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Arranon

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Arranon

Warnings
Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Neurologic Adverse Reactions

Neurotoxicity is the dose-limiting toxicity of nelarabine. Patients undergoing therapy with ARRANON should be closely observed for signs and symptoms of neurologic toxicity [see BOXED WARNING and DOSAGE AND ADMINISTRATION]. Common signs and symptoms of nelarabine-related neurotoxicity include somnolence, confusion, convulsions, ataxia, paresthesias, and hypoesthesia. Severe neurologic toxicity can manifest as coma, status epilepticus, craniospinal demyelination, or ascending neuropathy similar in presentation to Guillain-Barre syndrome.

Patients treated previously or concurrently with intrathecal chemotherapy or previously with craniospinal irradiation may be at increased risk for neurologic adverse events.

Hematologic Adverse Reactions

Leukopenia, thrombocytopenia, anemia, and neutropenia, including febrile neutropenia have been associated with nelarabine therapy. Complete blood counts including platelets should be monitored regularly [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS].

Pregnancy

Pregnancy Category D

ARRANON can cause fetal harm when administered to a pregnant woman.

Nelarabine administered during the period of organogenesis caused increased incidences of fetal malformations, anomalies, and variations in rabbits (see Use In Specific Populations].

There are no adequate and well-controlled studies of ARRANON in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of child-bearing potential should be advised to avoid becoming pregnant while receiving treatment with ARRANON.

Hyperuricemia

Patients receiving ARRANON should receive intravenous hydration according to standard medical practice for the management of hyperuricemia in patients at risk for tumor lysis syndrome. Consideration should be given to the use of allopurinol in patients at risk of hyperuricemia [see DOSAGE AND ADMINISTRATION].

Vaccinations

Administration of live vaccines to immunocompromised patients should be avoided.

Patient Counseling Information

Patient labeling is provided as a tear-off leaflet at the end of this full prescribing information. However, inform the patients of the following:

  • Since patients receiving nelarabine therapy may experience somnolence, they should be cautioned about operating hazardous machinery, including automobiles.
  • Patients should be instructed to contact their physician if they experience new or worsening symptoms of peripheral neuropathy (see BOXED WARNING, WARNINGS AND PRECAUTIONS, and DOSAGE AND ADMINISTRATION]. These signs and symptoms include: tingling or numbness in fingers, hands, toes, or feet; difficulty with the fine motor coordination tasks such as buttoning clothing; unsteadiness while walking; weakness arising from a low chair; weakness in climbing stairs; increased tripping while walking over uneven surfaces.
  • Patients should be instructed that seizures have been known to occur in patients who receive nelarabine. If a seizure occurs, the physician administering ARRANON should be promptly informed.
  • Patients who develop fever or signs of infection while on therapy should notify their physician promptly.
  • Patients should be advised to use effective contraceptive measures to prevent pregnancy and to avoid breast-feeding during treatment with ARRANON.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity testing of nelarabine has not been done. However, nelarabine was mutagenic when tested in vitro in L5178Y/TK mouse lymphoma cells with and without metabolic activation. No studies have been conducted in animals to assess genotoxic potential or effects on fertility. The effect on human fertility is unknown.

Use In Specific Populations

Pregnancy

Pregnancy Category D [see WARNINGS AND PRECAUTIONS]

ARRANON can cause fetal harm when administered to a pregnant woman. Nelarabine administered to rabbits during the period of organogenesis caused increased incidences of fetal malformations, anomalies, and variations at doses > 360 mg/m² /day (8-hour IV infusion; approximately V the adult dose compared on a mg/m² basis), which was the lowest dose tested. Cleft palate was seen in rabbits given 3,600 mg/m² /day (approximately 2-fold the adult dose), absent pollices (digits) in rabbits given > 1,200 mg/m /day (approximately % the adult dose), while absent gall bladder, absent accessory lung lobes, fused or extra sternebrae and delayed ossification was seen at all doses. Maternal body weight gain and fetal body weights were reduced in rabbits given 3,600 mg/m² /day (approximately 2-fold the adult dose), but could not account for the increased incidence of malformations seen at this or lower administered doses.

There are no adequate and well-controlled studies of ARRANON in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of child-bearing potential should be advised to avoid becoming pregnant while receiving treatment with ARRANON.

Nursing Mothers

It is not known whether nelarabine or ara-G are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ARRANON, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of ARRANON has been established in pediatric patients [see DOSAGE AND ADMINISTRATION and Clinical Studies].

Geriatric Use

Clinical studies of ARRANON 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 neurologic adverse reactions. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Renal Impairment

Ara-G clearance decreased as renal function decreased [see CLINICAL PHARMACOLOGY]. Because the risk of adverse reactions to this drug may be greater in patients with moderate (CLcr 30 to 50 mL/min) or severe (CLcr < 30 mL/min) renal impairment, these patients should be closely monitored for toxicities when treated with ARRANON [see DOSAGE AND ADMINISTRATION].

Hepatic Impairment

The influence of hepatic impairment on the pharmacokinetics of nelarabine has not been evaluated. Because the risk of adverse reactions to this drug may be greater in patients with severe hepatic impairment (total bilirubin > 3 times upper limit of normal), these patients should be closely monitored for toxicities when treated with ARRANON.

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

Warnings
Precautions
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