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5/20/2004

Azacitidine Approved for Bone Marrow Disease

Cheryl A. Thompson

The Food and Drug Administration (FDA) and Pharmion Corp. on Wednesday announced the marketing approval of azacitidine, or Vidaza (PDF), for the treatment of all five subtypes of myelodysplastic syndrome, a condition in which the bone marrow produces immature blood cells that function abnormally.

According to FDA, the new drug is the first effective treatment for patients with myelodysplastic syndrome, also known as preleukemia.

Patients with the condition typically feel weak and fatigued, bruise and bleed easily, and frequently incur infections and fever.

The National Cancer Institute, which sponsored the major studies of azacitidine in the United States, describes azacitidine as an antimetabolite resembling cytidine, a component of RNA.

Patients with advanced malignant hepatic tumors or a hypersensitivity to azacitidine or mannitol must not receive azacitidine. The product's labeling also notes that the drug may cause fetal harm; thus women should be advised not to become pregnant while receiving azacitidine and men should be counseled not to father a child while under treatment.

Nausea, vomiting, anemia, thrombocytopenia, leukopenia, neutropenia, fever, diarrhea, constipation, fatigue, and discoloration at the injection site were the most common adverse reactions reported during the studies, according to the product's labeling.

The recommended starting dosage is 75 mg of azacitidine per square meter of body surface area injected subcutaneously every day for seven days. This regimen should be repeated every four weeks for at least four cycles and as long as the patient continues to benefit. Medication to prevent nausea and vomiting should be administered before each azacitidine treatment. Neither the product's labeling nor the journal article describing the Phase III study of azacitidine specify a regimen for preventing nausea and vomiting.

If after two treatment cycles the patient's status has not improved and no toxicity has occurred other than nausea and vomiting, then the azacitidine dosage may be increased to 100 mg/m2

The dosage and time between seven-day treatments should be adjusted on the basis of hematology laboratory values and concentrations of serum bicarbonate and creatinine and blood urea nitrogen.

Vidaza will be supplied in vials containing 100 mg of azacitidine and 100 mg of mannitol. The product's labeling states that the lyophilized drug powder should be reconstituted with 4 mL of sterile water for injection to yield a cloudy suspension of azacitidine 25 mg/mL. Doses with a volume greater than 4 mL should be split evenly between two syringes. The cloudy preservative-free suspension may be stored at room temperature for up to one hour or at 2–8 degrees C for up to eight hours. Once removed from refrigeration, the suspension may be kept at room temperature for up to 30 minutes before administration to the patient. Regardless of the storage condition, each syringe must be inverted two or three times and gently rolled for 30 seconds immediately before administration to ensure an even suspension of the drug particles.

The product's labeling advises administering each new injection at least one inch from an old injection site and distributing the injections among the thigh, abdomen, and upper arm. Injections must not be made into sites that are tender, bruised, red, or hard. If two syringes are used to deliver a dose, then the injections should be made into separate sites.

Because azacitidine is a cytotoxic agent, the product's labeling states that the drug should be handled and disposed of like an anticancer drug.

Pharmion President Patrick J. Manhaffy said this morning during a webcast that the company plans to make Vidaza commercially available by July 1.