EnglishBD Zadine Azacitidine Tablets
[Drug Name]
Generic Name: Azacitidine Tablets
English Name: Azacitidine Tablets
Brand Names: ONUREG, BD Zadine
Specification: 200 mg × 14 tablets/box; 300 mg × 14 tablets/box
Manufacturer: BDR PHARMACEUTICALS PVT LTD
[Composition]
Active Ingredient: Azacitidine
Excipients: Microcrystalline cellulose, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate, hypromellose, polyethylene glycol, red iron oxide, etc.
[Description]
This product is a film-coated tablet; when the coating is removed, it appears white to off-white.
[Indications]
Indicated for the continued treatment of adult patients with acute myeloid leukemia (AML) who achieved a first complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) following intensive induction chemotherapy, and who are unable to proceed to intensive curative therapy (such as hematopoietic stem cell transplantation).
[Dosage and Administration]
Recommended Dosage
300 mg once daily. Tablets should be swallowed whole; do not cut, crush, or chew.
A treatment cycle consists of 28 days: take the medication on Days 1 through 14, and discontinue on Days 15 through 28.
Continue treatment until disease progression or until unacceptable toxicity occurs.
May be taken with or without food; it is recommended to take the medication at a fixed time each day.
Antiemetic Prophylaxis
For the first 2 treatment cycles, administer prophylactic antiemetics 30 minutes prior to each dose.
If no significant nausea or vomiting occurs after 2 cycles, antiemetic prophylaxis may be discontinued following a physician's assessment.
Dosage Adjustments (Myelosuppression)
On Day 1 of a cycle, if ANC < 0.5 × 10⁹/L: Delay the start of the cycle until ANC ≥ 0.5 × 10⁹/L.
Febrile Neutropenia (ANC < 1 × 10⁹/L accompanied by fever)
First occurrence: Suspend treatment; resume at the original dose once recovered.
Occurring in 2 consecutive cycles: Suspend treatment; resume at a reduced dose of 200 mg/day once recovered. Relapse after dose reduction: Shorten the treatment course to 7 days; if relapse persists, permanently discontinue the drug.
Platelet count < 50 × 10⁹/L accompanied by bleeding: Temporarily suspend medication; resume at the original dose once recovered.
Management of Missed Doses / Vomiting
Missed Dose: If discovered on the same day, take the missed dose as soon as possible; resume the regular schedule the following day. Do not take two doses on the same day.
Vomiting after Dosing: Do not take a replacement dose on the same day; resume the scheduled dose the following day.
[Contraindications]
Contraindicated in patients with hypersensitivity to azacitidine or to any of the excipients in this product.
Contraindicated in patients with advanced malignant hepatic tumors (specifically for the injectable formulation; the oral formulation requires strict monitoring of liver function).
[Adverse Reactions]
Common Adverse Reactions (≥ 10%)
Gastrointestinal: Nausea, vomiting, diarrhea, constipation, abdominal pain, decreased appetite.
Systemic: Fatigue/asthenia, fever.
Musculoskeletal: Arthralgia, pain in extremities.
Nervous System: Dizziness.
Infections: Pneumonia, upper respiratory tract infection.
Hematologic: Neutropenia, thrombocytopenia, anemia.
Serious Adverse Reactions
Myelosuppression (Most Common): Febrile neutropenia, thrombocytopenia leading to bleeding, severe anemia.
Severe Infections: Pneumonia, sepsis, fungal infections.
Hepatic and Renal Impairment: Elevated transaminases, elevated bilirubin, elevated serum creatinine.
Other: Tumor lysis syndrome, interstitial lung disease, embryo-fetal toxicity.
[Precautions]
Monitoring for Myelosuppression
Monitor complete blood counts weekly during the first 2 cycles; once stable, monitor at least once per cycle thereafter.
In the event of Grade 3 or 4 cytopenias, suspend, reduce the dose, or discontinue the drug according to the treatment protocol.
Monitoring of Hepatic and Renal Function
Assess hepatic and renal function prior to treatment and at the beginning of each cycle.
Reduce the dose or temporarily suspend treatment in patients with hepatic impairment or elevated bilirubin/transaminases.
Use with caution and increase monitoring in patients with renal impairment.
Risk of Drug Substitution
Strictly prohibited to substitute this product for the intravenous or subcutaneous formulations of azacitidine (indications, dosages, and treatment regimens differ significantly). Contraception and Fertility
Females: Contraception is required during treatment and for at least 6 months after discontinuing the medication.
Males: Contraception is required during treatment and for at least 3 months after discontinuing the medication.
The drug may impair fertility; preservation of gametes prior to treatment is recommended.
Pregnant and Lactating Women
Pregnant Women: Contraindicated (may cause fetal malformations or miscarriage).
Lactating Women: Breastfeeding should be discontinued during treatment (the drug may be excreted into breast milk).
Pediatric Use
Safety and efficacy have not been established; use is not recommended.
Geriatric Use
Routine dosage adjustment is not required; however, as hepatic, renal, and bone marrow functions may be more susceptible to impairment in this population, enhanced monitoring is recommended.
[Pharmacology and Toxicology]
Mechanism of Action: A cytidine nucleoside analog.
1. Demethylation: Inhibits DNA methyltransferases, thereby restoring the expression of tumor suppressor genes.
2. Cytotoxicity: Incorporated into DNA and RNA, inhibiting synthesis and inducing apoptosis.
Toxicology: Exhibits genotoxicity, reproductive toxicity, and carcinogenicity; animal studies have demonstrated embryonic death and malformations.
[Pharmacokinetics]
Rapidly absorbed following oral administration; Tmax is approximately 1 hour.
Absolute bioavailability is approximately 33%.
Primarily metabolized in the liver and excreted via the kidneys.
Elimination half-life is approximately 1.5 hours.
[Storage]
Store at 20–25°C; excursions between 15–30°C are permitted.
Keep tightly sealed, in a dry place, protected from light, and out of the reach of children.
[Shelf Life]
24 months