8.1Pregnancy Risk Summary
The limited available data with CLARINEX-D 12 HOUR in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. There are no adequate and well-controlled studies of desloratadine and pseudoephedrine in combination in pregnant women. Neither are there animal reproduction studies conducted with the combination of desloratadine and pseudoephedrine or pseudoephedrine alone .
Desloratadine given during organogenesis to pregnant rats was not teratogenic at the summed area under the concentration-time curve (AUC)-based exposures of desloratadine and its metabolite approximately 320 times that at the recommended human daily oral dose (RHD) of 5 mg/day. Desloratadine given during organogenesis to pregnant rabbits was not teratogenic at the AUC-based exposures of desloratadine approximately 230 times that at the RHD.
Desloratadine given to pregnant rats during organogenesis through lactation resulted in reduced body weight and slow righting reflex of F 1 pups at the summed AUC-based exposures of desloratadine and its metabolite approximately 70 times or greater than that at the RHD [see Data ]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data Human Data Pseudoephedrine The majority of studies examining the use of pseudoephedrine in pregnancy did not find an association with an increased risk of congenital anomalies. A few case-control studies conducted reported potential associations with isolated congenital disorders. However, several similar studies did not find statistically significant associations. Methodological limitations of these studies included small sample size, selection bias, recall bias, inadequate adjustment for risk factors, residual confounding, exposure misclassification, and lack of information regarding dose and timing of exposure.
Animal Data No animal reproduction studies were conducted with the combination of desloratadine and pseudoephedrine or pseudoephedrine alone. Desloratadine Desloratadine was given orally during organogenesis to pregnant rats at doses of 6, 24 and 48 mg/kg/day (approximately 50, 200 and 320 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD). No fetal malformations were present. Reduced fetal weights and skeletal variations noted at doses of 24 and 48 mg/kg/day were likely secondary to the maternal toxicities of reduced body weight gain and food consumption observed at the same doses.
Desloratadine was also given orally during organogenesis to pregnant rabbits at doses of 15, 30 and 60 mg/kg/day (approximately 30, 70 and 230 times the AUC-based exposure of desloratadine at the RHD). No adverse effects to the fetus were noted. Reduced maternal body weight gain was noted in rabbits at 60 mg/kg/day. In a peri- and post-natal development study, desloratadine was given to rats orally during the peri-natal (Gestation Day 6) through lactation periods (Postpartum Day 21) at doses of 3, 9 and 18 mg/kg/day.
Reduced body weight and slow righting reflex were reported in F 1 pups at doses of 9 mg/kg/day or greater (approximately 70 times or greater than the summed AUC-based exposure of desloratadine and its metabolite at the RHD). Desloratadine had no effect on F 1 pup development at 3 mg/kg/day (approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD). Maternal toxicities including reduced body weight gain and food consumption were noted at 18 mg/kg/day for F 0 dams.
F 1 offspring were subsequently mated and there was no developmental toxicity for F 2 pups observed.
