Atriance

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



2 

This medicinal product is subject to additional monitoring. This will allow quick identification of 

new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 

See section 4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT 
 

Atriance 5 mg/ml solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each ml of solution contains 5 mg of nelarabine. 

 

Each vial contains 250 mg of nelarabine. 

 

Excipient with known effect 

 

Each ml of solution contains 1.725 mg (75 micromols) of sodium. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 
 

Solution for infusion. 

 

Clear, colourless solution. 

 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

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. 

 

4.2 Posology and method of administration 

 

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. 

 

  



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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 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. 

 

4.3 Contraindications 
 

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

 

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 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. 



4 

 

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 1.725 mg/ml (75 micromols/ml) of sodium. To be taken into 

consideration by patients on a controlled sodium diet. 

 

4.5 Interaction with other medicinal products and other forms of interaction 
 

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. 

 

4.6 Fertility, pregnancy and lactation 
 

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. 

 

  



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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. 

 

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. 

 

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. 

 

4.8 Undesirable effects 

 

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) 

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%) 



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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 

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 



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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. 

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. 

 

  



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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) 

studies of nelarabine. The following additional adverse reactions were seen: 

 

Neoplasms benign and malignant (including cysts and polyps) 

Tumour lysis syndrome – 7 cases (see sections 4.2 and 4.4) 

 

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. 

 

4.9 Overdose 
 

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. 

 

 

  



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5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Antineoplastic agents, antimetabolites, purine analogues, ATC code: 

L01B B 07 

 

Nelarabine is a pro-drug of the deoxyguanosine analogue ara-G. Nelarabine is rapidly demethylated by 

adenosine deaminase (ADA) to ara-G and then phosphorylated intracellularly by deoxyguanosine 

kinase and deoxycytidine kinase to its 5’-monophosphate metabolite. The monophosphate metabolite 

is subsequently converted to the active 5’-triphosphate form, ara-GTP. Accumulation of ara-GTP in 

leukaemic blasts allows for preferential incorporation of ara-GTP into deoxyribonucleic acid (DNA) 

leading to inhibition of DNA synthesis. This results in cell death. Other mechanisms may contribute to 

the cytotoxic effects of nelarabine. In vitro, T-cells are more sensitive than B-cells to the cytotoxic 

effects of nelarabine. 

 

Clinical efficacy and data 

 

Adult clinical study in relapsed or refractory T-ALL and T-LBL 

In an open-label study carried out by the Cancer and Leukaemia Group B and the Southwest Oncology 

Group, the safety and efficacy of nelarabine were evaluated in 39 adults with T-cell acute 

lymphoblastic leukaemia (T-ALL) or lymphoblastic lymphoma (T-LBL). Twenty–eight of the 

39 adults had relapsed or were refractory to at least two prior induction regimens and aged between 16 

to 65 years of age (mean 34 years). Nelarabine at a dose of 1500 mg/m2/day was administered 

intravenously over two hours on days 1, 3 and 5 of a 21 day cycle. Five of the 28 patients (18 %) 

[95 % CI: 6 %—37 %] treated with nelarabine achieved a complete response (bone marrow blast 

counts ≤ 5 %, no other evidence of disease, and full recovery of peripheral blood counts). A total of 

6 patients (21 %) [95 % CI: 8 %–41 %] achieved a complete response with or without haematological 

recovery. Time to complete response in both classifications of response ranged from 2.9 to 

11.7 weeks. Duration of response (in both classifications of response (n=5) ranged between 15 and 

195+ weeks. Median overall survival was 20.6 weeks [95 % CI: 10.4–36.4]. Survival at one year was 

29 % [95 % CI: 12 %–45 %]. 

 

Paediatric clinical study in relapsed or refractory T-ALL and T-LBL 

In an open-label, multicenter study carried out by Childrens Oncology Group, nelarabine was 

administered intravenously over 1 hour for 5 days to 151 patients ≤ 21 years of age, 149 of whom had 

relapsed or refractory T-cell acute lymphoblastic leukaemia (T-ALL) or T-cell lymphoblastic 

lymphoma (T-LBL). Eighty-four (84) patients, 39 of whom had received two or more prior induction 

regimens and 31 whom had received one prior induction regimen, were treated with 650 mg/m2/day of 

nelarabine administered intravenously over 1 hour daily for 5 consecutive days repeated every 

21 days. 

