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Atriance is a brand name for Nelarabine. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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…
Verbatim from this product's EMA label. Tap a section to expand.
Nelarabine must only be administered under the supervision of a physician experienced in the use of cytotoxic agents. 8). Adults and adolescents (aged 16 years and older) The recommended dose of nelarabine for adults and adolescents aged 16 years and older is 1,500 mg/m2 administered intravenously over two hours on days 1, 3 and 5 and repeated every 21 days.
Children and adolescents (aged 21 years and younger) The recommended dose of nelarabine for children and adolescents (aged 21 years and younger) is 650 mg/m2 administered intravenously over one hour daily for 5 consecutive days, repeated every 3 21 days.
In clinical studies, the 650 mg/m2 and 1,500 mg/m2 dose have both been used in patients in the age range 16 to 21 years. Efficacy and safety were similar for both regimens. The prescribing physician should consider which regimen is appropriate when treating patients in this age range.
2). Dose modification Nelarabine must be discontinued at the first sign of neurological events of National Cancer Institute Common Terminology Criteria Adverse Event (NCI CTCAE) grade 2 or greater. Delaying subsequent dosing is an option for other toxicities, including haematological toxicity.
2). Renal impairment Nelarabine has not been studied in individuals with renal impairment. 2). There are insufficient data to support a dose adjustment recommendation for patients with a renal clearance of creatinine Clcr less than 50 ml/min.
Patients with renal impairment must be closely monitored for toxicities when treated with nelarabine. Hepatic impairment Nelarabine has not been studied in patients with hepatic impairment. These patients should be treated with caution.
Method of administration Nelarabine is for intravenous use only and must not be diluted prior to administration. The appropriate dose of nelarabine must be transferred into polyvinylchloride (PVC) or ethyl vinyl acetate (EVA) infusion bags or glass containers and administered intravenously as a two-hour infusion in adult patients and as a one-hour infusion in paediatric patients.
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.
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) N=103 Children (650 mg/m2) N=84 Infections and infestations Infection (including but not limited to; sepsis, bacteraemia, pneumonia, fungal infection) Very common: 40 (39%) Very common: 13 (15%) Neoplasms benign, malignant and unspecified (including cysts and polyps) Tumour lysis syndrome (see also data from compassionate use programme and non- pivotal studies) Common: 1 (1%) N/A 6 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 (99%) Very common: 80 (95%) 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 Common: 9 (9%) N/A Psychiatric disorders Confusional state Common: 8 (8%) Common: 2 (2%) Nervous system disorders Seizures (including convulsions, grand mal convulsions, status epilepticus) Common: 1 (1%) Common: 5 (6%) Amnesia Common: 3 (3%) N/A Somnolence Very common: 24 (23%) Common: 6 (7%) Peripheral neurological disorders (sensory and motor) Very common: 22 (21%) Very common: 10 (12%) Hypoesthesia Very common: 18 (17%) Common: 5 (6%) Paraesthesia Very common: 15 (15%) Common: 3 (4%) Ataxia Common: 9 (9%) Common: 2 (2%) Balance disorder Common: 2 (2%) N/A Tremor Common: 5 (5%) Common: 3 (4%) Dizziness Very common: 22 (21%) N/A Headache Very common: 15 (15%) Very common: 14 (17%) Dysgeusia Common: 3 (3%) N/A Eye disorders Blurred vision Common: 4(4%) N/A Vascular disorders Hypotension Common: 8 (8%) N/A Respiratory, thoracic and mediastinal disorders Pleural effusion Common: 10 (10%) N/A Wheezing Common: 5 (5%) N/A Dyspnoea Very common: 21 (20%) N/A Cough Very common: 26 (25%) N/A 7 Gastrointestinal disorders Diarrhoea Very common: 23 (22%) Common: 2 (2%) Stomatitis Common: 8 (8%) Common: 1 (1%) Vomiting Very common: 23 (22%) Common: 8 (10%) Abdominal pain Common: 9 (9%) N/A Constipation Very common: 22 (21%) Common: 1 (1%) Nausea Very common: 42 (41%) Common: 2 (2%) Hepatobiliary disorders Hyperbilirubinaemia Common: 3 (3%) Common: 8 (10%) Transaminases increased N/A Very common: 10(12%) Aspartate aminotransferase increased Common: 6 (6%) N/A Musculoskeletal and connective tissue disorders Muscle weakness Common: 8 (8%) N/A Myalgia Very common: 13 (13%) N/A Arthralgia Common: 9 (9%) Common: 1 (1%) Back pain Common: 8 (8%) N/A Pain in extremity Common: 7 (7%) Common: 2 (2%) Rhabdomyolysis, blood creatine phosphokinase increased (see “Post – marketing data”) Rare: N/A Rare: N/A Renal and urinary disorders Blood creatinine increased Common: 2 (2%) Common: 5 (6%) General disorders and administration site conditions Oedema Very common: 11 (11%) N/A Gait abnormal Common: 6 (6%) N/A Oedema peripheral Very common: 15 (15%) N/A Pyrexia Very common: 24 (23%) Common: 2 (2%) Pain Very common: 11 (11%) N/A Fatigue Very common: 51 (50%) Common: 1 (1%) Asthenia Very common: 18 (17%) Common: 5 (6%) Description of selected adverse reactions Infection and infestations There was a single additional report of biopsy confirmed progressive multifocal leukoencephalopathy in the adult population.
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. 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. 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.
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.
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There have been reports of sometimes fatal opportunistic infections in patients receiving nelarabine therapy. Nervous system disorders There have been reports of events associated with demyelination and ascending peripheral neuropathies similar in appearance to Guillain-Barré syndrome.
Two paediatric patients had fatal neurological events. Data from NCI studies/compassionate use programme and phase I studies In addition to the adverse reactions seen in the pivotal clinical studies, there are also data from 875 patients from NCI studies/compassionate use programme (694 patients) and Phase I (181 patients) 8 studies of nelarabine.
4) Post–marketing data Rhabdomyolysis and increased blood creatine phosphokinase have been identified during post- approval use of nelarabine. This includes spontaneous case reports as well as serious adverse events from ongoing studies.
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 via the national reporting system listed in Appendix V.
Carcinogenicity and mutagenicity Carcinogenicity testing of nelarabine has not been performed. 3). 4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.