Medicinal Products

ATRIANCE 5 mg / mL

Generic drug of the therapeutic class: Oncology and Hematology
Active ingredients: Nelarabine
laboratory: Glaxo Group Ltd

Injection solution for IV infusion
Box of 6 bottles of 50 ml
All forms

Indication

Nelarabine is indicated for the treatment of patients with acute T-cell lymphoblastic leukemia (T-ALL) or non-responder or relapsed T-cell lymphoblastic lymphoma after at least two lines of chemotherapy.

Due to the small patient population in these conditions, the information supporting these indications is based on limited data.

Dosage ATRIANCE 5 mg / mL Solution for IV infusion Pack of 6 vials of 50 ml

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


Dosage

Nelarabine-treated patients should be given intravenous hydration in accordance with standard medical practices for the management of hyperuricemia in patients who may develop Tumor Lysis Syndrome. For patients who may develop hyperuricemia, the use of allopurinol should be considered (see Warnings and Precautions ).

The blood count including the platelet count should be regularly monitored (see Warnings and Precautions and Adverse Reactions sections).

Adults and adolescents (aged 16 years and over)

In adults, the recommended dose of nelarabine is 1500 mg / m 2, administered intravenously for two hours per day, on days 1, 3, and 5, every 21 days.

Pediatric population

Children and adolescents (aged 21 or under)

In children and adolescents, the recommended dose of nelarabine is 650 mg / m 2 administered intravenously for one hour per day for 5 consecutive days every 21 days.

In clinical studies, doses of 650 mg / m 2 and 1500 mg / m 2 were studied in patients aged 16 to 21 years. Efficacy and safety were similar for both regimens. The doctor should consider the most appropriate dosage when treating a patient in this age range.

Clinical pharmacology data are limited in patients younger than 4 years of age (see section 5.2 ).

Modification of the dosage

Treatment with nelarabine should be discontinued at the onset of the first signs of a grade 2 or greater neurological adverse event, as defined by the National Cancer Institute Common Terminology Criteria Adverse Event (NCI - CTCAE) classification. In case of occurrence of other toxicities, including haematological, postponement of the next course of treatment may be considered.

Elderly

The number of patients aged 65 years or older treated with nelarabine is not sufficient to determine whether their response to treatment differs from that of younger patients (see sections Warnings and Precautions and Pharmacokinetic Properties ).

Renal failure

Nelarabine has not been studied in subjects with renal impairment. Nelarabine and 9- | 3-D-arabinofuranosyl guanine (ara-G) are partially excreted by the kidneys (see section Pharmacokinetic properties ). There is insufficient evidence to establish a dose adjustment recommendation for patients with renal creatinine clearance Cr < 50 ml / min. Patients with renal impairment should be closely monitored for nelarabine toxicities.

Hepatic insufficiency

Nelarabine has not been studied in patients with hepatic impairment. These patients will need special attention.


Administration mode

Nelarabine should not be diluted before administration. The required dose of nelarabine should be transferred to plastic infusion bags (PVC or EVA) or glass vials, and administered intravenously as a two-hour infusion in adults, and one hour as child.

Against indications

Hypersensitivity to the active substance or to any of the excipients listed under Composition .

Atriance side effects

Summary of the security profile

The safety profile determined in pivotal clinical trials at the recommended nelarabine doses in adults (1500 mg / m 2 ) and in children (650 mg / m 2 ) is based on data obtained from 103 adults and 84 children. The most commonly observed adverse reactions were fatigue, gastrointestinal disturbances, haematological disorders, respiratory disorders, nervous system disorders and pyrexia. Neurotoxicity is the dose-limiting toxicity of nelarabine (see Warnings and Precautions ).


Tabulated summary of adverse effects

The following convention was used for their classification: very common (≥ 1/10), common (≥ 1/100 and <1/10), uncommon (≥ 1/1000 and <1/100), rare (≥ 1 / 10, 000 and <1/1000), very rare (<1 / 10, 000) and frequency not known (can not be estimated from the available data)

Side effects)

Adults (1500 mg / m 2 )
N = 103 (%)

Children (650 mg / m 2 )
N = 84 (%)

Infections and infestations

Infection (including but not limited to: sepsis, bacteremia, pneumonia, fungal infection).

