PHENYLPROPANOLAMINE

Fetal Risk Summary

Phenylpropanolamine is a sympathomimetic used for anorexia and to alleviate the symptoms of allergic disorders or upper respiratory infections. Uterine vessels are normally maximally dilated and they have only a-adrenergic receptors (1). Use of the a- and b-adrenergic stimulant phenylpropanolamine could cause constriction of these vessels and reduce uterine blood flow, thereby producing fetal hypoxia (bradycardia). This drug is a common component of proprietary mixtures containing antihistamines and other drugs. Thus, it is difficult to separate the effects of phenylpropanolamine on the fetus from other drugs, disease states, and viruses.

Sympathomimetic amines are teratogenic in some animal species, but human teratogenicity has not been suspected (2,3). The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 726 of which had 1st trimester exposure to phenylpropanolamine (4, pp. 345–356). For use anytime during pregnancy, 2,489 exposures were recorded (4, p. 439). An association was found between 1st trimester use of phenylpropanolamine and malformations; association with minor defects was greater than with major defects (4, pp. 345–356). For individual malformations, several possible associations were found (4, pp. 345–356,477,491): First trimester Hypospadias (4 cases) Eye and ear (7 cases) (statistically significant) Polydactyly (6 cases) Cataract (3 cases) Pectus excavatum (7 cases) Anytime use Congenital dislocation of hip (12 cases) Except for eye and ear defects, the statistical significance of these associations is not known and independent confirmation is required. For the sympathomimetic class of drugs as a whole, an association was found between 1st trimester use and minor malformations (not life-threatening or major cosmetic defects), inguinal hernia, and clubfoot (4, pp. 345–356). Indiscriminate use of this class of drugs, especially in the 1st trimester, is not without risk.

A case of infantile malignant osteopetrosis was described in a 4-month-old boy exposed in utero on several occasions to Contac (chlorpheniramine, phenylpropanolamine, and belladonna alkaloids), but this is a known genetic defect (5). The infant also had a continual “stuffy” nose.

Breast Feeding Summary

No data are available.

References

1. Smith NT, Corbascio AN. The use and misuse of pressor agents. Anesthesiology 1970;33:58–101.
2. Nishimura H, Tanimura T. Clinical Aspects of the Teratogenicity of Drugs. Amsterdam: Excerpta Medica, 1976:231.
3. Shepard TH. Catalog of Teratogenic Drugs. 3rd ed. Baltimore, MD: Johns Hopkins University Press, 1980:134–5.
4. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977.
5. Golbus MS, Koerper MA, Hall BD. Failure to diagnose osteopetrosis in utero. Lancet 1976;2:1246.