2. Do antibiotics decrease the efficacy of oral contraceptives?
It’s unlikely, but antibiotics may reduce the efficacy of OCs.
There have been few, but well documented, reports of women using OCs who became pregnant after taking antimicrobials.14 It is recognized that rifampin, an inducer of enzymes that metabolize estrogens, decreases the efficacy of OCs.15 Ketoconazole’s interaction seems less well documented, but combining the agent with low-estrogen (low-dose) OCs warrants caution.16 What is not well understood is whether more common or broad-spectrum antibiotics also increase the risk of OC failure.
Three mechanisms have been proposed:16
- Antimicrobials affect hepatic enzyme induction, which increases metabolism of hormones.
- Broad-spectrum antibiotics reduce gut bacteria, which alters enterohepatic circulation and reduces plasma hormone concentrations.
- Antibiotics increase gastrointestinal motility, which decreases absorption (and reabsorption) of OCs.
A 2007 study found that when physicians and pharmacists were surveyed and asked if broad-spectrum antibiotics have a clinically significant interaction with OCs, 83% of physicians and 89% of pharmacists answered “Yes;”17 however, a large epidemiologic study performed in the United States showed no association between antibiotic use and OC failure.18
After this report, investigators in the Netherlands completed a similar cross-over analysis and found that there was a relationship between the use of antibiotics and breakthrough pregnancy in a population-based prescription database, but that the results didn’t hold for broad-spectrum antibiotics or in a sensitivity analysis.19 Pharmacokinetic studies are also conflicting, as some have shown an effect on serum hormone levels, while others have not.15,20-22
High- vs low-risk agents. Ciprofloxacin did not affect hormone levels in 2 studies.20,21 Rifampin and voriconazole may enhance systemic exposure to OCs.15,22 And erythromycin and azithromycin may interact with OCs, but the clinical significance of this interaction is still unknown.16
Short-courses of TMP/SMX are generally thought to be safe;16 a small study looked at cotrimoxazole 1 g twice daily in 9 women taking long-term OC steroids and found that short courses of the drug were unlikely to cause any adverse effects on contraceptive control.23 Tetracyclines and penicillins were the antibiotics most frequently involved in case reports of pregnancy from the United Kingdom (TABLE 32).16
It is hypothesized that some women may have a higher risk of OC failure than others due to how they metabolize ethinyl estradiol.24 Another hypothesis is that some women have gut flora that is more susceptible to the antibiotic being used. And still another possibility is that lower doses of hormones are being used in OCs than were studied for this interaction.15 Anything that decreases the concentration of these lower-dose OCs is concerning, especially in patients with a higher body mass index (BMI). The few pharmacokinetic studies that have been conducted show that it takes longer for OCs to reach a steady state in obese women and that they have a lower area under the curve (AUC) and maximum estrogen concentration than women with a normal BMI.25
THE BOTTOM LINE Because the degree of variability between patients is unknown and obesity rates are increasing, concern that low-dose OCs may lose efficacy when combined with antibiotics is warranted. While the absolute risk of breakthrough pregnancy seems small, the most conservative approach is to advise patients to use a back-up method of contraception during times of antibiotic use.