TRIPROLIDINE

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.

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 6,837 and 6,509 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 hydrochloride 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 club foot, 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.

Breast Feeding Summary

Triprolidine is excreted into human 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. 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 the area under the concentration-time curves 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 considers triprolidine to be compatible with breast feeding (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 1994;93:137–50.