II. Indications
- Chronic Lymphocytic Leukemia (17p deletion)
- Small Lymphocytic Lymphoma
- Acute Myeloid Leukemia (when intensive induction Chemotherapy is contraindicated)
III. Mechanism
- BCL2 (B-Cell Leukemia/Lymphoma 2)
- BCL2 is an anti-apoptotic Protein allows for cancer cell resistance to Chemotherapy
- BCL2 Gene is over-expressed in some cancers including Chronic Lymphocytic Leukemia
- BCL2 Gene is normally found on Chromosome 18
- BCL2 Gene is translocated to other Chromosomes in CLL, B-Cell Leukemia
- BCL2 Inhibitors
- Inhibit BCL2, allowing for apoptosis and normal cell death
- BCL-2 Inhibitors are a subcategory of BH3-mimetics
- BH3-mimetics inhibit antiapoptotic Proteins (BCL-2, BCL-w, BCL-X)
IV. Medications
- Venetoclax (Venclexta): Tablets (10, 50, 100 mg)
V. Dosing
- See other references for disease specific dosing protocols
VI. Adverse Effects
-
Pancytopenia (severe)
- Monitor Complete Blood Count for severe Neutropenia
-
Tumor Lysis Syndrome
- Includes Hyperuricemia and Acute Kidney Injury Risk
- Maximize hydration (and IV hydration as needed)
- Pretreatment with anti-hyperuricemics
VII. Safety
- Avoid in Lactation
- Avoid in pregnancy (all trimesters)
- Pregnancy category X
- Use reliable Contraception
- Associated with fetal loss after implantation and IUGR
VIII. Drug Interactions
- Venetoclax is metabolized by CYP3A4, CYP3A5
-
Immunizations
- Avoid Live Vaccines
-
CYP3A Inhibitors
- Avoid strong CYP3A Inhibitors with Venetoclax (or decrease Venetoclax dose 75%)
- Avoid moderate CYP3A Inhibitors with Venetoclax (or decrease Venetoclax dose 50%)
-
CYP3A Inducers
- Avoid moderate or strong CYP3A Inducers with Venetoclax
-
P-Glycoprotein Inhibitors (P-Gp Inhibitors)
- Avoid P-Gp Inhibitors with Venetoclax (or decrease Venetoclax dose 50%)
- Narrow-Therapeutic Index P-Glycoprotein Substrates (P-Gp Substrates)
- Avoid Narrow-Therapeutic Index P-Gp Substrates (or give at least 6 hours before Venetoclax)