Terazosin

Co-administration of verapamil with terazosin increases the systemic exposure of terazosin [see Clinical Pharmacology (12.3)] , which may increase the risk of hypotenstion. To reduce the risk of hypotension, dosage reduction and re-titration of either agent may be necessary [see Warnings and Precautions (5.3)] . Co-administration of verapamil with terazosin increases the systemic exposure of terazosin and may lead to hypotension. Dosage reduction and re-titration of either agent may be necessary. (7)

8.1 Pregnancy Risk Summary The limited available data on terazosin use in pregnant women are insufficient to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed when terazosin was orally administered to pregnant rats and rabbits during the period of organogenesis at doses of up to 230 and 60 times, respectively, the maximum recommended human dose on a body surface area (mg/m 2 ) basis.

In the rat and rabbit oral doses at 230 and 60 times, respectively, the maximum recommended human dose on a body surface area basis, reduced fetal survival was observed [see Data]. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data Animal Data Studies in rats and rabbits at oral doses up to 230 and 60 times, respectively, the maximum recommended human dose on a body surface area (mg/m 2 ) basis, have revealed no evidence of adverse developmental effects. In rats, fetal resorptions were observed at 480 mg/kg/day, approximately 230 times the maximum recommended human dose on a body surface area basis. In rabbits,. increased fetal resorptions, decreased fetal weight and an increased number of supernumerary ribs were observed at 60 mg/kg/day, 60 times the maximum recommended human dose on a body surface area basis. These findings (in both species) were most likely secondary to maternal toxicity.

In a peri- and post-natal development study in rats, significantly more pups died at 120 mg/kg/day (60 times the maximum recommended human dose on a body surface area basis) than in the control group during the three-week postpartum period.