Antibiotics and oral contraceptives.
With the exception of rifampin-like drugs, there is a lack of scientific evidence supporting the ability of commonly prescribed antibiotics, including all those routinely employed in outpatient dentistry, to either reduce blood levels and/or the effectiveness of oral contraceptives. To date, all clinical trials studying the effects of concomitant antibiotic therapy (with the exception of rifampin and rifabutin) have failed to demonstrate an interaction. Like all drugs, oral contraceptives are not 100% effective with the failure rate in the typical United States population reported to be as high as 3%. It is thus possible that the case reports of unintended pregnancies during antibiotic therapy may simply represent the normal failure rate of these drugs. Considering that both drug classes are prescribed frequently to women of childbearing potential, one would expect a much higher rate of oral contraceptive failure in this group of patients if a true drug:drug interaction existed. On the other hand, if the interaction does exist but is a relatively rare event, occurring in, say, 1 in 5000 women, clinical studies such as those described in this article would not detect the interaction. The pharmacokinetic studies of simultaneous antibiotic and oral contraceptive ingestion, and the retrospective studies of pregnancy rates among oral contraceptive users exposed to antibiotics, all suffer from one potential common weakness, i.e., their relatively small sample size. Sample sizes in the pharmacokinetic trials ranged from 7 to 24 participants, whereas the largest retrospective study of pregnancy rates still evaluated less than 800 total contraceptive users. Still, the incidence of such a rare interaction would not differ from the accepted normal failure rate of oral contraceptive therapy. The medico-legal ramifications of what looks like at best a rare interaction remains somewhat "murky." On one hand, we have medico-legal experts advising the profession to exercise caution and warn all oral contraceptive users of a potential reduction in efficacy during antibiotic therapy. These opinions are not evidence-based and rely heavily on one or two legal proceedings that cannot even be substantiated. On the other hand, there is one recently published legal proceeding in which the outcome was in favor of the oral surgeon. There is clearly a need for additional scientific research in oral contraceptive users that incorporates larger sample sizes, different time courses (prophylactic use versus standard 7-10 day use versus extended use), and different delivery systems (systemic administration versus local-controlled delivery) of antibiotic therapy. Though experts on this topic still recommend informing oral contraceptive users of the potential for a rare interaction, and for clinicians to advise them to employ additional barrier techniques of birth control during antibiotic therapy and for at least 1 week beyond the last dose [40], it is hoped that a set of guidelines regarding this controversy will eventually be published that is evidence-based, and not solely the results of anecdotal reports, expert opinions, and legal proceedings.
DeRossi
Scott S
SS
Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, 4001 Spruce Street, Philadelphia, PA 19104-6003, USA.
Hersh
Elliot V
EV
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015982:Bias; D001682:Biological Availability; D002986:Clinical Trials as Topic; D003276:Contraceptives, Oral / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007603:Jurisprudence; D011247:Pregnancy; D012189:Retrospective Studies; D017828:Rifabutin / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D018401:Sample Size
D000900:Anti-Bacterial Agents; D003276:Contraceptives, Oral; D017828:Rifabutin; D012293:Rifampin