Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

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 ATR API AUG21 V1                                                                                EU SmPC 11.20 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 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 mammalian cells (see section 5.3).

Sodium warning

This medicinal product contains 88.51 mg (3.85 mmol) sodium per vial (50 ml), equivalent to 4.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving

4.7    Effects on ability to drive and use machines

Atriance has major influence on the ability to drive and use machines.
Patients treated with nelarabine are potentially at risk of suffering from somnolence during and for several days after treatment. Patients must be cautioned that somnolence can affect performance of skilled tasks, such as driving.