Cladribine

Dose-dependent myelosuppression (neutropenia, anemia, and thrombocytopenia) is common and generally reversible. Use with caution in patients with preexisting hematologic or immunologic abnormalities. Monitor blood counts, especially during the first 4 to 8 weeks after treatment.

Treatment is associated with fever (≥100°F), with or without neutropenia, and is observed more commonly in the first month of treatment.

Infections (bacterial, viral, and fungal) were reported more commonly in the first month after treatment (generally mild or moderate in severity, although serious infections including sepsis have been reported); the incidence is reduced in the second month. Due to neutropenia and T-cell depletion, risk versus benefit of treatment should be evaluated in patients with active infections. If active infection is present, manage appropriately prior to administering cladribine (Grever 2017).

Serious, dose-related neurologic toxicity (including irreversible paraparesis and quadriparesis) has been reported with continuous infusions of higher doses (4 to 9 times the approved dose); may also occur at approved doses (rare). Neurotoxicity may be delayed and may present as progressive, irreversible motor weakness of the upper and/or lower extremities; diagnostics with electromyography and nerve conduction studies were consistent with demyelinating disease. Neurotoxicity after high-dose administration was first noted 35 to 84 days after therapy initiation.

Acute nephrotoxicity (eg, acidosis, anuria, increased serum creatinine), possibly requiring dialysis, has been reported with high doses (4 to 9 times the approved dose), particularly when administered with other nephrotoxic agents. Per the manufacturer, nephrotoxicity has not occurred when used at the dose approved for hairy cell leukemia.

With high tumor burden, tumor lysis syndrome and subsequent hyperuricemia may occur (rare); consider antihyperuricemics and hydrate accordingly. Disease-related concerns:

Use with caution in patients with hepatic impairment.

Use with caution in patients with renal impairment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Dosage form specific issues:

Weekly (7-day) infusion preparation recommends further dilution with bacteriostatic normal saline which contains benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

Multiple sclerosis: Use is contraindicated in patients with active or latent tuberculosis. Complete immunizations at least 6 weeks prior to treatment initiation. Evaluate hepatitis B and C status prior to treatment. Assess varicella zoster virus (VZV) antibody status prior to treatment; if no confirmed history of chicken pox or vaccination and VZV antibody is negative, vaccination is recommended (delay cladribine for 6 weeks after vaccination). Only initiate treatment if lymphocyte counts are normal, Obtain a baseline MRI if patient has previously received MS therapy associated with progressive multifocal leukoencephalopathy (PML); do not initiate or re-initiate therapy until PML has been excluded. May be associated with an increased risk of malignancies. Other warnings/precautions:

Should be administered under the supervision of an experienced cancer chemotherapy physician.

Administration of live vaccines is not recommended during treatment with cladribine (may increase the risk of infection due to immunosuppression).