Cladribine (DB00242): A Comprehensive Pharmacological and Clinical Monograph

I. Executive Summary

Cladribine is a synthetic purine nucleoside analogue that occupies a unique and dichotomous position in contemporary pharmacotherapy. It exists as two distinct therapeutic entities, defined by formulation and indication, each addressing a fundamentally different pathological process. As an intravenous infusion sold under brand names such as Leustatin, it functions as a potent antineoplastic agent for the treatment of hairy cell leukemia (HCL), a rare hematological malignancy.[1] In its oral tablet formulation, marketed as Mavenclad, it serves as a high-efficacy, short-course immune reconstitution therapy for adults with relapsing forms of multiple sclerosis (MS), including relapsing-remitting and active secondary progressive disease.[1]

The therapeutic utility of Cladribine in these disparate fields is rooted in a single, powerful mechanism of action: the selective induction of apoptosis in B and T lymphocytes.[2] As a prodrug, Cladribine is metabolically activated intracellularly to its cytotoxic triphosphate form. Its selectivity is not achieved through targeted binding to surface receptors, but rather by exploiting an intrinsic enzymatic imbalance within lymphocytes, which possess high levels of the activating kinase (deoxycytidine kinase) and low levels of the deactivating nucleotidase. This leads to the accumulation of the active metabolite, which disrupts DNA synthesis and repair, triggers cellular energy depletion, and initiates mitochondrial-mediated cell death.[1] This targeted depletion of lymphocytes underpins its efficacy in both B-cell malignancies and autoimmune demyelinating disease.