Azacitidine

VIDAZA is a nucleoside metabolic inhibitor indicated for the treatment of: • Adult patients with the following FAB myelodysplastic syndrome (MDS) subtypes: Refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL). • Pediatric patients aged 1 month and older with newly diagnosed Juvenile Myelomonocytic Leukemia (JMML).

VIDAZA is a pyrimidine nucleoside analog of cytidine. VIDAZA is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine.

• Do not substitute VIDAZA for oral azacitidine. The indications and dosing regimen for VIDAZA differ from that of oral azacitidine. • MDS: The recommended starting dosage for the first treatment cycle, for all patients regardless of baseline hematology values, is VIDAZA 75 mg/m 2 daily for 7 days to be administered by subcutaneous injection or intravenous infusion. See full prescribing information for schedule for subsequent cycles. Premedicate for nausea and vomiting. • JMML: See full prescribing information for recommended dosage and schedule. • Continue treatment as long as the patient continues to benefit, up to 6 cycles for pediatric patients with JMML. • Monitor all patients for hematologic response and for renal toxicity, delay or reduce dosage as appropriate.

• Advanced Malignant Hepatic Tumors. • Hypersensitivity to Azacitidine or Mannitol. Advanced Malignant Hepatic Tumors VIDAZA is contraindicated in patients with advanced malignant hepatic tumors.

• Risks of Substitution with Other Azacitidine Products: Do not substitute VIDAZA for oral azacitidine. • Anemia, Neutropenia and Thrombocytopenia: Monitor complete blood counts (CBC) frequently. • Hepatotoxicity: Patients with severe preexisting hepatic impairment are at higher risk for toxicity. • Renal Toxicity: Monitor patients with renal impairment for toxicity since azacitidine and its metabolites are primarily excreted by the kidneys. • Tumor Lysis Syndrome: VIDAZA may cause fatal or serious tumor lysis syndrome, including in patients with MDS. Assess baseline risk and monitor and treat as appropriate. • Embryo-Fetal Toxicity: VIDAZA can cause fetal harm. Advise female patients and male patients with female partners of reproductive potential of the potential risk to a fetus and to use effective contraception.

The following adverse reactions are described in other labeling sections: o Anemia, Neutropenia and Thrombocytopenia o Hepatotoxicity in Patients with Severe Pre-existing Hepatic Impairment o Renal Toxicity o Tumor Lysis Syndrome Most common adverse reactions (>30%) in adult patients with MDS by subcutaneous route are: nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, injection site erythema, constipation, neutropenia and ecchymosis. Most common adverse reactions by intravenous route also included petechiae, rigors, weakness and hypokalemia. Most common adverse reactions (>30%) by intravenous route in pediatric patients with JMML are pyrexia, rash, upper respiratory tract infection, and anemia.

Store unreconstituted vials at 25º C (77º F), excursions permitted to 15º-30º C (59º-86º F).