CHLORPHENIRAMINE

Fetal Risk Summary

The Collaborative Perinatal Project monitored 50,282 mother-child pairs, 1,070 of whom had 1st trimester exposure to chlorpheniramine (1, pp. 322–334). For use anytime during pregnancy, 3,931 exposures were recorded (1, pp. 437, 488). In neither group was evidence found to suggest a relationship to large categories of major or minor malformations. Several possible associations with individual malformations were found, but the statistical significance of these is unknown. Independent confirmation is required to determine the actual risk.

Polydactyly in blacks (7 cases in 272 blacks) Gastrointestinal defects (13 cases) Eye and ear defects (7 cases) Inguinal hernia (22 cases) Hydrocephaly (8 cases) Congenital dislocation of the hip (16 cases) Malformations of the female genitalia (6 cases) A 1971 study found that significantly fewer infants with malformations were exposed to antihistamines in the 1st trimester as compared to controls (2). Chlorpheniramine was the sixth most commonly used antihistamine.

In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 61 newborns had been exposed to chlorpheniramine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). Most of the exposures involved decongestant combinations including adrenergics. Two (3.3%) major birth defects were observed (three expected), including one case of polydactyly (none expected). No anomalies were observed in five other categories of defects (cardiovascular defects, oral clefts, spina bifida, limb reduction defects, and hypospadias) for which specific data were available. These data do not support an association between the drug and congenital defects.

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 (3). The boy also had a continual “stuffy” nose.

An association between exposure during the last 2 weeks of pregnancy to antihistamines in general and retrolental fibroplasia in premature infants has been reported. See Brompheniramine for details.

Breast Feeding Summary

No data are available.

References

1. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA:Publishing Sciences Group, 1977.
2. Nelson MM, Forfar JO. Associations between drugs administered during pregnancy and congenital abnormalities of the fetus. Br Med J 1971;1:523–7.
3. Golbus MS, Koerper MA, Hall BD. Failure to diagnose osteopetrosis in utero. Lancet 1976;2:1246.