CLADRIBINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CLADRIBINE (CLADRIBINE).

How it works

Cladribine is a purine nucleoside analog that is phosphorylated intracellularly to its active triphosphate form, which inhibits DNA synthesis and repair, leading to cell death, particularly in lymphocytes. It also depletes adenosine deaminase (ADA) and accumulates in cells with high deoxycytidine kinase activity.

What the body does with it

Metabolism	Cladribine is primarily metabolized intracellularly by deoxycytidine kinase to its active triphosphate. It is also phosphorylated by deoxyguanosine kinase in mitochondria. Catabolism involves deamination by adenosine deaminase (ADA) to 2-chloroadenine, which is further metabolized.
Excretion	Renal (approximately 50% as unchanged drug); fecal elimination is minimal (<5%).
Half-life	Terminal elimination half-life is approximately 5.4 hours (range 4.6–6.7 hours) after intravenous administration; prolonged in renal impairment.
Protein binding	Approximately 20–30% bound to plasma proteins.
Volume of Distribution	Approximately 4.5 L/kg (range 2.3–9.6 L/kg), indicating extensive tissue distribution.
Bioavailability	Oral: approximately 37–55% (first-pass metabolism); subcutaneous: approximately 100%.
Onset of Action	Intravenous: clinical response may be observed within 1–2 weeks; oral: similar onset after absorption.
Duration of Action	Duration of pharmacodynamic effect (lymphocyte depletion) may persist for weeks to months after a single course; repeated dosing used for cumulative effect.

Classification & Brands

Dosing & administration

0.09 mg/kg/day IV over 2 hours for 7 consecutive days; or 0.14 mg/kg/day IV over 2 hours for 5 consecutive days (total dose 0.7 mg/kg per course).

Dosage form	TABLET
Renal impairment	GFR <50 mL/min: reduce dose by 50%; GFR <10 mL/min: avoid use.
Liver impairment	Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated.
Pediatric use	0.09 mg/kg/day IV over 2 hours for 7 consecutive days; or 0.14 mg/kg/day IV over 2 hours for 5 consecutive days (total dose 0.7 mg/kg per course). No specific pediatric dose adjustments beyond weight-based dosing.
Geriatric use	No specific dose adjustment recommended; monitor renal function and adjust accordingly.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CLADRIBINE (CLADRIBINE).

Breastfeeding	Contraindicated during breastfeeding. Cladribine is excreted into human milk; M/P ratio not determined. Potential for severe adverse effects in nursing infants, including myelosuppression and immunosuppression. Discontinue breastfeeding during therapy and for at least 7 days after last dose.
Teratogenic Risk	FDA Pregnancy Category D. First trimester: Avoid due to known teratogenicity in animal studies (skeletal and visceral malformations) and potential for MDS and AML. Second and third trimesters: Risk of fetal myelosuppression, intrauterine growth restriction, and preterm labor. Cladribine crosses the placenta and may cause fetal hematopoietic suppression.

Warnings & precautions

■ FDA Black Box Warning

WARNING: Neurotoxicity and Hematologic Toxicity. Cladribine can cause severe bone marrow suppression (neutropenia, anemia, thrombocytopenia) and neurotoxicity (including paralysis, coma, and death). Dose-dependent and more frequent in high doses.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to cladribine or any component of the formulation.","Pre-existing severe bone marrow suppression (e.g., neutropenia, thrombocytopenia) unless due to underlying disease.","Pregnancy: Can cause fetal harm.","Lactation: Discontinue nursing or drug."]

Clinical Precautions

Precautions

["Myelosuppression: Monitor blood counts regularly; dose adjustment or discontinuation may be needed.","Neurotoxicity: Risk increased with high doses and in patients with renal impairment.","Nephrotoxicity: Use with caution in renal impairment; reduce dose if CrCl < 60 mL/min.","Hepatotoxicity: Monitor liver function tests.","Secondary malignancies: Increased risk of myelodysplasia and acute myeloid leukemia.","Infections: Increased susceptibility due to lymphopenia; consider prophylaxis."]

Clinical Tips & Counseling

Drug interactions

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CLADRIBINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CLADRIBINE (CLADRIBINE).

How it works

What the body does with it

Metabolism	Cladribine is primarily metabolized intracellularly by deoxycytidine kinase to its active triphosphate. It is also phosphorylated by deoxyguanosine kinase in mitochondria. Catabolism involves deamination by adenosine deaminase (ADA) to 2-chloroadenine, which is further metabolized.
Excretion	Renal (approximately 50% as unchanged drug); fecal elimination is minimal (<5%).
Half-life	Terminal elimination half-life is approximately 5.4 hours (range 4.6–6.7 hours) after intravenous administration; prolonged in renal impairment.
Protein binding	Approximately 20–30% bound to plasma proteins.
Volume of Distribution	Approximately 4.5 L/kg (range 2.3–9.6 L/kg), indicating extensive tissue distribution.
Bioavailability	Oral: approximately 37–55% (first-pass metabolism); subcutaneous: approximately 100%.
Onset of Action	Intravenous: clinical response may be observed within 1–2 weeks; oral: similar onset after absorption.
Duration of Action	Duration of pharmacodynamic effect (lymphocyte depletion) may persist for weeks to months after a single course; repeated dosing used for cumulative effect.

Classification & Brands

Dosing & administration

0.09 mg/kg/day IV over 2 hours for 7 consecutive days; or 0.14 mg/kg/day IV over 2 hours for 5 consecutive days (total dose 0.7 mg/kg per course).

Dosage form	TABLET
Renal impairment	GFR <50 mL/min: reduce dose by 50%; GFR <10 mL/min: avoid use.
Liver impairment	Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated.
Pediatric use	0.09 mg/kg/day IV over 2 hours for 7 consecutive days; or 0.14 mg/kg/day IV over 2 hours for 5 consecutive days (total dose 0.7 mg/kg per course). No specific pediatric dose adjustments beyond weight-based dosing.
Geriatric use	No specific dose adjustment recommended; monitor renal function and adjust accordingly.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CLADRIBINE (CLADRIBINE).

Breastfeeding	Contraindicated during breastfeeding. Cladribine is excreted into human milk; M/P ratio not determined. Potential for severe adverse effects in nursing infants, including myelosuppression and immunosuppression. Discontinue breastfeeding during therapy and for at least 7 days after last dose.
Teratogenic Risk	FDA Pregnancy Category D. First trimester: Avoid due to known teratogenicity in animal studies (skeletal and visceral malformations) and potential for MDS and AML. Second and third trimesters: Risk of fetal myelosuppression, intrauterine growth restriction, and preterm labor. Cladribine crosses the placenta and may cause fetal hematopoietic suppression.