Fetal Risk Summary
No reports linking this second-generation histamine H1-receptor antagonist with congenital anomalies or other adverse fetal outcomes have been located. Similarly, no abnormalities or adverse fetal effects were observed in rats fed 300 mg/kg/day or in rabbits given 500 mg/kg/day (1).
One report described the use of terfenadine in a woman with hereditary angioedema and immunoglobulin A deficiency who was treated throughout most of her pregnancy with the drug. She eventually delivered a 2523-g male infant at 36 weeks’ gestation (2). No details of the infant’s condition were provided.
A 1994 abstract summarized the results of a prospective study that compared the outcomes of 134 women who took terfenadine during the 1st and early 2nd trimesters with 134 matched controls (3). Nine (6.7%) of the study patients were lost to follow-up. Among the remaining 125 study patients, there were 98 (78.4%) normal outcomes, 16 (12.8%) spontaneous abortions, 4 (3.2%) elective terminations, 1 (0.8%) stillbirth (cord accident), and 6 (4.8%) infants with congenital malformations. The malformations observed in the 6 infants were: trisomy 21 (maternal age 41 years), a chromosomal anomaly (45,X/46,XY), patent ductus arteriosus, hemangioma, underdeveloped earlobe, and dislocated hips. No differences were found in the outcomes between the study patients and the control group (3).
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 1,034 newborns had been exposed to terfenadine during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 51 (4.9%) major birth defects were observed (44 expected). Specific data were available for six defect categories, including (observed/expected) 13/10 cardiovascular defects, 2/2 oral clefts, 0/0.5 spina bifida, 12/3 polydactyly, 3/2 limb-reduction defects, and 2/2 hypospadias. The suggested association of terfenadine with polydactyly remains to be confirmed in other studies.
Breast Feeding Summary
The excretion of terfenadine into human milk was described in a 1995 report (4). Four lactating women were given terfenadine (60 mg every 12 hours for 4 doses), and then milk and plasma samples were collected after the last dose at various times for 30 hours. None of the parent compound was detected in the milk or plasma. The maximum concentrations of the active metabolite in the plasma and milk were 309 and 41 ng/mL, respectively, both occurring approximately 4 hours after the last dose. Based on the 12-hour excretion, the mean milk:plasma ratio was 0.21. The maximum exposure of a nursing infant was estimated to be 0.45% of the recommended maternal weight-corrected dose (4).
Although the amounts of terfenadine measured in the above study appear to be clinically insignificant, there is still no reported experience of infants nursing while their mothers are being treated with the antihistamine. Thus, the clinical effects of exposure to terfenadine via the milk are still unknown.
- Gibson JP, Huffman KW, Newborne JW. Preclinical safety studies with terfenadine. Arzneimittelforschung 1982;22:117984. As cited in Shepard TH. Catalog of Teratogenic Agents. 6th ed. Baltimore, MD: Johns Hopkins University Press, 1989:599.
- Peters M, Ryley D, Lockwood C. Hereditary angioedema and immunoglobulin A deficiency in pregnancy. Obstet Gynecol 1988;72:4545.
- Schick B, Hom M, Librizzi R, Arnon J, Donnenfeld A. Terfenadine (Seldane) exposure in early pregnancy (abstract). Teratology 1994;49:417.
- Lucas BD Jr, Purdy CY, Scarim SK, Benjamin S, Abel SR, Hilleman DE. Terfenadine pharmacokinetics in breast milk in lactating women. Clin Pharmacol Ther 1995;57:398402.