Nelzarabine

Nelzarabine Uses, Dosage, Side Effects, Food Interaction and all others data.

Nelzarabine is an antineoplastic agent that is typically employed to treat acute T-cell lymphoblastic leukemia. Nelzarabine is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity.

Nelzarabine is a prodrug of the cytotoxic deoxyguanosine analogue 9-ß-D-arabinofuranosylguanine (ara-G). Nelzarabine is demethylated by adenosine deaminase (ADA) to ara-G. Ara-G is then transported into cells, where it undergoes three phosphorylation steps, resulting in the formation of ara-G triphosphate (ara-GTP). In the first phosphorylation step, ara-G is converted to ara-G monophosphate (ara-GMP). Ara-GMP is then monophosphorylated by deoxyguanosine kinase and deoxycytidine kinase to ara-G diphosphate, and then subsequently to the active ara-G triphosphate (ara-GTP). Ara-GTP is the one that exerts the pharmacological effect. Pre-clinical studies have demonstrated that targeted T-cells possess marked sensitivity to the agent.

Trade Name Nelzarabine
Availability Prescription only
Generic Nelarabine
Nelarabine Other Names Nelarabina, Nelarabine, Nelzarabine
Related Drugs prednisone, methotrexate, dexamethasone, doxorubicin, Revlimid, imatinib, Gleevec, Imbruvica, mercaptopurine, Sprycel
Type
Formula C11H15N5O5
Weight Average: 297.2673
Monoisotopic: 297.107318615
Protein binding

Nelarabine and ara-G are not substantially bound to human plasma proteins (<25%) in vitro, and binding is independent of nelarabine or ara-G concentrations up to 600 mM.

Groups Approved, Investigational
Therapeutic Class
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
Nelzarabine
Nelzarabine

Uses

Nelzarabine is a purine nucleoside analog and antineoplastic agent used for the treatment of with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma with inadequate clinical response to prior chemotherapeutic treatments.

For the treatment of pediatric and adult patients with acute T-cell lymphoblastic leukemia and T-cell lymphoblastic lymphoma whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens.

Nelzarabine is also used to associated treatment for these conditions: Lymphoblastic lymphoma (Precursor T-lymphoblastic lymphoma/leukemia) refractory, Refractory Acute Lymphoblastic Leukemia

How Nelzarabine works

Once nelarabine is metabolized into ara-GTP, the metabolite accumulates in leukemic blasts and incorporates into DNA to exert its S phase-specific cytotoxic effects, leading to the induction of fragmentation and apoptosis. Ara-GTP competes with endogenous deoxyGTP (dGTP) for incorporation into DNA. Once ara-GTP is incorporated at the 3' end of DNA, further DNA elongation is inhibited, which signals apoptosis and leads to cellular destruction. Additional cytotoxic activities may exist, but these are not fully understood.

Toxicity

A single IV dose of 4,800 mg/m^2 was lethal in monkeys, and was associated with CNS signs including reduced/shallow respiration, reduced reflexes, and flaccid muscle tone. It is anticipated that overdosage would result in severe neurotoxicity (possibly including paralysis, coma), myelosuppression, and potentially death.

Food Interaction

No interactions found.

Half Life

Nelzarabine and ara-G are rapidly eliminated from plasma with a half-life of approximately 30 minutes and 3 hours.

Clearance

  • 197  +/-  189 L/h/m2 [Adult patients with refractory leukemia or lymphoma receiving doses of 199 to 2,900 mg/m2]
  • 259  +/-  409 L/h/m2 [Pediatric patients with refractory leukemia or lymphoma receiving doses of 104 to 2,900 mg/m2]

Elimination Route

Excretion: Nelzarabine and ara-G are partially eliminated by the kidneys.

Innovators Monograph

You find simplified version here Nelzarabine

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