PHENYLEPHRINE

Fetal Risk Summary

Phenylephrine is a sympathomimetic used in emergency situations to treat hypotension and to alleviate allergic symptoms of the eye and ear. Uterine vessels are normally maximally dilated and they have only a-adrenergic receptors (1). Use of the predominantly a-adrenergic stimulant, phenylephrine, could cause constriction of these vessels and reduce uterine blood flow, thereby producing fetal hypoxia (bradycardia). Phenylephrine may also interact with oxytocics or ergot derivatives to produce severe persistent maternal hypertension (1). Rupture of a cerebral vessel is possible. If a pressor agent is indicated, other drugs such as ephedrine should be considered. 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, 1,249 of which had 1st trimester exposure to phenylephrine (4, pp. 345–356). For use anytime during pregnancy, 4,194 exposures were recorded (4, p. 439). An association was found between 1st trimester use of phenylephrine 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, 476, 491): First trimester Eye and ear (8 cases) Syndactyly (6 cases) Preauricular skin tag (4 cases) Clubfoot (3 cases) Anytime use Congenital dislocation of hip (15 cases) Other musculoskeletal defects (4 cases) Umbilical hernia (6 cases) 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).

Sympathomimetics are often administered in combination with other drugs to alleviate the symptoms of upper respiratory infections. Thus, the fetal effects of sympathomimetics, other drugs, and viruses cannot be totally separated. However, indiscriminate use of this class of drugs, especially in the 1st trimester, is not without risk.

Phenylephrine has been used as a stress test to determine fetal status in high-risk pregnancies (5). In the United States, however, this test is normally conducted with oxytocin.

Breast Feeding Summary

No reports describing the use of phenylephrine during human lactation have been located. The molecular weight (about 167) of the drug, however, is low enough that passage into breast milk should be expected. The effects of this exposure on a nursing infant are unknown.

References

1. Smith NT, Corbascio AN. The use and misuse of pressor agents. Anesthesiology 1970;33:58–101.
2. Nashimura H, Tanimura T. Clinical Aspects of the Teratogenicity of Drugs. Amsterdam: Excerpta Medica, 1976:231.
3. Shepard TH. Catalog of Teratogenic Agents. 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. Eguchi K, Yonezawa M, Hagegawa T, Lin TT, Ejiri K, Kudo T, Sekiba K, Takeda Y. Fetal activity determination and Neosynephrine test for evaluation of fetal well-being in high risk pregnancies. Nippon Sank Fujinka Gakkai Zasshi 1980;32:663–8.