Azarest

Azacitidine is a pyrimidine nucleoside analog of cytidine, and it works by inhibiting DNA and RNA methyltransferases. Once it enters the cell, enzymes convert it into nucleotide triphosphates, and these are then built into DNA and RNA.

In laboratory studies on cancer cells, including acute myeloid leukemia cells, azacitidine that had been incorporated into DNA inhibited DNA methyltransferases. This reduced DNA methylation and altered gene expression, including re-expression of genes that regulate tumor suppression and cell differentiation. When azacitidine was incorporated into the RNA of cancer cells, including leukemic cells, it inhibited RNA methyltransferases, reduced RNA methylation, decreased RNA stability and decreased protein synthesis.

Antileukemic activity of azacitidine was shown in AML cell lines in vitro, where it reduced cell viability and induced apoptosis. In leukemic tumor models in vivo, azacitidine decreased tumor burden and increased survival.

Pregnancy: Azacitidine can cause harm to an unborn baby when given to a pregnant woman. This is based on how the medicine works and on what was seen in animals. There are no data on Azacitidine use in pregnant women, so the risk linked to the medicine can't be properly assessed. In animals, Azacitidine was teratogenic and caused embryo-fetal lethality at doses lower than the recommended human daily dose of oral Azacitidine on a mg/m2 basis. Pregnant women should be told about the possible risk to the baby. The background risk of major birth defects and miscarriage for the population this medicine is given to is unknown. Every pregnancy carries some background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation: There are no data on whether Azacitidine passes into human milk, or on its effects on a breastfed child or on milk production. Because the breastfed child could have serious adverse reactions, women should be advised not to breastfeed during treatment with Azacitidine and for 1 week after the last dose.

Pediatric Use: The safety and effectiveness of Azacitid in children have not been established.

Geriatric Use: In the QUAZAR study, 238 patients received Azacitid. Of these, 72% were 65 years of age or older, and 12% were 75 years of age or older. Azacitid showed no overall differences in safety or effectiveness between these patients and younger patients.

Renal Impairment: Patients with severe renal impairment (creatinine clearance 15 to 29 mL/min, calculated by the Cockcroft-Gault formula) should be monitored more often for adverse reactions, and the Azacitid dosage should be changed if adverse reactions occur. No dose adjustment of Azacitid is recommended for patients with mild to severe renal impairment (CrCl 15 to 89 mL/min).

Hepatic Impairment: Azacitid has not been studied in patients with pre-existing severe hepatic impairment (total bilirubin >3 × ULN). A recommended dosage of Azacitid has not been established for patients with moderate hepatic impairment (total bilirubin >1.5 to 3 × ULN). No dose adjustment of Azacitid is recommended for patients with mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 1.5 × ULN and any AST).

Azacitid overdose was reported in one case during clinical trials. The patient had diarrhea, nausea and vomiting after a single IV dose of about 290 mg/m2, which is almost 4 times the recommended starting dose. These events resolved without sequelae, and the correct dose was resumed the next day.

If an overdose happens, the patient should be monitored with appropriate blood counts and given supportive treatment as necessary. There is no known specific antidote for Azacitid overdosage.

Keep Azacitidine below 25°C, in a cool and dry place, and away from light. Keep it out of the reach of children.