AZACITIDINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AZACITIDINE (AZACITIDINE).
Azacitidine is a pyrimidine nucleoside analog of cytidine that inhibits DNA methyltransferase, leading to hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in bone marrow. It incorporates into RNA and DNA, causing disruption of nucleic acid metabolism and apoptosis.
| Metabolism | Azacitidine is primarily metabolized by hydrolysis and deamination. It undergoes spontaneous hydrolysis and is also deaminated by cytidine deaminase in the liver. The major metabolites are 5-azacytidine and 5-azauridine derivatives. |
| Excretion | Renal (primarily as metabolites, ~50-85% of administered dose within 72 hours); fecal/biliary negligible. |
| Half-life | Terminal half-life approximately 4 hours (subcutaneous or intravenous); reflects rapid deamination by cytidine deaminase. |
| Protein binding | ~5% bound to plasma proteins (albumin). |
| Volume of Distribution | Vd approximately 6 L/kg (extensive distribution into tissues, including bone marrow). |
| Bioavailability | Subcutaneous: ~89% relative to intravenous; intravenous: 100%. |
| Onset of Action | Subcutaneous: Clinical response (e.g., hematologic improvement) typically observed after 2-4 cycles (each cycle 28 days, treatment 7 days). Intravenous: Similar timing; no difference in onset. |
| Duration of Action | Duration of myelosuppression and clinical effect per cycle lasts approximately 4-6 weeks; repeated cycles are required for sustained response. |
75 mg/m² subcutaneously or intravenously once daily for 7 days every 28 days.
| Dosage form | POWDER |
| Renal impairment | For serum creatinine >2 mg/dL or blood urea nitrogen >50 mg/dL, reduce dose to 50% of starting dose on Day 1; if unresolved after 7 days, delay next cycle until resolution. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose to 75% of starting dose. Child-Pugh C: reduce dose to 50% of starting dose. |
| Pediatric use | 75 mg/m² subcutaneously or intravenously once daily for 7 days every 28 days (same as adult dosing). |
| Geriatric use | No specific dose adjustment required; monitor for increased myelosuppression due to renal function decline with age. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AZACITIDINE (AZACITIDINE).
| Breastfeeding | It is unknown if azacitidine or its metabolites are excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 1 week after the last dose. No M/P ratio is available. |
| Teratogenic Risk | Azacitidine is embryotoxic and teratogenic in animal studies. It should not be used during pregnancy, especially in the first trimester, due to potential fetal harm. It may cause congenital anomalies and fetal death. Effective contraception is recommended during treatment and for at least 3 months after the last dose in women of childbearing potential. |
■ FDA Black Box Warning
Azacitidine causes fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid pregnancy during treatment. Additionally, administration of azacitidine is associated with an increased risk of developing severe, sometimes fatal, myelosuppression, including neutropenia, thrombocytopenia, and anemia.
| Serious Effects |
["Hypersensitivity to azacitidine or mannitol.","Advanced malignant hepatic tumors."]
| Precautions | ["Myelosuppression: Monitor complete blood counts frequently; dose adjustments may be required for nadir counts.","Hepatotoxicity: Elevations of liver enzymes and bilirubin can occur; monitor hepatic function.","Renal toxicity: Renal impairment may require dose modification; monitor serum creatinine.","Tumor lysis syndrome: Risk in patients with rapidly proliferating disease; monitor and manage appropriately.","Embryo-fetal toxicity: Can cause fetal harm; advise women of reproductive potential to use effective contraception.","Lactation: Discontinue breastfeeding during treatment due to potential for serious adverse reactions in nursing infants.","Injection site reactions: Necrosis, ulceration, and granuloma formation have been reported; proper administration technique is important."] |
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| Fetal Monitoring | Complete blood counts (CBC) should be monitored frequently due to myelosuppression. Liver function tests (LFTs) and renal function tests (serum creatinine, BUN) should be assessed periodically. In pregnant women, fetal ultrasound and monitoring for intrauterine growth restriction (IUGR) should be considered. |
| Fertility Effects | Azacitidine may impair fertility in males and females. In males, it can cause oligospermia, azoospermia, and testicular atrophy. In females, it may lead to amenorrhea, ovarian failure, and reduced fertility. These effects may be reversible or permanent. |
| Food/Dietary | No significant food interactions. Avoid alcohol due to potential hepatotoxicity. Maintain adequate hydration to prevent renal toxicity. |
| Clinical Pearls | Premedicate with antiemetics (e.g., 5-HT3 antagonist) for 30 min prior to infusion. Administer subcutaneously or intravenously; rotate SC injection sites. Monitor CBC weekly during first 2 cycles. Dose reduction or delay for neutropenia (ANC <0.5) or thrombocytopenia (platelets <25K). Avoid live vaccines. Contraindicated in hypersensitivity to mannitol. |
| Patient Advice | Take anti-nausea medication as prescribed before each treatment. · Report any signs of infection (fever, chills) or bleeding (bruising, blood in stool) immediately. · Use effective contraception during treatment and for at least 1 month after the last dose. · Do not receive live vaccines during therapy. · Stay hydrated and avoid alcohol to reduce liver strain. · May cause fatigue; avoid driving if drowsy. |