FEXOFENADINE

Fetal Risk Summary

Fexofenadine is a second generation (peripherally selective), histamine H1-receptor antagonist that is used for the relief of symptoms associated with seasonal allergic rhinitis. It is a metabolite of another second-generation antihistamine, terfenadine (no longer available). As a group, second-generative antihistamines are less sedating than first generation agents.

Fertility studies in rats and reproduction studies in rats and rabbits have been conducted with fexofenadine (1). In rats, doses producing plasma area under the concentration curve values that were equal to or greater than three times the human therapeutic value based on a 60-mg twice-daily dose (HTD) were associated with a dose-related decrease in the number of implantations and an increase in the number of postimplantation losses. No evidence of teratogenicity was noted in pregnant rats and rabbits at oral doses up to 4 and 47 times the HTD, respectively. However, dose-related decreases in pup weight gain and survival were observed in rats at three times the HTD (1).

It is not known if fexofenadine crosses the human placenta to the fetus. The molecular weight (about 538 for the hydrochloride salt) is low enough, however, that transfer to the fetus should be expected.

No reports describing the use of fexofenadine during human pregnancy have been located. However, studies in rats found dose-related embryo and fetal toxicity, but the risk to a human fetus cannot be assessed at this time. Because of the extensive human data available, several reviews have recommended that oral first generation antihistamines (e.g., chlorpheniramine or tripelennamine) should be considered if antihistamine therapy during pregnancy (especially in the 1st trimester) is required (2,3 and 4). The second generation agents, cetirizine or loratadine, were considered acceptable alternatives, except during the 1st trimester, if a first generation antihistamine was not tolerated.

Breast Feeding Summary

No reports describing the use of fexofenadine during human lactation have been located. The molecular weight (about 538 for the hydrochloride salt) is low enough that excretion into breast milk should be expected. The effect of this exposure on a nursing infant is unknown.

References

1. Product information. Allegra. Hoechst Marion Roussel, 2000.
2. Mazzotta P, Loebstein R, Koren G. Treating allergic rhinitis in pregnancy. Safety considerations. Drug Saf 1999;20:361–75.
3. Horak F, Stubner UP. Comparative tolerability of second generation antihistamines. Drug Saf 1999;20:385–401.
4. Position statement of a joint committee of the American College of Obstetricians and Gynecologists and the American College of Allergy, Asthma and Immunology. The use of newer asthma and allergy medications during pregnancy. Ann Allergy Asthma Immunol 2000;84:475–80.