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Antibiotics and Oral Contraceptive Failure
Kevin E. Burroughs, MD;
M. Lee Chambliss, MD, MSPH
Greensboro, NC
Arch Fam Med. 2000;9:81-82.
QUESTION
Are antibiotics related to oral combination contraceptive failures?
SOLUTION
SEARCH STRATEGY
A MEDLINE search was performed (1966 to present, limited to the English language) on the following medical subject heading (MeSH) terms: antibiotics and contraceptives, oral, hormonal.
BACKGROUND
Throughout the English-language literature, there are reports and concerns that antibiotics may decrease the effectiveness of oral contraceptives. Studies estimate 11 million women in the United States1 and 60 to 70 million women in the world2 use oral contraceptives. This review focuses on combination oral contraceptives, as most literature does not specifically focus on the progestin-only pills.
Pharmacological agents such as antibiotics may interfere with the effectiveness of combination oral contraceptive birth control pills (OCPs) by decreasing the steroid hormone's plasma concentrations. The proposed mechanisms of these interactions are many but include hepatic microsomal enzyme induction or inhibition, interference with the enterohepatic circulation of steroid metabolites, interference with absorption from the gastrointestinal tract, competition between 2 drugs for the same metabolizing enzyme, alterations in plasma protein binding, or induction of an opposite physiologic effect3 or increased urinary or fecal excretion of the contraceptive.4
LITERATURE
On review of the literature by the above search criteria, there are 2 main types of studies that examine the interaction of combination OCPs and antibiotics. The first type measures the effect of antibiotics on the hormone levels of OCPs. This type of study shows the strongest findings, statistically, regarding decreased efficacy of OCPs.
In studies by Back et al5 as well as Reimers and Jezek,6 a significant decrease in the hormonal levels of OCPs was noted in women taking rifampin even after a single dose. Wermeling et al7 showed that while dirithromycin slightly decreased plasma ethinyl estradiol levels, the clinical importance of this was negligible because the women remained anovulatory. Adlercreutz et al8 showed a decrease in plasma-conjugated estrogens in a small study of 3 women in the last trimester of pregnancy. Conversely, Friedman et al9 reported that ampicillin did not diminish the induction of anovulation in women taking the combination drug ethynodiol diacetate and ethinyl estradiol (Demulen). Murphy et al10 measured the plasma ethinyl estradiol or norethindrone concentrations in 7 women and found no decrease in the concentration of either hormone with the concomitant administration of tetracycline. Finally, Neely et al11 performed a prospective controlled clinical trial using norethindrone and ethinyl estradiol (Ortho-Novum 1/35) and doxycycline and showed no statistically significant differences in serum levels of ethinyl estradiol, norethindrone, or endogenous progesterone between the control and treatment phases.
The second category of studies looked at unintended pregnancy as the outcome. Although some reviews report an increased rate in certain antibiotics,12-13 most articles cited in these refer to case reports or case series. In a small survey that looked at erythromycin, tetracycline, and minocycline, London and Lookingbill14 reported a pregnancy rate that did not vary statistically from the accepted failure rate of oral contraception. In a retrospective chart review by Helms et al,2 there was no increase in pregnancy rates vs the published standard. Helms also obtained a control group of women who took OCPs but not antibiotics during the study period. Again, there was no significant difference in pregnancy rates between the treatment and control group.
Respected medical references such as the Medical Letter15 and Contraceptive Technology16 as well as opinions expressed by many authors in reviews and editorials acknowledge a low but unpredictable incidence of combination OCP failure with concomitant antibiotic use. All recommend using alternate contraception with antibiotic use. Contraceptive Technology further defines this recommendation by suggesting the use of alternate contraception for the length of antibiotic therapy (or 14 days, whichever is longer) plus 7 days, initiating this at the start of antibiotic therapy. Other considerations for interactions with OCPs17 should not be forgotten when counseling all women about contraception.
