|Systematic (IUPAC) name|
|Trade names||Leustatin, others|
|Intravenous, subcutaneous, oral|
|Protein binding||25% (range 5-50%)|
|Metabolism||Mostly via intracellular kinases; 15-18% if excreted unchanged|
|Biological half-life||5.4 hours (range 3-22 hours)|
|ATC code||L01BB04 (WHO)|
|Molar mass||285.687 g/mol|
As a purine analog, it is a synthetic anti-cancer agent that also suppresses the immune system. Chemically, it mimics the nucleoside adenosine and thus inhibits the enzyme adenosine deaminase, which interferes with the cell's ability to process DNA. It is easily destroyed by normal cells except for blood cells, with the result that it produces relatively few side effects and results in very little non-target cell loss.
Cladribine suppresses the body's ability to make new blood cells (called Myelosuppression); about 70% of people taking the drug have fewer white blood cells and about 30% developed infections and some of those progressed to septic shock; about 40% of people taking the drug have fewer red blood cells and become severely anemic; and about 10% of people have too few platelets.
Many people have mild rashes and many have nausea; the nausea generally does not lead to vomiting.
Cladribine was designed by Dennis A. Carson as an anti-lymphocyte compound, while he was at The Scripps Research Institute in La Jolla, California. It was first synthesized at Brigham Young University. The pharmacology and clinical applications were researched by scientists at Johnson and Johnson , which filed the New Drug Application and launched the drug in 1993.
Cladribine was designed based on information about an immune deficiency disease called adenosine deaminase deficiency. Carson described it as "a targeted agent directed against lymphocytes at a time when there was no such thing as targeted agents".
In 2008, Ernest Beutler of The Scripps Research Institute won the Wallace H. Coulter Award for Lifetime Achievement in Hematology from the Coulter Foundation and the American Society of Hematology in part because of the clinical trials he ran, which established cladribine as the most effective treatment for hairy cell leukemia (HCL).
In 2010, a by mouth form of cladribine was studied for the treatment of multiple sclerosis. Russia was the first country to approve it for treating multiple sclerosis on July 12, 2010. Other applications, including in Europe and North America, were initially rejected by drug regulatory agencies due to weak evidence of safety and efficacy. In June 2011, Merck withdrew all marketing applications for cladribine tablets, and to stop selling it in Russia and Australia, where it had been approved it.
- Drugs.com International trade names for Cladribine Page accessed Jan 14, 2015
- "PRODUCT INFORMATION LITAK© 2 mg/mL solution for injection" (PDF). TGA eBusiness Services. St Leonards, Australia: Orphan Australia Pty. Ltd. 10 May 2010. Retrieved 27 November 2014.
- Else M, Dearden CE, Matutes E, et al. (March 2009). "Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis". Br. J. Haematol. 145 (6): 733–40. doi:10.1111/j.1365-2141.2009.07668.x. PMID 19344416.
- Cladribine label, last updated July 2012. Page accessed January 14, 2015
- Histiocytosis Association
- Lichtman, Marshall A.; Josef Prchal & Karl Blume (1 January 2008). "Wallace H. Coulter Award for Lifetime Achievement in Hematology: Inaugural Award Winner Ernest Beutler, MD". The Hematologist (American Society of Hematology).
- Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 258. ISBN 0-471-89979-8.
- Fikes, Bradley J. (24 June 2015). "Leukemia drug cladribine may get new use". The San Diego Union-Tribune.
- Hasanali, Zainul S.; Saroya, Bikramajit Singh; Stuart, August; Shimko, Sara; Evans, Juanita; Shah, Mithun Vinod; Sharma, Kamal; Leshchenko, Violetta V.; Parekh, Samir (24 June 2015). "Epigenetic therapy overcomes treatment resistance in T cell prolymphocytic leukemia". Science Translational Medicine 7 (293): 293ra102–293ra102. doi:10.1126/scitranslmed.aaa5079. ISSN 1946-6234. PMID 26109102.
- Giovannoni G, et al., NEJM 2010
- Hirschler, Ben (July 12, 2010). "UPDATE 1-Russia okays Merck KGaA's multiple sclerosis pill". Reuters.