Melphalan Hcl

1 INDICATIONS AND USAGE Multiple Myeloma-Palliative Treatment IVRA is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate. IVRA is an alkylating drug indicated for palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate. ( 1 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Bone Marrow Suppression [see Warnings and Precautions ( 5.1 )] Gastrointestinal Toxicity [see Warnings and Precautions ( 5.2 )] Hepatotoxicity [see Warnings and Precautions ( 5.3 )] Hypersensitivity [see Warnings and Precautions ( 5.4 )] Secondary Malignancies [see Warnings and Precautions ( 5.5 )] Most common adverse reactions (≥50%) are neutrophil count decreased, white blood cell count decreased, lymphocyte count decreased, platelet count decreased, diarrhea, nausea, fatigue, hypokalemia, anemia, and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

8.1 Pregnancy Risk Summary Based on its mechanism of action and findings from animal studies, IVRA can cause fetal harm when administered to a pregnant woman. There are no available data on IVRA use in pregnant women to evaluate for a drug-associated risk. In rats, melphalan was embryolethal and teratogenic at doses lower than the highest recommended clinical dose (see Data). If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus. The background risk in the U.S.

WARNING: SEVERE BONE MARROW SUPPRESSION, HYPERSENSITIVITY and LEUKEMOGENICITY Severe bone marrow suppression with resulting infection or bleeding may occur. Controlled trials comparing intravenous melphalan to oral melphalan have shown more myelosuppression with the intravenous formulation. Monitor hematologic laboratory parameters [see Warnings and Precautions ( 5.1 )] . 5 WARNINGS AND PRECAUTIONS Gastrointestinal toxicity: Nausea, vomiting, diarrhea, or oral mucositis may occur; provide supportive care using antiemetic and antidiarrheal medications as needed. ( 5.2 ) Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of potential risk to fetus and to use effective contraception. ( 5.6 , 8.1 ) Infertility: Melphalan may cause ovarian function suppression or testicular suppression. ( 5.7 ) 5.1 Bone Marrow Suppression IVRA causes bone marrow suppression in most patients. Obtain complete blood counts with differential at the start of therapy and prior to each subsequent dose of IVRA. 4 CONTRAINDICATIONS IVRA is contraindicated in patients with a history of severe hypersensitivity to melphalan. Reactions have included anaphylaxis [see Warnings and Precautions ( 5.4 )]. History of severe hypersensitivity to melphalan. ( 4 )