margenza

Important safety information

Infusion-Related Reactions (IRRs): Monitor for signs and symptoms. If a significant infusion-associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies. ( 5.3 ) 5.1 Left Ventricular Dysfunction Left ventricular cardiac dysfunction can occur with MARGENZA. In SOPHIA, left ventricular dysfunction occurred in 1.9% of patients treated with MARGENZA. MARGENZA has not been studied in patients with a pretreatment LVEF value of < 50%, a prior history of myocardial infarction or unstable angina within 6 months, or congestive heart failure NYHA class II-IV. Withhold MARGENZA for ≥ 16% absolute decrease in LVEF from pretreatment values or LVEF value below institutional limits of normal (or 50% if no limits are available) and ≥ 10% absolute decrease in LVEF from pretreatment values. Permanently discontinue MARGENZA if LVEF decline persists for greater than 8 weeks, or if dosing is interrupted on greater than 3 occasions due to LVEF decline [see Dosage and Administration (2.2) ]. Cardiac Monitoring Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan. The following schedule is recommended: Baseline LVEF measurement within 4 weeks prior to initiation of MARGENZA LVEF measurements (MUGA/echocardiogram) every 3 months during and upon completion of MARGENZA Repeat LVEF measurement at 4-week intervals if MARGENZA is withheld for significant left ventricular cardiac dysfunction [see Dosage and Administration (2.2) ] . 5.2 Embryo-Fetal Toxicity Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman. There are no available data on the use of MARGENZA in pregnant women to inform the drug-associated risk. In postmarketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities and neonatal death. In an animal reproduction study, intravenous administration of margetuximab-cmkb to pregnant cynomolgus monkeys once every 3 weeks starting at gestational day (GD) 20 until delivery resulted in oligohydramnios and delayed infant kidney development. Animal exposures were ≥ 3 times the human exposures at the recommended dose, based on C max . Verify pregnancy status of females of reproductive potential prior to initiation of MARGENZA. Advise pregnant women and females of reproductive potential that exposure to MARGENZA during pregnancy or within 4 months prior to conception can result in fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 4 months following the last dose of MARGENZA [see Use in Specific Populations (8.1 , 8.3) ]. 5.3 Infusion-Related Reactions MARGENZA can cause infusion-related reactions (IRRs) [see Adverse Reactions (6.1) ]. Symptoms may include fever, chills, arthralgia, cough, dizziness, fatigue, nausea, vomiting, headache, diaphoresis, tachycardia, hypotension, pruritus, rash, urticaria, and dyspnea. In SOPHIA, IRRs were reported by 13% of patients on MARGENZA plus chemotherapy. Most of the IRRs occur during Cycle 1. Grade 3 IRRs were reported in 1.5% of MARGENZA-treated patients. All IRRs resolved within 24 hours, irrespective of severity. In SOPHIA, IRRs leading to interruption of treatment occurred in 9% of patients treated with MARGENZA and chemotherapy. One patient (0.4%) on MARGENZA discontinued treatment due to IRR. An infusion substudy in 88 patients in SOPHIA evaluated MARGENZA administered over 120 minutes for the initial dose, then 30 minutes from Cycle 2 forward. IRRs were ≤ Grade 2 and most occurred during the first (120 minutes) administration of MARGENZA. From Cycle 2 onward, one patient (1.1%) had an IRR (Grade 1). Monitor patients for IRRs during MARGENZA administration and as clinically indicated after completion of infusion. Have medications and emergency equipment to treat IRRs available for immediate use. Monitor patients carefully until resolution of signs and symptoms. In patients who experience mild or moderate IRRs, consider premedications, including antihistamines, corticosteroids, and antipyretics. Decrease the rate of infusion for mild or moderate IRRs. Interrupt MARGENZA infusion in patients experiencing dyspnea or clinically significant hypotension and intervene with medical therapy which may include epinephrine, corticosteroids, diphenhydramine, bronchodilators and oxygen. Patients should be evaluated and carefully monitored until complete resolution of signs and symptoms. Permanently discontinue MARGENZA in all patients with severe or life-threatening IRRs.