Overview
11 DESCRIPTION Nelarabine injection (nelarabine) is a prodrug of the cytotoxic deoxyguanosine analogue, 9-β- D arabinofuranosylguanine (ara-G). The chemical name for nelarabine is 2-amino-9-β- D -arabinofuranosyl-6-methoxy-9 H -purine. It has the molecular formula C 11 H 15 N 5 O 5 and a molecular weight of 297.27.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Nelarabine is a prodrug of the deoxyguanosine analogue 9-β- D -arabinofuranosylguanine (ara-G), a nucleoside metabolic inhibitor. Nelarabine is demethylated by adenosine deaminase (ADA) to ara-G, mono-phosphorylated by deoxyguanosine kinase and deoxycytidine kinase, and subsequently converted to the active 5’-triphosphate, ara-GTP. Accumulation of ara-GTP in leukemic blasts allows for incorporation into deoxyribonucleic acid (DNA), leading to inhibition of DNA synthesis and cell death. Other mechanisms may contribute to the cytotoxic and systemic toxicity of nelarabine. 12.
Indications
- 1 INDICATIONS AND USAGE Nelarabine injection is indicated for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in adult and pediatric patients age 1 year and older whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. Nelarabine injection is a nucleoside metabolic inhibitor indicated for the treatment of patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in adult and pediatric patients age 1 year and older whose disease has not responded to or has...
Common Doses
- 500 mg
- 650 mg
- 50 mL
Dosage
2 DOSAGE AND ADMINISTRATION Adult Dose : 1,500 mg/m² administered intravenously over 2 hours on Days 1, 3, and 5 repeated every 21 days. ( 2.1 ) Pediatric Dose : 650 mg/m² administered intravenously over 1 hour daily for 5 consecutive days repeated every 21 days. ( 2.1 ) Discontinue treatment for neurologic reactions greater than or equal to Grade 2. ( 2.2 ) Dosage may be delayed for hematologic reactions. ( 2.2 ) Take measures to prevent hyperuricemia. ( 2.4 ) 2.1 Recommended Dosage This product is for intravenous use only.
Black Box Warning
WARNING: NEUROLOGIC ADVERSE REACTIONS See full prescribing information for complete boxed warning. Severe neurologic adverse reactions have been reported with the use of nelarabine injection. These adverse reactions have included altered mental states including severe somnolence, central nervous system effects including convulsions, and peripheral neuropathy ranging from numbness and paresthesias to motor weakness and paralysis.
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically-significant adverse reactions are discussed in greater detail in other sections of the label: Neurologic [see Boxed Warning, Warnings and Precautions ( 5.1 )] Hematologic [see Warnings and Precautions ( 5.2 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.4 )] Effects on Ability to Drive and Use Machines [see Warnings and Precautions ( 5.6 )] The most common (≥ 20%) adverse reactions were: Adult: anemia, thrombocytopenia, neutropenia, nausea, diarrhea, vomiting, constipation, fatigue, pyrexia, cough, and dyspnea ( 6.
Interactions
- 7 DRUG INTERACTIONS Administration of nelarabine injection in combination with adenosine deaminase inhibitors, such as pentostatin, is not recommended [see Clinical Pharmacology (12.3)] . Administration in combination with adenosine deaminase inhibitors, such as pentostatin, is not recommended. ( 7 , 12.3 )