nelarabine

Action and Spectrum

Actions and spectrum: 

nelarabine is an antineoplastic agent that is used for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), which are aggressive malignancies arising from the lymphoid lineage of the bone marrow. nelarabine is a prodrug that is rapidly converted to its active metabolite, ara-G, in vivo.

Ara-G is a purine analog that incorporates into the DNA of T-lymphocytes, causing DNA damage and leading to apoptosis of the cancerous cells. The specificity of nelarabine for T-lymphocytes makes it particularly useful for the treatment of T-cell malignancies. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% (selected) 

Ataxia (in adults) 

Anorexia (in adults) 

Seizures (in peds) 

Insomnia (in adults) 

Decreased Mg/Ca (in peds)  

>10% 

Neutropenia (>50%) 

Fatigue (in adults) 

Dizziness (in adults) 

Peripheral neurologic disorder
Paresthesia 

Pain (in adults) 

Edema (in adults) 

Cough (in adults) 

Pleural effusion (in adults) 

Nausea (in adults) 

Constipation (in adults) 

Hepatobiliary (in peds) 

Anemia (>50%) 

Thrombocytopenia (>50%) 

Somnolence (in adults) 

Headache
Hypoesthesia 

Asthenia (in adults) 

Pyrexia (in adults) 

Petechiae (in adults) 

Dyspnea (in adults) 

Diarrhea (in adults) 

Vomiting 

Leukopenia (in peds) 

Myalgia (in adults)  

Post marketing Reports 

Tumor lysis syndrome 

Fatal opportunistic infections 

ascending peripheral neuropathies and demyelination 

Black Box Warning

Black Box Warning: 

nelarabine has a black box warning for neurologic toxicity, which includes severe neuropathy, paraparesis, quadriparesis, confusion, and seizures. These adverse events may be irreversible and potentially fatal.

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

nelarabine is contraindicated in patients with a history of severe hypersensitivity or anaphylaxis to nelarabine or any of its components. It should also not be used in patients with advanced hepatic or renal disease or in patients having creatinine clearance of less than 50 mL/min. Additionally, it is contraindicated in patients who have received prior treatment with fludarabine phosphate or cladribine because of the potential for increased neurotoxicity.  

Caution: 

nelarabine should be used with caution in patients with a history of seizures, peripheral neuropathy, or neurologic disorders. It should also be used with caution in patients who have received prior radiation therapy or chemotherapy, as they may be at increased risk for adverse effects. Patients with impaired hepatic or renal function may require dose adjustments. 

Comorbidities: 

nelarabine is an antineoplastic agent used to treat T-cell acute lymphoblastic leukemia and lymphoma. Since it is a chemotherapy drug, it can cause bone marrow suppression leading to decreased WBC, RBC, and platelets and increasing the risk of infections, bleeding, and anemia. Therefore, it should be used under caution in patients with preexisting bone marrow suppression or other blood disorders. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned. 

Lactation: It is not known whether nelarabine is excreted in human milk  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

nelarabine is a prodrug of arabinosylguanine nucleotide triphosphate, which is phosphorylated by deoxycytidine kinase and other enzymes into the active triphosphate form within lymphoid cells. It is an antineoplastic agent that acts as a purine analog, disrupting DNA synthesis and repair. nelarabine is primarily metabolized in the liver, and its elimination half-life is approximately 30 minutes. It is excreted in the urine, with about 30% of the dose excreted unchanged.  

Pharmacodynamics: 

nelarabine is an antineoplastic drug that is converted to ara-G triphosphate in vivo, which competes with deoxyguanosine triphosphate for incorporation into DNA, leading to DNA damage and apoptosis of the tumor cells. It is a prodrug of the nucleoside analog guanosine arabinoside (ara-G) and exhibits activity against T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. It acts specifically on T-cells, and its mechanism of action involves the inhibition of DNA synthesis through incorporation into DNA and the termination of DNA chain elongation.  

Pharmacokinetics: 

Absorption 

nelarabine is administered as an intravenous infusion, so it is fully absorbed upon administration. 

Distribution 

nelarabine and its active metabolite, ara-G, have a volume of distribution of approximately 1 L/kg. It is widely distributed throughout the body and can cross the blood-brain barrier. 

Metabolism 

nelarabine is rapidly and extensively converted to its active metabolite, ara-G, primarily by adenosine deaminase (ADA) in erythrocytes and in other tissues. The active metabolite undergoes further metabolism to guanine and xanthine metabolites. 

Elimination and excretion 

nelarabine and its active metabolites are primarily eliminated through the kidneys. The plasma half-life of nelarabine is approximately 15 minutes, while that of its active metabolite, ara-G, is approximately 30 hours. 

Adminstartion

Administration: 

nelarabine is given as an intravenous (IV) infusion. The infusion is typically given over a period of two hours. The exact dosing and schedule will depend on the individual’s age, weight, overall health status, and type and stage of the cancer being treated. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: nelarabine 

Pronounced: [ nel-AR-a-been]  

Why do we use nelarabine? 

nelarabine is an antineoplastic medication used to treat T-cell acute lymphoblastic leukemia and lymphoma that has relapsed on other treatments. It is usually given as an intravenous infusion. nelarabine works by interfering with the DNA in cancer cells, causing them to stop growing and dividing. It is typically used in combination with other chemotherapy drugs as part of a treatment regimen.