Risk for Hepatic Decompensation in Patients with Chronic Hepatitis C

• In patients with chronic hepatitis C, PROMACTA® in combination with interferon and ribavirin may increase the risk of hepatic decompensation.
• May increase the risk of severe and potentially lifethreatening hepatotoxicity. Monitor hepatic function and discontinue dosing as recommended. One patient (<1>

Increased Risk of Death and Progression of Myelodysplastic Syndromes (MDS) to Acute Myeloid Leukemia (AML)

• A randomized, double-blind, placebo-controlled, multicenter trial in patients with International Prognostic Scoring System (IPSS) intermediate-1, intermediate-2 or high risk MDS with thrombocytopenia, receiving azacitidine in combination with either PROMACTA (n=179) or placebo (n=177) was terminated due to lack of efficacy and safety reasons, including increased progression to AML. Patients received PROMACTA or placebo at a starting dose of 200 mg once daily, up to a maximum of 300 mg once daily, in combination with azacitidine for at least six cycles. The incidence of death (overall survival) was 32% (57/179) in the PROMACTA arm versus 29% (51/177) in the placebo arm (HR [95% CI] = 1.42 [0.97, 2.08], showing an increased relative risk of death in this trial by 42% in the PROMACTA arm). The incidence of progression to AML was 12% (21/179) in the PROMACTA arm versus 6% (10/177) in the placebo arm (HR [95% CI] = 2.66 [1.31, 5.41], showing an increased relative risk of progression to AML in this trial by 166% in the PROMACTA arm.