 

Of the 39 patients who had received two or more prior induction regimens, 5 (13 %) [95 % CI: 4 %–

27 %] achieved a complete response (bone marrow blast counts ≤ 5 %, no other evidence of disease, 

and full recovery of peripheral blood counts) and 9 (23 %) [95 % CI: 11 %–39 %] achieved complete 

responses with or without full haematological recovery. Duration of response in both classifications of 

response ranged between 4.7 and 36.4 weeks and median overall survival was 13.1 weeks [95 % CI: 

8.7–17.4] and survival at one year was 14 % [95 % CI: 3 %–26 %]. 

 

Thirteen (42 %) of the 31 patients treated with one prior induction regimen achieved a complete 

response overall. Nine of these 31 patients failed to respond to prior induction (refractory patients). 

Four (44 %) of the nine refractory patients experienced a complete response to nelarabine. 

 

This medicinal product has been authorised under “exceptional circumstances”. This means that due to 

the rarity of the disease it has not been possible to obtain complete information on this medicinal 

product. 

 



10 

The European Medicines Agency will review any new information which may become available every 

year and this SmPC will be updated as necessary. 

 

5.2 Pharmacokinetic properties 

 

Nelarabine is a pro-drug of the deoxyguanosine analogue ara-G. Nelarabine is rapidly demethylated by 

adenosine deaminase (ADA) to ara-G and then phosphorylated intracellularly by deoxyguanosine 

kinase and deoxycytidine kinase to its 5’-monophosphate metabolite. The monophosphate metabolite 

is subsequently converted to the active 5’-triphosphate from, ara-GTP. Accumulation of ara-GTP in 

leukaemic blasts allows for preferential incorporation of ara-GTP into deoxyribonucleic acid (DNA) 

leading to inhibition of DNA synthesis. This results in cell death. Other mechanisms may contribute to 

the cytotoxic effects of nelarabine. In vitro, T-cells are more sensitive than B-cells to the cytotoxic 

effects of nelarabine. 

 

In a cross-study analysis using data from four Phase I studies, the pharmacokinetics of nelarabine and 

ara-G were characterized in patients aged less than 18 years and adult patients with refractory 

leukaemia or lymphoma. 

 

Absorption 

 

Adults 

Plasma ara-G Cmax values generally occurred at the end of the nelarabine infusion and were generally 

higher than nelarabine Cmax values, suggesting rapid and extensive conversion of nelarabine to ara-G. 

After infusion of 1,500 mg/m2 nelarabine over two hours in adult patients, mean (%CV) plasma 

nelarabine Cmax and AUCinf values were 13.9 µM (81 %) and 13.5 µM.h (56 %) respectively. Mean 

plasma ara-G Cmax and AUCinf values were 115 µM (16 %) and 571 µM.h (30 %), respectively. 

 

Intracellular Cmax for ara-GTP appeared within 3 to 25 hours on day 1. Mean (%CV) intracellular ara-

GTP Cmax and AUC values were 95.6 µM (139 %) and 2214 µM.h (263 %) at this dose. 

 

Paediatric patients 

After infusion of 400 or 650 mg/m2 nelarabine over one hour in 6 paediatric patients, mean (%CV) 

plasma nelarabine Cmax and AUCinf values, adjusted to a 650 mg/m2 dose, were 45.0 µM (40 %) and 

38.0 µM.h (39 %), respectively. Mean plasma ara-G Cmax and AUCinf values were 60.1 µM (17 %) and 

212 µM.h (18 %), respectively. 

 

Distribution 

 

Nelarabine and ara-G are extensively distributed throughout the body based on combined Phase I 

pharmacokinetic data at nelarabine doses of 104 to 2,900 mg/m2. Specifically, for nelarabine, mean 

(%CV) VSS values were 115 l/m2 (159 %) and 89.4 l/m2 (278 %) in adult and paediatric patients, 

respectively. For ara-G, mean VSS/F values were 44.8 l/m2 (32 %) and 32.1 l/m2 (25 %) in adult and 

paediatric patients, respectively. 

