To Dr Kaplan and Dr Juch,
We appreciate your interest in our paper, ‘The Need for Contraception in Patients Taking Prescription Drugs: A Review of FDA Warning Labels, Duration of Effects, and Mechanisms of Action’, published in Expert Opinion on Drug Safety (3 November 2018). We are in complete agreement with most of the points made by the letter writers. However, while we have indeed included all agents for each category, regardless of the nature of the evidence, we do clearly state in numerous places, throughout the paper (Abstract, Highlights, Sections 3.1.2., 3.2, 3.2.3, 4.1 and the Expert Opinion), that the majority of the evidence is not from human studies. We clearly indicate that this is a limitation of this review, as well as a limitation impacting the ability to safely and effectively treat patients of reproductive age.
In addition, the summary table (Table 1) delineates this by stratifying the risk as ‘potential fetal harm’ vs. ‘fetal harm’ to indicate the level of evidence as non-human vs. human case reports/series or clinical trials.
Our primary goal was to provide a comprehensive overview of ALL drugs with potential negative effects. We do not disagree that some of these agents may be of relatively minor concern because the existing data are highly dependent on studies in animals or mechanistic data, which do not necessarily translate to effects in humans. However, we intended the review to serve as a reminder that reproductive toxicity is a possible side effect of drugs from diverse classes, with diverse structures, and with unrelated mechanisms of action. In addition, unless the risk of fetal harm is zero, the warning should continue to be included, and the possible risk should be explained to the patient.
We agree with the letter writers that the use of some agents will remain the gold standard despite possible risks, either because they are safer than the alternatives, or because the condition being addressed is of greater concern that the potential adverse effect. As human data accumulate, it will be easier to stratify the risk the various agents pose, and to better identify which patients are likely to benefit from treatment and which may be more likely to experience issues with fertility or fetal development. It is lamentable that the pregnancy category classification has been abolished, because an adequately updated classification system would be useful for explaining the level of evidence and making the risk clearer to health-care providers, pharmacists, and patients.
As noted in the article, although we believe the presented information is limited by the over-reliance on animal and mechanistic data, the review and summary table give an overview that can provide guidance on the agents that should be used with caution in patients of reproductive age, and highlights areas where further research is urgently needed.
Sincerely,
Haibo Li, PhD and
Elizabeth Rayburn, PhD, DABT, NRCC
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.