LEUSTATIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LEUSTATIN (LEUSTATIN).

How it works

Cladribine is a purine nucleoside analog that is phosphorylated intracellularly to its active triphosphate form, which inhibits DNA synthesis and repair by incorporating into DNA and inhibiting ribonucleotide reductase and DNA polymerase. It is particularly toxic to lymphocytes due to high levels of deoxycytidine kinase activity in these cells.

What the body does with it

Metabolism	Cladribine is phosphorylated intracellularly by deoxycytidine kinase to cladribine monophosphate, then to cladribine triphosphate. It is eliminated primarily by renal excretion, with minimal hepatic metabolism via CYP450 enzymes.
Excretion	Renal excretion of unchanged drug accounts for approximately 30-50% of the dose; the remainder is metabolized. Fecal excretion is minimal (<5%).
Half-life	Terminal elimination half-life is approximately 5.4 hours (range 3-9 hours) in patients with normal renal function; may be prolonged in renal impairment.
Protein binding	Approximately 5% bound to plasma proteins.
Volume of Distribution	Volume of distribution is approximately 0.42 L/kg (range 0.2-0.6 L/kg), indicating distribution primarily into total body water.
Bioavailability	Not applicable; administered only intravenously (bolus or continuous infusion).
Onset of Action	Intravenous: Clinical response (e.g., reduction in neutrophil count) may be observed within 24-48 hours.
Duration of Action	Duration of hematologic suppression (neutropenia, thrombocytopenia) is typically 4-6 weeks after a single 7-day continuous infusion; recovery may take longer.

Classification & Brands

Dosing & administration

0.09 mg/kg/day IV continuous infusion for 7 days for hairy cell leukemia; 5 mg/m²/day IV over 2 hours for 5 days for chronic lymphocytic leukemia.

Dosage form	INJECTABLE
Renal impairment	Cladribine is not recommended in severe renal impairment (CrCl <30 mL/min). For moderate impairment (CrCl 30-60 mL/min), reduce dose by 25-50% or use with caution.
Liver impairment	No specific guidelines for hepatic impairment. Use caution in severe hepatic impairment (Child-Pugh C) as metabolism may be affected; consider dose reduction based on toxicity.
Pediatric use	Safety and efficacy not established. Limited data: 0.1 mg/kg/day IV continuous infusion for 7 days in some protocols for Langerhans cell histiocytosis.
Geriatric use	No specific dose adjustments. Monitor renal function and hematologic toxicity closely due to age-related decline in renal function and bone marrow reserve.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LEUSTATIN (LEUSTATIN).

Breastfeeding	No data on excretion in human milk. M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants, breastfeeding is contraindicated during therapy and for at least 1 week after last dose.
Teratogenic Risk	Cladribine (Leustatin) is classified as pregnancy category D. It is embryotoxic and teratogenic in animals. First trimester exposure may cause fetal malformations. Second and third trimester exposure may cause fetal bone marrow suppression, pancytopenia, and intrauterine growth restriction. Contraindicated in pregnancy unless benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

WARNING: NEUROTOXICITY, HEMATOLOGIC TOXICITY, AND INFECTION. Cladribine can cause severe neurologic toxicity, including irreversible paraplegia and quadriplegia, at high doses. Severe bone marrow suppression, including neutropenia, anemia, and thrombocytopenia, commonly occurs. Patients are at increased risk for severe infections, including opportunistic infections.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to cladribine or any component of the formulation","Severe active infections","Intrathecal administration (not for this route)","Concurrent use with other myelosuppressive drugs (relative)"]

Clinical Precautions

Precautions

["Bone marrow suppression: monitor blood counts regularly","Neurotoxicity: potential for severe myelopathy at high doses","Infections: increased risk of opportunistic infections, including herpes zoster and tuberculosis","Renal impairment: dose adjustment recommended for CrCl <50 mL/min","Pregnancy: may cause fetal harm based on animal data","Immunization: avoid live vaccines during treatment"]

Clinical Tips & Counseling

Drug interactions

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LEUSTATIN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for LEUSTATIN (LEUSTATIN).

How it works

What the body does with it

Metabolism	Cladribine is phosphorylated intracellularly by deoxycytidine kinase to cladribine monophosphate, then to cladribine triphosphate. It is eliminated primarily by renal excretion, with minimal hepatic metabolism via CYP450 enzymes.
Excretion	Renal excretion of unchanged drug accounts for approximately 30-50% of the dose; the remainder is metabolized. Fecal excretion is minimal (<5%).
Half-life	Terminal elimination half-life is approximately 5.4 hours (range 3-9 hours) in patients with normal renal function; may be prolonged in renal impairment.
Protein binding	Approximately 5% bound to plasma proteins.
Volume of Distribution	Volume of distribution is approximately 0.42 L/kg (range 0.2-0.6 L/kg), indicating distribution primarily into total body water.
Bioavailability	Not applicable; administered only intravenously (bolus or continuous infusion).
Onset of Action	Intravenous: Clinical response (e.g., reduction in neutrophil count) may be observed within 24-48 hours.
Duration of Action	Duration of hematologic suppression (neutropenia, thrombocytopenia) is typically 4-6 weeks after a single 7-day continuous infusion; recovery may take longer.

Classification & Brands

Dosing & administration

0.09 mg/kg/day IV continuous infusion for 7 days for hairy cell leukemia; 5 mg/m²/day IV over 2 hours for 5 days for chronic lymphocytic leukemia.

Dosage form	INJECTABLE
Renal impairment	Cladribine is not recommended in severe renal impairment (CrCl <30 mL/min). For moderate impairment (CrCl 30-60 mL/min), reduce dose by 25-50% or use with caution.
Liver impairment	No specific guidelines for hepatic impairment. Use caution in severe hepatic impairment (Child-Pugh C) as metabolism may be affected; consider dose reduction based on toxicity.
Pediatric use	Safety and efficacy not established. Limited data: 0.1 mg/kg/day IV continuous infusion for 7 days in some protocols for Langerhans cell histiocytosis.
Geriatric use	No specific dose adjustments. Monitor renal function and hematologic toxicity closely due to age-related decline in renal function and bone marrow reserve.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for LEUSTATIN (LEUSTATIN).

Breastfeeding	No data on excretion in human milk. M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants, breastfeeding is contraindicated during therapy and for at least 1 week after last dose.
Teratogenic Risk	Cladribine (Leustatin) is classified as pregnancy category D. It is embryotoxic and teratogenic in animals. First trimester exposure may cause fetal malformations. Second and third trimester exposure may cause fetal bone marrow suppression, pancytopenia, and intrauterine growth restriction. Contraindicated in pregnancy unless benefit outweighs risk.