CAN ROBITUSSIN® DM BE USED TO TREAT COUGH DURING PREGNANCY?

Medicine and Health Rhode Island, Mar 2005 by Ward, Kristina E

During cough and cold season, the question of whether Robitussin® DM is safe for use during pregnancy often arises. Robitussin® DM is available genetically and contains guaifenesin (100 mg/5 mL) and dextromethorphan (10 mg/5 mL). Because both dextromethorphan and guaifenesin were marketed prior to the requirement for pregnancy information in labeling, a pregnancy category was not assigned to either ingredient; however, there is information available in the literature about the use of the individual ingredients during pregnancy.

DEXTROMETHORPHAN

Dextromethorphan is the antitussive component of the combination and is a derivative of morphinan, a structural analog of codeine.12 Use of the d-isomer avoids the addictive and analgesic properties present in the l-isomer and other codeine derivatives. Compared with codeine, the antitussive potency of dextromethorphan is nearly similar.3,4 Dextromethorphan acts centrally in the medulla oblongata to raise the cough threshold and is also known to act as an antagonist at N-methyl-D-aspartate (NMDA) receptors; however, it is unclear whether its NMDA activity contributes to the antitussive effect since codeine does not bind to NMDA receptors.1,5 Dextromethorphan is rapidly absorbed from the gastrointestinal (GI) tract with onset of cough suppression within 15 to 30 minutes and duration of effect between five to six hours.1,2 Metabolism occurs in the liver via cytochrome P450 2D6 forming two inactive metabolites and one active metabolite. Cytochrome P450 2D6 activity may be increased during pregnancy potentially causing alterations in clearance of medications metabolized through this pathway, including dextromethorphan.6

A controversial animal reproduction study injected dextromethorphan into chick embryos consecutively for three days.7 At the highest dose, increases in congenital anomalies (e.g., spinal and craniofacial defects) were observed. However, the findings were heavily criticized. The findings were not replicated in rats or rabbits at doses up to 100 times the human therapeutic dose.8 Dextromethorphan has a molecular weight of 271 daltons which is small enough to be transferred to the fetus.9 However, data from two surveillance studies of women who had taken dextromethorphan during the first trimester, one being the Collaborative Perinatal Project, found no relationship between the use of dextromethorphan and the incidence of congenital malformations.10, 11 Additionally, two recent casecontrol studies also found no evidence of increased risk of congenital malformations with dextromethorphan use during the first trimester.12,13

GUAIFENESIN

Guaifenesin is an expectorant with no antitussive effect. Although guaifenesin's mechanism of action is not completely known, it increases the volume and decreases the viscosity of respiratory tract secretions.14,15 Guaifenesin is well-absorbed from the GI tract with approximately 60% of guaifenesin hydrolyzed in the blood.14

Peer-reviewed evidence supporting the effectiveness of guaifenesin as an expectorant is limited.15 One study evaluating the effectiveness of guaifenesin in patients with bronchitis found it ineffective.16 A second study in patients with colds found that guaifenesin subjectively thinned mucus; however, the guaifenesin treatment dose was two times the recommended dose.17

Guaifenesin has a molecular weight of 198 daltons, indicating possible placental transfer. Data from three surveillance studies regarding the use of guaifenesin during the first trimester is available.9-11 An increase in the risk of inguinal hernias was noted with the first trimester use of guaifenesin in 197 mother-child pairs during the Collaborative Perinatal Project.4 However, when analyzed for guaifenesin exposure anytime during pregnancy this association was not significant. Two other surveillance studies assessing 241 and 141 newborns whose mothers ingested guaifenesin during the first trimester found no associations between guaifenesin use and congenital defects.9,11

CONCLUSION

The use of dextromethorphan for cough during pregnancy does not appear to produce an increased risk of congenital malformations in newborns. Similar data with guaifenesin also suggests it is safe to use during pregnancy. However, in general, the use of drugs should be minimized whenever possible during pregnancy. Because the efficacy data supporting the use of guaifenesin as an expectorant is scant, the use of a dextromethorphan-only cough suppressant (see Table 1) should be considered. Additionally, patients should be advised to avoid cough preparations that contain alcohol.

REFERENCES

1. Gutstein HB, Akil H. Opioid analgesics. In: Hardman JG, Limbird LE, Goodman Gilman A, editors. Goodman & Gilman's the pharmacological basis of therapeutics. 10th ed. New York: McGraw-Hill; 2001.

2. McEvoy GK, Miller J, et al., editors. AHFS Drug Information. Bethesda, (MD): American Society for Health-System Pharmacists, Inc. 2005.

3. Aylward M, Maddock |, et al. Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects. Eur J Respir Dis 1984;65:283-291.