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Arranon

Arranon

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of the label:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

ARRANON was studied in 459 patients in Phase I and Phase II clinical trials.

Adults

The safety profile of ARRANON is based on data from 103 adult patients treated with the recommended dose and schedule in 2 studies: an adult T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL) study and an adult chronic lymphocytic leukemia study.

The most common adverse reactions in adults, regardless of causality, were fatigue; gastrointestinal (GI) disorders (nausea, diarrhea, vomiting, and constipation); hematologic disorders (anemia, neutropenia, and thrombocytopenia); respiratory disorders (cough and dyspnea); nervous system disorders (somnolence and dizziness); and pyrexia.

The most common adverse reactions in adults, by System Organ Class, regardless of causality, including severe or life threatening adverse reactions (NCI Common Toxicity Criteria grade 3 or grade 4) and fatal adverse reactions (grade 5) are shown in Table 1.

Table 1: Most Commonly Reported ( > 5% Overall) Adverse Reactions Regardless of Causality in Adult Patients Treated with 1,500 mg/m² of ARRANON Administered Intravenously Over 2 Hours on Days 1, 3, and 5 Repeated Every 21 Days

System Organ Class
Preferred Term
Percentage of Patients (N = 103)
Toxicity Grade
Grade 3
%
Grade 4 and 5a
%
All Grades
%
Blood and Lymphatic System Disorders
  Anemia 20 14 99
  Thrombocytopenia 37 22 86
  Neutropenia 14 49 81
  Febrile neutropenia 9 1 12
Cardiac Disorders
  Sinus tachycardia 1 0 8
Gastrointestinal Disorders
  Nausea 0 0 41
  Diarrhea 1 0 22
  Vomiting 1 0 22
  Constipation 1 0 21
  Abdominal pain 1 0 9
  Stomatitis 1 0 8
  Abdominal distension 0 0 6
General Disorders and Administration Site Conditions
  Fatigue 10 2 50
  Pyrexia 5 0 23
  Asthenia 0 1 17
  Edema, peripheral 0 0 15
  Edema 0 0 11
  Pain 3 0 11
  Rigors 0 0 8
  Gait, abnormal 0 0 6
  Chest pain 0 0 5
  Non-cardiac chest pain 0 1 5
Infections
  Infection 2 1 9
  Pneumonia 4 1 8
  Sinusitis 1 0 7
Hepatobiliary Disorders
  AST increased 1 1 6
Metabolism and Nutrition Disorders
  Anorexia 0 0 9
  Dehydration 3 1 7
  Hyperglycemia 1 0 6
Musculoskeletal and Connective Tissue Disorders
  Myalgia 1 0 13
  Arthralgia 1 0 9
  Back pain 0 0 8
  Muscular weakness 5 0 8
  Pain in extremity 1 0 7
Nervous System Disorders (see Table 2)
Psychiatric Disorders
  Confusional state 2 0 8
  Insomnia 0 0 7
  Depression 1 0 6
Respiratory, Thoracic, and Mediastinal Disorders
  Cough 0 0 25
  Dyspnea 4 2 20
  Pleural effusion 5 1 10
  Epistaxis 0 0 8
  Dyspnea, exertional 0 0 7
  Wheezing 0 0 5
Vascular Disorders
  Petechiae 2 0 12
  Hypotension 1 1 8
a Five patients had a fatal adverse reaction. Fatal adverse reactions included hypotension (n = 1), respiratory arrest (n = 1), pleural effusion/pneumothorax (n = 1), pneumonia (n = 1), and cerebral hemorrhage/coma/leukoencephalopathy (n = 1).

Other Adverse Events: Blurred vision was also reported in 4% of adult patients.

There was a single report of biopsy confirmed progressive multifocal leukoencephalopathy in the adult patient population.

Neurologic Adverse Reactions: Nervous system adverse reactions, regardless of drug relationship, were reported for 76% of adult patients across the Phase I and Phase II studies. The most common neurologic adverse reactions ( > 2%) in adult patients, regardless of causality, including all grades (NCI Common Toxicity Criteria) are shown in Table 2.

Table 2: Neurologic Adverse Reactions ( > 2%) Regardless of Causality in Adult Patients Treated with 1,500 mg/m² of ARRANON Administered Intravenously Over 2 Hours on Days 1, 3, and 5 Repeated Every 21 Days

Nervous System Disorders
Preferred Term
Percentage of Patients (N =103)
Grade 1
%
Grade 2
%
Grade 3
%
Grade 4
%
All Grades
%
Somnolence 20 3 0 0 23
Dizziness 14 8 0 0 21
Peripheral neurologic disorders, any adverse reaction 8 12 2 0 21
  Neuropathy 0 4 0 0 4
  Peripheral neuropathy 2 2 1 0 5
  Peripheral motor neuropathy 3 3 1 0 7
  Peripheral sensory neuropathy 7 6 0 0 13
Hypoesthesia 5 10 2 0 17
Headache 11 3 1 0 15
Paresthesia 11 4 0 0 15
Ataxia 1 6 2 0 9
Depressed level of consciousness 4 1 0 1 6
Tremor 2 3 0 0 5
Amnesia 2 1 0 0 3
Dysgeusia 2 1 0 0 3
Balance disorder 1 1 0 0 2
Sensory loss 0 2 0 0 2

One patient had a fatal neurologic adverse reaction, cerebral hemorrhage/coma/leukoencephalopathy.

Most nervous system adverse reactions in the adult patients were evaluated as grade 1 or 2. The additional grade 3 adverse reactions in adult patients, regardless of causality, were aphasia, convulsion, hemiparesis, and loss of consciousness, each reported in 1 patient (1%). The additional grade 4 adverse reactions, regardless of causality, were cerebral hemorrhage, coma, intracranial hemorrhage, leukoencephalopathy, and metabolic encephalopathy, each reported in one patient (1%).

