zynlonta

Important safety information

Effusion and Edema, Including Capillary Leak Syndrome : Monitor for the development of pleural effusion, pericardial effusion, ascites, peripheral edema, and general edema. Consider diagnostic imaging when symptoms develop or worsen. ( 5.1 ) Myelosuppression: Monitor blood cell counts. Withhold, reduce, or discontinue ZYNLONTA based on severity. ( 5.2 ) Infections : Monitor for infection and treat promptly. ( 5.3 ) Hepatotoxicity, Including Drug-Induced Liver Injury : Monitor liver function tests during treatment. Withhold or permanently discontinue ZYNLONTA based on severity. ( 5.4 ) Cutaneous Reaction s: Monitor patients for new or worsening cutaneous reactions, including photosensitivity reactions. Dermatologic consultation should be considered. ( 5.5 ) Embryo-Fetal Toxic ity: Can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.6 , 8.1 , 8.3 ) 5.1 Effusion and Edema, Including Capillary Leak Syndrome Serious effusion and edema, including capillary leak syndrome, occurred in patients treated with ZYNLONTA. Grade 3 edema occurred in 3% (primarily peripheral edema or ascites) and Grade 3 pleural effusion occurred in 3%, and Grade 3 or 4 pericardial effusion occurred in 1% [see Adverse Reactions (6.1) ] . Rare cases of cardiac tamponade have been reported in patients with Grade 3 or 4 pericardial effusion. Grade 3 or higher capillary leak syndrome occurred in 0.6%. Monitor patients for new or worsening edema or effusions. Consider diagnostic imaging in patients who develop symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnea, chest pain, and/or ascites such as swelling in the abdomen and bloating. Institute appropriate medical management for edema or effusions. Evaluate and institute appropriate medical management for capillary leak syndrome in patients experiencing worsening effusion or edema, with signs and symptoms of weight gain, severe hypotension, hypoalbuminemia, and/or hemoconcentration (by elevated hemoglobin/hematocrit, etc.). Withhold or discontinue ZYNLONTA based on severity [see Dosage and Administration (2.3) ] . 5.2 Myelosuppression Treatment with ZYNLONTA can cause serious or severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Grade 3 or 4 neutropenia occurred in 32%, thrombocytopenia in 20%, and anemia in 12% of patients. Grade 4 neutropenia occurred in 21% and thrombocytopenia in 7% of patients. Febrile neutropenia occurred in 3% [see Adverse Reactions (6.1) ]. Monitor complete blood counts throughout treatment. Cytopenias may require interruption, dose reduction, or discontinuation of ZYNLONTA. Consider prophylactic granulocyte colony-stimulating factor administration as applicable [see Dosage and Administration (2.3) ]. 5.3 Infections Fatal and serious infections, including opportunistic infections, occurred in patients treated with ZYNLONTA. Grade 3 or higher infections occurred in 10% of patients, with fatal infections occurring in 2%. The most frequent Grade ≥3 infections included sepsis and pneumonia [see Adverse Reactions (6.1) ] . Monitor for any new or worsening signs or symptoms consistent with infection. For Grade 3 or 4 infection, withhold ZYNLONTA until infection has resolved [see Dosage and Administration (2.3) ] . 5.4 Hepatotoxicity, Including Drug-Induced Liver Injury Cholestatic and hepatocellular liver injury, including severe, life-threatening, and fatal cases of drug-induced liver injury (DILI), have occurred in patients treated with ZYNLONTA. Monitor liver function tests at baseline and throughout treatment with ZYNLONTA. In the event of suspected DILI or Grade ≥3 increase in ALT or AST, withhold ZYNLONTA until toxicity resolves to Grade 1 or lower. Upon confirmation of DILI, discontinue ZYNLONTA. [see Dosage and Administration (2.3) ] . ZYNLONTA should be avoided in patients with severe hepatic impairment [see Clinical Pharmacology (8.6 , 12.3) ] . 5.5 Cutaneous Reactions Serious cutaneous reactions occurred in patients treated with ZYNLONTA. Grade 3 cutaneous reactions occurred in 4% and included photosensitivity reaction, rash (including exfoliative and maculo-papular), and erythema [see Adverse Reactions (6.1) ]. Monitor patients for new or worsening cutaneous reactions, including photosensitivity reactions. Withhold ZYNLONTA for severe (Grade 3) cutaneous reactions until resolution [see Dosage and Administration (2.3) ] . Advise patients to minimize or avoid exposure to direct natural or artificial sunlight including exposure through glass windows. Instruct patients to protect skin from exposure to sunlight by wearing sun-protective clothing and/or the use of sunscreen products. If a skin reaction or rash develops, dermatologic consultation should be considered [see Nonclinical Toxicology (13) ]. 5.6 Embryo-Fetal Toxicity Based on its mechanism of action, ZYNLONTA can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (SG3199) and affects actively dividing cells. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ZYNLONTA and for 10 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZYNLONTA, and for 7 months after the last dose [see Use in Specific Populations (8.1 , 8.3) ] .