ONUREG
Clinical safety rating
cautionComprehensive clinical and safety monograph for ONUREG (ONUREG).
Comprehensive clinical and safety monograph for ONUREG (ONUREG).
Continued treatment of adult patients with acute myeloid leukemia (AML) who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapyTreatment of adult patients with myelodysplastic syndromes (MDS) (off-label)Treatment of chronic myelomonocytic leukemia (CMML) (off-label)
Azacitidine is a pyrimidine nucleoside analog of cytidine. It is incorporated into RNA and DNA, leading to inhibition of DNA methyltransferase, causing hypomethylation of DNA, and direct cytotoxicity of abnormal hematopoietic cells in the bone marrow.
| Metabolism | Azacitidine is metabolized primarily by hydrolysis in the liver via cytidine deaminase (CDA) and also undergoes spontaneous hydrolysis. The major metabolite is 5-azacytosine. Less than 10% is excreted unchanged in urine. |
| Excretion | Renal: 18% unchanged; fecal: 57% (as metabolites); biliary: not significant. |
| Half-life | Terminal half-life: 1.8 hours (range 0.7–3.6 h) for oral azacitidine; clinical context: supports twice-daily dosing, minimal accumulation. |
| Protein binding | ~5% bound to plasma proteins (albumin and others). |
| Volume of Distribution | 72 L (approx. 1.0 L/kg) based on oral administration; indicates extensive tissue distribution. |
| Bioavailability | Oral: ~20% (range 11–29%) relative to subcutaneous azacitidine. |
| Onset of Action | Oral: 7–14 days for initial hematologic improvement (median time to first response in MDS). |
| Duration of Action | Duration: 28-day cycle with clinical effect measured over multiple cycles; epigenetic changes persist for weeks after treatment. |
| Molecular Weight | 244.2 |
200 mg orally once daily on days 1-14 of a 28-day cycle.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: reduce dose to 150 mg daily. GFR 15-29 mL/min: 100 mg daily. GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: 200 mg daily. Child-Pugh B: 150 mg daily. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required; monitor for toxicity. |
| 1st trimester | Contraindicated due to teratogenicity (embryo-fetal toxicity) based on animal studies and mechanism of action (pyrimidine analog). |
| 2nd trimester | Contraindicated due to potential fetal harm; avoid use. |
| 3rd trimester | Contraindicated due to potential fetal harm; avoid use. |
Clinical note
Comprehensive clinical and safety monograph for ONUREG (ONUREG).
| Placental transfer | Expected to cross placenta based on molecular weight (244.2 Da) and lipophilic nature; animal studies confirm transfer. |
| Breastfeeding | Not recommended due to potential for serious adverse reactions in breastfed infants; advise women not to breastfeed during treatment and for at least 1 week after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Based on its mechanism as a cytidine analog and animal studies, ONUREG (azacitidine) is expected to cause fetal harm. First trimester: high risk of teratogenicity, including structural anomalies and embryotoxicity. Second and third trimesters: risk of fetal growth restriction, myelosuppression, and potential long-term developmental effects. Pregnancy should be excluded prior to treatment. |
| Fetal Monitoring | Monitor complete blood counts (CBC) with differential prior to each cycle. Assess for myelosuppression. Perform pregnancy testing in females of reproductive potential prior to initiation. Monitor for gastrointestinal toxicity, renal function, and hepatic transaminases as clinically indicated. |
| Fertility Effects | ONUREG may impair fertility in males and females based on animal studies. In males, azacitidine affects spermatogenesis and may cause irreversible infertility. In females, it can disrupt ovarian function and reduce fertility; contraception is recommended during treatment and for 6 months after the last dose. |
■ FDA Black Box Warning
ONUREG (oral azacitidine) can cause severe or fatal myelosuppression, including neutropenia, thrombocytopenia, and anemia. Monitor blood counts at baseline and before each cycle. Do not administer to patients with a platelet count less than 50 x 10^9/L or absolute neutrophil count less than 1.0 x 10^9/L at the start of a cycle.
| Serious Effects |
PregnancySevere renal impairment (CrCl <30 mL/min)
| Precautions | Myelosuppression: Monitor blood counts and delay or reduce dose as needed, Increased early mortality in patients with stable MDS/AML (not relevant to ONUREG indication), Use in patients with hepatic impairment: No specific studies; use with caution in severe hepatic impairment, Use in patients with renal impairment: Reduce dose in severe renal impairment (CrCl < 30 mL/min), Embryo-fetal toxicity: Can cause fetal harm; advise females of reproductive potential of potential risk and use effective contraception |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase azacitidine exposure. Administer ONUREG on an empty stomach: no food or water for at least 2 hours before and 1 hour after dosing. There are no specific restrictions on other foods, but maintaining adequate hydration and nutrition is important. |
| Clinical Pearls | ONUREG (azacitidine) is indicated for continued treatment of acute myeloid leukemia (AML) after achieving first complete remission (CR) or CR with incomplete blood count recovery (CRi). It is a hypomethylating agent that must be administered orally on days 1-14 of a 28-day cycle. Important: Do not break, crush, or chew tablets; swallow whole with water. Administer on an empty stomach (no food or water for at least 2 hours before and 1 hour after). Monitor for myelosuppression (neutropenia, thrombocytopenia, anemia) and gastrointestinal toxicity (nausea, vomiting, diarrhea). Consider antiemetic prophylaxis. Avoid concomitant use with strong CYP3A4 inducers (e.g., rifampin) as they may reduce azacitidine exposure. |
| Patient Advice | Take ONUREG exactly as prescribed: once daily for 14 days, then 14 days off (28-day cycle). · Swallow tablets whole; do not break, crush, or chew them. · Take on an empty stomach: no food or water for at least 2 hours before and 1 hour after. · If you vomit after taking a dose, do not take another; wait for the next scheduled dose. · Common side effects include nausea, vomiting, diarrhea, fatigue, and low blood counts. Contact your doctor if you have fever, signs of infection, or unusual bleeding/bruising. · Avoid grapefruit and grapefruit juice during treatment. · Tell your doctor about all medications you take, including over-the-counter drugs and supplements. |
Loading safety data…