Dacogen Adverse Reactions

Summary of the safety profile: The most common adverse drug reactions (≥ 35%) reported are pyrexia, anaemia and thrombocytopaenia.
The most common Grade 3/4 adverse drug reactions (≥ 20%) included pneumonia, thrombocytopaenia, neutropaenia, febrile neutropaenia and anaemia.
In clinical studies, 30% of patients treated with Dacogen and 25% of patients treated in the comparator arm had adverse events with an outcome of death during treatment or within 30 days after the last dose of study drug.
In the Dacogen treatment group, there was a higher incidence of treatment discontinuation due to adverse events in women compared to men (43% versus 32%).
Tabulated list of adverse drug reactions: Adverse drug reactions reported in 293 AML patients treated with Dacogen are summarised in Table 3. The following table reflects data from AML clinical studies and from post-marketing experience. The adverse drug reactions are listed by frequency category. Frequency categories are defined as follows: 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 (frequency cannot be estimated from the available data).
Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. (See Table 3.)

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Description of selected adverse drug reactions: Haematologic adverse drug reactions: The most commonly reported haematologic adverse drug reactions associated with Dacogen treatment included febrile neutropaenia, thrombocytopaenia, neutropaenia, anaemia and leukopaenia.
Serious bleeding-related adverse drug reactions, some of which lead to a fatal outcome, such as central nervous system (CNS) haemorrhage (2%) and gastrointestinal (GI) haemorrhage (2%), in the context of severe thrombocytopaenia, were reported in patients receiving decitabine.
Haematological adverse drug reactions should be managed by routine monitoring of complete blood counts and early administration of supportive treatments as required. Supportive treatments include, administration of prophylactic antibiotics and/or growth factor support (e.g., G-CSF) for neutropaenia and transfusions for anaemia or thrombocytopaenia according to institutional guidelines. For situations where decitabine administration should be delayed, see Dosage & Administration.
Infections and infestations adverse drug reactions: Serious infection-related adverse drug reactions, with potentially fatal outcome, such as septic shock, sepsis, pneumonia, and other infections (viral, bacterial and fungal) were reported in patients receiving decitabine.
Gastrointestinal disorders: Occurrences of enterocolitis, including neutropaenic colitis, caecitis have been reported during treatment with decitabine. Enterocolitis may lead to septic complications and may be associated with fatal outcome.
Respiratory, thoracic and mediastinal disorders: Cases of interstitial lung disease (including pulmonary infiltrates, organising pneumonia and pulmonary fibrosis) without signs of infectious aetiology have been reported in patients receiving decitabine.
Differentiation syndrome: Cases of differentiation syndrome (also known as retinoic acid syndrome) have been reported in patients receiving decitabine. Differentiation syndrome may be fatal and symptoms and clinical findings include respiratory distress, pulmonary infiltrates, fever, rash, pulmonary oedema, peripheral oedema, rapid weight gain, pleural effusions, pericardial effusions, hypotension and renal dysfunction. Differentiation syndrome may occur with or without concomitant leucocytosis. Capillary leak syndrome and coagulopathy can also occur (see Precautions).
Paediatric population: The safety assessment in paediatric patients is based on the limited safety data from a Phase I/II study to evaluate pharmacokinetics, safety and efficacy of Dacogen in paediatric patients (aged 1 to 14 years) with relapsed or refractory AML (n = 17) (see Pharmacology: Pharmacodynamics under Actions). No new safety signal was observed in this paediatric study.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.