I. Basic Drug Information

Generic Name: Azacitidine Tablets

English Name: Azacitidine Tablets

Brand Names: Onureg, Azashine

Active Ingredient: Azacitidine

Chemical Name: 4-amino-1-β-D-ribofuranosyl-1,3,5-triazin-2(1H)-one

Molecular Formula: C₈H₁₂N₄O₅

Molecular Weight: 244.20

Dosage Form: Film-coated tablets

Specifications: 200 mg × 14 tablets/box; 300 mg × 14 tablets/box

Manufacturer: Hetero Healthcare Limited

Storage: Store at 20–25°C (excursions permitted between 15–30°C); protect from light, keep tightly sealed, and store in a dry place.

Shelf Life: 24 months

Drug Category: Prescription Drug; Nucleoside Metabolic Inhibitor (Hypomethylating Agent)

II. Indications

Indicated for adult patients with Acute Myeloid Leukemia (AML) who:

Have achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy;

AND are unable to complete intensive consolidation therapy.

III. Dosage and Administration

1. Recommended Dosage and Cycle

Dosage: 300 mg, once daily.

Cycle: One cycle consists of 28 days; take the medication continuously from Day 1 through Day 14, followed by a medication-free period from Day 15 through Day 28.

Duration of Therapy: Continue treatment until disease progression or the occurrence of unacceptable toxicity.

Administration: Swallow tablets whole; do not cut, crush, or chew. May be taken with or without food.

Timing: Take the medication at the same time each day.

2. Management of Missed Doses/Vomiting

Missed Dose: Take the missed dose as soon as possible on the same day. Resume the regular schedule the following day; do not take two doses on the same day.

Vomiting: If vomiting occurs after taking a dose, do not take a replacement dose on that day; resume the scheduled dosage the following day.

3. Dosage Adjustment (Hematologic Toxicity)

The 200 mg dosage represents a dose reduction regimen—to be implemented under the guidance of a physician—for use when a patient experiences severe adverse reactions (such as myelosuppression), in order to maintain treatment while reducing toxicity. Cycle Day 1 ANC < 0.5 × 10⁹/L: Withhold medication and delay cycle initiation until ANC ≥ 0.5 × 10⁹/L.

Grade 3–4 Neutropenia/Thrombocytopenia: Withhold medication; resume at the original dose or a reduced dose once recovered.

Persistent Severe Myelosuppression: Consider permanent discontinuation.

4. Dosage for Special Populations

Hepatic Impairment: No adjustment required for mild to moderate impairment; use with caution in severe impairment and monitor liver function closely.

Renal Impairment: No adjustment required for mild to moderate impairment; use with caution in severe impairment and monitor renal function.

Elderly Patients (≥ 65 years): No routine dose reduction required; enhance monitoring for toxicity.

Children/Adolescents: Safety and efficacy have not been established; use is not recommended.

IV. Contraindications

Patients with hypersensitivity to azacitidine or any of the tablet excipients.

Pregnant and breastfeeding women (unless the benefit clearly outweighs the risk).

V. Precautions

1. Hematologic Toxicity (Most Common)

Myelosuppression: Neutropenia, thrombocytopenia, anemia; monitor complete blood counts prior to each cycle and during treatment.

Febrile Neutropenia: Requires immediate anti-infective therapy and granulocyte-stimulating support.

2. Gastrointestinal Toxicity

Nausea, Vomiting, Diarrhea, Constipation: Administer antiemetics 30 minutes prior to each dose during the first two cycles; may discontinue after two cycles if nausea and vomiting do not occur.

Severe Diarrhea/Vomiting: Requires fluid and electrolyte support; withhold medication if necessary.

3. Hepatotoxicity

May cause elevated transaminases; monitor liver function prior to treatment and before each cycle; use with caution in patients with liver disease.

4. Nephrotoxicity

Renal impairment is rare; monitor serum creatinine and electrolytes; use with caution in patients with renal impairment.

5. Embryo-Fetal Toxicity

Teratogenicity/Mutagenicity: Women of childbearing potential must use effective contraception during treatment and for 6 months after the last dose; men must use effective contraception during treatment and for 3 months after the last dose.

6. Other Considerations

Infection Risk: Immunosuppression; prophylaxis/treatment for bacterial, fungal, and viral infections is required.

Tumor Lysis Syndrome: Characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia; prevention involves hydration, urine alkalinization, and uric acid reduction.

Driving/Operating Machinery: May cause fatigue and dizziness; avoid high-risk activities.

VI. Adverse Reactions (≥10%)

1. Hematologic System

Neutropenia, thrombocytopenia, anemia, febrile neutropenia.

2. Gastrointestinal Tract

Nausea, vomiting, diarrhea, constipation, decreased appetite, abdominal pain.

3. General and Other

Fatigue, fever, dizziness, headache, rash, elevated transaminases, elevated serum creatinine.

4. Grade 3–4 Adverse Reactions (Common)

Febrile neutropenia, thrombocytopenia, neutropenia, anemia.

VII. Drug Interactions

Myelosuppressive Agents (Chemotherapy, Radiotherapy, Other Hypomethylating Agents): May exacerbate myelosuppression; dose reduction or regimen adjustment is required.

Hepatotoxic Agents: Increased risk of liver injury; avoid concomitant use or monitor closely.

Nephrotoxic Agents: Increased risk of kidney injury; avoid concomitant use or monitor closely.

Anticoagulants (e.g., Warfarin): Monitor coagulation parameters and adjust anticoagulant dosage.

P-gp/BCRP/OAT/OATP Substrates: No significant interactions observed; no dose adjustment required.

VIII. Use in Specific Populations

1. Pregnant Women (Category D)

Contraindicated due to teratogenic risk; women of childbearing potential must undergo pregnancy testing prior to treatment and practice strict contraception during treatment.

2. Breastfeeding Women

Discontinue breastfeeding or discontinue the drug, as it may be excreted in breast milk.

3. Children

Safety and efficacy have not been established; use is not recommended.

4. Elderly Patients

Routine dose reduction is not required; enhance monitoring of hematologic, hepatic, and renal function.

5. Hepatic/Renal Impairment

Mild to Moderate: No dose adjustment required; monitor closely.

Severe: Use with caution; reduce dosage and intensify monitoring.

IX. Overdosage

Manifestations: Severe myelosuppression, hepatic and renal failure, gastrointestinal bleeding, infection.

Management: Discontinue the drug immediately; provide supportive care including hematopoietic growth factors, anti-infective therapy, hepatoprotective and nephroprotective measures, and fluid replacement.

X. Pharmacological Actions

1. Mechanism of Action

A nucleoside analog that inhibits DNA methyltransferase, thereby inducing the demethylation of tumor suppressor genes and restoring their expression.

It inhibits tumor cell proliferation and induces differentiation and apoptosis, serving as a targeted therapy for AML.

2. Pharmacokinetics

Good oral bioavailability; time to peak concentration is 1–2 hours.

Elimination half-life is approximately 4 hours; primarily excreted via the kidneys.

Food does not affect absorption; may be taken with or without food.

XI. Packaging and Shelf Life

Shelf Life: 24 months when stored unopened at 20–25°C; use as soon as possible after opening.

XII. Important Information

1. This product is a prescription drug and must be used under the guidance of a hematologist or oncologist.

2. It is not interchangeable with injectable azacitidine; their indications, methods of administration, and dosages differ completely.

3. During treatment, strictly monitor complete blood counts as well as hepatic and renal function, and adjust the dosage in a timely manner.

4. Patients of childbearing potential must practice strict contraception during treatment and continue to use contraception as required after discontinuing the drug.