e been conducted in patients with hepatic impairment (see section 4.4). Patients with severe hepatic organ impairment should be carefully monitored for adverse events. No specific modification to the starting dose is recommended for patients with hepatic impairment prior to starting treatment; subsequent dose modifications should be based on haematology laboratory values. Vidaza is contraindicated in patients with advanced malignant hepatic tumours (see sections 4.3 and 4.4).
Elderly: No specific dose adjustments are recommended for the elderly. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.
Children and adolescents: Vidaza is not recommended for use in children below 18 years due to insufficient data on safety and efficacy.
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.
Method of administration
Reconstituted Vidaza should be injected subcutaneously into the upper arm, thigh or abdomen. Injection sites should be rotated. New injections should be given at least 2.5 cm from the previous site and never into areas where the site is tender, bruised, red, or hardened.
After reconstitution, the suspension should not be filtered.
Detailed instructions for the reconstitution and administration procedure for Vidaza are provided in section 6.6.
4.3 Contraindications
Known hypersensitivity to the active substance or to any of the excipients.
Advanced malignant hepatic tumours (see section 4.4).
Breastfeeding (see section 4.6).
4.4 Special warnings and precautions for use
Haematological toxicity
Treatment with azacitidine is associated with anaemia, neutropenia and thrombocytopenia, particularly during the first 2 cycles (see section 4.8). 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 section 4.2). 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. Azacitidine is contraindicated in patients with advanced malignant hepatic tumours (see section 4.3).
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 azacitidi |
