Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
AZCT(MNT-PO)
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
For maintenance treatment in patients with newly diagnosed AML* who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment, and who are not eligible for hematopoietic stem cell transplantation.
*de novo or secondary to prior myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), with intermediate- or poor-risk cytogenetics
azaCITIDine (tablets)
Exceptional Access Program
(azaCITIDine (tablets) - For maintenance therapy in adult patients with AML who achieved complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment, and who are not eligible for hematopoietic stem cell transplantation)
(EAP Website)
Note: Azacitidine tablets are not interchangeable with, and should not be substituted with or for, azacitidine for injection. Verify drug name, dose, and administration route. The different dosage forms are not bioequivalent.
Oral azacitidine should be started within 4 months of achieving CR or CRi.
| azaCITIDine (tablets) | 300 mg | PO | Daily on days 1 to 14 |
Moderate – Consider prophylaxis daily (Administer an antiemetic 30 minutes prior to each dose of azacitidine for the first 2 cycles. Administer antiemetic prophylaxis as needed after 2 cycles if there has been no nausea and vomiting.)
- Also refer to CCO Antiemetic Recommendations.
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Other Supportive Care:
- Consider the use of granulocyte colony stimulating factor (GCSF) as clinically indicated.
- Consider the use of antidiarrheal medication for prophylaxis against diarrhea and for prompt treatment at the onset of symptoms.
Doses should be modified according to the protocol by which the patient is being treated.
At the start of each cycle, initiate azacitidine only when ANC ≥ 0.5 x 109/L.
Dosage with toxicity
| Dose Level | Azacitidine (tablets) Dose (mg/day) |
| 0 | 300 |
| -1 | 200 |
| Toxicity | Criteria | Occurrence | Action |
| Neutropenia |
ANC < 0.5 x 109/L OR ANC < 0.5-1 x 109/L with fever |
First |
Hold; consider use of GCSF as clinically indicated. Resume at same dose after recovery to ≤ grade 2. |
| 2 Consecutive Cycles |
Hold; consider use of GCSF as clinically indicated. Resume at ↓ 1 dose level after recovery to ≤ grade 2.
|
||
| Continued or recurrent toxicity after dose reduction | Reduce treatment duration to 7 days (e.g. treat on days 1-7 instead of days 1-14 every 28 days). Consider use of GCSF as clinically indicated. | ||
| Continued toxicity or recurrence after dose and schedule reduction | Discontinue. | ||
| Thrombocytopenia |
Platelets < 25 x 109/L OR Platelets < 25-50 x 109/L with bleeding |
First | Hold; resume at same dose after recovery to ≤ grade 2. |
| 2 Consecutive Cycles |
Hold; resume at ↓ 1 dose level after recovery to ≤ grade 2. |
||
| Continued or recurrent toxicity after dose reduction | Reduce treatment duration to 7 days (e.g. treat on days 1-7 instead of days 1-14 every 28 days). | ||
| Continued toxicity or recurrence after dose and schedule reduction |
Discontinue. | ||
| Nausea, Vomiting or Diarrhea | ≥ Grade 3 | First | Hold; resume at same dose after recovery to ≤ grade 1. |
| Second | Hold; resume at ↓ 1 dose level after recovery to ≤ grade 1. | ||
| Continued or recurrent toxicity after dose reduction | Reduce treatment duration to 7 days (e.g. treat on days 1-7 instead of days 1-14 every 28 days). | ||
| Continued toxicity or recurrence after dose and schedule reduction | Discontinue. | ||
| All other nonhematologic toxicities | ≥ Grade 3 | First | Hold and provide medical support; resume at same dose after recovery to ≤ grade 1. |
| Second | Hold; resume at ↓ 1 dose level after recovery to ≤ grade 1. | ||
| Continued or recurrent toxicity after dose reduction | Reduce treatment duration to 7 days (e.g. treat on days 1-7 instead of days 1-14 every 28 days). | ||
| Continued toxicity or recurrence after dose and schedule reduction | Discontinue. |
Hepatic Impairment
| Hepatic Impairment | Azacitidine (tablets) Dose (mg/day) |
|
Mild impairment (total bilirubin ≤ ULN and AST > ULN or total bilirubin 1 to 1.5 x ULN and any AST) |
No dose adjustment is required |
|
Moderate impairment (total bilirubin >1.5 to 3 x ULN) |
Dose adjustment has not been established |
|
Severe impairment (total bilirubin >3 x ULN) |
Has not been studied |
Renal Impairment
| Creatinine Clearance (mL/min) | Azacitidine (tablets) Dose (mg/day) |
| ≥30 | No dose adjustment is required |
| <30 | No initial dose adjustment required; monitor patients more frequently and modify dosage for adverse reactions. |
Dosage in the Elderly
No dose adjustment is required. No overall differences in safety or effectiveness were observed between younger patients and patients ≥ 65 years.
