Haematological toxicity: Treatment with azacitidine is associated with anaemia, neutropenia and thrombocytopenia, particularly during the first 2 cycles (see Adverse Reactions). Complete blood counts should be performed as needed to monitor response and toxicity, but at least prior to each treatment cycle. After administration of the recommended dose for the first cycle, the dose for subsequent cycles should be reduced or its administration delayed based on nadir counts and haematological response (see Dosage & Administration). 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: 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. Azacitidine is contraindicated in patients with advanced malignant hepatic tumours (see Contraindications).
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) with chronic myelogenous leukaemia (CML) treated with azacitidine and etoposide. If unexplained reductions in serum bicarbonate (< 20 mmol/L) or elevations of serum creatinine or BUN occur, the dose should be reduced or administration delayed (see Dosage & Administration).
Patients should be advised to report oliguria and anuria to the health care provider immediately.
Although no clinically relevant differences in the frequency of adverse reactions were noted, patients with renal impairment should be closely monitored for toxicity since azacitidine and/or its metabolites are primarily excreted by the kidney (see Dosage & Administration).
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 (see Adverse Reactions).
Cardiac and pulmonary disease: Patients with a known history of cardiovascular or pulmonary disease showed a significantly increased incidence of cardiac events with azacitidine (see Adverse Reactions). 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 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.
Effects on ability to drive and use machines: Azacitidine has minor or moderate influence on the ability to drive and use machines. Fatigue has been reported with the use of azacitidine. Therefore, caution is recommended when driving or operating machines.