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Cladribine

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Cladribine, Leustatin, Chlorodeoxyadenosine, 2-CDA, Mavenclad

  • See Also
  1. Chemotherapy
  2. Antimetabolite Chemotherapy
  • Indications
  1. FDA Approved
    1. Hairy Cell Leukemia
    2. Multiple Sclerosis (progressive, relapsing forms)
  2. Off-Label Use
    1. Acute Myelogenous Leukemia (adults and children)
    2. Advanced Cutaneous T Cell Lymphoma
    3. Autoimmune Hemolytic Anemia
    4. Chronic Lymphocytic Leukemia (CLL)
    5. Langerhans Cell Histiocytosis (children)
    6. Non-Hodgkin Lymphoma
    7. Sezary Syndrome
    8. Waldenstrom's Macroglobulinemia
  • Contraindications
  1. Active malignancy
  2. Moderate to severe Renal Insufficiency
  3. Moderate to severe hepatic insufficiency
  4. Acute infections
  5. Chronic Infections (exclude before administration)
    1. HIV Infection
    2. Hepatitis BVirus
    3. Hepatitis CVirus
    4. Tuberculosis
  • Mechanism
  1. Purine Nucleoside antimetabolite analog
  2. Cladribine is metabolized intracellularly to 2-CdATP (Cladribine triphosphate, an active metabolite)
  3. 2-CdATP incorporates into DNA
    1. Results in DNA single strand breaks
  4. Also depletes energy molecules
    1. Nicotinamide Adenine Dinucleotide (NAD)
    2. Adenosine Triphosphate (ATP)
  5. Selectively more toxic to cancerous Lymphocytes and Monocytes
    1. Cladribine is resistant to Adenosine deaminase (therefore selective for Lymphocytes and Monocytes)
    2. Noncancerous Lymphocytes and Monocytes are less responsive to Cladribine
  • Medications
  1. Leustatin IV Solution: 10 mg per 10 ml vials (Hairy Cell Leukemia)
  2. Mavenclad oral tablets: 10 mg (Multiple Sclerosis)
  • Dosing
  1. See other references for disease specific dosing protocols
  • Adverse Effects
  1. Alopecia
  2. Fever
  3. Headache
  4. Impaired future fertility
  5. Myelosuppression (with prolonged drop in CD4 Count)
  6. Nephrotoxicity
  7. Neurotoxicity
  8. Hepatotoxicity
  9. Rash
  10. Secondary malignancy
  • Safety
  1. Avoid in Pregnancy (any trimester)
    1. Men and women should use reliable Contraception for at least 6 months after last dose
  2. Avoid in Lactation
    1. Avoid Breast Feeding for at least 10 days after last dose
  3. Monitoring
    1. MRI Brain
      1. Risk of Progressive Multifocal Leukoencephalopathy
      2. Baseline within first 3 months of starting Cladribine
    2. Complete Blood Count
      1. Lymphocytes should be in normal range before first treatment
      2. Lymphocytes should be >800 cells/uL before second treatment (may required delayed course)
    3. Renal Function tests
    4. Liver Function Tests
  • Drug Interactions
  1. Live attenuated Vaccinations
    1. Give all Live Vaccines at least 4 to 6 weeks before starting Cladribine
  • Resources
  1. Cladribine IV Solution (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a2592a9b-bca6-4a5a-89c2-855a0634d5fe
  2. Mavenclad Oral Tablets (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9c75e30a-a410-40f1-b653-04d532bd9144