Drug Groups

approved; investigational

Description

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

Indication

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.

Pharmacology

Cladribine is a synthetic purine nucleoside that acts as an antineoplastic agent with immunosuppressive effects. Cladribine 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. Cladribine 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.

Toxicity

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

Affected Organisms

Biotransformation

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

Absorption

Oral bioavailability is 34 to 48%.

Half Life

5.4 hours

Protein Binding

20%

Distribution

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

Clearance

* 978 +/- 422 mL/h/kg

References

External Links