tropenia 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. Most haematological adverse reactions were managed by routine monitoring of complete blood counts and delaying azacitidine administration in the next cycle, prophylactic antibiotics and/or growth factor support (e.g. G-CSF) for neutropenia and transfusions for anaemia or thromobocytopenia as required.
Infections
Myelosupression may lead to neutropenia and an increased risk of infection. Serious infections such as neutropenic sepsis (0.8 %) and pneumonia (2.5 %) were reported in patients receiving azacitidine, some with a fatal outcome. Infections may be managed with the use of anti-infectives plus growth factor support (e.g. G-CSF) for neutropenia.
Bleeding
Bleeding may occur with patients receiving azacitidine. Serious adverse reactions such as gastrointestinal haemorrhage (0.8 %) and intracranial haemorrhage (0.5 %) have been reported. Patients should be monitored for signs and symptoms of bleeding, particularly those with pre-existing or treatment-related thrombocytopenia.
Hypersensitivity
Serious hypersensitivity reactions (0.25 %) have been reported in patients receiving azacitidine. In case of an anaphylactic-like reaction, treatment with azacitidine should be immediately discontinued and appropriate symptomatic treatment initiated.
Skin and subcutaneous tissue adverse reactions
The majority of skin and subcutaneous adverse reactions were associated with the injection site. None of these adverse reactions led to temporary or permanent discontinuation of azacitidine, or reduction of azacitidine dose in the pivotal study. The majority of adverse reactions occurred during the first 2 cycles and tended to decrease with subsequent cycles. Subcutaneous adverse reactions such as injection site rash/inflammation/pruritus, rash, erythema and skin lesion may require management with concomitant medicinal products, such as antihistamines, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs).
Gastrointestinal adverse reactions
The most commonly reported gastrointestinal adverse reactions associated with azacitidine treatment included constipation, diarrhoea, nausea and vomiting. These adverse reactions were managed symptomatically with anti-emetics for nausea and vomiting; antidiarrhoeals for diarrhoea, and laxatives and/or stool softeners for constipation.
Renal adverse reactions
Renal abnormalities, ranging from elevated serum creatinine and haematuria to renal tubular acidosis, renal failure and death were reported in patients treated with azacitidine (see section 4.4).
Hepatic adverse reactions
Patients with extensive tumour burden due to metastatic disease have been reported to experience hepatic failure, progressive hepatic coma and death during azacitidine treatment (see section 4.4).
4.9 Overdose
One case of overdose with azacitidine was reported during clinical trials. A patient experienced diarrhoea, nausea, and vomiting after receiving a single intravenous dose of approximately 290 mg/m2, almost 4 times the recommended starting dose.
In the event of overdose, the patient should be monitored with appropriate blood counts and should receive supportive treatment, as necessary. There is no kno |
