Azadine

Instructions for Azacitidine for Injection

Common name: Azacitidine
Trade name: Vidasa
Full names: Azacytidine, azacitidine for injection, Vidasa, 5-azacytidine, 5-azacytidine nucleoside, 5-Azacytidine, Ladakamycin, Azaci tidine, vidaza

Indications:
Myelodysplastic syndrome (MDS), acute non-lymphocytic leukemia, breast cancer, intestinal cancer, melanoma

Usage and dosage:
Intravenous injection or intravenous infusion, 1-2 mg/kg once a day, once a day.

Adverse reactions:
Anemia, neutropenia and thrombocytopenia
Hepatic coma
Elevated serum creatinine, renal failure and renal tubular acidosis
Swelling syndrome
The most common adverse reactions: nausea, anemia, thrombocytopenia, vomiting, fever, leukopenia, diarrhea, injection site erythema, constipation, neutropenia, ecchymosis.

Contraindications:
Contraindicated in patients with advanced malignant liver tumors.
Contraindicated in patients with known hypersensitivity to azacitidine or mannitol.

Precautions:
Anemia, neutropenia and thrombocytopenia: Azacitidine causes anemia, neutropenia and low platelet storage. Monitor complete blood counts multiple times to assess response and/or toxicity, at least before each dosing cycle. After the first cycle of administration at the recommended dose, the dose in subsequent weeks will be adjusted based on nadir blood cell counts and blood response.
Azacitidine Toxicity in Patients with Previous Severe Hepatic Impairment: Due to the potential hepatotoxicity of azacitidine in patients with previous severe hepatic impairment, caution is required when administering the drug to patients with liver disease. Due to the metastatic nature of the disease, progressive hepatic coma and death have been reported in patients with extensive tumor burden during treatment with azacitidine, particularly in these patients with baseline albumin <30 g/L. Azacitidine is contraindicated in patients with advanced malignant liver tumors.
Nephrotoxicity: Toxic reactions of varying degrees, ranging from increases in serum creatinine to renal failure and death, have been reported in patients receiving intravenous azacitidine in combination with other chemotherapy drugs used for non-MDS. In addition, five CML patients treated with azacitidine and etoposide developed renal tubular acidosis, defined as a decrease in serum bicarbonate to <20 mEq/L with alkaline urine and hypokalemia (serum potassium <3 mEq/L). If an unexplained decrease in serum bicarbonate <20 mEq/L or an increase in BUN or serum creatinine occurs, the dose should be reduced or administration should be suspended. Patients with renal impairment may be at increased risk for nephrotoxicity. In addition, azacitidine and its metabolites are mainly excreted by the kidneys. Therefore, nephrotoxicity should be closely monitored. MDS patients with renal impairment were excluded from clinical trials.
Drugs during pregnancy: When pregnant women use this product, it may cause harm to the fetus. Azacitidine causes congenital malformations in animals. Women of childbearing potential should be advised to avoid pregnancy while receiving azacitidine. There are no adequate and well-controlled studies of the use of azacitidine in pregnant women. If a patient uses this product during pregnancy or becomes pregnant while taking this product, the patient should be informed of the potential harm to the fetus.
Male use: Male patients should be advised not to have children during treatment with azacitidine). In animal studies, preconception treatment of male mice and rats with azacitidine resulted in an increased rate of embryonic abortion in mated female animals.
Tumor lysis syndrome: Patients at risk for tumor lysis syndrome are those with high pre-treatment tumor burden. These patients should be closely monitored and appropriate precautions taken.
Effects on ability to drive or operate machinery: The effects of this product on the ability to drive or operate machinery have not been studied.

Storage:
Save below 25℃.

Mechanism of action:
Azacitidine is a cytosine nucleoside analogue that produces anti-tumor effects by causing DNA demethylation and direct cytotoxic effects on abnormal hematopoietic cells in the bone marrow. The concentration at which azacitidine has the maximum arranging effect on DNA methylation in vitro has no obvious inhibitory effect on DNA synthesis. Demethylation of DNA can repair the normal function of genes, which plays a key role in cell differentiation and proliferation. The cytotoxic effect of azacitidine can cause the death of rapidly dividing cells, including cancer cells that do not respond to normal growth regulatory mechanisms. Cells in the non-proliferating phase are relatively insensitive to azacitidine.

Safety and efficacy:
There are several phase 3 clinical trial results supporting the effect of azacitidine. For example, in the 2009 "Lancet Oncology", in a large trial for patients with intermediate-risk/high-risk myelodysplastic syndrome, Vidaza significantly prolonged the median overall survival of such patients for the first time in history! The median overall survival in the Vidaza group was 24.5 months, while the median overall survival in the traditional therapy group (including supportive care, low-dose cytarabine, or high-dose chemotherapy) was only 15 months. At 2 years, 51% of patients in the Vidaza group were alive, but only 26% in the control group.