ATRIANCE Solution for infusion Ref.[9065] Active ingredients: Nelarabine

Nelarabine must only be administered under the supervision of a physician experienced in the use of cytotoxic agents.

Posology

Complete blood counts including platelets must be monitored regularly (see sections 4.4 and 4.8).

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 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.

Limited clinical pharmacology data are available for patients below the age of 4 years (see section 5.2).

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.

Special populations

Elderly

Insufficient numbers of patients aged 65 years of age and older have been treated with nelarabine to determine whether they respond differently than younger patients (see sections 4.4 and 5.2).

Renal impairment

Nelarabine has not been studied in individuals with renal impairment. Nelarabine and 9-β-D-arabinofuranosylguanine (ara-G) are partially renally excreted (see section 5.2). There are insufficient data to support a dose adjustment recommendation for patients with a renal clearance of creatinine Cl_cr 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.

No case of overdose has been reported.

Nelarabine has been administered in clinical studies up to a dose of 75 mg/kg (approximately 2,250 mg/m²) daily for 5 days to a paediatric patient, up to a dose of 60 mg/kg (approximately 2,400 mg/m²) daily for 5 days to 5 adult patients and up to 2,900 mg/m² in a further 2 adults on days 1, 3 and 5.

Symptoms and signs

It is likely that nelarabine overdose would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression and potentially death. At a dose of 2200 mg/m² given on days 1, 3 and 5 every 21 days, 2 patients developed a significant grade 3 ascending sensory neuropathy. MRI evaluations of the 2 patients demonstrated findings consistent with a demyelinating process in the cervical spine.

Treatment

There is no known antidote for nelarabine overdose. Supportive care consistent with good clinical practice should be provided.

Shelf life: 3 years.

Atriance is stable for up to 8 hours at up to 30°C once the vial is opened.

For storage conditions after first opening of the medicinal product, see section 6.3.

Clear glass (Type I) vial with a bromobutyl rubber stopper, and an aluminium seal with a red snap-off cap.

Each vial contains 50 ml of solution. Atriance is supplied in packs of 1 vial or 6 vials.

The normal procedures for proper handling and disposal of cytotoxic anti-tumour medicinal products should be adopted, namely:

• Staff should be trained in how to handle and transfer the medicinal product.
• Pregnant staff should be excluded from working with this medicinal product.
• Personnel handling this medicinal product during handling/transfer should wear protective clothing including mask, goggles and gloves.
• All items for administration or cleaning, including gloves, should be placed in high-risk, waste disposal bags for high-temperature incineration. Any liquid waste from the preparation of the nelarabine solution for infusion may be flushed with large amounts of water.
• Accidental contact with the skin or eyes should be treated immediately with copious amounts of water.
• Any unused medicinal product or waste material should be disposed of in accordance with local requirements.