AZACITIDINE KABI

Azacitidine treatment should be initiated and monitored under the supervision of a physician experienced in the use of chemotherapeutic agents. Patients should be premedicated with anti-emetics for nausea and vomiting. Posology The recommended starting dose for the first treatment cycle, for all patients regardless of baseline haematology laboratory values, is 75 mg/m2 of body surface area, injected subcutaneously, daily for 7 days, followed by a rest period of 21 days (28-day treatment cycle).

It is recommended that patients be treated for a minimum of 6 cycles. Treatment should be continued for as long as the patient continues to benefit or until disease progression. 4); a delay in starting the next cycle or a dose reduction as described below may be necessary.

Azacitidine should not be used interchangeably with oral azacitidine. Due to differences in the exposure, the dose and schedule recommendations for oral azacitidine are different from those for injectable azacitidine. Healthcare professionals are recommended to verify the name of the medicinal product, dose and administration route.

Laboratory tests Liver function tests, serum creatinine and serum bicarbonate should be determined prior to initiation of therapy and prior to each treatment cycle. Complete blood counts should be performed prior to initiation of therapy and as needed to monitor response and toxicity, but at a minimum, prior to each treatment cycle.

0 × 109/L and/or absolute neutrophil count (ANC) ≤ 1 × 109/L. e. 5 × [|baseline count nadir count|]). e. 0 x 109/L) prior to the first treatment If haematological toxicity is observed following azacitidine treatment, the next cycle of the therapy should be delayed until the platelet count and the ANC have recovered.

If recovery is achieved within 14 days, no dose adjustment is necessary. However, if recovery has not been achieved within 14 days, the dose should be reduced according to the following table. Following dose modifications, the cycle duration should return to 28 days.

e. 0 x 109/L) prior to the first treatment Following azacitidine treatment, if the decrease in WBC or ANC or platelets from that prior to treatment is ≤ 50%, or greater than 50% but with an improvement in any cell line differentiation, the next cycle should not be delayed and no dose adjustment made.

Summary of the safety profile Adult population with MDS, CMML and AML (20-30% marrow blasts) Adverse reactions considered to be possibly or probably related to the administration of azacitidine have occurred in 97% of patients. 3%), which were also reported in the supporting studies (CALGB 9221 and CALGB 8921).

g. 5%]). 1%; usually Grade 1-2). 6%). 1%). 1%;usually Grade 3-4). Tabulated list of adverse reactions Table 1 below contains adverse reactions associated with azacitidine treatment obtained from the main clinical studies in MDS and AML and post marketing surveillance.

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Adverse reactions are presented in the table below according to the highest frequency observed in any of the main clinical studies. 4 Description of selected adverse reactions Haematologic adverse reactions The most commonly reported (≥ 10%) haematological adverse reactions associated with azacitidine treatment include anaemia, thrombocytopenia, neutropenia, febrile neutropenia and leukopenia, and were usually Grade 3 or 4.

There is a greater risk of these events occurring during the first 2 cycles, after which they occur with less frequency in patients with restoration of haematological function. […]

8). Complete blood counts should be performed as needed to monitor response and toxicity, but at least prior to each treatment cycle. 2). Patients should be advised to promptly report febrile episodes. Patients and physicians are also advised to be observant for signs and symptoms of bleeding.

Hepatic impairment No formal studies have been conducted in patients with hepatic impairment. Patients with extensive tumour burden due to metastatic disease have been reported to experience progressive hepatic coma and death during azacitidine treatment, especially in such patients with baseline serum albumin < 30 g/L.

3) Renal impairment Renal abnormalities ranging from elevated serum creatinine to renal failure and death were reported in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents. In addition, renal tubular acidosis, defined as a fall in serum bicarbonate to < 20 mmol/L in association with an alkaline urine and hypokalaemia (serum potassium < 3 mmol/L) developed in 5 subjects with chronic myelogenous leukaemia (CML) treated with azacitidine and etoposide.

2). Patients should be advised to report oliguria and anuria to the health care provider immediately. 2). Laboratory tests Liver function tests, serum creatinine and serum bicarbonate should be determined prior to initiation of therapy and prior to each treatment cycle.

8). Cardiac and pulmonary disease Patients with a history of severe congestive heart failure, clinically unstable cardiac disease or pulmonary disease were excluded from the pivotal registration studies (AZA PH GL 2003 CL 001 and AZA AML 001) and therefore the safety and efficacy of azacitidine in these patients has not been established.

8). It is therefore advised to exercise caution when prescribing azacitidine to these patients. Cardiopulmonary assessment before and during the treatment should be considered. Necrotising fasciitis Necrotising fasciitis, including fatal cases, have been reported in patients treated with azacitidine therapy should be discontinued in patients who develop necrotising fasciitis and appropriate treatment should be promptly initiated.

1. 4). 6).