 

Nelarabine and ara-G are not substantially bound to human plasma proteins (less than 25 %) in vitro, 

and binding is independent of nelarabine or ara-G concentrations up to 600 µM. 

 

No accumulation of nelarabine or ara-G was observed in plasma after nelarabine administration on 

either a daily or a day 1, 3, 5 schedule. 

 

Intracellular ara-GTP concentrations in leukaemic blasts were quantifiable for a prolonged period after 

nelarabine administration. Intracellular ara-GTP accumulated with repeated administration of 

nelarabine. On the day 1, 3, and 5 schedule, Cmax and AUC(0-t) values on day 3 were approximately 

50 % and 30 %, respectively, greater than Cmax and AUC(0-t) values on day 1. 

 



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Biotransformation 

 

The principal route of metabolism for nelarabine is O-demethylation by adenosine deaminase to form 

ara-G, which undergoes hydrolysis to form guanine. In addition, some nelarabine is hydrolysed to 

form methylguanine, which is O-demethylated to form guanine. Guanine is N-deaminated to form 

xanthine, which is further oxidized to yield uric acid. 

 

Elimination 

 

Nelarabine and ara-G are rapidly eliminated from plasma with a half-life of approximately 30 minutes 

and 3 hours, respectively. These findings were demonstrated in patients with refractory leukaemia or 

lymphoma given a dose of 1,500 mg/m2 nelarabine (adults) or a 650 mg/m2 (paediatrics). 

 

Combined Phase 1 pharmacokinetic data at nelarabine doses of 104 to 2,900 mg/m2 indicate that mean 

(%CV) clearance (Cl) values for nelarabine are 138 l/h/m2 (104 %) and 125 l/h/m2 (214 %) in adult 

and paediatric patients, respectively, on day 1 (n = 65 adults, n = 21 paediatric patients). The apparent 

clearance of ara-G (Cl/F) is comparable between the two groups [9.5 l/h/m2 (35 %) in adult patients 

and 10.8 l/h/m2 (36 %) in paediatric patients] on day 1. 

 

Nelarabine and ara-G are partially eliminated by the kidneys. In 28 adult patients, 24 hours after 

nelarabine infusion on day 1, mean urinary excretion of nelarabine and ara-G was 5.3 % and 23.2 % of 

the administered dose, respectively. Renal clearance averaged 9.0 l/h/m2 (151 %) for nelarabine and 

2.6 l/h/m2 (83 %) for ara-G in 21 adult patients. 

 

Because the timecourse of intracellular ara-GTP was prolonged, its elimination half-life could not be 

accurately estimated. 

 

Paediatric population 

 

Limited clinical pharmacology data are available for patients below the age of 4 years. 

 

Combined Phase 1 pharmacokinetic data at nelarabine doses of 104 to 2,900 mg/m2 indicate that the 

clearance (Cl) and Vss values for nelarabine and ara-G are comparable between the two groups. 

Further data with respect to nelarabine and ara-G pharmacokinetics in the paediatric population are 

provided in other subsections. 

 

Gender 

 

Gender has no effect on nelarabine or ara-G plasma pharmacokinetics. Intracellular ara-GTP Cmax and 

AUC(0–t) values at the same dose level were 2– to 3– fold greater on average in adult female than in 

adult male patients. 

 

Race 

 

The effect of race on nelarabine and ara-G pharmacokinetics has not been specifically studied. In a 

pharmacokinetic/pharmacodynamic cross study analysis, race had no apparent effect on nelarabine, 

ara-G, or intracellular ara-GTP pharmacokinetics. 

