Therapeutic Classification: antineoplastics
Pharmacologic Classification: bcl 2 inhibitors
Absorption: Well absorbed with food following oral administration; bioavailability ↑ by high-fat foods.
Distribution: Extensively distributed to tissues.
Protein Binding: 99%.
Metabolism/Excretion: Primarily metabolized by CYP3A4/5. 99% excreted in feces (21% as unchanged drug).
Half-Life: 26 hr.
Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia
- PO (Adults ): Monotherapy: Start with the following 5–wk venetoclax ramp-up phase: 20 mg once daily during Wk 1, then 50 mg once daily during Wk 2, then 100 mg once daily during Wk 3, then 200 mg once daily during Wk 4, then 400 mg once daily during Wk 5. After completion of ramp-up phase, continue venetoclax therapy at 400 mg once daily until disease progression or unacceptable toxicity. In combination with rituximab: Start with the following 5–wk venetoclax ramp-up phase: 20 mg once daily during Wk 1, then 50 mg once daily during Wk 2, then 100 mg once daily during Wk 3, then 200 mg once daily during Wk 4, then 400 mg once daily during Wk 5. After completion of ramp-up phase, start rituximab which will be administered on Day 1 of each 28–day cycle for a total of 6 cycles. Continue venetoclax therapy at 400 mg once daily starting on Day 1 of Cycle 1 and continue for 24 mo (from Day 1 of Cycle 1). In combination with obinutuzumab: Start with obinutuzumab on Days 1, 2, 8, and 15 of Cycle 1 and then on Day 1 of each subsequent 28–day cycle for a total of 6 cycles. On Day 22 of Cycle 1, start 5–wk venetoclax ramp-up phase: 20 mg once daily during Wk 1, then 50 mg once daily during Wk 2, then 100 mg once daily during Wk 3, then 200 mg once daily during Wk 4, then 400 mg once daily during Wk 5. After completion of ramp-up phase on Day 28 of Cycle 2, continue venetoclax therapy at 400 mg once daily from Day 1 of Cycle 3 until Day 28 of Cycle 12. Concurrent use of strong CYP3A inhibitors (including posaconazole) (during ramp–up phase): Contraindicated; Concurrent use of posaconazole (after ramp–up phase): ↓venetoclax dose to 70 mg once daily. Concurrent use of strong CYP3A inhibitors other than posaconazole (after ramp–up phase): ↓venetoclax dose to 100 mg once daily. Concurrent use of moderate CYP3A inhibitors or P-gp inhibitors (during or after ramp–up phase): ↓venetoclax dose by≥50%.
Hepatic Impairment
- PO (Adults ): Severe hepatic impairment: ↓dose by 50%.
Acute Myeloid Leukemia
- PO (Adults ): In combination with azacitidine or decitabine: Start with the following venetoclax ramp-up phase: 100 mg on Day 1, then 200 mg on Day 2, then 400 mg on Day 3, then 400 mg on Day 4. After completion of ramp-up phase, continue venetoclax therapy at 400 mg once daily until disease progression or unacceptable toxicity. Start azacitidine or decitabine on Day 1. In combination with low-dose cytarabine: Start with the following venetoclax ramp-up phase: 100 mg on Day 1, then 200 mg on Day 2, then 400 mg on Day 3, then 600 mg on Day 4. After completion of ramp-up phase, continue venetoclax therapy at 600 mg once daily until disease progression or unacceptable toxicity. Start low-dose cytarabine on Day 1. Concurrent use of posaconazole: ↓venetoclax dose during ramp-up phase to 10 mg on Day 1, then 20 mg on Day 2, then 50 mg on Day 3, then 70 mg on Day 4. After completion of ramp-up phase, ↓ venetoclax dose to 70 mg once daily. Concurrent use of strong CYP3A inhibitors other than posaconazole: ↓venetoclax dose during ramp-up phase to 10 mg on Day 1, then 20 mg on Day 2, then 50 mg on Day 3, then 100 mg on Day 4. After completion of ramp-up phase, ↓ venetoclax dose to 100 mg once daily. Concurrent use of moderate CYP3A inhibitors or P-gp inhibitors: ↓venetoclax dose by≥50% during or after completion of ramp-up phase.
Hepatic Impairment
- PO (Adults ): Severe hepatic impairment: ↓dose by 50%.
