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抗生素与口服避孕药

Antibiotics and oral contraceptives.

作者信息

DeRossi Scott S, Hersh Elliot V

机构信息

Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, 4001 Spruce Street, Philadelphia, PA 19104-6003, USA.

出版信息

Dent Clin North Am. 2002 Oct;46(4):653-64. doi: 10.1016/s0011-8532(02)00017-4.

Abstract

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.

摘要

除利福平类药物外,缺乏科学证据支持常用抗生素(包括门诊牙科常规使用的所有抗生素)有降低血液中口服避孕药水平和/或降低其有效性的能力。迄今为止,所有研究联合使用抗生素治疗(利福平和利福布汀除外)效果的临床试验均未证明存在相互作用。与所有药物一样,口服避孕药并非100%有效,据报道,美国普通人群中的失败率高达3%。因此,抗生素治疗期间意外怀孕的病例报告可能仅仅代表了这些药物的正常失败率。鉴于这两类药物都经常开给有生育潜力的女性,如果确实存在药物与药物之间的相互作用,那么在这组患者中口服避孕药的失败率应该会高得多。另一方面,如果这种相互作用确实存在,但相对罕见,比如每5000名女性中出现1例,那么本文所述的这类临床研究就无法检测到这种相互作用。同时服用抗生素和口服避孕药的药代动力学研究,以及接触抗生素的口服避孕药使用者怀孕率的回顾性研究,都存在一个潜在的共同弱点,即样本量相对较小。药代动力学试验的样本量在7至24名参与者之间,而关于怀孕率的最大规模回顾性研究评估的口服避孕药使用者总数仍不到800人。即便如此,这种罕见相互作用的发生率与公认的口服避孕药治疗正常失败率并无差异。这种看似极为罕见的相互作用所带来的医学法律后果仍有些“模糊不清”。一方面,医学法律专家建议该行业要谨慎行事,并警告所有口服避孕药使用者在抗生素治疗期间药效可能会降低。这些观点并非基于证据,且严重依赖一两个甚至无法证实的法律诉讼。另一方面,最近有一项已公布的法律诉讼,其结果对口腔外科医生有利。显然,有必要针对口服避孕药使用者开展更多科学研究,纳入更大的样本量、不同的疗程(预防性使用与标准的7 - 10天使用与延长使用)以及不同的抗生素给药系统(全身给药与局部控制给药)。尽管关于这个话题的专家仍然建议告知口服避孕药使用者存在罕见相互作用的可能性,并建议临床医生告知她们在抗生素治疗期间以及最后一剂之后至少1周采用额外的屏障避孕技术[40],但人们希望最终能发布一套基于证据而非仅仅基于轶事报告、专家意见和法律诉讼结果的关于这一争议的指南。

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