 

  



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Renal impairment 

 

The pharmacokinetics of nelarabine and ara-G have not been specifically studied in renally impaired 

or haemodialysed patients. Nelarabine is excreted by the kidney to a small extent (5 to 10 % of the 

administered dose). Ara-G is excreted by the kidney to a greater extent (20 to 30 % of the 

administered nelarabine dose). Adults and children in clinical studies were categorized into the three 

groups according to renal impairment: normal with Clcr greater than 80 ml/min (n = 56), mild with Clcr 

equalling 50 to 80 ml/min (n = 12), and moderate with Clcr less than 50 ml/min (n = 2). The mean 

apparent clearance (Cl/F) of ara-G was about 7 % lower in patients with mild renal impairment than in 

patients with normal renal function (see section 4.2). No data are available to provide a dose advice for 

patients with Clcr less than 50 ml/min. 

 

Elderly 

 

Age has no effect on the pharmacokinetics of nelarabine or ara-G. Decreased renal function, which is 

more common in the elderly, may reduce ara-G clearance (see section 4.2). 

 

5.3 Preclinical safety data 
 

Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to 

clinical exposure levels and with possible relevance to clinical use were as follows: nelarabine caused 

histopathological changes to the central nervous system (white matter vacuolation and degenerative 

changes in cerebrum, cerebellum and spinal cord) of monkeys after daily treatment with nelarabine for 

23 days, at exposures below the human therapeutic exposure. Nelarabine showed in vitro cytotoxicity 

to monocytes and macrophages. 

 

Carcinogenicity 

 

Carcinogenicity testing of nelarabine has not been performed. 

 

Mutagenicity 

 

Nelarabine was mutagenic to L5178Y/TK mouse lymphoma cells with and without metabolic 

activation. 

 

Reproduction toxicity 

 

Compared to controls, nelarabine caused increased incidences of foetal malformations, anomalies, and 

variations in rabbits when given at doses approximately 24 % of the adult human dose on a mg/m2 

basis during the period of organogenesis. Cleft palate was seen in rabbits given a dose approximately 

2-fold the adult human dose, absent pollices in rabbits given a dose approximately 79 % of the adult 

human dose while absent gall bladder, accessory lung lobes, fused or extra sternebrae and delayed 

ossification was seen at all doses. Maternal body weight gain and foetal body weights were reduced in 

rabbits given a dose approximately 2-fold the adult human dose. 

 

Fertility 

 

No studies have been conducted in animals to assess the effects of nelarabine on fertility. However, no 

undesirable effects were seen in the testes or ovaries of monkeys given nelarabine intravenously at 

doses up to approximately 32 % of the adult human dose on a mg/m2 basis for 30 consecutive days. 

 

 



13 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 
 

Sodium chloride 

Water for injections 

Hydrochloric acid (to adjust the pH) 

Sodium hydroxide (to adjust the pH) 

 

6.2 Incompatibilities 
 

Not applicable. 

 

6.3 Shelf life 
 

3 years. 

 

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

 

6.4 Special precautions for storage 
 

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

 

6.5 Nature and contents of container 
 

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. 

 

6.6 Special precautions for disposal and other handling 

 

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. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

  



14 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/403/001-002 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 22 August 2007 

Date of latest renewal: 16 June 2017 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

  



15 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 
 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 

RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 

E. SPECIFIC OBLIGATION TO COMPLETE POST-

AUTHORISATION MEASURES FOR THE MARKETING 

AUTHORISATION UNDER EXCEPTIONAL 

CIRCUMSTANCES 

 



16 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) responsible for batch release 

 

EBEWE Pharma Ges.m.b.H. Nfg.KG 

Mondseestrasse 11 

4866 Unterach am Attersee 

Austria 

 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

 Periodic Safety Update Reports 
 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 

agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 

updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 

 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

  



17 

 

E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 

FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL 

CIRCUMSTANCES 

 

This being an approval under exceptional circumstance and pursuant to Article 14(8) of Regulation 

(EC) No 726/2004, the MAH shall conduct, within the stated timeframe, the following measures: 

 

Description Due date 

The MAH shall provide yearly updates on any new information concerning the 

efficacy and safety of the product in 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. 

