Antihistamine
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
The animal reproduction data suggest low risk, but the absence of human pregnancy experience prevents a full assessment of the risk. Although there are no reports describing the use of desloratadine in human pregnancy, there are reports for loratadine, the parent compound. (See Loratadine.) The data for loratadine are adequate to demonstrate that it is not a major human teratogen. Because desloratadine is a major metabolite of loratadine, it is reasonable to presume that desloratadine also is not a major teratogen (1). Moreover, antihistamines, in general, are not thought to cause human developmental toxicity at recommended doses. Although subjects classified as slow metabolizers will probably have greater embryo–fetal exposure to desloratadine, and possibly to its active metabolite, there is no reported evidence that such exposure will result in embryo–fetal toxicity. If an oral antihistamine is required during pregnancy, first-generation agents such as chlorpheniramine or tripelennamine should be considered. However, if a woman has taken desloratadine during a known or unknown pregnancy, the absolute embryo–fetal risk appears to be low.
FETAL RISK SUMMARY
Desloratadine is a second-generation, peripherally selective H1-receptor histamine antagonist that is indicated for the relief of nasal and nonnasal symptoms of allergic rhinitis. It is a major active metabolite of loratadine. (See also Loratadine.) Desloratadine itself is metabolized to an active metabolite by an enzyme that has not been identified. About 7% of the general population has decreased ability (i.e., slow metabolizers) to metabolize desloratadine, but the incidence is about 20% in blacks. The median exposure to desloratadine, based on AUC, was about six-fold greater in subjects classified as slow metabolizers than in those with unaltered metabolism. Protein binding of desloratadine and its active metabolite is in the range of 82%–89%. In patients with unaltered metabolism, the mean elimination half-life of desloratadine is 27 hours, but it exceeds 50 hours in slow metabolizers (2).
Reproduction studies with desloratadine have been conducted in rats and rabbits. There was no evidence of teratogenicity or effect on fertility in rats at desloratadine and active metabolite exposures up to about 210 and 130 times, respectively, the AUC in humans at the recommended daily oral dose (RDOD). However, at about 120 times the RDOD, an increase in preimplantation loss and a decrease in the number of implantations and fetuses were observed. At about 50 times the RDOD, reduced body weight and slow righting reflex were noted. At about 7 times the RDOD, no effect was noted on pup development. In rabbits, there was no evidence of teratogenicity at desloratadine exposure up to about 230 times the RDOD (2).
It is not known if desloratadine (or its active metabolite) crosses the placenta. The molecular weight of desloratadine (about 311) and the prolonged elimination half-life suggest that it will cross to the embryo–fetal compartment. Moreover, patients who are slow metabolizers will have much higher plasma concentrations of desloratadine and an approximate doubling of the elimination time. Both of these properties should increase the amount of drug reaching the embryo–fetus.
BREASTFEEDING SUMMARY
Although there are no reports describing the use of desloratadine during human lactation, the parent compound (loratadine) has been studied. Both loratadine and desloratadine are excreted into human breast milk. The American Academy of Pediatrics classifies loratadine as compatible with breastfeeding. (See Loratadine.)
References
1.Gilbert C, Mazzotta P, Loebstein R, Koren G. Fetal safety of drugs used in the treatment of allergic rhinitis: a critical review. Drug Saf 2005;28:707–19.
2.Product information. Clarinex. Schering Corporation, 2005.