Purine deoxyadenosine analog with high specificity for lymphoid cells.
Presence of the 2-chloro group on adenine ring renders cladribine resistant to breakdown by adenosine deaminase.
Antitumor activity against both dividing and resting cells.
Metabolized intracellularly to 5'-triphosphate form (Cld-ATP), which is the presumed active species.
Triphosphate metabolite incorporates into DNA resulting in inhibition of DNA chain extension and inhibition of DNA synthesis and function.
Inhibition of ribonucleotide reductase.
Depletes nicotine adenine dinucleotide (NAD) concentration, resulting in depletion of ATP.
Induction of apoptosis (programmed cell death).
Decreased expression of the activating enzyme deoxycytidine kinase, resulting in decreased formation of cytotoxic cladribine metabolites.
Increased expression of 5'-nucleotidase, which dephosphorylates cladribine nucleotide metabolites Cld-AMP and Cld-ATP.
Widely distributed throughout the body. About 20% of drug is bound to plasma proteins. Crosses the blood-brain barrier, but CSF concentrations reach only 25% of those in plasma.
Recommended dose is 0.09 mg/kg/day IV via continuous infusion for 7 days. One course is usually administered. If the patient does not respond to one course, it is unlikely that a response will be seen with a second course of therapy.
Use with caution in patients with abnormal renal function.
Monitor for signs of infection. Patients are at increased risk for opportunistic infections, including herpes, fungus, and Pneumocystis jiroveci (PJP).
Monitor for signs of tumor lysis syndrome. Increased risk in patients with a high tumor cell burden.
Allopurinol should be given before initiation of therapy to prevent hyperuricemia.
Pregnancy category D. Breastfeeding should be avoided.
Myelosuppression is dose-limiting toxicity. Neutropenia more commonly observed than anemia or thrombocytopenia, and neutrophil nadir occurs at 7-14 days, with recovery in 3-4 weeks.
Immunosuppression with decrease in CD4 and CD8 cells. Increased risk of opportunistic infections, including fungus, herpes, and PJP. Complete recovery of CD4 counts to normal may take up to 40 months.
Fever occurs in 40%-50% of patients. Most likely due to release of pyrogens and/or cytokines from tumor cells. Associated with fatigue, malaise, myalgias, arthralgias, and chills. Incidence decreases with continued therapy.
Mild nausea and vomiting observed in less than 30% of patients.
Tumor lysis syndrome. Rare event most often in the setting of high tumor cell burden.
Skin reaction at the site of injection.