The other neurologic adverse reactions, regardless of causality, reported as grade 1, 2, or unknown in adult patients were abnormal coordination, burning sensation, disturbance in attention, dysarthria, hyporeflexia, neuropathic pain, nystagmus, peroneal nerve palsy, sciatica, sensory disturbance, sinus headache, and speech disorder, each reported in one patient (1%).

Pediatrics

The safety profile for children is based on data from 84 pediatric patients treated with the recommended dose and schedule in a T-cell acute lymphoblastic leukemia (T- ALL)/T-cell lymphoblastic lymphoma (T-LBL) treatment study.

The most common adverse reactions in pediatric patients, regardless of causality, were hematologic disorders (anemia, leukopenia, neutropenia, and thrombocytopenia). Of the non- hematologic adverse reactions in pediatric patients, the most frequent adverse reactions reported were headache, increased transaminase levels, decreased blood potassium, decreased blood albumin, increased blood bilirubin, and vomiting.

The most common adverse reactions in pediatric patients, by System Organ Class, regardless of causality, including severe or life threatening adverse reactions (NCI Common Toxicity Criteria grade 3 or grade 4) and fatal adverse reactions (grade 5) are shown in Table 3.

Table 3: Most Commonly Reported ( > 5% Overall) Adverse Reactions Regardless of Causality in Pediatric Patients Treated with 650 mg/m² of ARRANON Administered Intravenously Over 1 Hour Daily for 5 Consecutive Days Repeated Every 21 Days

System Organ Class
Preferred Term
Percentage of Patients (N = 84)
Toxicity Grade
Grade 3
%
Grade 4 and 5a
%
All Grades
%
Blood and Lymphatic System Disorders
  Anemia 45 10 95
  Neutropenia 17 62 94
  Thrombocytopenia 27 32 88
  Leukopenia 14 7 38
Hepatobiliary Disorders
  Transaminases increased 4 0 12
  Blood albumin decreased 5 1 10
  Blood bilirubin increased 7 2 10
Metabolic/Laboratory
  Blood potassium decreased 4 2 11
  Blood calcium decreased 1 1 8
  Blood creatinine increased 0 0 6
  Blood glucose decreased 4 0 6
  Blood magnesium decreased 2 0 6
Nervous System Disorders (see Table 4)
Gastrointestinal Disorders
  Vomiting 0 0 10
General Disorders & Administration Site Conditions
  Asthenia 1 0 6
Infections & Infestations
  Infection 2 1 5
a Three patients had a fatal adverse reaction. Fatal adverse reactions included neutropenia and pyrexia (n = 1), status epilepticus/seizure (n = 1), and fungal pneumonia (n = 1).

Neurologic Adverse Reactions: Nervous system adverse reactions, regardless of drug relationship, were reported for 42% of pediatric patients across the Phase I and Phase II studies. The most common neurologic adverse reactions ( > 2%) in pediatric patients, regardless of causality, including all grades (NCI Common Toxicity Criteria) are shown in Table 4.

Table 4: Neurologic Adverse Reactions ( > 2%) Regardless of Causality in Pediatric Patients Treated with 650 mg/m² of ARRANON Administered Intravenously Over 1 Hour Daily for 5 Consecutive Days Repeated Every 21 Days

Nervous System Disorders
Preferred Term
Percentage of Patients
(N = 84)
Grade 1
%
Grade 2
%
Grade 3
%
Grade 4 and 5a
%
All Grades
%
Headache 8 2 4 2 17
Peripheral neurologic disorders, any adverse reaction 1 4 7 0 12
  Peripheral neuropathy 0 4 2 0 6
  Peripheral motor neuropathy 1 0 2 0 4
  Peripheral sensory neuropathy 0 0 6 0 6
Somnolence 1 4 1 1 7
Hypoesthesia 1 1 4 0 6
Seizures 0 0 0 6 6
  Convulsions 0 0 0 3 4
  Grand mal convulsions 0 0 0 1 1
  Status epilepticus 0 0 0 1 1
Motor dysfunction 1 1 1 0 4
Nervous system disorder 1 2 0 0 4
Paresthesia 0 2 1 0 4
Tremor 1 2 0 0 4
Ataxia 1 0 1 0 2
a One (1) patient had a fatal neurologic adverse reaction, status epilepticus.

The other grade 3 neurologic adverse reaction in pediatric patients, regardless of causality, was hypertonia reported in 1 patient (1%). The additional grade 4 neurologic adverse reactions, regardless of causality, were 3rd nerve paralysis, and 6th nerve paralysis, each reported in 1 patient (1%).

The other neurologic adverse reactions, regardless of causality, reported as grade 1, 2, or unknown in pediatric patients were dysarthria, encephalopathy, hydrocephalus, hyporeflexia, lethargy, mental impairment, paralysis, and sensory loss, each reported in 1 patient (1%).

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ARRANON. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Infections and Infestations: Fatal opportunistic infections.

Metabolism and Nutrition Disorders: Tumor lysis syndrome.

Nervous System Disorders: Demyelination and ascending peripheral neuropathies similar in appearance to Guillain-Barre syndrome.

Musculoskeletal and Connective Disorders: Rhabdomyolysis, blood creatine phosphokinase increased.

Read the Arranon (nelarabine) Side Effects Center for a complete guide to possible side effects

DRUG INTERACTIONS

Administration of nelarabine in combination with adenosine deaminase inhibitors, such as pentostatin, is not recommended [see CLINICAL PHARMACOLOGY].

Read the Arranon Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 2/15/2012
This monograph has been modified to include the generic and brand name in many instances.

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Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


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