Azacitidine Celgene

Azacitidine Celgene 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 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.

Laboratory tests Liver function tests, serum creatinine and serum bicarbonate should be determined prior to initiation of therapy and prior to each treatment cycle. 0 x 109/l and/or absolute neutrophil count (ANC) ≤ 1 x 109/l. e. 5 x [baseline count – nadir count]).

e. 0 x 109/l) prior to the first treatment If haematological toxicity is observed following Azacitidine Celgene 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 Celgene 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.

If the decrease in WBC or ANC or platelets is greater than 50% from that prior to treatment, with no improvement in cell line differentiation, the next cycle of Azacitidine Celgene 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, bone marrow cellularity should be determined. If the bone marrow cellularity is > 50%, no dose adjustments should be made.

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.

Azacitidine Celgene therapy should be discontinued in patients who develop necrotising fasciitis and appropriate treatment should be promptly initiated. Tumour lysis syndrome The patients at risk of tumour lysis syndrome are those with high tumour burden prior to treatment.

These patients should be monitored closely and appropriate precautions taken. 5 Interaction with other medicinal products and other forms of interaction Based on in vitro data, azacitidine metabolism does not appear to be mediated by cytochrome P450 isoenzymes (CYPs), UDP-glucuronosyltransferases (UGTs), sulfotransferases (SULTs), and glutathione transferases (GSTs); interactions related to these metabolizing enzymes in vivo are therefore considered unlikely.

2). No formal clinical drug interaction studies with azacitidine have been conducted. 6 Fertility, pregnancy and lactation Women of childbearing potential / Contraception in males and females Women of childbearing potential and men have to use effective contraception during and up to 3 months after treatment.

Pregnancy There are no adequate data from the use of azacitidine in pregnant women. 3). The potential risk for humans is unknown. Based on results from animal studies and its mechanism of action, azacitidine should not be used during pregnancy, especially during the first trimester, unless clearly necessary.

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). 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.

1. 4). 6).