Leustatin: Full Drug Profile

Leustatin - General Information

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

Pharmacology of Leustatin

Leustatin is a synthetic antineoplastic agent with immunosuppressive effects. Leustatin is one of a group of chemotherapy drugs known as the anti-metabolites. Anti-metabolites stop cells making and repairing DNA. Cancer cells need to make and repair DNA in order to grow and multiply.

Leustatin for patients

LEUSTATIN (cladribine) Injection should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. Suppression of bone marrow function should be anticipated. This is usually reversible and appears to be dose dependent. Serious neurological toxicity (including irreversible paraparesis and quadraparesis) has been reported in patients who received LEUSTATIN Injection by continuous infusion at high doses (4 to 9 times the recommended dose for Hairy Cell Leukemia). Neurologic toxicity appears to demonstrate a dose relationship; however, severe neurological toxicity has been reported rarely following treatment with standard cladribine dosing regimens. Acute nephrotoxicity has been observed with high doses of LEUSTATIN (4 to 9 times the recommended dose for Hairy Cell Leukemia), especially when given concomitantly with other nephrotoxic agents/ therapies.

Leustatin Interactions

There are no known drug interactions with LEUSTATIN Injection. Caution should be exercised if LEUSTATIN Injection is administered before, after, or in conjunction with other drugs known to cause immunosuppression or myelosuppression.

Leustatin Contraindications

LEUSTATIN (cladribine) Injection is contraindicated in those patients who are hypersensitive to this drug or any of its components.

Additional information about Leustatin

Leustatin Indication

For the treatment of active hairy cell leukemia (leukemic reticuloendotheliosis) as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms.

Mechanism Of Action

Leustatin is structurally related to fludarabine and pentostatin but has a different mechanism of action. It is phosphorylated to its corresponding nucleotide CdATP, which accumulates and is incorporated into the DNA of cells such as lymphocytes. High levels of CdATP lead to DNA strand breaks, inhibition of DNA synthesis, 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.

Generic Name

Cladribine

Synonyms

2-Chloro-2'-deoxy-beta-adenosine; 2-CdA; 2-Chloro-2'-deoxyadenosine; 2-Chlorodeoxyadenosine; Chlorodeoxyadenosine

Drug Category

Immunosuppressive Agents; Antineoplastic Agents

Drug Type

Small Molecule; Approved; Investigational

Other Brand Names containing Cladribine

Leustatin;

Absorption

Oral bioavailability is 34 to 48%.

Toxicity (Overdose)

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

Protein Binding

20%

Biotransformation

Metabolized in all cells with deoxycytidine kinase activity to 2-chloro-2'-deoxyadenosine-5'-triphosphate

Half Life

5.4 hours

Dosage Forms of Leustatin

Solution Intravenous

Chemical IUPAC Name

(2R,3S,5R)-5-(6-amino-2-chloropurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol

Chemical Formula

C10H12ClN5O3

Cladribine on Wikipedia

https://en.wikipedia.org/wiki/Cladribine

Organisms Affected

Humans and other mammals