• Chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) (as monotherapy or in combination with obinutuzumab or rituximab).
• Newly diagnosed acute myeloid leukemia (AML) in patients who are ≥75 yr old or who have comorbidities that prevent the use of intensive induction chemotherapy (in combination with azacitidine or decitabine or low-dose cytarabine).

Contraindicated in:

• Concurrent use with strong CYP3A inhibitors during initiation and ramp-up phases
• Concurrent use with moderate CYP3A inhibitors or P-gp inhibitors
• Concurrent use with strong or moderate CYP3A inducers
• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• High tumor burden (↑ risk of tumor lysis syndrome)
• Renal impairment (CCr <80 mL/min) (↑ risk of tumor lysis syndrome)
• Splenomegaly (↑ risk of tumor lysis syndrome)
• Severe hepatic impairment (↓ dose)
• Women of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: peripheral edema.

F and E: hyperkalemia, hyperphosphatemia, hypokalemia, hyperuricemia, hypocalcemia.

GI: constipation, diarrhea, nausea, vomiting.

GU: ↓ fertility (males).

Hemat: anemia, neutropenia, thrombocytopenia.

MS: back pain.

Neuro: headache.

Resp: cough.
Misc: fatigue, fever, INFECTION, TUMOR LYSIS SYNDROME.

Drug-Drug:

• Strong CYP3A inhibitors, including itraconazole, conivaptan, clarithromycin, lopinavir, ritonavir, posaconazole, and voriconazole may ↑ levels; concurrent use during initiation and ramp-up phase in CLL/SLL contraindicated; ↓ venetoclax dose during initiation and ramp-up phase in AML; ↓ venetoclax dose after ramp-up phase for CLL, SLL, and AML if concurrent use necessary.
• Moderate CYP3A4 inhibitors, including erythromycin, ciprofloxacin, diltiazem, dronedarone, fluconazole, or verapamil or P-gp inhibitors, including amiodarone, azithromycin, captopril, carvedilol, cyclosporine, felodipine, quinidine, ranolazine, or ticagrelor may ↑ levels; avoid concurrent use; ↓ venetoclax dose if concurrent use necessary.
• Strong CYP3A4 inducers, including carbamazepine, phenytoin, or rifampin or moderate CYP3A inducers, including bosentan, efavirenz, etravirine, modafinil, or nafcillin may ↓ levels; avoid concurrent use.
• May ↑ levels of P-gp substrates with a narrow therapeutic index, including digoxin, sirolimus, and everolimus; if concurrent therapy necessary, give P-gp substrate ≥6 hr before venetoclax.
• May ↑ levels of warfarin.
• May ↓ antibody response to live-virus vaccine and ↑ risk of adverse reactions; do not administer concurrently.

Drug-Natural Products:

• St. John's wort may ↓ levels; avoid concurrent use.

Drug-Food:

• Grapefruit products, Seville oranges, and starfruit may ↑ levels; avoid concurrent use.

• Tablets: 10 mg; 50 mg; 100 mg;

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%.

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.

Venclexta

• Inhibits BCL-2 which is overexpressed on CLL, SLL, and AML cells, thereby inducing apoptosis.

• Reduced disease progression.

Therapeutic Classification: antineoplastics

Pharmacologic Classification:

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.

(blood levels)

• Instruct patient to take venetoclax as directed; do not change dose or stop taking venetoclax without consulting health care professional. Keep in original packaging for first 4 wk of therapy; do not transfer to another container. Take missed doses as soon as possible within 8 hrs of usual dose time. If missed by >8 hrs, omit and resume next day. If patient vomits do not replace dose.
• Advise patient to avoid grapefruit products, Seville oranges, or starfruit during therapy.
• Advise patient to avoid live vaccines prior to, during, or after treatment until B-cell recovery occurs.
• Advise patient to notify health care professional immediately if signs and symptoms of neutropenia (fever, signs of infection) or tumor lysis syndrome (fever, chills, nausea, vomiting, confusion, shortness of breath, seizure, irregular heartbeat, dark or cloudy urine, unusual tiredness, muscle pain, joint discomfort) occur. Advise patient to hydrate with 6–8 glasses of water/day starting 2 days before and on day of 1st dose and every dose increase to reduce risk of tumor lysis syndrome.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Emphasize importance of regular blood work and laboratory tests.
• May cause fetal harm. Use effective contraception during and for at least 30 days after last dose and avoid breastfeeding during and for 1 wk after last dose of therapy. May impair male fertility; consider sperm banking for males of reproductive potential.

ven-ET-oh-klax