The Safety of Dextromethorphan in Pregnancy: Results of a Controlled Study

; ; and , Motherisk Program, Division of Clinical Pharmacology, The Hospital for Sick Children, University Of Toronto, Ontario, Canada.

Disclosures

CHEST. 2001;119(2) 

In This Article

Abstract and Introduction

Background: Dextromethorphan (DM), the d-isomer of the codeine analog levorphanol, is an active ingredient present in a variety of cough and cold remedies. Recently, data generated from a study in chick embryos were extrapolated to suggest that pregnant women should not use this drug because of the risk of birth defects. We conducted a controlled study of pregnant women who used DM, to examine the possible teratogenic risk in humans.
Materials and Methods: We followed up women who used DM and had been counseled by the Motherisk Program during their pregnancy. A control group of women was matched for age, smoking, alcohol use, and disease state (upper respiratory tract infection, not treated with DM).
Results: We were able to ascertain pregnancy outcome in 184 women. There were 172 live births, 10 spontaneous abortions, 1 therapeutic abortion, and 1 stillbirth. One hundred twenty-eight of the women used the drug during the first trimester of pregnancy. There were three major malformations (2.3%) among the babies of women who used DM in the first trimester, seven minor malformations, and the mean (± SD) birth weight was 3,381 ± 670 g. In the control group, there were 174 live births, 8 spontaneous abortions, and 2 therapeutic abortions. There were five major malformations, one of which was a chromosomal abnormality (2.8%), eight minor malformations, and the mean birth weight was 3,446 ± 571 g.
Conclusion: This study fails to show that DM use during pregnancy increases the rates of major malformations above the expected baseline rate of 1% to 3%.

Dextromethorphan (DM) is the d-isomer of the codeine analog levorphanol, an antitussive that is an active ingredient in a variety of over-the-counter cough and cold medications. It is a synthetic, nonnarcotic, centrally acting cough suppressant that is available either alone (eg, as lozenges or oral solution) or in combination with a large number of other compounds used for upper respiratory tract infections.[1]

No information is available on the placental transfer of DM. Its molecular weight (about 271), however, is low enough that transfer to the fetus probably occurs. Animal reproductive studies have not been conducted with DM. In an in ovo study[2] examining the effects of DM on chick embryos, the authors hypothesized that N-methyl-D-aspartate receptor antagonists, such as ethanol and DM, induce neural crest (craniofacial and cardiac septal defects) and neural tube defects. They also cited published evidence that during early development, the receptors blocked by DM in the chick embryos are analogous to receptors in other species and therefore concluded that the drug would also block these receptors, resulting in similar malformations in humans.[2]

In humans, the only published studies[3] to date are from the Collaborative Perinatal Project, which monitored 50,282 mother-child pairs, 300 of whom used DM during the first trimester. There was no increase above the baseline rate of 1% to 3% for major malformations and no increase in the relative risk for any specific malformation.[3] A surveillance study,[4] which linked automated pharmacy records and the outcome of pregnancies in 59 women who were assumed to have used DM sometime in the first trimester of their pregnancy, documented one malformation in this group. These data have formed the widely accepted view that DM is probably safe to use during pregnancy, and this information has been included in several reviews.[5,6,7,8,9]

A study[2] in chick embryos concluded that women should not use DM during pregnancy. These data, although very limited in terms of their applicability to humans, received wide publicity, causing high levels of anxiety among pregnant women and their health-care professionals.[10]

The Motherisk Program at The Hospital for Sick Children is a counseling service for pregnant and lactating women and their health professionals. Following the publication of the results of the chick embryo study in the newspapers, we received many calls from women who were pregnant, had used DM, read the article, and became quite concerned. Because of the paucity of studies specifically examining DM, we carried out the present study to provide additional evidence-based information on pregnancy outcome following gestational exposure to this drug.

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