Ticagrelor

⛔ FDA Black Box Warning

WARNING: BLEEDING RISK Ticagrelor, like other antiplatelet agents, can cause significant, sometimes fatal bleeding ( 5 .1 , 6.1 ). Do not use ticagrelor in patients with active pathological bleeding or a history of intracranial hemorrhage ( 4.1 , 4.2 ). Do not start ticagrelor in patients undergoing urgent coronary artery bypass graft surgery (CABG) ( 5.1 , 6.1 ). If possible, manage bleeding without discontinuing ticagrelor. Stopping ticagrelor increases the risk of subsequent cardiovascular events ( 5.2 ). WARNING: BLEEDING RISK See full prescribing information for complete boxed warning. Ticagrelor, like other antiplatelet agents, can cause significant, sometimes fatal bleeding. ( 5.1 , 6.1 ) Do not use ticagrelor in patients with active pathological bleeding or a history of intracranial hemorrhage. ( 4.1 , 4.2 ) Do not start ticagrelor in patients undergoing urgent coronary artery bypass graft surgery (CABG). ( 5.1 , 6.1 ) If possible, manage bleeding without discontinuing ticagrelor. Stopping ticagrelor increases the risk of subsequent cardiovascular events. ( 5.2 )

Contraindications

4 CONTRAINDICATIONS History of intracranial hemorrhage. ( 4.1 ) Active pathological bleeding. ( 4.2 ) Hypersensitivity to ticagrelor or any component of the product. ( 4.3 ) 4.1 History of Intracranial Hemorrhage Ticagrelor tablets are contraindicated in patients with a history of intracranial hemorrhage (ICH) because of a high risk of recurrent ICH in this population [see Clinical Studies (14.1) , (14.2) ] . 4.2 Active Bleeding Ticagrelor tablets are contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . 4.3 Hypersensitivity Ticagrelor tablets are contraindicated in patients with hypersensitivity (e.g., angioedema) to ticagrelor or any component of the product.

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary Available data from case reports with ticagrelor use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Ticagrelor given to pregnant rats and pregnant rabbits during organogenesis caused structural abnormalities in the offspring at maternal doses about 5 to 7 times the maximum recommended human dose (MRHD) based on body surface area. When ticagrelor was given to rats during late gestation and lactation, pup death and effects on pup growth were seen at approximately 10 times the MRHD (see Data) . 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% to 4% and 15% to 20%, respectively. Data Animal Data In reproductive toxicology studies, pregnant rats received ticagrelor during organogenesis at doses from 20 to 300 mg/kg/day. 20 mg/kg/day is approximately the same as the MRHD of 90 mg twice daily for a 60 kg human on a mg/m 2 basis. Adverse outcomes in offspring occurred at doses of 300 mg/kg/day (16.5 times the MRHD on a mg/m 2 basis) and included supernumerary liver lobe and ribs, incomplete ossification of sternebrae, displaced articulation of pelvis, and misshapen/misaligned sternebrae. At the mid-dose of 100 mg/kg/day (5.5 times the MRHD on a mg/m 2 basis), delayed development of liver and skeleton was seen. When pregnant rabbits received ticagrelor during organogenesis at doses from 21 to 63 mg/kg/day, fetuses exposed to the highest maternal dose of 63 mg/kg/day (6.8 times the MRHD on a mg/m 2 basis) had delayed gall bladder development and incomplete ossification of the hyoid, pubis and sternebrae occurred. In a prenatal/postnatal study, pregnant rats received ticagr