Temsirolimus Injection

Contraindications

4 CONTRAINDICATIONS Temsirolimus injection is contraindicated in patients with bilirubin >1.5xULN [see Warnings and Precautions ( 5.2 )] . Temsirolimus injection is contraindicated in patients with bilirubin >1.5 x ULN. ( 4 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Based on findings in animal studies and its mechanism of action, temsirolimus can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . Although there are no data on the use of temsirolimus injection in pregnant women, there are limited data on the use of sirolimus, the active metabolite of temsirolimus, during pregnancy; however, these data are insufficient to inform a drug-associated risk of adverse developmental outcomes. In animal reproductive studies, oral daily administration of temsirolimus to pregnant rats and rabbits during organogenesis caused adverse embryo-fetal effects at approximately 0.04 and 0.12 times the AUC in patients at the recommended dose, respectively (see Data) . Advise pregnant women of the potential hazard to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. 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 Animal Data Temsirolimus administered daily as an oral formulation throughout organogenesis caused adverse embryo-fetal effects in rats and rabbits at human sub-therapeutic exposures. Embryo-fetal adverse effects in rats consisted of reduced fetal weight and reduced ossifications, and in rabbits included reduced fetal weight, omphalocele, bifurcated sternabrae, notched ribs, and incomplete ossifications. In rats, the adverse embryo-fetal effects were observed at the oral dose of 2.7 mg/m 2 /day (approximately 0.04-fold the AUC in patients with cancer at the human recommended dose). In rabbits, the adverse embryo-fetal effects were observed at the oral dose of ≥7.2 mg/m 2 /day (approximately 0.12-fold the AUC in patients with cancer at the recommended human dose).