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 . However, the validity of chick embryos as good model for
predicting teratogenic potential in humans has been questioned by several
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
. 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
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 .
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 .
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
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.
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.
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.
Over the Counter Cold Medications in Pregnancy
1998 Illinois Teratogen Information Service