Dextromethorphan in Pregnancy and Breastfeeding
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Dextromethorphan  Hydrobromide (Benylin DM®, Robitussin DM ® )
Antitussive . D-isomer of the codeine analog levorphanol. N-methyl-D-aspartate (NMDA) receptor antagonist. Molecular weight: 370.33

In developmental studies involving chick embryos dextromethorphan at 500 nmol/embryo/d killed more than half the embryos and induced congenital defects in about one-eighth of the survivors; dextromethorphan was also highly lethal at 50 nmol/embryo/d [2]. However, the validity of chick embryos as good model for predicting teratogenic potential in humans has been questioned by several investigators [3,4].

Retrospective data from the Collaborative Perinatal Project showed no increased rate of major or minor anomalies after exposure to dextromethorphan during the first four months of pregnancy in 300 women [5]. In addition cohort studies involving 187 women exposed to dextromethorphan during the first trimester did not demonstrate an increase in the rate of major malformations above the expected baseline rate [6,7].  Epidemiologic data from the Spanish Collaborative Study of Congenital Malformations also did not support an association between the use of dextromethorphan during pregnancy and an increased risk of congenital defects [8].

Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal life triggered widespread apoptotic neurodegeneration in the developing rat brain in a study by Ikonomidou C, et al [9]. Debus O and coworkers have urged caution in the use of dextromethorphan during pregnancy until long term neurodevelopmental studies have been conducted on the offspring of mothers who received dextromethorphan during their pregnancies [10].

BREAST FEEDING: It is not known whether dextromethorphan or its metabolites are excreted in human breast milk.


1. Briggs GG,Freeman RK, Yaffe SJ, Drugs in Pregnancy and Lactation 6th edition,Baltimore, MD: Williams & Wilkins,2002 p 384
2. Andaloro VJ, et al Dextromethorphan and other N-methyl-D-aspartate receptor antagonists are teratogenic in the avian embryo model.Pediatr Res. 1998;43:1-7.MEDLINE
3.Brent RL. The teratogenicity of N-methyl-D-aspartate (NMDA) receptor antagonists.Pediatr Res. 1998; 44: 415-7. PMID: MEDLINE
4. Brent RL. et al. Response to Dr. Rosenquist's comments pertaining to the paper by Andaloro et al. ('98) "Dextromethorphan and other N-methyl-D-aspartate receptor antagonists are teratogenic in the avian embryo model" and letters to the editor by Polifka JE and Shepard TH ('98) and Brent RL ('98)Teratology. 1999 ; 60: 61-2.MEDLINE
5.Heinonen OP et al: Birth Defects and Drugs in Pregnancy, Littleton, Publishing Sciences Group, 1977. p 378-383
6. Aselton P, Jick H, Milunsky A et al: First-trimester drug use and congenital disorders. Obstet Gynecol 65:451-5, 1985.  451-5.MEDLINE
7.Einarson A, Lyszkiewicz D, Koren G.The safety of dextromethorphan in pregnancy : results of a controlled study. Chest. 2001;119:466-9. MEDLINE
8. Martinez-Frias ML, Rodriguez-Pinilla E.Epidemiologic analysis of prenatal exposure to cough medicines containing dextromethorphan: no evidence of human teratogenicity.Teratology. 2001;63:38-41. MEDLINE
9.Ikonomidou C, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain.Science. 1999;283:70-4.MEDLINE
10. Debus O, et al. Dextromethorphan in pregnancy.[Letter] Chest. 2001;120:1038-40. MEDLINE


  • Over the Counter Cold Medications in Pregnancy
    1998 Illinois Teratogen Information Service

    Created: 11/17/2000
    Updated: 11/30/2002
    Updated: 1/10/2004

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