Antihistamine
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
The human pregnancy experience with triprolidine suggests low risk. In general, antihistamines are considered low risk in pregnancy. However, exposure near birth of premature infants has been associated with an increased risk of retrolental fibroplasia.
FETAL RISK SUMMARY
Triprolidine is an antihistamine in the same class as brompheniramine, chlorpheniramine, and dexchlorpheniramine. The drug is used in a number of proprietary decongestant–antihistamine mixtures.
It is not known if triprolidine crosses the human placenta. The molecular weight (about 279 for the nonhydrated free base) suggests that exposure of the embryo–fetus should be expected.
The Collaborative Perinatal Project monitored 50,282 mother–child pairs, 16 of whom had 1st trimester exposure to triprolidine (1). From this small sample, no evidence was found to suggest a relationship to large categories of major or minor malformations or to individual malformations.
In a 1971 study, infants and mothers who had ingested antihistamines during the 1st trimester actually had fewer abnormalities when compared with controls (2). Triprolidine was the third most commonly used antihistamine. The manufacturer claims that in more than 20 years of marketing the drug, no reports of triprolidine teratogenicity have been received (M.F. Frosolono, personal communication, Burroughs Wellcome, 1980). Their animal studies have also been negative.
Two studies, one appearing in 1981 (3) and the second in 1985 (4), described the 1st trimester drug exposures of 6837 and 6509 mothers, respectively, treated by the Group Health Cooperative of Puget Sound and whose pregnancies terminated in a live birth. Both studies covered 30-month periods, 1977–1979 and 1980–1982, respectively. From the total of 13,346 mothers, 628 (4.7%) consumed during the 1st trimester (based on the filling of a prescription) a proprietary product containing triprolidine and pseudoephedrine (Actifed). Nine (1.4%) of the exposed infants had a major congenital abnormality (type not specified). Spontaneous or induced abortions, stillbirths, and many minor anomalies, such as clubfoot, syndactyly, polydactyly, clinodactyly, minor ear defects, coronal or first-degree hypospadias, and hernia, were excluded from the data.
In two surveillance studies of Michigan Medicaid recipients involving 333,440 completed pregnancies conducted between 1980 and 1983, and 1985 and 1992, 910 newborns had been exposed to triprolidine during the 1st trimester (F. Rosa, personal communication, FDA, 1994). Of the 900 exposed newborns identified in the 1980–1983 group, 65 (7.2%) had major birth defects (59 expected), 10 of which were cardiovascular defects (8 expected). No cases of cleft lip and/or palate were observed. None of the 10 newborns included in the 1985–1992 data had congenital malformations.
BREASTFEEDING SUMMARY
Triprolidine is excreted into breast milk (5). Three mothers, who were nursing healthy infants, were given an antihistamine–decongestant preparation containing 2.5 mg of triprolidine and 60 mg of pseudoephedrine. The women had been nursing their infants for 14 weeks, 14 weeks, and 18 months, respectively. Triprolidine was found in the milk of all three subjects, with milk:plasma ratios in one woman at 1, 3, and 12 hours of 0.5, 1.2, and 0.7, respectively. Using AUCs in the other two women gave more reliable results of 0.56 and 0.50 (5). The authors calculated that a milk production of 1000 mL/24 hours would contain 0.001–0.004 mg of triprolidine base, or about 0.06%–0.2% of the maternal dose. The American Academy of Pediatrics classifies triprolidine as compatible with breastfeeding (6).
References
1.Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Littleton, MA: Publishing Sciences Group, 1977:323.
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.Jick H, Holmes LB, Hunter JR, Madsen S, Stergachis A. First-trimester drug use and congenital disorders. JAMA 1981;246:343–6.
4.Aselton P, Jick H, Milunsky A, Hunter JR, Stergachis A. First-trimester drug use and congenital disorders. Obstet Gynecol 1985;65:451–5.
5.Findlay JWA, Butz RF, Sailstad JM, Warren JT, Welch RM. Pseudoephedrine and triprolidine in plasma and breast milk of nursing mothers. Br J Clin Pharmacol 1984;18:901–6.
6.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;108:776–89.