ISOPROTERENOL

Fetal Risk Summary

No reports linking the use of isoproterenol with congenital defects have been located. Isoproterenol is teratogenic in some animal species, but human teratogenicity has not been suspected (1,2).

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 31 of which had 1st trimester exposure to isoproterenol (3, pp. 346–347). No evidence was found to suggest a relationship between large categories of major or minor malformations or to individual defects. However, an association in the 1st trimester was found between the sympathomimetic class of drugs as a whole and minor malformations (not life-threatening or major cosmetic defects), inguinal hernia, and clubfoot (3, pp. 345–356).

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 16 newborns had been exposed to isoproterenol during the 1st trimester (F. Rosa, personal communication, FDA, 1993). One (6.3%) major birth defect was observed (0.7 expected), an oral cleft.

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.

Isoproterenol has been used during pregnancy to accelerate heart rhythm when high-grade atrioventricular block is present and to treat ventricular arrhythmias associated with prolonged QT intervals (4). Because of its b-adrenergic effect, the agent will inhibit contractions of the pregnant uterus (4). Of incidental interest, five-term, nonlaboring pregnant women were discovered to have an increased resistance to the chronotropic effect of isoproterenol in comparison to nonpregnant women (5). One fetus had an isolated 5-beats/minute late deceleration 2 minutes after the mother received 0.25 µg of the drug (5).

Breast Feeding Summary

No data are available.

References

1. Nishimura H, Tanimura T. Clinical Aspects of The Teratogenicity of Drugs. New York, NY:American Elsevier, 1976;231–2.
2. Shepard TH. Catalog of Teratogenic Agents. 3rd ed. Baltimore, MD:Johns Hopkins University Press, 1980;191.
3. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
4. Tamari I, Eldar M, Rabinowitz B, Neufeld HN. Medical treatment of cardiovascular disorders during pregnancy. Am Heart J 1982;104:1357–63.
5. DeSimone CA, Leighton BL, Norris MC, Chayen B, Menduke H. The chronotropic effect of isoproterenol is reduced in term pregnant women. Anesthesiology 1988;69:626–8.