Dacogen

HOS-216160 · has-adverse-reaction-information · PDF-Seite 5

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. 5 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 Frequency Frequency All Gradesa Grades 3-4a System Organ Class (all Grades) Adverse Drug Reaction (%) (%) Infections and Very common pneumonia* 24 20 infestations urinary tract infection* 15 7 All other infections (viral, 63 39 bacterial, fungal)*, b, c, d Common septic shock* 6 4 sepsis* 9 8 sinusitis 3 1 Neoplasms benign, Not known differentiation syndrome Not known Not known malignant and unspecified (incl. cysts and

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HOS-216156 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to decitabine or to any of the excipients, listed in section 6.1. Breast-feeding (see section 4.6)

HOS-216155 · has-indication-information · PDF-Seite 2

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.

HOS-216158 · has-interaction-information · PDF-Seite 4

No formal clinical drug interaction studies with decitabine have been conducted. There is the potential for a drug-drug interaction with other agents which are also activated by sequential phosphorylation (via intracellular phosphokinase activities) and/or metabolised by enzymes implicated in the inactivation of decitabine (e.g., cytidine deaminase). Therefore, caution should be exercised if these active substances are combined with decitabine. 4 Impact of co-administered medicinal products on decitabine Cytochrome (CYP) 450-mediated metabolic interactions are not anticipated as decitabine metabolism is not mediated by this system but by oxidative deamination. Impact of decitabine on co-administered medicinal products Given its low in vitro plasma protein binding ( 1%), decitabine is unlikely to displace co-administered medicinal products from their plasma protein binding. Decitabine has been shown to be a weak inhibitor of P-gp mediated transport in vitro and is therefore, also not expected to affect P-gp mediated transport of co-administered medicinal products (see section 5.2).

HOS-216159 · has-pregnancy-information · PDF-Seite 5

Women of childbearing potential/Contraception in men and women Due to the genotoxic potential of decitabine (see section 5.3), women of childbearing potential must use effective contraceptive measures and avoid becoming pregnant while being treated with Dacogen and for 6 months following completion of treatment. Men should use effective contraceptive measures and be advised to not father a child while receiving Dacogen, and for 3 months following completion of treatment (see section 5.3). The use of decitabine with hormonal contraceptives has not been studied. Pregnancy There are no adequate data on the use of Dacogen in pregnant women. Studies have shown that decitabine is teratogenic in rats and mice (see section 5.3). The potential risk for humans is unknown. Based on results from animal studies and its mechanism of action, Dacogen should not be used during pregnancy and in women of childbearing potential not using effective contraception. A pregnancy test should be performed on all women of childbearing potential before treatment is started. If Dacogen is used during pregnancy, or if a patient becomes pregnant while receiving this medicinal product, the patient should be apprised of the potential hazard to the foetus. Breast-feeding It is not known whether decitabine or its metabolites are excreted in breast milk. Dacogen is contraindicated during breast-feeding; therefore, if treatment with this medicine is required, breast-feeding must be discontinued (see section 4.3). Fertility No human data on the effect of decitabine on fertility are available. In non-clinical animal studies, decitabine alters male fertility and is mutagenic. Because of the possibility of infertility as a consequence of Dacogen therapy, men should seek advice on conservation of sperm and female patients of childbearing potential should seek consultation regarding oocyte cryopreservation prior to initiation of treatment.

HOS-216157 · has-warning-information · PDF-Seite 3

Myelosuppression Myelosuppression and complications of myelosuppression, including infections and bleeding that occur in patients with AML may be exacerbated with Dacogen treatment. Therefore, patients are at increased risk for severe infections (due to any pathogen such as bacterial, fungal and viral), with potentially fatal outcome (see section 4.8). 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 3 indicated and prior to each treatment cycle. In the presence of myelosuppression or its complications, treatment with Dacogen may be interrupted and/or supportive measures instituted (see sections 4.2 and 4.8). 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. If ILD is confirmed, appropriate treatment should be initiated (see section 4.8). 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. Liver function tests should be performed prior to initiation of therapy and prior to each treatment cycle, and as clinically indicated (see sections 4.2 and 5.2). 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). Renal function tests should be performed prior to initiation of therapy and prior to each treatment cycle, and as clinically indicated (see section 4.2). Cardiac disease Patients with a history of severe congestive heart failure or clinically unstable cardiac diseas

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