BOTTOM LINE
To date there have been few controlled studies and no prospective randomized trials of the effects of antibiotics on combination oral contraceptives. The literature does not specifically delineate warnings between intravenous and oral contraceptives; therefore, the same warnings would apply to both. Most of the available data do not indicate any major reduction in the efficacy of OCPs with concurrent common antibiotic use. However, these studies cannot reliably exclude a small decrease in efficacy especially in the "low-dose" (<35 µg of estrogen) combination OCPs. With several well-known resources suggesting alternative contraception during antibiotic use, pragmatically it is important to inform all female patients of the possible interaction.
| Editor's Note: We are happy to provide a new series, Solutions to Often-Asked Problems (SOAP). In this series, we start with questions that have arisen in the day-to-day practice of family medicine but are not easily answered from standard textbooks. Select authors will search the literature and formulate succinct practical answers. The discussions will be as evidence based as possible but will also give experience-based opinions when necessary to provide clear applicable answers. Each SOAP will be arranged in a standard Question, Search Strategy, Details, and Bottom Line format.
Our series editor is M. Lee Chambliss, MD, MSPH, clinical assistant professor of family medicine at Moses Cone Family Medicine Residency, Greensboro, NC. Dr Chambliss previously published an article called "Answering Clinical Questions" (J Fam Pract. 1996;43:140-144) and has had 2 question-and-answer columns already published in the ARCHIVES. He is involved in ongoing collaborative research on physicians' clinical questions (BMJ. 1999;319:358-361).—Marjorie A. Bowman, MD, MPA
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REFERENCES
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1. Miller DM, Helms SE, Brodell RT. A practical approach to antibiotic treatment in women taking oral contraceptives. J Am Acad Dermatol. 1994;30:1008-1011.
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2. Helms SE, Bredle DL, Zajic J, Jarjoura D, Brodell RT, Krishnarao I. Oral contraceptive failure rates and oral antibiotics. J Am Acad Dermatol. 1997;36: 705-710.
3. Fazio A. Oral contraceptive drug interactions: important considerations. South Med J. 1991;84:997-1002.
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4. Rasmussen JE. The effect of antibiotics on the efficacy of oral contraceptives: a controversy revisited. Arch Dermatol. 1989;125:1562-1564.
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5. Back DJ, Breckenridge AM, Crawford F, et al. The effect of rifampin on the pharmacokinetics of ethynlestradiol in women. Contraception. 1980;21:135-143.
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6. Reimers D, Jezek A. Simultaneous use of rifampicin and other antituberculous agents with oral contraceptives. Prax Pneumol. 1971;25:255-262.
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7. Wermeling DP, Chandler MH, Sides GD, et al. Dirithromycin increases ethinyl estradiol clearance without allowing ovulation. Obstet Gynecol. 1995;86:78-84.
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8. Adlercreutz H, Martin F, Lehtinen T, Tikkanen MJ, Pulkkinen MO. Effect of ampicillin administration on plasma conjugated and unconjugated estrogen and progesterone levels in pregnancy. Am J Obstet Gynecol. 1977;128:266-271.
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9. Friedman CI, Huneke AL, Kim MH, Powell J. The effect of ampicillin on oral contraceptive effectiveness. Obstet Gynecol. 1980;55:33-37.
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10. Murphy AA, Zacur HA, Charache P, Burkman RT. The effect of tetracycline on levels of oral contraceptives. Am J Obstet Gynecol. 1991;164:28-33.
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11. Neely JL, Abate M, Swinker M, D'Angio R. The effect of doxycycline on serum levels of ethinyl estradiol, norethindrone, and endogenous progesterone. Obstet Gynecol. 1991;77:416-420.
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12. Zachariasen RD. Loss of oral contraceptive efficacy by concurrent antibiotic administration. Womens Health. 1994;22:17-26.
13. Bainton R. Interaction between antibiotic therapy and contraceptive medication. Oral Surg. 1986;61:453-455.
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14. London BM, Lookingbill DP. Frequency of pregnancy in acne patients taking oral antibiotics and oral contraceptives. Arch Dermatol. 1994;130:392-393.
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15. The Medical Drug Interactions Program [computer program]. New Rochelle, NY: The Medical Letter Inc; 1999.
16. Hatcher RA, Trussell J, Stewart F, et al. Contraceptive Technology. 17th rev ed. New York, NY: Ardent Media Inc;1998.
17. Sparrow MJ. Pregnancies in reliable pill takers. N Z Med J. 1989;102:575-577.
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SECTION EDITOR: M. LEE CHAMBLISS, MD, MSPH
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