HERCULES study. In the HERCULES study, TE ADA were further characterized as havingneutralizing potential. There was no clinically apparent impact on clinical efficacy or safety [see

Clinical Pharmacology (12.3)].

7 DRUG INTERACTIONS

Concomitant Use of Anticoagulants

Concomitant use of CABLIVI with any anticoagulant may increase the risk of bleeding. Assessand monitor closely for bleeding with concomitant use [see Warnings and Precautions (5.1) and

Clinical Pharmacology (12.3)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data on CABLIVI use in pregnant women to inform a drug-associated riskof major birth defects and miscarriage. However, there are potential risks of hemorrhage in the

mother and fetus associated with use of CABLIVI (see Clinical Considerations). In animalreproduction studies, there was no evidence of adverse developmental outcomes with

intramuscular administration of caplacizumab-yhdp during organogenesis in guinea pigs atexposures approximately 30 times the AUC in humans at the recommended subcutaneous

injection dose of 11 mg (see Data).

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. Thebackground rate of major birth defects and miscarriage in the indicated population is unknown.

In the U.S. general population, the estimated background rate of major birth defects andmiscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical ConsiderationsFetal/neonatal adverse reactionsCABLIVI may increase the risk of bleeding in the fetus and neonate. Monitor neonates forbleeding [see Warnings and Precautions (5.1)].

Maternal adverse reactionsAll patients receiving CABLIVI, including pregnant women, are at risk for bleeding. Pregnantwomen receiving CABLIVI should be carefully monitored for evidence of excessive bleeding

[see Warnings and Precautions (5.1)].

Data

Animal data

Two separate reproduction studies were conducted in pregnant guinea pigs with administrationof caplacizumab-yhdp during the organogenesis period.

In an embryo-fetal development study, caplacizumab-yhdp was administered intramuscularly atdoses up to 20 mg/kg/day from gestational day (GD) 6 to GD 41 in guinea pigs. No maternal

toxicity or adverse developmental outcomes were observed.

In a toxicokinetic study assessing the exposure of caplacizumab-yhdp in the dams and fetuses,caplacizumab-yhdp was administered once daily to female guinea pigs at doses up to

40 mg/kg/day (corresponding to a drug exposure of approximately 30 times the AUC in humansat the recommended dose of 11 mg) by intramuscular injection from GD 6 to GD 41 or GD 61.

Exposure to caplacizumab-yhdp was observed in the dams and fetuses, with no effects on embryo-fetal development.

8.2 Lactation

Risk Summary

There is no information regarding the presence of caplacizumab-yhdp in human milk, the effectson the breastfed child or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with themother’s clinical need for CABLIVI and any potential adverse effects on the breastfed child

from CABLIVI, or from the underlying maternal condition.

8.4 Pediatric Use