Azacitidine

Azacitidine is a nucleoside metabolic inhibitor indicated for the treatment of 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).

Azacitidine is a pyrimidine nucleoside analog of cytidine. Azacitidine 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.

Most common adverse reactions (>30%) by SC route are: nausea, anemia, thrombocytopenia, vomiting, pyrexia, leukopenia, diarrhea, injection site erythema, constipation, neutropenia and ecchymosis. Most common adverse reactions by IV route also included petechiae, rigors, weakness and hypokalemia.

Pregnancy Category D. Azacitidine may cause fetal harm when administered to a pregnant woman. It is not known whether azacitidine or its metabolites are excreted in human milk. Because of the potential for tumorigenicity shown for azacitidine in animal studies and the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into consideration the importance of the drug to the mother.

Anemia, neutropenia and thrombocytopenia. Perform complete blood counts (CBC) prior to each treatment cycle and as needed to monitor response and toxicity.

Hepatotoxicity: Use with caution in patients with severe preexisting liver impairment.

Renal abnormalities. Monitor patients with renal impairment for toxicity since azacitidine and its metabolites are primarily excreted by the kidneys.

Monitor liver chemistries and serum creatinine prior to initiation of therapy and with each cycle.

Azacitidine may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be apprised of the potential hazard to a fetus.

Men should be advised not to father a child while receiving Azacitidine.

One case of overdose with azacitidine was reported during clinical trials. A patient experienced diarrhea, nausea, and vomiting after receiving a single IV dose of approximately 290 mg/m2, almost 4 times the recommended starting dose. The events resolved without sequelae, and the correct dose was resumed the following day. In the event of overdosage, the patient should be monitored with appropriate blood counts and should receive supportive treatment, as necessary. There is no known specific antidote for azacitidine overdosage.