Leustatin: profile and news

CLAG-M Regimen Effective in Refractory Acute Myeloid Leukemia Sep 2, 2005
...conducted a clinical trial to evaluate the treatment regimen CLAG-M. CLAG-M includes the chemotherapy agents cladribine (Leustatin®), fludarabine (Fludara ... - Cancer Consultants (press release),

FDA Sends SuperGen Warning Letter Over Nipent Handout Aug 22, 2005
...of ADA inhibition is "unique." Indeed, it appears that another purine analog, cladribine, also possesses this activity [LEUSTATIN® (cladribine) Injection full ... - PharmaLive.com (press release),

A guide to multiple sclerosis Mar 20, 2005
...management of MS. Studies are also being conducted with the immune system modulating drug cladribine (Leustatin). Another potential ... - The Wichita Eagle,

Will Scripps really be worth it? Mar 14, 2005
As an example, he trots out one of Scripps' best-known discoveries, the cancer drug Leustatin. It's manufactured in New Jersey, not San Diego. ... - Palm Beach Post,

Other information

Indication
For the treatment of active Hairy Cell Leukemia as defined by clinically significant anemia, neutropenia, thrombocytopenia or disease-related symptoms

Pharmacology
Cladribine is a synthetic antineoplastic agent indicated for the treatment of active Hairy Cell Leukemia as defined by clinically significant anemia, neutropenia, thrombocytopenia or disease-related symptoms. Cladribine is an antimetabolite. Cladribine's action is cell cycle-phase nonspecific; cladribine affects both dividing and resting lymphocytes.

Mechanism Of Action
Cladribine is structurally related to fludarabine and pentostatin but has a different mechanism of action. It is phosphorylated by deoxycytidine kinase to the corresponding nucleotide CdATP which accumulates and is incorporated into the DNA of cells such as lymphocytes. The phosphorylated metabolites of cladribine tend to accumulate in cells with a high ratio of deoxycytidine kinase activity to 5' nucleotidase activity (lymphocytes, monocytes ) and are converted to the active triphosphate deoxynucleotide. Intracellular accumulation of toxic deoxynucleotides selectively kills these cells, which become unable to properly repair single-strand DNA breaks, leading to disruption of cell metabolism. In addition, there is some evidence that deoxynucleotides are incorporated into the DNA of dividing cells and impair DNA synthesis. Cladribine also induces apoptosis (a form of programmed cell death in sensitive cells). Cladribine is resistant to the action of adenosine deaminase (ADA), which normally deaminates deoxyadenosine to deoxyinosine.

Drug Category
Immunosuppressive Agents; Antineoplastic Agents; ATC:L01BB04

Brand Names/Synonyms
2 Chlorodeoxyadenosine; Chlorodeoxyadenosine; Cladribine; Cladribine [Usan:Ban:Inn]; Leustatin

Dosage Forms
SOLUTION

Absorption
Oral bioavailability is 34-48%

Interactions
Interactions for Cladribine:

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.

Chemical IUPAC Name
5-(6-amino-2-chloro-purin-9-yl)-2-(hydroxymethyl)oxolan-3-ol

Chemical Formula
C10H12ClN5O3

Half Life
5.4 hours, with a half life in leukemic cells of 23 hours

Drug Type
Approved Drug

# Accession No
APRD00260

CAS Registry Number
4291-63-8