EVOMELA Important Safety Information

Contraindications

• History of serious allergic reaction to melphalan.

Warnings and Precautions

• Bone Marrow Suppression: For patients receiving EVOMELA as part of a conditioning regimen, myeloablation occurs in all patients. Do not begin the conditioning regimen if a stem cell product is not available for rescue. Monitor complete blood counts, and provide supportive care for infections, anemia and thrombocytopenia until there is adequate hematopoietic recovery.

• Gastrointestinal Toxicity: For patients receiving EVOMELA as part of a conditioning regimen, nausea, vomiting, mucositis, and diarrhea may occur in over 50% of patients. Use prophylactic antiemetic medication. Provide supportive care for nausea, vomiting, diarrhea, and mucositis. The frequency of grade 3/4 mucositis in clinical studies was 13%. Provide nutritional support and analgesics for patients with severe mucositis.
• Hepatotoxicity: Hepatic disorders ranging from abnormal liver function tests to clinical manifestations such as hepatitis and jaundice have been reported after treatment with melphalan. Hepatic veno-occlusive disease has also been reported. Monitor liver chemistries.
• Hypersensitivity: Acute hypersensitivity reactions, including anaphylaxis, have occurred in approximately 2% of patients who received an intravenous formulation of melphalan. Symptoms may include urticaria, pruritus, edema, and skin rashes and, in some patients, tachycardia, bronchospasm, dyspnea, and hypotension. Discontinue treatment with EVOMELA for serious hypersensitivity reactions.
• Secondary Malignancies: Secondary malignancies such as myeloproliferative syndrome or acute leukemia have been reported in multiple myeloma patients treated with melphalan-containing chemotherapy regimens. The potential benefit of EVOMELA therapy must be considered against the possible risk of the induction of a secondary malignancy.
• Embryo-Fetal Toxicity: EVOMELA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to fetus. Advise females of reproductive potential to use effective contraception during treatment with EVOMELA and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with EVOMELA and for 3 months after the last dose.
• Infertility: Melphalan-based chemotherapy regimens have been reported to cause suppression of ovarian function in premenopausal women, resulting in persistent amenorrhea in approximately 9% of patients. Reversible or irreversible testicular suppression has also been reported.

Adverse Events

• The most common adverse reactions observed in at least 50% of patients with multiple myeloma treated with EVOMELA were neutrophil count decreased, white blood cell count decreased, lymphocyte count decreased, platelet count decreased, diarrhea, nausea, fatigue, hypokalemia, anemia, and vomiting.
• For myeloablative conditioning in multiple myeloma patients undergoing ASCT, twelve (20%) patients experienced a treatment emergent serious adverse reaction while on study. The most common serious adverse reactions (>1 patient, 1.6%) were pyrexia, hematochezia, febrile neutropenia, and renal failure. Treatment-related serious adverse reactions reported in >1 patient were pyrexia (n=2, 3%), febrile neutropenia (n=2, 3%), and hematochezia (n=2, 3%).

Drug Interactions

• No formal drug interaction studies have been conducted. When nalidixic acid and IV melphalan are given simultaneously, the incidence of severe hemorrhagic necrotic enterocolitis has been reported to increase in pediatric patients.

Use in Specific Populations

• Lactation: Advise women not to breastfeed during treatment with EVOMELA and for one week after the last dose.

Please click here for full Prescribing Information, including BOXED WARNINGS, for EVOMELA.