Refer to azaCITIDine (tablets) drug monograph(s) for additional details of adverse effects.
|
Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
|
Refer to azaCITIDine (tablets) drug monograph(s) for additional details.
- No clinically relevant drug-drug interactions is expected when azacitidine tablets are coadministered with CYP or transporter inhibitors, inducers or substrates.
Refer to azaCITIDine (tablets) drug monograph(s) for additional details.
Administration
Azacitidine tablets are not interchangeable with, and should not be substituted with or for, azacitidine for injection. Verify drug name, dose, and administration route. The different dosage forms are not bioequivalent.
- Take with or without food at approximately the same time each day.
-
Swallow tablets whole with water. Do not split, crush or chew the tablets.
-
If a dose of azacitidine is missed, administer the dose as soon as possible on the same day, and return to the normal time of dose administration the following day. Do not take 2 doses on the same day.
-
If a dose is vomited, do not take another dose on the same day, return to the normal time of dose administration the following day.
-
Store blisters at 15º to 30ºC. Store in the original aluminum blisters.
Contraindications
-
Patients who are hypersensitive to the drug or to any component in the formulation.
-
Patients with advanced malignant hepatic tumors.
Other Warning/Precautions
-
DO NOT substitute azacitidine tablets for intravenous or subcutaneous azacitidine. There are substantial differences in the pharmacokinetic parameters. The recommended dose and schedule of azacitidine tablets are different from those of the intravenous or subcutaneous azacitidine products. Treatment of patients using intravenous or subcutaneous azacitidine at the recommended dosage of azacitidine tablets may result in a fatal adverse reaction. Treatment of patients using azacitidine tablets at the doses recommended for intravenous or subcutaneous azacitidine may not be effective.
-
The safety and effectiveness of azacitidine tablets for treatment of myelodysplastic syndromes have not been established. A higher incidence of early fatal and/or serious adverse reactions was observed in clinical trials. Treatment of patients with myelodysplastic syndromes is not recommended outside of controlled trials.
-
The safety and efficacy of azacitidine tablets in patients with a history of severe congestive heart failure, clinically unstable cardiac disease or pulmonary disease have not been established as they were excluded from the pivotal clinical study.
-
No thorough clinical QT/QTc study or in vitro studies were performed to rule out the effect of azacitidine tablets on QT prolongation. An in vivo safety pharmacology animal study reported increased QTc interval, but interpretation of the study is limited by confounding effects associated with toxicity.
-
Contains lactose; carefully consider use in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption
-
Patients should be advised that they may experience effects such as fatigue and asthenia and caution should be exercised when driving or operating a vehicle or potentially dangerous machinery.
Pregnancy/Lactation
-
This regimen is not recommended for use in pregnancy. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information
-
Breastfeeding is not recommended during treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
-
Fertility Effects: Observed in animal studies
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Recommended Clinical Monitoring
-
CBC; Every other week for the first 2 cycles (56 days), every other week for the next 2 cycles after any dose adjustment, then monthly before each cycle and as clinically indicated
-
Renal function tests; Baseline, before each cycle and as clinically indicated, more frequently in patients with severe renal impairment (ClCr <30 mL/min)
-
Liver function tests; Baseline, before each cycle and as clinically indicated
-
Clinical toxicity assessment for infection, bleeding, fatigue, hyperuricemia, falls, and cardiovascular and gastrointestinal effects; Baseline and as clinically indicated
back to top
Onureg (azacitidine tablets) Drug Monograph. Ontario Health (Cancer Care Ontario)
Wei AH, Dohner H, Pocock C, et al. Oral Azacitidine Maintenance Therapy for Acute Myeloid Leukemia in First Remission. N Engl J Med 2020;383:2526-37.
DOI: 10.1056/NEJMoa2004444
July 2023 Updated adverse effects section; Added link to hepatitis B virus screening and management guideline
Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.