VIDAZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VIDAZA (VIDAZA).
Azacitidine is a pyrimidine nucleoside analog of cytidine that inhibits DNA methyltransferase, causing hypomethylation of DNA and direct cytotoxicity in abnormal hematopoietic cells.
| Metabolism | Primarily metabolized by cytidine deaminase and possibly by deamination; not significantly metabolized by CYP450 enzymes. |
| Excretion | Renal: 50-85% as unchanged drug and metabolites; biliary/fecal: minimal (<10%) |
| Half-life | Terminal half-life: 5-7 hours (subcutaneous); 3-5 hours (intravenous); supports 7-day dosing cycle |
| Protein binding | Approximately 80-90% bound to human plasma proteins |
| Volume of Distribution | Vd: 4.5-8.9 L/kg; indicates extensive tissue distribution |
| Bioavailability | Subcutaneous: ~89% (relative to intravenous) |
| Onset of Action | Subcutaneous: Clinical effect (hematologic improvement) within 1-3 cycles (4-12 weeks); Intravenous: similar |
| Duration of Action | Duration of demethylation effect: ~2-4 weeks post-treatment; dosing cycle: 7 days of 28-day cycle |
| Molecular Weight | 244.21 |
75 mg/m2 subcutaneously or intravenously once daily for 7 days every 4 weeks.
| Dosage form | POWDER |
| Renal impairment | For serum creatinine >2 mg/dL or BUN >50 mg/dL, reduce dose to 50% of starting dose. For end-stage renal disease (GFR <15 mL/min/1.73 m2) not on dialysis, use with caution and monitor toxicity. |
| Liver impairment | No specific dose adjustment recommended for hepatic impairment. Use with caution in severe hepatic impairment. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; no standard pediatric dosing available. |
| Geriatric use | No specific dose adjustment required. Monitor for renal function and increased sensitivity to myelotoxicity. |
| 1st trimester | Contraindicated in the first trimester due to risk of embryotoxicity and teratogenicity based on animal studies; case reports of spontaneous abortion and congenital anomalies in humans. |
| 2nd trimester | Avoid use in second trimester due to potential risks; no adequate human studies, but animal data show developmental toxicity. |
| 3rd trimester | Avoid use in third trimester; may cause fetal myelosuppression and other adverse effects; use only if clearly needed and after careful risk-benefit assessment. |
Clinical note
Comprehensive clinical and safety monograph for VIDAZA (VIDAZA).
| Placental transfer | Evidence of placental transfer; azacitidine and its metabolites cross the placenta in animal studies; human data limited but likely significant. |
| Breastfeeding | Unknown whether excreted in human milk; due to potential for serious adverse reactions in nursing infants (e.g., myelosuppression), breastfeeding is not recommended during therapy and for at least 1 week after the last dose. |
■ FDA Black Box Warning
VIDAZA is contraindicated in patients with advanced malignant hepatic tumors. Use in patients with liver disease is associated with fatal hepatic coma.
| Serious Effects |
Known hypersensitivity to azacitidine or mannitolAdvanced malignant hepatic tumorsLactation
| Precautions | Hepatotoxicity: Fatal hepatic coma may occur in patients with severe preexisting hepatic impairment., Renal toxicity: Renal impairment may lead to increased toxicity; monitor renal function., Hematologic toxicity: May cause severe neutropenia, thrombocytopenia, and anemia; monitor blood counts., Tumor lysis syndrome: Risk in patients with high tumor burden., Embryo-fetal toxicity: Can cause fetal harm. |
| Food/Dietary | Avoid grapefruit and grapefruit juice; may increase azacitidine exposure. |
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| Lactation Rating | L5 |
| Teratogenic Risk | Azacitidine is a nucleoside analog that inhibits DNA methylation and is teratogenic in animals. Based on its mechanism of action, there is a potential risk of teratogenicity in humans. Limited human data exist. The drug should be avoided during pregnancy, especially in the first trimester, due to the risk of fetal malformations. In later trimesters, there may be risks of growth restriction and other adverse effects. Pregnancy testing is recommended before initiation. |
| Fetal Monitoring | Monitor complete blood count with differential, liver function tests, serum creatinine, and electrolytes regularly. Due to risk of tumor lysis syndrome, monitor uric acid, potassium, phosphate, and calcium. Perform pregnancy testing before starting therapy in women of reproductive potential. Fetal monitoring (ultrasound) may be considered if exposure occurs during pregnancy. |
| Fertility Effects | Azacitidine may impair fertility in both males and females based on animal studies. In humans, it can cause amenorrhea and spermatogenic arrest. Gonadal suppression may occur. Advise patients about fertility preservation options before treatment. |
| Clinical Pearls | First-line for higher-risk MDS; requires subcutaneous injection rotating sites; premedicate with antiemetics; monitor for injection site reactions and neutropenia. |
| Patient Advice | Inject subcutaneously as directed; rotate sites (abdomen, thigh, upper arm). · Take antiemetics before dose to prevent nausea and vomiting. · Report signs of infection (fever, cough) or bleeding (bruising, blood in stools). · Do not skip doses; if a dose is missed, contact your healthcare provider. · Avoid alcohol and NSAIDs due to increased bleeding risk. · Hydrate well; avoid grapefruit juice. |