ONUREG

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ONUREG (ONUREG).

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ONUREG (ONUREG).

Breastfeeding	It is not known if ONUREG is excreted in human milk. 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. The M/P ratio has not been established.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of hypersensitivity to azacitidine or any component of the formulation","Advanced malignant hepatic tumors (relative, per FDA labeling for injectable azacitidine; not specific to ONUREG)","Pregnancy"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

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ONUREG

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ONUREG (ONUREG).

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ONUREG (ONUREG).

Breastfeeding	It is not known if ONUREG is excreted in human milk. 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. The M/P ratio has not been established.
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.