Review
Drug interactions between oral contraceptives and antibiotics

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Abstract

OBJECTIVE:

To evaluate the evidence on possible drug interactions between antibiotics and oral contraceptives (OCs) that may lead to OC failure.

DATA SOURCES:

MEDLINE and Lexis/Nexis Medical Library searches for 1966–1999 using the key word “oral contraceptives,” cross-indexed with the terms “antibiotics,” “adverse effects,” and “pregnancy,” and MEDLINE search using the additional MeSH term “drug interactions.” No language restrictions were used.

METHODS OF STUDY SELECTION:

A total of 167 articles were retrieved for analysis. Another 32 articles were identified by review of the references cited in these publications. Articles were selected based on their ability to provide information on the relationship between antibiotic therapy and OC efficacy in otherwise compliant users (defined as women with unplanned pregnancies who reported compliance with their OC regimen). Additionally, studies that either directly measured the effects of antibiotics on the pharmacokinetics of OC components, or that analyzed the effects of antibiotics on measures of ovulation in OC users were accepted.

TABULATION, INTEGRATION, AND RESULTS:

At least 30 cases have been reported of pregnancies occurring in women taking OCs and antibiotics, particularly rifampin. Approximately 20% of pregnant women reporting to family planning or abortion clinics reported concomitant OC and antibiotic use. Information from adverse event reporting databases generally mirrors the types of information gleaned from these case reports and clinical surveys and accounts for approximately one-third of reported cases. Retrospective surveys, primarily from dermatology-based practices, also have reported 24 pregnancies in OC users who concomitantly received therapy with antibiotics, most commonly tetracyclines and penicillins. Apparent OC failure rates in clinical surveys were within the usual range expected for patterns of typical use. In pooled results obtained from relatively small populations, oral antibiotics, with the exception of rifampin, have not significantly affected the pharmacokinetics of ethinyl estradiol, levonorgestrel, and norethindrone or reduced the serum concentrations of gonadotropins. However, individual patients have been identified who experienced significant decreases in the plasma concentration of these components of OCs and who appeared to ovulate.

CONCLUSION:

Rifampin impairs the effectiveness of OCs. Pharmacokinetic studies of other antibiotics have not shown any systematic interaction between antibiotics and OC steroids. However, individual patients do show large decreases in the plasma concentrations of ethinyl estradiol when they take certain other antibiotics, notably tetracycline and penicillin derivatives. Because it is not possible to identify these women in advance, a cautious approach is advised.

Section snippets

Sources

Published studies from 1966 through December 1999 were identified through MEDLINE and Lexis/Nexis Medical Library searches (without language restriction) using the term “oral contraceptives,” cross-indexed with “antibiotics,” “adverse effects,” and “pregnancy.” Related articles in the MEDLINE database using the additional MeSH term “drug interactions” also were identified. A total of 167 articles were retrieved for analysis, and another 32 articles were identified by review of the references

Clinical reports of antibiotics apparently causing OC failure

The first report of potential interactions between antibiotics and OCs appeared in 1971 when Reimers and Jezek6 reported an increased incidence of intermenstrual breakthrough bleeding in 38 of 51 women treated concomitantly with OCs and rifampin. Shortly thereafter, rifampin was implicated in five unplanned pregnancies among 88 women with tuberculosis who were taking both rifampin and OCs. Another 62 women suffered from menstrual irregularities.7 Over the next decade, another 13 reports

Discussion

Based on retrospective case series (usually without control groups) and individual case reports, it has long been suspected that the prescription of oral antibiotics to women using OCs may occasionally result in OC failure in otherwise compliant patients. Caution must be exercised in the interpretation of these data because of recall bias and the possibility that individuals may underreport poor compliance when they are confronted with an unplanned (or unwanted) pregnancy or are requesting

Conclusions

The following statements, recommended by the Council on Scientific Affairs, were adopted as American Medical Association policy in June 2000.

  • 1.

    Women prescribed rifampin concomitantly with OCs faced significant risk of OC failure and should be counseled about the additional use of nonhormonal contraceptive methods during the course of rifampin therapy.

  • 2.

    Women using combined OCs should be informed about the small risk of interactions with antibiotics and that it is not possible to identify in

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    1

    Members and staff of the Council on Scientific Affairs at the time this report was prepared were: Myron Genel, MD (Chair), New Haven, CT; Michael A. Williams, MD (Chair-Elect), Baltimore, MD; Roy D. Altman, MD, Miami, FL; Scott D. Deitchman, MD, MPH, Duluth, GA; J. Chris Hawk III, MD, Charleston, SC; John P. Howe III, MD, San Antonio, TX; Hillary D. Johnson, St. Louis, MO; Nancy H. Nielsen, MD, PhD, Buffalo, NY; John F. Schneider, MD, PhD, Chicago, IL; Melvyn L. Sterling, MD, FACP, Orange, CA; Zoltan Trizna, MD, PhD, Galveston, TX; and Donald C. Young, MD, Iowa City, IA. Staff: Barry D. Dickinson, PhD (Secretary); James M. Lyznicki, MS, MPH (Assistant Secretary); and Marsha Meyer (Editor), Chicago, IL.

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