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.

Adult:

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. 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 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 (in combination with azacitidine or decitabine) or 600mg once daily (in combination with low-dose cytarabine) 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.

Children:

Not established.

Contraindications:

Concomitant strong CYP3A inhibitors at initiation or during dose ramp-up phase in CLL/SLL patients.

Warnings/Precautions:

Risk of tumor lysis syndrome (esp. with high tumor burden, comorbidities, CrCl <80mL/min); perform tumor burden assessment, radiographic evaluation, blood chemistry (at baseline, 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 reduce dose if severe. Monitor for signs/symptoms of infection; treat if develops; withhold if Grade 3 and higher. Severe hepatic impairment: see Adults. Severe renal impairment or on dialysis. Embryo-fetal toxicity. Pregnancy: avoid; exclude status prior to initiation. Females of reproductive potential should use effective contraception during and for ≥30 days after final dose. Nursing mothers: not recommended.

Pharmacologic Class:

BCL-2 inhibitor.

Interactions:

See Contraindications. Potentiated by strong 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; 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. Increased mortality in those with multiple myeloma when combined with bortezomib plus dexamethasone; not recommended. Monitor INR closely with concomitant warfarin.

Adverse Reactions:

Neutropenia, diarrhea, nausea, upper RTI, anemia, fatigue, thrombocytopenia, musculoskeletal pain, edema, cough, constipation, vomiting, pyrexia, pneumonia, dyspnea, hemorrhage, rash, abdominal pain, sepsis, back pain, myalgia, dizziness, oropharyngeal pain, hypotension; tumor lysis syndrome, infections (may be fatal).

Generic Availability:

NO

How Supplied:

Starting Packs—1; Wallets 10mg—14; 50mg—7; Tabs 100mg—120, 180

Pricing for VENCLEXTA

100mg tablet (Qty: 120)
Appx. price $12172
GoodRx