Yearly 

 

  



18 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



19 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

  



20 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atriance 5 mg/ml solution for infusion 

nelarabine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml contains 5 mg of nelarabine. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: Sodium chloride, water for injections, hydrochloric acid, sodium hydroxide. See the leaflet 

for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for infusion 

 

6 x 50 ml vials 

250 mg/50 ml 

1 x 50 ml vial 

250 mg/50 ml 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

WARNING: Cytotoxic agent, special handling instructions (see package leaflet). 

 

 

8. EXPIRY DATE 

 

EXP 

 

  



21 

 

9. SPECIAL STORAGE CONDITIONS 

 

Stable for up to 8 hours at up to 30ºC once the vial is opened. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/403/001 6 x 50 ml vials 

EU/1/07/403/002 1 x 50 ml vial 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

Justification for not including Braille accepted 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 
NN: 

  



22 

 

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING 

 

VIAL LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Atriance 5 mg/ml solution for infusion 

nelarabine 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each ml contains 5 mg of nelarabine. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: Sodium chloride, water for injections, hydrochloric acid, sodium hydroxide. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for infusion 

 

250 mg/50 ml 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Cytotoxic 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

  



23 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Novartis Europharm Limited 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/07/403/001 6 x 50 ml vials 

EU/1/07/403/002 1 x 50 ml vial 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

Justification for not including Braille accepted 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

 

  



24 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



25 

Package leaflet: Information for the patient 

 

Atriance 5 mg/ml solution for infusion 
 

nelarabine 

 

This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 

for how to report side effects. 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 
- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 

- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 
effects not listed in this leaflet. See section 4. 

 

What is in this leaflet: 

1. What Atriance is and what it is used for 

2. What you need to know before you are given Atriance 

3. How Atriance is given 

4. Possible side effects 

5. How to store Atriance 

6. Contents of the pack and other information 

 

 

1. What Atriance is and what it is used for 
 

Atriance contains nelarabine which belongs to a group of medicines known as antineoplastic agents, 

used in chemotherapy to kill some types of cancer cells. 

 

Atriance is used to treat patients with: 
 a type of leukaemia, called T-cell acute lymphoblastic leukaemia. Leukaemia causes an 

abnormal increase in the number of white blood cells. The abnormal high number of white 

blood cells can appear in the blood and other parts of the body. The type of leukaemia relates to 

the type of white blood cell mainly involved. In this case, its cells are called lymphoblasts. 

 a type of lymphoma, called T-cell lymphoblastic lymphoma. This lymphoma is caused by a 

mass of lymphoblasts, a type of white blood cell. 

 

If you have any questions about your illness, talk to your doctor. 

 

 

2. What you need to know before you are given Atriance 
 

You (or your child, if he/she is being treated) must not receive Atriance 
 if you (or your child, if he/she is being treated) are allergic to nelarabine or any of the other 

ingredients of this medicine (listed in section 6). 

 

Warnings and precautions 
Severe nervous system side effects have been reported with the use of Atriance. Symptoms may be 

mental (e.g. tiredness) or physical (e.g. convulsions, feelings of numbness or tingling, weakness and 
paralysis). Your doctor will check for these symptoms regularly during treatment (see also 

section 4, "Possible side effects"). 
  



26 

 

Your doctor also needs to know the following before you are given this medicine: 

 if you (or your child, if he/she is being treated) have any kidney or liver problems. Your 

dose of Atriance may need to be adjusted. 

 if you (or your child, if he/she is being treated) have recently been, or plan to be vaccinated 
with a live vaccine (for example polio, varicella, typhoid). 

 if you (or your child, if he/she is being treated) have any blood problems (for example 

anaemia). 

 

Blood tests during treatment 

Your doctor should perform blood tests regularly during treatment to check for blood problems that 

have been associated with the use of Atriance. 

 

Elderly 

If you are an elderly person, you could be more sensitive to nervous system side effects (see the list 

above under “Warnings and precautions”). Your doctor will check for these symptoms regularly 

during treatment. 

 

Tell your doctor if any of these apply to you. 
 

Other medicines and Atriance 
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. This includes any herbal products or medicines you have bought without a prescription 

 

Remember to tell your doctor if you start to take any other medicines while you are on Atriance. 

