Detrusitol SR Use In Pregnancy & Lactation

Pregnancy: Risk Summary: There are no available data with DETRUSITOL SR use in pregnant women to inform drug-associated risks. In animal reproduction studies, oral administration of tolterodine and its 5-HMT metabolite to pregnant mice during organogenesis did not produce adverse developmental outcomes at doses approximately 9 to 12 times the clinical exposure at a dose of 20 mg/kg/day; however, higher doses produced adverse developmental outcomes (see Data as follows).
In the U.S. general population, the estimated background rate of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data: Animal Data: No anomalies or malformations were observed after oral administration of tolterodine to pregnant mice during organogenesis at approximately 9-12 times the clinical exposure to the pharmacologically active components of DETRUSITOL SR (based on the AUC of tolterodine and its 5-HMT metabolite at a dose of 20 mg/kg/day). At 14-18 times the clinical exposure (doses of 30 to 40 mg/kg/day) in mice, tolterodine was embryo-lethal, caused reduced fetal weight, and increased the incidence of fetal abnormalities (cleft palate, digital abnormalities, intra-abdominal hemorrhage, and various skeletal abnormalities, primarily reduced ossification). Pregnant rabbits administered tolterodine subcutaneously at about 0.3 - 2.5 times the clinical exposure (dose of 0.8 mg/kg/day) did not show any embryotoxicity or teratogenicity.
Lactation: Risk Summary: There is no information on the presence of tolterodine or its 5-HMT metabolite in human milk, the effects on the breastfed infant, or the effects on milk production. Based on limited data, tolterodine is excreted into the milk in mice in low amounts (see Animal Data as follows). The development and health benefits of breastfeeding should be considered along with the mother's clinical need for DETRUSITOL SR and any potential adverse effects on the breastfed infant from DETRUSITOL SR or from the underlying maternal condition.
Animal Data: The use of radiolabeled tolterodine in pregnant mice produced milk: plasma ratios that ranged between 0.0 and 0.7.