Leitlinien & Arzneimittelsicherheit

HOS-154176 · has-adverse-reaction-information · PDF-Seite 5

Summary of the safety profile The safety profile from pivotal clinical studies at the recommended doses of nelarabine in adults (1,500 mg/m2) and children (650 mg/m2) is based on data from 103 adults and 84 paediatric patients respectively. The most frequently occurring adverse events were fatigue; gastrointestinal disorders; haematological disorders; respiratory disorders; nervous system disorders (somnolence, peripheral neurological disorders [sensory and motor], dizziness, hypoaesthesia, paraesthesia, headache); and pyrexia. Neurotoxicity is the dose-limiting toxicity associated with nelarabine therapy (see section 4.4). Tabulated list of adverse reactions The following convention has been utilised for the classification of frequency: 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), and not known (cannot be estimated from the available data). Adverse reactions Adults (1,500 mg/m2) Children (650 mg/m2) N=103 N=84 Infections and infestations Infection (including but not limited to; sepsis, Very common: 40 (39%) Very common: 13 (15%) bacteraemia, pneumonia, fungal infection) Neoplasms benign, malignant and unspecified (including cysts and polyps) Tumour lysis syndrome (see also data from Common: 1 (1%) N/A compassionate use programme and non- pivotal studies) 5 Blood and lymphatic system disorders Febrile neutropenia Very common: 12 (12%) Common: 1 (1%) Neutropenia Very common: 83 (81%) Very common: 79 (94%) Leukopenia Common: 3 (3%) Very common: 32 (38%) Thrombocytopenia Very common: 89 (86%) Very common: 74 (88%) Anaemia Very common: 102 Very common: 80 (95%) (99%) Metabolism and nutrition disorders Hypoglycaemia N/A Common: 5 (6%) Hypocalcaemia Common: 3 (3%) Common: 7 (8%) Hypomagnesaemia Common: 4 (4%) Common: 5 (6%) Hypokalaemia Common: 4 (4%) Very common: 9 (11%) Anorexia

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HOS-154172 · has-contraindication-information · PDF-Seite 3

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-154171 · has-indication-information · PDF-Seite 2

Nelarabine is indicated for the treatment of patients with T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. Due to the small patient populations in these disease settings, the information to support these indications is based on limited data.

HOS-154174 · has-interaction-information · PDF-Seite 4

Nelarabine and ara-G did not significantly inhibit the activities of the major hepatic cytochrome P450 (CYP) isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 in vitro. Concomitant administration of nelarabine in combination with adenosine deaminase inhibitors such as pentostatin is not recommended. Concomitant administration may reduce the efficacy of nelarabine and/or change the adverse event profile of either active substance.

HOS-154175 · has-pregnancy-information · PDF-Seite 4

Contraception in males and females Both sexually active men and women should use effective methods of contraception during treatment with nelarabine. Men with partners who are pregnant or could become pregnant should use condoms during treatment with nelarabine and for at least three months following cessation of treatment. Pregnancy There are no or limited amount of data from the use of nelarabine in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk in humans is unknown, however, exposure during pregnancy will likely lead to anomalies and malformations of the foetus. 4 Nelarabine should not be used during pregnancy unless clearly necessary. If a patient becomes pregnant during treatment with nelarabine, they should be informed of the possible risk to the foetus. Breast-feeding It is unknown whether nelarabine or its metabolites are excreted in human breast milk. A risk to the newborn/infant cannot be excluded. Breast-feeding should be discontinued during treatment with Atriance. Fertility The effect of nelarabine on fertility in humans is unknown. Based on the pharmacological action of the compound, undesirable effects on fertility are possible. Family planning should be discussed with patients as appropriate.

HOS-154173 · has-warning-information · PDF-Seite 3

NEUROLOGICAL ADVERSE REACTIONS Severe neurological reactions have been reported with the use of nelarabine. These reactions have included altered mental states including severe somnolence, confusion and coma, central nervous system effects including convulsions, ataxia and status epilepticus, and peripheral neuropathy including hypoesthesia ranging from numbness and paresthesias to motor weakness and paralysis. There have also been reports of reactions associated with demyelination, and ascending peripheral neuropathies similar in appearance to Guillain-Barré Syndrome. (see section 4.8). Neurotoxicity is the dose-limiting toxicity of nelarabine. Full recovery from these reactions has not always occurred with cessation of nelarabine. Therefore, close monitoring for neurological reactions is strongly recommended, and nelarabine must be discontinued at the first sign of neurological reactions of NCI CTCAE Grade 2 or greater. Patients treated previously or concurrently with intrathecal chemotherapy or previously with craniospinal irradiation are potentially at increased risk for neurological adverse events (see 3 section 4.2 - dose modification) and therefore concomitant intrathecal therapy and/or craniospinal irradiation is not recommended. Immunisation using a live organism vaccine has the potential to cause infection in immunocompromised hosts. Therefore, immunisations with live organism vaccines are not recommended. Leukopenia, thrombocytopenia, anaemia, and neutropenia, (including febrile neutropenia) have been associated with nelarabine therapy. Complete blood counts including platelets must be monitored regularly (see sections 4.2 and 4.8). Patients receiving nelarabine are recommended to receive intravenous hydration according to standard medical practice for the management of hyperuricaemia in patients at risk of tumour lysis syndrome. For patients at risk of hyperuricaemia, the use of allopurinol should be considered. Elderly Clinical studies of nelarabine did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In an exploratory analysis, increasing age, especially age 65 years and older, appeared to be associated with increased rates of neurological adverse events. Carcinogenicity and mutagenicity Carcinogenicity testing of nelarabine has not been performed. Nelarabine however, is known to be genotoxic to mammali

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