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Dacogen is a brand name for Decitabine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Dacogen is indicated for the treatment of adult patients with newly diagnosed de novo or secondary acute myeloid leukaemia (AML), according to the World Health Organisation (WHO) classification, who are not candidates for standard induction chemotherapy.
Verbatim from this product's EMA label. Tap a section to expand.
Dacogen administration must be initiated under the supervision of physicians experienced in the use of chemotherapeutic medicinal products. , a total of 5 doses per treatment cycle). The total daily dose must not exceed 20 mg/m2 and the total dose per treatment cycle must not exceed 100 mg/m2.
If a dose is missed, treatment should be resumed as soon as possible. The cycle should be repeated every 4 weeks depending on the patient's clinical response and observed toxicity. It is recommended that patients be treated for a minimum of 4 cycles; however, a complete or partial remission may take longer than 4 cycles to be obtained.
, in the absence of overt progression. , platelet counts or absolute neutrophil count), have not returned to pre-treatment levels or if disease progression occurs (peripheral blast counts are increasing or bone marrow blast counts are worsening), the patient may be considered to be a non-responder and alternative therapeutic options to Dacogen should be considered.
Pre-medication for the prevention of nausea and vomiting is not routinely recommended but may be administered if required. 3 Management of myelosuppression and associated complications Myelosuppression and adverse events related to myelosuppression (thrombocytopaenia, anaemia, neutropaenia, and febrile neutropaenia) are common in both treated and untreated patients with AML.
Complications of myelosuppression include infections and bleeding. , requiring intravenous anti-infectives or extensive supportive care) Haemorrhage (gastrointestinal, genito-urinary, pulmonary with platelets < 25,000/μL or any central nervous system haemorrhage) Treatment with Dacogen may be resumed once these conditions have improved or have been stabilised with adequate treatment (anti-infective therapy, transfusions, or growth factors).
In clinical studies, approximately one-third of patients receiving Dacogen required a dose-delay. Dose reduction is not recommended. Paediatric population Dacogen should not be used in children with AML aged < 18 years, because efficacy was not established.
2. Hepatic impairment Studies in patients with hepatic impairment have not been conducted. The need for dose adjustment in patients with hepatic impairment has not been evaluated. 2). Renal impairment Studies in patients with renal impairment have not been conducted.
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.
6 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 1. 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.
Table 1:
Adverse drug reactions identified with Dacogen System Organ Class Frequency (all Grades) Adverse Drug Reaction Frequency All Gradesa (%) Grades 3-4a (%) Infections and infestations Very common pneumonia* 24 20 urinary tract infection* 15 7 All other infections (viral, bacterial, fungal)*, b, c, d 63 39 Common septic shock* 6 4 sepsis* 9 8 sinusitis 3 1 Neoplasms benign, malignant and unspecified (incl.
Myelosuppression Myelosuppression and complications of myelosuppression, including infections and bleeding that occur in patients with AML may be exacerbated with Dacogen treatment. 8). Patients should be monitored for signs and symptoms of infection and treated promptly.
In clinical studies, the majority of patients had baseline Grade 3/4 myelosuppression. In patients with baseline Grade 2 abnormalities, worsening of myelosuppression was seen in most patients and more frequently than in patients with baseline Grade 1 or 0 abnormalities.
Myelosuppression caused by Dacogen is reversible. Complete blood and platelet counts should be performed regularly, as clinically 4 indicated and prior to each treatment cycle. 8). Respiratory, thoracic and mediastinal disorders Cases of interstitial lung disease (ILD) (including pulmonary infiltrates, organising pneumonia and pulmonary fibrosis) without signs of infectious aetiology have been reported in patients receiving decitabine.
Careful assessment of patients with an acute onset or unexplained worsening of pulmonary symptoms should be performed to exclude ILD. 8). Hepatic impairment Use in patients with hepatic impairment has not been established. Caution should be exercised in the administration of Dacogen to patients with hepatic impairment and in patients who develop signs or symptoms of hepatic impairment.
2). Renal impairment Use in patients with severe renal impairment has not been studied. Caution should be exercised in the administration of Dacogen to patients with severe renal impairment (Creatinine Clearance [CrCl] < 30 ml/min). 2).
Cardiac disease Patients with a history of severe congestive heart failure or clinically unstable cardiac disease were excluded from clinical studies and therefore, the safety and efficacy of Dacogen in these patients has not been established.
Cases of cardiomyopathy with cardiac decompensation, in some cases reversible after treatment discontinuation, dose reduction or corrective treatment, have been reported in the postmarketing setting. Patients, especially those with cardiac disease history, should be monitored for signs and symptoms of heart failure.
1. 6)
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2). Method of administration Dacogen is administered by intravenous infusion. A central venous catheter is not required. 6.
cysts and polyps) Not known differentiation syndrome Not known Not known Blood and lymphatic disorders Very common febrile neutropaenia* 34 32 neutropaenia* 32 30 thrombocytopaenia*, e 41 38 anaemia 38 31 leukopaenia 20 18 Uncommon pancytopaenia* < 1 < 1 Immune system disorders Common hypersensitivity including anaphylactic reactionf 1 < 1 Metabolism and nutrition disorders Very common hyperglycaemia 13 3 Nervous system disorders Very common headache 16 1 Cardiac disorders Uncommon cardiomyopathy < 1 < 1 Respiratory, thoracic and mediastinal disorders Very common epistaxis 14 2 Not known interstitial lung disease Not known Not known Gastrointestinal disorders Very common diarrhoea 31 2 vomiting 18 1 nausea 33 < 1 Common stomatitis 7 1 7 Not known enterocolitis, including neutropaenic colitis, caecitis* Not known Not known Hepatobiliary disorders Very common hepatic function abnormal 11 3 Common hyperbilirubinaemiag 5 <1 Skin and subcutaneous tissue disorders Uncommon acute febrile neutrophilic dermatosis (Sweet’s syndrome) < 1 NA General disorders and administration site conditions Very common pyrexia 48 9 a Worst National Cancer Institute Common Terminology Criteria for Adverse Events Grade.
b Excluding pneumonia, urinary tract infection, sepsis, septic shock and sinusitis. c The most frequently reported "other infections" in study DACO-016 were: oral herpes, oral candidiasis, pharyngitis, upper respiratory tract infection, cellulitis, bronchitis, nasopharyngitis.
d Including enterocolitis infectious. e Including haemorrhage associated with thrombocytopaenia, including fatal cases. f Including preferred terms hypersensitivity, drug hypersensitivity, anaphylactic reaction, anaphylactic shock, anaphylactoid reaction, anaphylactoid shock.
g In clinical studies in AML and myelodysplastic syndrome (MDS), the reporting frequency for hyperbilirubinaemia was 11% for All Grades and 2% for Grade 3-4. * Includes events with a fatal outcome. NA = Not applicable 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. , G-CSF) for neutropaenia and transfusions for anaemia or thrombocytopaenia according to institutional guidelines.
2. 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.
8 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. […]
Differentiation syndrome Cases of differentiation syndrome (also known as retinoic acid syndrome) have been reported in patients receiving decitabine. 8). Treatment with high-dose IV corticosteroids and haemodynamic monitoring should be considered at first onset of symptoms or signs suggestive of differentiation syndrome.
Temporary discontinuation of Dacogen should be considered until resolution of symptoms and if resumed, caution is advised. 5 mmol potassium per vial. e. essentially ‘potassium- free’. 67 mg) sodium per vial. 7-7% of the WHO recommended maximum daily intake of 2 g sodium for an adult.