Siltuximab

Contraindications

4 CONTRAINDICATIONS Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT [see Warnings and Precautions (5.3) ] . Hypersensitivity reactions, including anaphylactic reaction, hypersensitivity, and drug hypersensitivity have been reported in patients treated with siltuximab. Severe hypersensitivity reaction to siltuximab or any of the excipients in SYLVANT. ( 4 )

Pregnancy & Breastfeeding

8.1 Pregnancy Risk-Summary In an animal reproduction study, intravenous administration of a human antibody to IL-6 to pregnant monkeys from the onset of organogenesis through delivery caused functional impairment in pregnant animals and in the offspring. Siltuximab and the human antibody to IL-6 crossed the placenta in monkeys ( see Data ). The limited available information on SYLVANT use during pregnancy is not sufficient to inform a drug-associated risk of major birth defects or miscarriage. Infants born to pregnant women treated with SYLVANT may be at increased risk of infection (see Clinical Considerations ). Advise pregnant women of the potential risk to a fetus. The estimated background risk 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 is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Clinical Considerations Fetal/Neonatal adverse reactions Monoclonal antibodies are transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester. Infants born to pregnant women treated with SYLVANT may be at increased risk of infection. Consider the risks and benefits of administering live or live-attenuated vaccines to infants exposed to SYLVANT in utero [see Warnings and Precautions (5.2) ] . Data Animal Data In an embryo-fetal development study in cynomolgus monkeys, pregnant animals received intravenous doses of siltuximab of 9.2 or 46 mg/kg/week during gestation days (GD) 20 to 118, which includes the period of organogenesis. Fetuses were evaluated on GD 140, approximately 25 days prior to the natural birth. Exposures at the low and high dose after the 25 th administration were approximately 3 and 7 times, respectively, the human exposure based on AUC in patients with MCD at the recommended dose of 11 mg/kg every three