98:853.5. Osborne NG. Erythromycin. J Gynecol Surg 1991;7:257.6. Osborne NG. Erythromycin: A safe antibiotic for women? J Gynecol Surg 1999;15:65.7. Shaver K. Antibiotic-oral contraceptive drug interactions. Prescriber’s Lett 2002;9:9.

Address reprint requests to:Newton G. Osborne, M.D., Ph.D.

Department of Obstetrics and GynecologyHoward University College of Medicine

2041 Georgia Avenue, NorthwestWashington, DC 20060

E-mail: NewtonOsborne@aol.com

Journal of Gynecologic Surgery172 Osborne