decnupaz

Important safety information

I nfusion -related reactions (IRR) : DECNUPAZ can cause serious, life-threatening IRR. Premedicate with a corticosteroid the day before infusion, and premedicate with a corticosteroid, antihistamine, and an antipyretic prior to DECNUPAZ infusion. Monitor patients for IRR. Interrupt, reduce the rate of infusion, or permanently discontinue DECNUPAZ based on the severity. ( 5.2 ) Edema : Monitor for the development of edema and fluid retention. Depending on severity, delay, consider resuming at a lower dose, or permanently discontinue DECNUPAZ. ( 5.3 ) Sulfite Allergic Reactions : DECNUPAZ contains sodium metabisulfite, which may cause allergic type reactions, including anaphylactic symptoms and asthmatic episodes in certain susceptible people. ( 5.4 ) Embryo-fetal toxicity : Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.5 ) 5.1 Hepatotoxicity , Including Hepatic Veno-occlusive Disease (VOD) (also known as Sinusoidal Obstruction Syndrome) DECNUPAZ can cause hepatotoxicity, including VOD, a severe form of hepatotoxicity. In CADENZA, VOD occurred in 6% (7/116) of adult patients during treatment or following a subsequent hematopoietic stem cell transplantation (HSCT). Of the 7 total patients who developed VOD, 3 patients had treatment-naïve BPDCN and 4 patients had relapsed/refractory BPDCN. Among all 116 patients treated with DECNUPAZ at 0.045 mg/kg, VOD occurred in 2/116 (2%) during treatment, with onset up to 30 days after the last dose. Among 19 patients with BPDCN who proceeded to HSCT, VOD occurred in 5/19 patients (26%), including two fatal cases. The median time from subsequent HSCT to onset of VOD was 11 days (range: 7 – 25 days). After receiving DECNUPAZ, patients should be closely monitored for signs and symptoms of VOD including elevations in ALT, AST, total bilirubin, hepatomegaly (which may be painful), rapid weight gain, and ascites. Monitor liver tests, including ALT, AST, and total bilirubin, prior to each dose of DECNUPAZ. Based on elevations of liver tests, delay DECNUPAZ. In patients who experience VOD, discontinue DECNUPAZ and treat according to standard medical practice [see Dosage and Administration ( 2.4 )] . 5.2 Infusion-Related Reactions DECNUPAZ can cause serious, life-threatening infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting. In CADENZA, IRRs occurred in 26% (30/116) of patients during treatment with DECNUPAZ at 0.045 mg/kg once every three weeks, including Grade 1 in 4.3% (5/116), Grade 2 in 16% (19/116), and Grade 3 in 5% (6/116) of patients. IRR occurred in Cycle 1 in 25% (29/116) of patients with decreasing frequency in subsequent cycles. IRR led to discontinuation in one patient. Premedicate with a corticosteroid the day before infusion, and premedicate with a corticosteroid, antihistamine, and antipyretic prior to dosing [ see Dosage and Administration ( 2.3 )] . Premedication the day before infusion and prior to dosing led to reduced frequency and severity of IRRs. Monitor patients closely for potential IRR during the infusion and for at least four hours, or longer as clinically indicated, after the first infusion and for at least 1 hour after subsequent infusions. Interrupt infusion of DECNUPAZ and institute appropriate medical management if an infusion-related reaction occurs. Depending on the severity of the infusion-related reaction, reduce infusion rate or permanently discontinue [see Dosage and Administration ( 2.4 )]. 5.3 Edema DECNUPAZ can cause edema and fluid retention, including serious events. In CADENZA, Grade 3-4 edema occurred in 16% (18/116) of patients treated with DECNUPAZ, including Grade 3-4 generalized edema in 2.6% (3/116) of patients [see Adverse Reactions ( 6.1 )]. Monitor patients for new or worsening edema. For Grade 2 or Grade 3 edema, delay further dosing of DECNUPAZ until edema has returned to Grade 0-1 or baseline. For Grade 3 edema or Grade 2 edema with dose delay for more than 2 weeks, consider resuming at a lower dose. For Grade 4 edema, permanently discontinue. Institute appropriate medical management for edema [see Dosage and Administration ( 2.4 )] . 5.4 Sulfite Allergic Reactions DECNUPAZ contains sodium metabisulfite, a sulfite that may cause allergic type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people. 5.5 Embryo-Fetal Toxicity Based on its mechanism of action, DECNUPAZ can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (FGN849) and affects actively dividing cells [see Clinical Pharmacology ( 12.1 ), Nonclinical Toxicology ( 13.1 )] . Advise patients of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with DECNUPAZ and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with DECNUPAZ, and for 4 months after the last dose [see Use in Specific Populations ( 8.1 , 8.3 )] .