 

Pregnancy, breast-feeding and fertility 
Atriance is not recommended for pregnant women. It may harm a baby if conceived before, during or 

soon after treatment. Consideration to appropriate birth control is recommended to be discussed with 

your doctor. Do not try and become pregnant/father a child until your doctor advises you it is safe to 

do so. 

 

Male patients, who may wish to father a child, should ask their doctor for family planning advice or 

treatment. If pregnancy occurs during treatment with Atriance, you must tell your doctor immediately. 

 

It is not known whether Atriance is passed on through breast milk. Breast-feeding must be 

discontinued while you are taking Atriance. Ask your doctor for advice before taking any medicine. 

 

Driving and using machines 
Atriance can make people feel drowsy or sleepy, both during and for some days after treatment. If you 

feel tired or weak, do not drive, and do not use any tools or machines. 

 

Atriance contains sodium 
This medicine contains at least 23 mg sodium per dose. This is to be taken into consideration if you 

are on a controlled sodium diet. 

 

 

  



27 

3. How Atriance is given 
 

The dose of Atriance you are given will be based on: 

 your/your child's (if he/she is being treated) body surface area (which will be calculated by 
your doctor based on your height and weight). 

 the results of blood tests carried out before treatment 
 

Adults and adolescents (aged 16 years and older) 
The usual dose is 1,500 mg/m2 of body surface area per day. 

 

A doctor or nurse will give you the dose of Atriance as an infusion (a drip). It is usually dripped into 

your arm over a period of about 2 hours. 

 

You will have an infusion (a drip) once a day on days 1, 3 and 5 of treatment. This pattern of 

treatment will normally be repeated every three weeks. This treatment may vary, depending on the 

results of your regular blood tests. Your doctor will decide how many treatment cycles are required. 

 

Children and adolescents (aged 21 years and younger) 
The recommended dose is 650 mg/m2 of body surface area per day. 

 

A doctor or nurse will give you/your child (if he/she is being treated) a suitable dose of Atriance as 

an infusion (a drip). It is usually dripped into your arm over a period of about 1 hour. 

 

You/your child (if he/she is being treated) will have an infusion (a drip) once a day for 5 days. 

This pattern of treatment will normally be repeated every three weeks. This treatment may vary, 

depending on the results of regular blood tests. Your doctor will decide how many treatment cycles are 

required. 

 

Stopping treatment with Atriance 
Your doctor will decide when to stop the treatment. 

 

If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 

 

 

4. Possible side effects 
 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

The majority of side effects reported with Atriance were seen in adults, children and adolescents. 

Some of the side effects were reported more often in adult patients. There is no known reason for this. 

 

If you have any concerns, discuss them with your doctor. 

 

Most serious side effects 
 

These may affect more than 1 in 10 people treated with Atriance. 

 Signs of infection. Atriance may reduce the number of white blood cells and lower your 

resistance to infection (including pneumonia). This can even be life threatening. Signs of an 

infection include: 

- fever 
- serious deterioration of your general condition 
- local symptoms such as sore throat, sore mouth or urinary problems (for example, a 

burning sensation when urinating, which may be a urinary infection) 

Tell your doctor immediately if you get any of these. A blood test will be taken to check possible 

reduction of white blood cells. 

 



28 

Other very common side effects 
These may affect more than 1 in 10 people treated with Atriance 

 Changes in the sense of feeling in hands or feet, muscle weakness appearing as difficulty getting 

up from a chair, or difficulty walking (peripheral neuropathy); reduced sensitivity to light 

touch, or pain; abnormal sensations such as burning and, prickling, a sensation of something 

crawling on the skin. 

 Feeling generally weak and tired (temporary anaemia). In some cases you may need a blood 

transfusion. 

 Unusual bruising or bleeding, caused by a decrease in the number of clotting cells in the blood. 

This can lead to severe bleeding from relatively small injuries such as a small cut. Rarely, it can 

lead to even more severe bleeding (haemorrhage). Talk to your doctor for advice on how to 

minimize the risk of bleeding. 

 Feeling drowsy and sleepy; headache; dizziness. 

