DRUG STUDY AND INFORMATION FORM Generic Name: Cladribine Trade Name: Litak, Movectro Drug Class: Purine

Analogs Structure/Chemistry: Adenosine deaminase-resistant purine analog.

Pharmacodynamics

Mechanism of Action: Taken up by nucleoside transport and phosphorylated intracellularly by deoxycytidine kinase to cladribine triphosphate for incorporation into DNA. It produces DNA strand breaks and depletion of NAD and ATP, leading to apoptosis. Also, it is a potent inhibito of RNR (ribonucleotide reductase).

Pharmacologic Effects: Destroys genomic integrity and depletes NAD and ATP which all lead to cellular apoptosis

Drug Resistance or Tolerance: Decreased deoxycytidine kinase, increased expression of RNR, or increased active efflux by ABCG2 or other members of the ABC cassette family of transporters

Pharmacokinetics

Absorption: Usually given IV (0.09 mg/kg/day for 7 days). Moderately well absorbed orally (55%).

Distribution: Can cross blood-brain barrier into CSF (reaches about 25% of plasma concentration) Elimination: t1/2 of 6.7 hours in plasma. Excreted by kidneys (adjust dose for renal dysfunction).

Metabolism:

Adverse Side Effects/Toxicity: Mainly myelosuppression but also thrombocytopenia and decreased CD4+ counts (increased opportunistic infections). Other toxic effects include nausea, high fever, headache, fatigue, skin rashes, and tumor lysis syndrome.

Drug Interactions:

Therapeutic uses: Potent and probably curable activity against hairy cell leukemia (drug of choice for), CLL (chronic lymphocytic leukemia), Langerhans cell histiocytosis, CTCLs and low-grade lymphomas

Miscellaneous: