Terfenadine(Seldane ®)
Anihistamine.  Molecular weight:471.68

Terfenadine was removed from the marketplace in the United States in 1998 after the approval of a safer alternative drug Allegra (fexofenadine hydrochloride). Fexofenadine hydrochloride provides the same benefits of terfenadine, but appears to have less potential for the cardiac toxicity of terfenadine.

CATEGORY:C [1]

Studies performed in pregnant rats and rabbits at daily oral doses up to 300 mg/kg/day were not teratogenic in either rats or rabbits [2].

Briggs et. al. reported on data from a surveillance study of Michigan Medicaid recipients conducted between 1985 and 1992. Amongst 1,034 newborns who had been exposed to terfenadine during the first trimester there were 12 cases of  polydactyly (3 cases were expected). The data did not otherwise support an association between terfenadine and major malformations (cardiovascular defects, oral clefts, spina bifida, limb reduction defects, and hypospadias) [1].

Schick et al. compared the outcomes of 125 mothers who used terfenadine during early pregnancy with a matched control group. There was no significant difference in adverse pregnancy outcomes between the two groups [3].

In a multicenter prospective study of one hundred eighteen women exposed to terfenadine during pregnancy 65 women were exposed to terfenadine during the first trimester. Among women exposed during the first trimester rates of major malformations in the terfenadine group did not differ from rates in matched control subjects.  Gestational age at delivery, rates of preterm deliveries, and developmental milestones were comparable between the groups. Although the birth weight in the terfenadine-exposed newborns was significantly lower compared with that in their matched control subjects the rate of small for gestational age infants was not different between the groups [4]

The Israeli Teratogen Information Service prospectively identified two birth defects (one child with congenital hip dysplasia and one with bilateral inguinal hernia) amongst 27 pregnancies exposed to terfenadine during the first trimester. The authors of the study reported that the rate of anomalies was not significantly different from that of a control group with nonteratogenic exposures[5].

BREAST FEEDING:  In a study of  four healthy lactating mothers subjects received 60 mg terfenadine every 12 hours over a period of 48 hours. Terfenadine was not detected in milk or plasma. However, fexofenadine (the active metabolite of terfenadine) was found in milk and plasma.

The AUC_milk/AUC_{plasma (0-12)} ratio for fexofenadine was 0.21 (range 0.12 to 0.28)

Newborn dosage estimates based on the highest measured concentration of fexofenadine in milk suggest the maximum level of newborn exposure would not exceed 0.45% of the recommended maternal weight-corrected dose  [6]

SEARCH LITERATURE

1. Briggs GG,Freeman RK, Yaffe SJ, Drugs in Pregnancy and Lactation 6th edition,Baltimore, MD: Williams & Wilkins,2002 p 1321-22
2. Gibson JP et al. Preclinical safety studies with terfenadine.  Arzneimittelforschung. 1982;32:1179-84.MEDLINE
3. Schick B, et al. Terfenadine (Seldane) exposure in early pregnancy. Teratology [Abstract] 1994;49:417.
4. Loebstein R, et al. Pregnancy outcome after gestational exposure to terfenadine: A multicenter, prospective controlled study.J Allergy Clin Immunol. 1999 Nov;104(5):953-6. MEDLINE
5. Diav-Citrin O, et al. Pregnancy outcome after gestational exposure to loratadine or antihistamines: a prospective controlled cohort study.J Allergy Clin Immunol. 2003; 111: 1239-43. MEDLINE
6. Lucas BD, et al. Terfenadine pharmacokinetics in breast milk in lactating women.Clin Pharmacol Ther. 1995;57:398-402. MEDLINE

Created: 11/17/2000
Updated: 11/30/2002
Updated: 4/17/2004