Leukemias, lymphomas, and other hematologic cancers:
Indications for: VENCLEXTA
Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Newly-diagnosed acute myeloid leukemia (AML) in adults age ≥75yrs or who have comorbidities that preclude use of intensive induction chemotherapy, in combination with azacitidine, or decitabine, or low-dose cytarabine.
Assess for level of tumor lysis syndrome risk; provide prophylactic hydration and anti-hyperuricemics prior to 1st dose. Swallow whole. Take with food and water at the same time each day. CLL/SLL (initiate with 5-week ramp-up): 20mg once daily for Week 1, then 50mg once daily for Week 2, then 100mg once daily for Week 3, then 200mg once daily for Week 4, then 400mg once daily for Week 5. Monotherapy: continue 400mg once daily until disease progression or unacceptable toxicity. In combination with rituximab: initiate rituximab after 5-week ramp-up phase and has received venetoclax 400mg for 7 days; give rituximab on Day 1 of each 28-day cycle for 6 cycles and continue venetoclax 400mg once daily for 24 months from Cycle 1 Day 1 of rituximab (see full labeling). In combination with obinutuzumab: initiate obinutuzumab on Cycle 1 Day 1 (see full labeling); on Cycle 1 Day 22, initiate venetoclax 5-week ramp up schedule, then continue venetoclax 400mg once daily from Cycle 3 Day 1 until the last day of Cycle 12. AML: confirm WBC is <25×109/L prior to initiation; initiate combination therapy on Cycle 1 Day 1. Ramp-up phase: 100mg on Day 1, then 200mg on Day 2, followed by 400mg on Day 3; on Day 4 and beyond, continue 400mg once daily of each 28-day cycle (in combination with azacitidine or decitabine) or 600mg once daily of each 28-day cycle (in combination with low-dose cytarabine); continue until disease progression or unacceptable toxicity. Severe hepatic impairment (Child-Pugh C): reduce dose by 50%; monitor. Concomitant strong or moderate CYP3A inhibitors or P-gp inhibitors, dose modifications for toxicities, TLS prophylaxis: see full labeling.
Concomitant strong CYP3A inhibitors at initiation or during dose ramp-up phase in CLL/SLL patients.
Risk of tumor lysis syndrome (esp. with reduce renal function [CrCl <80mL/min], tumor burden, type of malignancy); perform tumor burden assessment, radiographic evaluation, blood chemistry (at pre-dose, 6–8hrs after each new dose, 24hrs after final dose); correct pre-existing abnormalities prior to initiation. Risk of neutropenia; monitor CBCs during therapy; interrupt or resume therapy based on occurrence. Monitor for infection; treat if develops; withhold if Grade 3 and higher. Severe hepatic impairment: see Adults. Severe renal impairment or on dialysis. Embryo-fetal toxicity. Advise females of reproductive potential to use effective contraception during and for ≥30 days after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 1 week after the last dose).
See Contraindications. Increased mortality in those with multiple myeloma when combined with bortezomib plus dexamethasone; not recommended. Potentiated by strong or moderate CYP3A or P-gp inhibitors (eg, ketoconazole, ritonavir, posaconazole); reduce doses and monitor (see full labeling). Concomitant moderate CYP3A inhibitors or P-gp inhibitors (eg, rifampin); consider alternatives (with CLL/SLL); if inhibitor necessary, reduce venetoclax dose by ≥50% and monitor closely. Resume at prior venetoclax dose 2–3 days after discontinuing the inhibitor. Avoid concomitant strong CYP3A inducers (eg, rifampin) or moderate CYP3A inducers. Avoid live attenuated vaccines until B-cell recovery. Avoid grapefruit, Seville oranges, and starfruit during treatment. Avoid concomitant P-gp substrates (eg, digoxin); if unavoidable, separate dosing by ≥6hrs before venetoclax. Monitor INR closely with concomitant warfarin.
Neutropenia, thrombocytopenia, anemia, diarrhea, nausea, upper RTI, cough, musculoskeletal pain, fatigue, edema, constipation, febrile neutropenia, vomiting, pyrexia, pneumonia, dyspnea, hemorrhage, rash, abdominal pain, sepsis, dizziness, oropharyngeal pain, hypotension; tumor lysis syndrome, infections (may be fatal).
Generic Drug Availability:
Starting Pack—1 (4 weeks); Wallets 10mg—14; 50mg—7; Tabs 100mg—28, 120, 180