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Analysis of reports of unintended pregnancies associated with the combined use of non-enzyme-inducing antibiotics and hormonal contraceptives
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  • Published on:
    Interaction of non-enzyme-inducing antibiotics with hormonal contraceptives
    • Jeffrey K Aronson, Consultant Physician and Clinical Pharmacologist Centre for Evidence Based Medicine, University of Oxford
    • Other Contributors:
      • Robin E Ferner, Honorary Professor of Clinical Pharmacology

    Drs Clure and Lazorwitz have misunderstood and misinterpreted the Yellow Card data that we adduced to test the null hypothesis that there is no interaction of antibiotics with hormonal contraceptives. Here we reply to their specific comments.

    “The medications in each group are not equivalent and bias the sample” We chose a wide range of medicines in order to minimize this. Clure and Lazorwitz have selected only two examples each from the group of nine control drugs and the group of nine non-enzyme-inducing antibiotics, and assert that the age distribution favours older women in the control group. However, they ignore the fact that the same could be asserted of the enzyme-inducing drugs, some of which are more likely to be used in older women, but had an even bigger effect than the antibiotics.

    “The rates of unintended pregnancy reported … are much lower than expected in general users of oral contraception” This is an important misunderstanding, which we sought to obviate in the paper, by making it clear that the data do not allow calculation of the absolute rates of unintended pregnancies. That is because the reported rates are not rates of unintended pregnancies in women taking hormonal contraceptives, but the frequencies of reports of unintended pregnancies as a proportion of all reports of suspected adverse reactions. It is the ratios of frequencies that are important. In other words, whatever the baseline risk is, the risk is 13 times higher with enzyme i...

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    Conflict of Interest:
    None declared.
  • Published on:
    Letter to the editor in response to “Analysis of reports of unintended pregnancies associated with the combined use of non-enzyme-inducing antibiotics and hormonal contraceptives”
    • Cara E Clure, Family Planning Fellow, Ob/Gyn University of Colorado
    • Other Contributors:
      • Aaron Lazorwitz, Assistant Professor, Ob/Gyn-Family Planning

    First available online on August 18, 2020 in BMJ Evidence-Based Medicine, Aronson and Ferner (1) concluded that women using hormonal contraceptives cannot rely on their contraceptive method if they take a short course of non-enzyme inducing antibiotics based on Yellow Card reports to the UK’s Medicines and Healthcare products Regulatory Agency.
    We believe that there are fundamental scientific issues and limitations with this study not adequately addressed by the authors. First, Yellow Card reports require provider reporting of an unintended pregnancy, which the authors acknowledge are subject to reporting bias. As the authors also acknowledge, many healthcare providers suspect there are drug-drug interactions between hormonal contraception and all antibiotics, despite the lack of definitive evidence (1). Therefore, there already exists a bias among providers that they would suspect and report an unintended pregnancy attributed to a drug-drug interaction among women taking antibiotics. The medications in each group are also not equivalent and bias the sample. For example, in the antibiotic group, metronidazole and nitrofurantoin are more commonly used in younger reproductive-aged and sexually active women (2,3), the population at highest risk of unintended pregnancies (4). In comparison, the control group includes such medications as propranolol and theophylline, which are used for treatment of cardiac and respiratory conditions more common among older women (5,6), wi...

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    Conflict of Interest:
    None declared.
  • Published on:

    Might it be helpful to clarify in the title or abstract that the paper relates solely to estrogen containing contraceptives, and essentially the oral versions?

    Conflict of Interest:
    None declared.