Xpreza — Azacitidine for Injection 100 mg, 1 Vial

Xpreza is supplied as a lyophilized powder for suspension for subcutaneous injection or solution for intravenous infusion.

Qualitative and Quantitative Composition per Vial:

• Active Ingredient: Azacitidine — 100 mg.
• Excipients: Mannitol (as a lyoprotectant/bulking agent).

Packaging and Presentation: White to off-white lyophilized powder or cake in a colorless glass vial. 1 vial with prescribing information per outer carton displaying Xpreza (Azacitidine for Injection 100 mg/vial) and Natco Pharma corporate graphics.

Pharmacodynamics:
Azacitidine exerts its antineoplastic effects through multiple mechanisms, including cytotoxicity to rapidly dividing hematopoietic cells and inhibition of DNA methylation. Low concentrations of azacitidine do not cause cell death but induce DNA hypomethylation by irreversibly inhibiting DNA methyltransferases. Hypomethylation of aberrantly methylated genes involved in cell cycle regulation, differentiation, and apoptosis can restore normal gene function in myelodysplastic syndromes.

Pharmacokinetics:

• Absorption: Following subcutaneous administration, azacitidine is rapidly absorbed with peak plasma concentrations ($C_{max}$) reached within 0.5 to 2 hours. Absolute bioavailability of subcutaneous administration is approximately 89% relative to intravenous administration.
• Distribution: Rapidly distributes into tissues. Volume of distribution is 76 ± 26 L. Plasma protein binding is negligible.
• Metabolism: Metabolized primarily via spontaneous hydrolysis and enzymatic deamination by cytidine deaminase.
• Elimination: Excreted predominantly renally (as metabolites and unchanged drug). Terminal elimination half-life ($T_{1/2}$) following subcutaneous administration is approximately 41 minutes.

Xpreza is indicated in adult patients not eligible for hematopoietic stem cell transplantation for:

• Myelodysplastic Syndromes (MDS): Treatment of patients with intermediate-2 and high-risk MDS according to the International Prognostic Scoring System (IPSS).
• Acute Myeloid Leukemia (AML): Treatment of AML with 20 to 30% blasts and multi-lineage dysplasia according to WHO classification.
• Chronic Myelomonocytic Leukemia (CMML): Treatment of CMML without myeloproliferative features with 10 to 29% bone marrow blasts.

Xpreza is administered either subcutaneously (into the upper arm, thigh, or abdomen) or via intravenous infusion. Intravenous administration requires strict adherence to reconstitution protocols.

Dosing Regimen:
The recommended starting dose for the first treatment cycle for all patients (regardless of baseline blood counts) is 75 mg/m² body surface area daily for 7 consecutive days, followed by a rest period of 21 days (28-day treatment cycle).

Cycle Continuation Recommendations:
It is recommended that treatment cycles be repeated every 4 weeks. Patients should be treated for a minimum of 6 cycles until clinical response or disease progression is observed.

Administration of Xpreza is contraindicated in:

• Hypersensitivity: Known hypersensitivity to azacitidine or any excipient.
• Advanced Hepatic Tumors: Advanced malignant hepatic tumors (extensive metastatic involvement).
• Pregnancy and Lactation: Contraindicated in pregnant or breastfeeding women due to high teratogenic risk.

Clinical drug interaction trials with azacitidine have not been conducted:

• Cytochrome P450 (CYP450) System: In vitro studies indicate azacitidine metabolism is not mediated by CYP450 isoenzymes, making enzymatic drug interactions unlikely.
• Myelosuppressive Agents: Concurrent administration with other bone-marrow suppressing agents may increase hematologic toxicity. Blood count monitoring is required.

Pregnancy:
Xpreza is contraindicated during pregnancy. Azacitidine demonstrates proven reproductive toxicity and teratogenic potential. Women of childbearing potential and male partners must utilize effective contraception during treatment and for several months post-therapy.

Lactation:
Excretion of azacitidine and its metabolites into human breast milk is unknown. Breastfeeding is strictly prohibited during treatment.

The most frequent and clinically significant adverse reactions include:

• Hematologic Toxicity (Very Common): Myelosuppression, including thrombocytopenia, neutropenia, febrile neutropenia, and anemia. Regular complete blood counts are mandatory.
• Gastrointestinal Tract: Nausea, vomiting, diarrhea, constipation, abdominal pain, stomatitis.
• Injection Site Reactions (Subcutaneous): Erythema, pain, bruising, rash, or induration at the injection site.
• General Disorders: Fatigue, asthenia, pyrexia, night sweats, weight loss.
• Infections: Pneumonia, urinary tract infections, nasopharyngitis, neutropenic sepsis.

Symptoms:
Isolated cases of azacitidine overdose have been reported. Manifestations include intensified myelosuppression (severe neutropenia and thrombocytopenia) accompanied by diarrhea, somnolence, and pyrexia.

Treatment:
No specific antidote exists. Supportive and symptomatic care should be initiated (blood component transfusions, antibiotic therapy for infections) under close medical supervision.

Storage Requirements for Xpreza 100 mg:

• 🌡️ Temperature Range: Store protected from light at temperatures not exceeding 25 °C (or per package labeling).
• 💧 Reconstituted Suspension: Subcutaneous suspensions should be used immediately after preparation (or stored refrigerated at 2–8 °C for protocol-specified timeframes).
• 👶 Safety Precautions: Keep strictly out of reach of children.
• ⏳ Shelf Life: Stated on carton and vial. Do not use past expiration date. Prescription-only hospital medicine.

To verify authenticity of genuine Xpreza 100 mg manufactured by Natco Pharma, inspect the following features:

• ✅ Corporate Logo: Distinctive blue-green Natco Pharma corporate logo printed on the outer carton and vial label.
• ✅ Packaging Markings: Clear factory printing displaying Batch No., Mfg. Date, Exp. Date, and product designation Xpreza (Azacitidine for Injection 100 mg/vial).
• ✅ Vial Quantity: Standard box contains exactly 1 glass vial of lyophilized powder (100 mg).
• ✅ Print Quality: High-grade packaging artwork with anti-counterfeit features, clear typography, and zero spelling errors.