 Shortness of breath, difficult or laboured breathing; cough. 

 Feeling of an upset stomach (nausea); being sick/throwing up (vomiting); diarrhoea; 

constipation 

 Muscle pain. 

 Swelling of parts of the body due to accumulation of abnormal amounts of fluid (oedema). 

 High body temperature (fever); tiredness; feeling weak/loss of strength. 

Tell a doctor if any of these becomes troublesome. 

 

Common side effects 
 

These may affect up to 1 in 10 people treated with Atriance: 

 Violent, uncontrollable muscular contractions often accompanied by unconsciousness that can 

be due to an epileptic attack (seizures). 

 Clumsiness and lack of coordination affecting balance, walking, limb or eye movements, or 

speech. 

 Unintentional rhythmic shaking of one or more limbs (tremors). 

 Muscle weakness (possibly associated with peripheral neuropathy – see above), joint pain, back 

pain; pains in hands and feet including a sensation of pins and needles sensation and numbness. 

 Lowered blood pressure. 

 Weight loss and loss of appetite (anorexia); stomach pains; sore mouth, mouth ulcers or 

inflammation. 

 Problems with memory, feeling disoriented; blurred vision; altered or loss of sense of taste 

(dysgeusia). 

 Build up of fluid around the lungs leading to chest pain and difficulty in breathing (pleural 

effusion); wheezing 

 Increased amounts of bilirubin in your blood, which may cause yellowing of the skin and may 

make you feel lethargic. 

 Increases in blood levels of liver enzymes. 

 Increases in blood creatinine levels (a sign of kidney problems, which might lead less frequent 

urination). 

 The release of tumour cell contents (tumour lysis syndrome), which may put extra stress on your 

body. Initial symptoms including nausea and vomiting, shortness of breath, an irregular 

heartbeat, clouding of urine, lethargy and/or joint discomfort. If this does occur, it is most likely 

to occur at the first dose. Your doctor will take appropriate precautions to minimise the risk of 

this. 

 Low blood levels of some substances: 

- low calcium levels, which may cause muscle cramps, abdominal cramps or spasms 
- low magnesium levels, which may cause muscle weakness, confusion, "jerky" 

movements, high blood pressure, irregular heart rhythms and decreased reflexes with 

severely low blood magnesium levels. 

- low potassium levels may cause a feeling of weakness 
- low glucose levels, which may cause nausea, sweating, weakness, faintness, confusion or 

hallucinations. 

Tell a doctor if any of these becomes troublesome. 



29 

 

Rare side effects 

 

These may affect up to 1 in 1,000 people treated with Atriance 

 Serious disease that destroys skeletal muscle characterized by the presence of myoglobin (a 
breakdown product of muscle cells) in the urine (Rhabdomyolysis), increase in blood creatine 

phosphokinase. 

Tell a doctor if any of these becomes troublesome. 

 

Reporting of side effects 

If you get any of the side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. You can also report side effects directly via the national reporting 

system listed in Appendix V. By reporting side effects you can help provide more information on the 

safety of this medicine. 

 

 

5. How to store Atriance 
 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the carton and vial. 

 

This medicine does not require any special storage conditions. 

 

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

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicines you no longer use. These measures will help protect the environment. 

 

 

6. Contents of the pack and other information 

 

What Atriance contains 
 The active substance of Atriance is nelarabine. Each ml of Atriance solution for infusion 

contains 5 mg of nelarabine. Each vial contains 250 mg of nelarabine. 

 The other ingredients are sodium chloride, water for injections, hydrochloric acid, sodium 

hydroxide (see section 2 “Atriance contains sodium”). 

 

What Atriance looks like and contents of the pack 

Atriance solution for infusion is a clear, colourless solution. It is provided in clear glass vials with a 

rubber stopper and sealed with an aluminium cap. 

 

Each vial contains 50 ml. 

 

Atriance is supplied in packs of 1 vial or 6 vials. 

