Confusion about doxylamine safety in pregnancy

To the Editor: The Australian Therapeutic Goods Administration (TGA) categorisation system for prescribing medicines in pregnancy lists doxylamine as a Category A medicine — “Drugs which have been taken by a large number ofpregnantwomen … without any proven increase in the frequency of malformations”.1

However, despite this categorisation, many single‐ingredient non‐prescription doxylamine products continue to carry misleading product and consumer information. While correctly assigning Category A, they then contradictorily include warnings such as “do not use during pregnancy” and/or “studies to prove it is safe for the developing baby have not been done”.

There is no validity or justification to such statements, which are inconsistent with both available data and the Category A status.

Studies on the safety of doxylamine in pregnancy date from the 1980s, when the first meta‐analysis demonstrated that doxylamine was not a human teratogen and should not have been removed from the market by the manufacturer.2

Subsequently, there have been several studies, reinforcing both the safety and efficacy of doxylamine for the treatment of nausea and vomiting in pregnancy (NVP).3 This resulted in the United States Food and Drug Administration (FDA) once again approving doxylamine (with pyridoxine) in 2014 as safe to use in pregnancy, with a specific indication for managing NVP.

Furthermore, the Society of Obstetric Medicine of Australia and New Zealand’s practice guidelines recommend doxylamine (and pyridoxine) as first line treatment for NVP.4

MotherSafe — a New South Wales‐based teratogen information service — receives about 20 000 calls annually from health care providers and consumers. Many women call this service after receiving conflicting advice about using doxylamine in pregnancy from pharmacists and other health care professionals, including general practitioners and obstetricians. Moreover, pharmacists also identify a knowledge gap and concerns about off‐label use and discrepancies between the product information, categorisation and other available information sources.5 In some cases, pharmacists have refused to sell doxylamine to women with NVP because of the product information, considering the use of doxylamine for NVP to be off‐label and thus not indicated or safe.

Despite raising our concerns with the TGA about the confusing labelling, we are yet to see any progress in correcting this significant misinformation among health professionals and patients.

This specific issue highlights wider concerns around Australia’s confusing pregnancy risk classification and the imperative for the TGA to abandon the current alphabetical categorisation and move to a format similar to the one used by the FDA Pregnancy and Lactation Labeling Rule, which requires all packaging and consumer information to include consistent evidence‐based information on medication use in pregnancy and breastfeeding.6