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BCL2 Inhibitor

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BCL2 Inhibitor, B-Cell Leukemia/Lymphoma 2 Receptor Antagonist, Venetoclax, Venclexta

  • See Also
  1. Small Molecule Inhibitor-Mediated Chemotherapy
  2. Chemotherapy
  • Indications
  1. Chronic Lymphocytic Leukemia (17p deletion)
  2. Small Lymphocytic Lymphoma
  3. Acute Myeloid Leukemia (when intensive induction Chemotherapy is contraindicated)
  • Mechanism
  1. BCL2 (B-Cell Leukemia/Lymphoma 2)
    1. BCL2 is an anti-apoptotic Protein allows for cancer cell resistance to Chemotherapy
    2. BCL2 Gene is over-expressed in some cancers including Chronic Lymphocytic Leukemia
      1. BCL2 Gene is normally found on Chromosome 18
      2. BCL2 Gene is translocated to other Chromosomes in CLL, B-Cell Leukemia
  2. BCL2 Inhibitors
    1. Inhibit BCL2, allowing for apoptosis and normal cell death
    2. BCL-2 Inhibitors are a subcategory of BH3-mimetics
      1. BH3-mimetics inhibit antiapoptotic Proteins (BCL-2, BCL-w, BCL-X)
  • Medications
  1. Venetoclax (Venclexta): Tablets (10, 50, 100 mg)
  • Dosing
  1. See other references for disease specific dosing protocols
  • Adverse Effects
  1. Pancytopenia (severe)
    1. Monitor Complete Blood Count for severe Neutropenia
  2. Tumor Lysis Syndrome
    1. Includes Hyperuricemia and Acute Kidney Injury Risk
    2. Maximize hydration (and IV hydration as needed)
    3. Pretreatment with anti-hyperuricemics
  • Safety
  1. Avoid in Lactation
  2. Avoid in pregnancy (all trimesters)
    1. Pregnancy category X
    2. Use reliable Contraception
    3. Associated with fetal loss after implantation and IUGR
  • Drug Interactions
  1. Venetoclax is metabolized by CYP3A4, CYP3A5
  2. Immunizations
    1. Avoid Live Vaccines
  3. CYP3A Inhibitors
    1. Avoid strong CYP3A Inhibitors with Venetoclax (or decrease Venetoclax dose 75%)
    2. Avoid moderate CYP3A Inhibitors with Venetoclax (or decrease Venetoclax dose 50%)
  4. CYP3A Inducers
    1. Avoid moderate or strong CYP3A Inducers with Venetoclax
  5. P-Glycoprotein Inhibitors (P-Gp Inhibitors)
    1. Avoid P-Gp Inhibitors with Venetoclax (or decrease Venetoclax dose 50%)
  6. Narrow-Therapeutic Index P-Glycoprotein Substrates (P-Gp Substrates)
    1. Avoid Narrow-Therapeutic Index P-Gp Substrates (or give at least 6 hours before Venetoclax)
  • Resources
  1. Venetoclax (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b118a40d-6b56-cee3-10f6-ded821a97018
  • References
  1. Juárez-Salcedo (2019) Drugs Context 8:212574 +PMID: 31645879 [PubMed]