Letrozole And Ribociclib

Contraindications

4 CONTRAINDICATIONS Known hypersensitivity to the active substance (letrozole), or to any of the excipients of FEMARA. Refer to FEMARA Prescribing Information. Known hypersensitivity to letrozole, or to any excipients of FEMARA. ( 4 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Based on findings from animal studies and the mechanisms of action, KISQALI FEMARA CO-PACK can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available human data informing the drug-associated risk. In animal reproduction studies, administration of ribociclib to pregnant animals during organogenesis resulted in increased incidences of post implantation loss and reduced fetal weights in rats and increased incidences of fetal abnormalities in rabbits at exposures 0.6 or 1.5 times the exposure in humans, respectively, at the highest recommended dose of 600 mg/day based on AUC (see Data) . Advise pregnant women of the potential risk to a fetus. In animal reproduction studies, administration of letrozole to pregnant animals during organogenesis resulted in increased post-implantation pregnancy loss and resorptions, fewer live fetuses, and fetal malformations affecting the renal and skeletal systems in rats and rabbits at doses approximately 0.1 times the daily MRHD on a mg/m 2 basis (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk of major birth defects is 2% - 4% and of miscarriage is 15% - 20% of clinically recognized pregnancies in the U.S. general population. Data Animal Data - Ribociclib In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of ribociclib up to 1000 mg/kg/day and 60 mg/kg/day, respectively, during the period of organogenesis. In rats, 300 mg/kg/day resulted in reduced maternal body weight gain and reduced fetal weights accompanied by skeletal changes related to the lower fetal weights. There were no significant effects on embryo-fetal viability or fetal morphology at 50 or 300 mg/kg/day. In rabbits at doses ≥ 30 mg/kg/day, there were adverse effects on embryo-fetal development, including increased incidences of fetal abnormalities (malf