Very common: 40 (39)

Very common: 13 (15)

Benign and malignant tumors (including cysts and polyps)

Tumor lysis syndrome (see also Data from Early Delivery Program and non-pivotal studies)

Frequency: 1 (1)

Not applicable

Blood and lymphatic system disorders

Febrile neutropenia

Very common: 12 (12)

Frequency: 1 (1)

neutropenia

Very common: 83 (81)

Very common: 79 (94)

leukopenia

Frequency: 3 (3)

Very common: 32 (38)

thrombocytopenia

Very common: 89 (86)

Very common: 74 (88)

Anemia

Very common: 102 (99)

Very common: 80 (95)

Metabolism and nutrition disorders

hypoglycemia

Not applicable

Frequency: 5 (6)

hypocalcemia

Frequency: 3 (3)

Frequent: 7 (8)

hypomagnesemia

Frequency: 4 (4)

Frequency: 5 (6)

hypokalemia

Frequency: 4 (4)

Very common: 9 (11)

Anorexia

Frequency: 9 (9)

Not applicable

Psychiatric disorders

Mental confusion

Frequency: 8 (8)

Frequency: 2 (2)

Nervous system disorders

Seizures (including convulsions, "grand mal" convulsions, status epilepticus)

Frequency: 1 (1)

Frequency: 5 (6)

Amnesia

Frequency: 3 (3)

Not applicable

Drowsiness

Very common: 24 (23)

Frequency: 6 (7)

Peripheral neurological disorders (sensory and motor)

Very common: 22 (21)

Very common: 10 (12)

Hypoaesthesia

Very common: 18 (17)

Frequency: 5 (6)

paresthesia

Very common: 15 (15)

Frequency: 3 (4)

Ataxia

Frequency: 9 (9)

Frequency: 2 (2)

Balance disorders

Frequency: 2 (2)

Not applicable

tremors

Frequency: 5 (5)

Frequency: 3 (4)

Feeling dizzy

Very common: 22 (21)

Not applicable

headaches

Very common: 15 (15)

Very common: 14 (17)

dysgeusia

Frequency: 3 (3)

Not applicable

Eye disorders

Blurred vision

Frequency: 4 (4)

Not applicable

Vascular disorders

hypotension

Frequency: 8 (8)

Not applicable

Respiratory, thoracic and mediastinal disorders

Pleural effusion

Frequency: 10 (10)

Not applicable

Noisy or wheezing breathing

Frequency: 5 (5)

Not applicable

Dyspnea

Very common: 21 (20)

Not applicable

Cough

Very common: 26 (25)

Not applicable

Gastrointestinal disorders

Diarrhea

Very common: 23 (22)

Frequency: 2 (2)

stomatitis

Frequency: 8 (8)

Frequency: 1 (1)

vomiting

Very common: 23 (22)

Frequency: 8 (10)

Abdominal pain

Frequency: 9 (9)

Not applicable

Constipation

Very common: 22 (21)

Frequency: 1 (1)

nausea

Very common: 42 (41)

Frequency: 2 (2)

Hepatobiliary disorders

hyperbilirubinemia

Frequency: 3 (3)

Frequency: 8 (10)

Elevation of transaminases

Not applicable

Very common: 10 (12)

Elevation of aspartate aminotransferase

Frequency: 6 (6)

Not applicable

Musculoskeletal and systemic disorders

Muscular weakness

Frequency: 8 (8)

Not applicable

myalgia

Very common: 13 (13)

Not applicable

arthralgia

Frequency: 9 (9)

Frequency: 1 (1)

Back pain

Frequency: 8 (8)

Not applicable

Pain at the extremities

Frequency: 7 (7)

Frequency: 2 (2)

Rhabdomyolysis, serum phosphokinase creatine increase (see Postmarketing Data)

Rare: not applicable

Rare: not applicable

Renal and urinary disorders

Elevation of serum creatinine

Frequency: 2 (2)

Frequency: 5 (6)

General disorders and administration site conditions

Edema

Very common: 11 (11)

Not applicable

Walking disorders

Frequency: 6 (6)

Not applicable

Peripheral edema

Very common: 15 (15)

Not applicable

pyrexia

Very common: 24 (23)

Frequency: 2 (2)

pains

Very common: 11 (11)

Not applicable

Tired

Very common: 51 (50)

Frequency: 1 (1)

Asthenia

Very common: 18 (17)

Frequency: 5 (6)

Description of some adverse effects

Infections and infestations

Only one case of progressive multifocal leukoencephalopathy confirmed by biopsy has been reported in adults.

Opportunistic infections, sometimes fatal, have been reported in patients treated with nelarabine.

Nervous system disorders

Adverse events associated with demyelination and peripheral ascending neuropathies, similar in appearance to Guillain-Barré syndrome, have been reported. A child died as a result of a state of epilepticus.

Data from NCI (National Cancer Institute) Studies / Early Delivery Program and Phase I Studies

In addition to adverse events observed in the pivotal clinical studies, data were also obtained from 875 patients included in NCI / early-release product (694 patients) and Phase I studies (181). patients) with nelarabine. The following side effects have also been observed:

Benign and malignant tumors (including cysts and polyps)

Tumor lysis syndrome - 7 cases (see sections Posology and method of administration and Warnings and precautions for use )

Post-marketing data

The following side effects have been identified with nelarabine since its introduction; they include cases from spontaneous notification, as well as serious adverse events observed in ongoing clinical trials.


Musculoskeletal and systemic disorders
Rare: Rhabdomyolysis, serum phosphokinase creatine increase.

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