Leustatine

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

An antineoplastic agent used in the treatment of lymphoproliferative diseases including hairy-cell leukemia.

Leustatine is a synthetic purine nucleoside that acts as an antineoplastic agent with immunosuppressive effects. Leustatine differs structurally from deoxyadenosine only by the presence of a chlorine atom at position 2 of the purine ring, which results in resistance to enzymatic degradation by adenosine deaminase. Due to this resistance, cladribine exhibits a more prolonged cytotoxic effect than deoxyadenosine against resting and proliferating lymphocytes. Leustatine is one of a group of chemotherapy drugs known as the anti-metabolites. Anti-metabolites stop cells from making and repairing DNA, which are processes that are necessary for cancer cells to grow and multiply.

Trade Name Leustatine
Availability Prescription only
Generic Cladribine
Cladribine Other Names 2-CdA, 2-chloro-deoxyadenosine, 2-Chlorodeoxyadenosine, 2ClAdo, Cladribina, Cladribine, Cladribinum, CldAdo
Related Drugs Ocrevus, Aubagio, Zeposia, Mavenclad, Gilenya, Tysabri, Vumerity, Copaxone, Tecfidera, Avonex
Type
Formula C10H12ClN5O3
Weight Average: 285.687
Monoisotopic: 285.062866982
Protein binding

20%

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

Uses

Leustatine is a purine antimetabolite used for the management of relapsing forms of Multiple Sclerosis (MS), used in patients who have not responded to or who were unable to tolerate alternative MS drugs.

For the treatment of active hairy cell leukemia (leukemic reticuloendotheliosis) as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms. Also used as an alternative agent for the treatment of chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin's lymphoma, and cutaneous T-cell lymphoma.

Leustatine is also used to associated treatment for these conditions: Chronic Lymphocytic Leukaemia (CLL), Cutaneous T-Cell Lymphoma (CTCL), Hairy Cell Leukemia (HCL), Non-Hodgkin's Lymphoma (NHL), Active confirmed by clinical features, confirmed by imaging features relapsing multiple sclerosis (MS)

How Leustatine works

Leustatine is structurally related to fludarabine and pentostatin but has a different mechanism of action. Although the exact mechanism of action has not been fully determined, evidence shows that cladribine is phosphorylated by deoxycytidine kinase to the nucleotidecladribine triphosphate (CdATP; 2-chloro-2′-deoxyadenosine 5′-triphosphate), which accumulates and is incorporated into DNA in cells such as lymphocytes that contain high levels of deoxycytidine kinase and low levels of deoxynucleotidase, resulting in DNA strand breakage and inhibition of DNA synthesis and repair. High levels of CdATP also appear to inhibit ribonucleotide reductase, which leads to an imbalance in triphosphorylated deoxynucleotide (dNTP) pools and subsequent DNA strand breaks, inhibition of DNA synthesis and repair, nicotinamide adenine dinucleotide (NAD) and ATP depletion, and cell death. Unlike other antimetabolite drugs, cladribine has cytotoxic effects on resting as well as proliferating lymphocytes. However, it does cause cells to accumulate at the G1/S phase junction, suggesting that cytotoxicity is associated with events critical to cell entry into S phase. It also binds purine nucleoside phosphorylase (PNP), however no relationship between this binding and a mechanism of action has been established.

Toxicity

Symptoms of overdose include irreversible neurologic toxicity (paraparesis/quadriparesis), acute nephrotoxicity, and severe bone marrow suppression resulting in neutropenia, anemia and thrombocytopenia.

Food Interaction

  • Avoid echinacea. Echinacea should be used with caution, if at all, in patients receiving therapeutic immunosuppressants. Monitor for reduced efficacy of the immunosuppressant during concomitant use.

[Moderate] ADJUST DOSING INTERVAL: Oral cladribine may increase the bioavailability of other drugs, which may increase the risk or severity of adverse reactions.

Leustatine tablets may contain hydroxypropyl betadex, which could form a complex with the active ingredients of other drugs, especially agents with low solubility.

The clinical relevance of this interaction remains unknown.

MANAGEMENT: Administration of oral cladribine should be separated from any other oral drug by at least 3 hours.

Volume of Distribution

  • 4.5 ± 2.8 L/kg [patients with hematologic malignancies]
  • 9 L/kg

Elimination Route

Oral bioavailability is 34 to 48%.

Half Life

5.4 hours

Clearance

  • 978 +/- 422 mL/h/kg

Innovators Monograph

You find simplified version here Leustatine

*** Taking medicines without doctor's advice can cause long-term problems.
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