Azacitidine

Azacitidine Tablets (Azacitidine) Instructions

Common name: Azacitidine Tablets

Trade name: Onureg

All names: Azacitidine Tablets, Azacitidine, Onureg

Indications:

Applicable to adults with acute myeloid leukemia who continue to receive treatment and who have first complete remission (CR) or first complete remission without complete recovery of blood counts (CRi) after intensive induction chemotherapy and are unable to complete intensive treatment.

Dosage:

Do not use ONUREG as a substitute for intravenous or subcutaneous azacitidine. The indications and dosing regimen for ONUREG are different from those of intravenous or subcutaneous azacitidine.

Take ONUREG 300 mg orally once daily on days 1 through 14 of each 28-day cycle.

Antiemetics should be taken before each dose for at least the first 2 cycles.

Specifications:

200mg*14 tablets 300mg*14 tablets

Adverse reactions:

The most common adverse reactions (≥10%) are nausea, vomiting, diarrhea, fatigue/asthenia, constipation, pneumonia, abdominal pain, joint pain, decreased appetite, febrile neutropenia, dizziness and limb pain.

Contraindications:

History of severe hypersensitivity reaction to azacitidine or its components.

Precautions:

Risk of substitution by other azacitidine products: Do not substitute ONUREG for intravenous or subcutaneous azacitidine.

Myelosuppression: Monitor complete blood counts every other week for the first two cycles and before the start of each cycle thereafter. Increase monitoring every other week for the 2 cycles after dose reduction. After discontinuation, continue at the same or reduced dosage, or discontinue depending on severity.

Embryo-fetal toxicity: Can cause fetal harm. Advise patients to be aware of potential risks to the fetus and to use effective contraception.

Storage:

Store bottles at a temperature of 20ºC to 25ºC (68ºF to 77ºF); allowed excursions are 15ºC to 30ºC (59ºF to 86ºF)

Keep bottles tightly closed.

Store and dispense in original bottle.

Mechanism of action:

Azacitidine is a pyrimidine nucleoside analog of cytidine, which inhibits DNA/RNA methyltransferase. Azacitidine is incorporated into DNA and RNA following cellular uptake and enzymatic bioconversion to nucleotide triphosphates.

Incorporation of azacitidine into the DNA of cancer cells, including acute myeloid leukemia cells, in vitro inhibits DNA methyltransferases, reduces DNA methylation and alters gene expression, including re-expression of genes that regulate tumor suppression and cell differentiation. Azacitidine is incorporated into the RNA of cancer cells, including leukemia cells, where it inhibits RNA methyltransferase, reduces RNA methylation, decreases RNA stability and decreases protein synthesis.

The anti-leukemic activity of azacitidine was demonstrated by reducing cell viability and inducing apoptosis in AML cell lines in vitro. Azacitidine reduces tumor burden and increases survival in an in vivo leukemic tumor model.

Safety and efficacy:

Onureg is the first and only AML maintenance therapy approved by the FDA for patients in remission. This approval was based on the efficacy and safety results of the pivotal Phase III QUAZAR AML-001 study. The study evaluated the efficacy and safety of Onureg (azacitidine tablets) as first-line maintenance therapy in newly diagnosed AML patients who were in remission after intensive induction chemotherapy.

The results showed that in first-line maintenance treatment, Onureg (azacitidine tablets) significantly improved overall survival (OS, primary endpoint) by nearly 10 months compared with placebo (median OS: 24.7 months vs 14.8 months, p=0.0009). Significantly more than doubling relapse-free survival (RFS, the key secondary endpoint) (median PFS: 10.2 months vs 4.8 months, p=0.0001), a statistically significant and clinically meaningful improvement.