CLADRIBINE
Clinical safety rating
cautionComprehensive clinical and safety monograph for CLADRIBINE (CLADRIBINE).
Comprehensive clinical and safety monograph for CLADRIBINE (CLADRIBINE).
FDA-approved: Treatment of hairy cell leukemia.Off-label: Chronic lymphocytic leukemia (CLL), multiple sclerosis (relapsing forms), Waldenström macroglobulinemia, cutaneous T-cell lymphoma, and as part of conditioning regimens for hematopoietic stem cell transplantation.
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.
| 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. |
| Molecular Weight | 285.69 |
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. |
| 1st trimester | Cladribine is contraindicated in the first trimester due to teratogenic effects observed in animal studies and potential for fetal harm. Use only if benefit outweighs risk and no alternative exists. |
| 2nd trimester | Avoid use in second trimester unless absolutely necessary. Limited human data; animal studies show adverse effects including embryolethality and teratogenicity. |
| 3rd trimester | Avoid use in third trimester due to risk of neonatal myelosuppression and immunosuppression. Use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for CLADRIBINE (CLADRIBINE).
| Placental transfer | Cladribine crosses the placenta in humans; demonstrated by measurable drug concentrations in fetal umbilical cord blood after maternal administration. Active transport via nucleoside transporters may contribute to fetal exposure. |
| Breastfeeding | Cladribine is excreted into breast milk in animal studies. Due to potential for serious adverse reactions in nursing infants (e.g., myelosuppression, immunosuppression, carcinogenicity), breastfeeding is not recommended during therapy and for at least 5 days after the last dose. |
| Lactation Rating | L5 (Contraindicated) |
| 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. |
| Fetal Monitoring | Complete blood count with differential and platelets at baseline and weekly during therapy. Monitor for signs of myelosuppression, infection, bleeding, and hepatotoxicity. Fetal ultrasound for growth and anatomy if exposure occurs. Postpartum monitoring of infant for myelosuppression. |
| Fertility Effects | Preclinical studies indicate cladribine may impair male and female fertility (oligospermia, amenorrhea). Human data limited; potential for decreased sperm counts and ovarian failure. Recovery may occur but may be incomplete. |
■ 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.
| Serious Effects |
Hypersensitivity to cladribine or any excipientCurrent malignancy (except hairy cell leukemia)Active infections (particularly opportunistic infections)Severe bone marrow suppression (e.g., neutropenia, thrombocytopenia)Pregnancy and breastfeedingConcurrent use of myelosuppressive agents (relative but often absolute in practice)
| 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. |
| Food/Dietary | No significant food interactions. Avoid grapefruit juice due to potential CYP3A4 interaction (though minimal). Maintain adequate hydration to prevent tumor lysis syndrome in hematologic malignancies. |
| Clinical Pearls | Cladribine is a purine nucleoside analog that causes lymphocyte depletion, effective in hairy cell leukemia and multiple sclerosis. Monitor for severe lymphopenia, opportunistic infections (e.g., herpes zoster, tuberculosis), and delayed myelosuppression. Do not administer live vaccines during or after treatment. Due to high bioavailability after subcutaneous administration, adjust dose for renal impairment. Hypersensitivity reactions may occur; premedicate with antihistamines if needed. |
| Patient Advice | Cladribine can significantly lower your white blood cell count, increasing infection risk. Report fever, chills, or sore throat immediately. · Avoid live vaccines (e.g., MMR, shingles) during and for at least 6 months after treatment. · You may experience fatigue, nausea, headache, or skin reactions at injection site. These are common but report severe symptoms. · Use effective contraception during treatment and for at least 6 months after the last dose. Cladribine may harm a fetus. · You will need regular blood tests to monitor your blood cell counts, liver, and kidney function. |
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