 

Marketing Authorisation Holder 
Novartis Europharm Limited 

Vista Building 

Elm Park, Merrion Road 

Dublin 4 

Ireland 

 



30 

Manufacturer 

EBEWE Pharma Ges.m.b.H. Nfg.KG 

Mondseestrasse 11 

4866 Unterach am Attersee 

Austria 

 

Novartis Farmacéutica SA 

Ronda de Santa Maria 158 

08210 Barberà del Vallès, Barcelona 

Spain 

 

Novartis Pharma GmbH 

Roonstraße 25 

D-90429 Nuremberg 

Germany 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

België/Belgique/Belgien 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Lietuva 

SIA Novartis Baltics Lietuvos filialas 

Tel: +370 5 269 16 50 

 

България 

Novartis Bulgaria EOOD 

Тел: +359 2 489 98 28 

 

Luxembourg/Luxemburg 

Novartis Pharma N.V. 

Tél/Tel: +32 2 246 16 11 

 

Česká republika 

Novartis s.r.o. 

Tel: +420 225 775 111 

 

Magyarország 

Novartis Hungária Kft. 

Tel.: +36 1 457 65 00 

Danmark 

Sandoz A/S 

Tlf: +45 63 95 10 00 

 

Malta 

Novartis Pharma Services Inc. 

Tel: +356 2122 2872 

Deutschland 

Novartis Pharma GmbH 

Tel: +49 911 273 0 

 

Nederland 

Novartis Pharma B.V. 

Tel: +31 88 04 52 555 

Eesti 

SIA Novartis Baltics Eesti filiaal 

Tel: +372 66 30 810 

 

Norge 

Sandoz A/S 

Tlf: +45 63 95 10 00 

Ελλάδα 

Novartis (Hellas) A.E.B.E. 

Τηλ: +30 210 281 17 12 

 

Österreich 

Novartis Pharma GmbH 

Tel: +43 1 86 6570 

España 

BEXAL FARMACÉUTICA, S.A. 

Tel: +34 900 456 856 

 

Polska 

Novartis Poland Sp. z o.o. 

Tel.: +48 22 375 4888 

France 

Sandoz 

Tél: +33 800 45 57 99 

 

Portugal 

Novartis Farma - Produtos Farmacêuticos, S.A. 

Tel: +351 21 000 8600 



31 

Hrvatska 

Novartis Hrvatska d.o.o. 

Tel. +385 1 6274 220 

 

România 

Sandoz S.R.L. 

Tel: +40 021 4075160 

 

Ireland 

Novartis Ireland Limited 

Tel: +353 1 260 12 55 

 

Slovenija 

Novartis Pharma Services Inc. 

Tel: +386 1 300 75 50 

Ísland 

Vistor hf. 

Sími: +354 535 7000 

 

Slovenská republika 

Novartis Slovakia s.r.o. 

Tel: +421 2 5542 5439 

 

Italia 

Novartis Farma S.p.A. 

Tel: +39 02 96 54 1 

Suomi/Finland 

Novartis Finland Oy 

Puh/Tel: +358 (0)10 6133 200 

 

Κύπρος 

Novartis Pharma Services Inc. 

Τηλ: +357 22 690 690 

 

Sverige 

Sandoz A/S 

Tel: +45 63 95 10 00 

Latvija 

SIA Novartis Baltics 

Tel: +371 67 887 070 

 

United Kingdom 

Novartis Pharmaceuticals UK Ltd. 

Tel: +44 1276 698370 

 

 

This leaflet was last approved in 
 

This medicine has been authorised under “exceptional circumstances”. This means that because of the 

rarity of this disease it has been impossible to get complete information on this medicine. 

The European Medicines Agency will review any new information on the medicine every year and 

this leaflet will be updated as necessary. 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu. There are also links to other websites about rare diseases and treatments. 

 



32 

The following information is intended for medical or healthcare professionals only: 

 

INSTRUCTIONS ON HOW TO STORE AND DISPOSE OF ATRIANCE 

 

Storage of Atriance solution for infusion 

 

This medicinal product does not require any special storage conditions. 

 

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

 

Instructions for handling and disposal of Atriance 

 

The normal procedures for proper handling and disposal of 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. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES
	A. LABELLING
	B. PACKAGE LEAFLET