Azacitidine

Azacitidine is a prescription injectable drug used for the treatment of myelodysplastic syndromes (MDS) and acute myelogenous leukemia (AML). The former conditions are characterized by the inability of the bone marrow to produce mature blood cells, and the latter is characterized by the proliferation of immature blood cells that flood the bloodstream. Azacitidine is thought to restore normal synthesis of proteins involved in the maturation of blood cells and reduce the proliferation of cancer cells. The Food and Drug Administration approved azacitidine on May 19, 2004. Azacitidine is marketed by Pharmion under the name Vidaza.

Other Names

Azacitidine is sometimes called 5-azacytidine or azacytidine.

Uses

Azacitidine is used to treat AML as well as the following manifestations of MDS:

• uncontrolled anemia or uncontrolled anemia with evidence of red blood cell precursors in the blood
• uncontrolled anemia with deformed blood cell precursor cells (stem cells)
• chronic myelomonocytic leukemia (CMMoL)

How Azacitidine is Taken

Treatment with azacitidine occurs in two phases: one initial treatment cycle and several subsequent treatment cycles.

Azacitidine is provided as a solution of 25mg/ml. It is given either as a subcutaneous injection (under the skin), or intravenously (IV). The recommended starting dose for the first treatment cycle is 75 mg/m² (per meter of body surface area) daily for 7 days. Subsequent treatment cycles are repeated every four weeks thereafter. The dose is sometimes increased to 100 mg/m² if no positive effects are seen after 2 treatment cycles, and if no serious toxicity occurs. At least four cycles of treatment are usually needed to achieve a partial or full response.

How Azacitidine Works

The mechanism of action of azacitidine is not completely understood. Azacitidine may enter abnormal bone marrow stem cells and turn on genes that regulate their maturation. Activation of these genes also causes the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms.

How the Body Affects Azacitidine

Peak levels of azacitidine in the body occur approximately 30 minutes after injection. Azacitidine is primarily eliminated by excretion in the urine. Azacitidine is rapidly degraded in the body. The half-life, or time needed for the concentration of the drug in he blood to be reduced by half, after IV infusion is only about 22 minutes. The half-life is approximately 41 minutes after subcutaneous injection.

Side Effects

The most common side effects of azacitidine include the following:

• anemia(low red blood cell and/or hemoglobin levels)
• low blood platelet levels (thrombocytopenia)
• low white blood cell levels (leukopenia/neutropenia)
• nausea
• vomiting
• fever
• diarrhea
• fatigue
• skin redness at the site of injection
• constipation
• skin discoloration

Intravenous administration of azacitidine is associated with some other side effects in addition to the ones listed above:

• skin spotting
• cold skin and chills
• weakness
• low blood potassium levels (hypokalemia)

Risks and Precautions

Azacitidine is used with caution in people with liver disease because the drug is potentially toxic to the liver.

Rare reports of kidney toxicity, sometimes resulting in kidney failure and death, have surfaced in people being treated with IV azacitidine in combination with other chemotherapeutic agents.

Azacitidine could accumulate in the bloodstream of people with kidney impairment because the drug is largely eliminated in the urine. Accordingly, periodic monitoring of kidney function can reduce the risk of developing serious side effects in people with kidney impairment.

Drug Interactions

The liver may partly metabolize azacitidine. Therefore, interactions may occur with other drugs that are also metabolized by the liver. To date however, no significant interactions have occurred between azacitidine and co-administered drugs.

Clinical Trials

A controlled trial of azacitidine versus conventional treatment was performed in patients with high-risk MDS.^[1] More than half the patients treated with azacitidine survived for more than 24 months. Over half of the patients given conventional treatment did not survive more than 15 months.

References

1. ↑ MDS Foundation Web site. Vidaza Significantly Extends Overall Survival by 74% in Phase 3 Trial in Myelodysplastic Syndromes (MDS). PDF

External Links

Vidaza Home Page

CenterWatch

FDA: Patient Information Sheet