Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Bristol-Myers Squibb Pharma EEIG, Plaza 254, Blanchardstown Corporate Park 2, Dublin 15, D15 T867, Ireland
Onureg is indicated as maintenance therapy in adult patients with acute myeloid leukaemia (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 candidates for, including those who choose not to proceed to, hematopoietic stem cell transplantation (HSCT).
Onureg treatment should be initiated and monitored under the supervision of a physician experienced in the use of chemotherapeutic medicinal products.
Patients are to be treated with an anti-emetic 30 minutes prior to each dose of Onureg for the first 2 treatment cycles. Anti-emetic prophylaxis may be omitted after 2 cycles, if there has been no nausea and vomiting (see section 4.4).
The recommended dose is 300 mg azacitidine orally once daily. Each repeated cycle consists of a treatment period of 14 days followed by a treatment free period of 14 days (28-day treatment cycle).
Onureg treatment should be continued until no more than 15% blasts are observed in peripheral blood or bone marrow or until unacceptable toxicity (see dose schedule modification guidance for disease relapse).
Onureg should not be used interchangeably with injectable azacitidine due to differences in the exposure, dose and schedule of treatment. Healthcare professionals are recommended to verify the name of the medicinal product, dose and administration route.
Complete blood counts should be performed prior to initiation of therapy. Complete blood count monitoring is also recommended every other week for the first 2 cycles (56 days), every other week for the next 2 cycles after dose adjustment, and monthly thereafter, prior to the start of subsequent cycles of treatment (see section 4.4).
In the case of disease relapse, with 5% to 15% blasts in peripheral blood or bone marrow, in conjunction with a clinical assessment, an extension of the dosing schedule from 14 to 21 days of repeated 28-day cycles should be considered. Dosing should not exceed 21 days during any 28-day period. Onureg should be discontinued if more than 15% blasts are observed in either the peripheral blood or bone marrow or at the physician’s discretion.
Dose modification guidelines for haematologic and non-haematologic adverse reactions are recommended based on clinical and laboratory findings (see Table 1).
Table 1. Dose adjustments for haematologic and non-haematologic adverse reactions:
| Criteria* | Recommended action |
|---|---|
| Grade 4 neutropenia or Grade 3 neutropenia with fever | First occurrence: Interrupt Onureg. Resume the treatment cycle at the same dose once neutrophils return to Grade 2 or lower. Use supportive care such as granulocyte colony stimulating factor (GCSF), as clinically indicated (see section 4.4). Occurrence in 2 consecutive cycles: Interrupt Onureg. Resume the treatment cycle at a reduced dose of 200 mg after neutrophils return to Grade 2 or lower. If a patient continues to experience the toxicity after dose reduction, reduce the treatment duration by 7 days. If the toxicity continues or re-occurs after dose and schedule reduction, discontinue Onureg. Use supportive care such as GCSF, as clinically indicated (see section 4.4). |
| Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding | First occurrence: Interrupt Onureg. Resume the treatment cycle at the same dose once platelets return to Grade 2 or lower. Occurrence in 2 consecutive cycles: Interrupt Onureg. Resume the treatment cycle at a reduced dose of 200 mg after platelets return to Grade 2 or lower. If a patient continues to experience the toxicity after dose reduction, reduce the treatment duration by 7 days. If the toxicity continues or re-occurs after dose and schedule reduction, discontinue Onureg. |
| Grade 3 or higher nausea, vomiting or diarrhoea | Interrupt Onureg. Resume the treatment cycle at the same dose once toxicity has resolved to Grade 1 or lower. Use supportive care such as anti-emetic therapy and treat diarrhoea at the onset of symptoms (see section 4.4). If event re-occurs, interrupt dose until resolved to Grade 1 or lower and reduce the dose to 200 mg. If a patient continues to experience the toxicity after dose reduction, reduce the treatment duration by 7 days. If the toxicity continues or re-occurs after dose and schedule reduction, discontinue Onureg. |
| Other Grade 3 or higher non-haematological events | Interrupt Onureg and provide medical support according to local recommendations. Resume the treatment cycle at the same dose once toxicity has resolved to Grade 1 or lower. If the toxicity re-occurs, interrupt Onureg until resolved to Grade 1 or lower and reduce dose to 200 mg. If a patient continues to experience the toxicity after dose |
* Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening. Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.3 (NCI-CTCAE v4.3).
If a dose of Onureg is missed, or not taken at the usual time, the dose should be taken as soon as possible on the same day. Then, the next scheduled dose should be taken at the normal time the following day. Two doses should not be taken on the same day.
If a dose is vomited, another dose must not be taken on the same day. Instead return to the normal time of dose administration the following day.
No dose adjustments are recommended for patients over 65 years of age (see section 5.2).
Onureg can be administered to patients with mild, moderate or severe renal impairment without initial dose adjustment (see section 5.2).
No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin (BIL) ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN, or BIL 1 to 1.5 × ULN and any AST) (see section 5.2).
Patients with moderate (BIL >1.5 to 3 × ULN) and severe hepatic impairment (BIL >3 × ULN) should be monitored more frequently for adverse reactions and appropriate dose adjustment should be made (see Table 1).
The safety and efficacy of Onureg in children and adolescents below 18 years have not been established. No data are available.
Onureg is for oral use.
Onureg can be taken with or without food. The tablets should be swallowed whole with a glass of water at about the same time each day. They should not be split, crushed, dissolved or chewed (see section 6.6).
In the event of overdose, the patient should be monitored with appropriate blood counts and supportive treatment should be provided, as necessary, according to local recommendations. There is no known specific antidote for an overdose with Onureg.
3 years.
This medicinal product does not require any special storage conditions.
The film-coated tablets are packaged in nylon (OPA) / polyvinyl chloride (PVC) aluminium blisters with push through aluminium foil.
Pack size of 7 or 14 film-coated tablets.
Not all pack sizes may be marketed.
Onureg is a cytotoxic medicinal product. If powder from the film-coated tablets makes contact with the skin, the skin should be washed immediately and thoroughly with soap and water. If the powder comes in contact with mucous membranes, the area should be thoroughly flushed with water.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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