Venclexta

Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) — as monotherapy or in combination with obinutuzumab or rituximab; Acute myeloid leukemia (AML) — newly diagnosed, in combination with azacitidine, decitabine, or low-dose cytarabine in adults ≥75 years or with comorbidities precluding intensive induction chemotherapy

CLL/SLL ramp-up (5 weeks): Week 1: 20 mg daily → Week 2: 50 mg → Week 3: 100 mg → Week 4: 200 mg → Week 5: 400 mg
CLL/SLL full dose: 400 mg once daily
AML (with azacitidine/decitabine): Ramp-up over 4 days (100→200→400→600 mg), then 400 mg daily starting Day 1 of each subsequent cycle
Take with a meal and water at approximately the same time each day
TLS prophylaxis: Adequate hydration (6-8 glasses water daily); anti-hyperuricemics 2-3 days before starting

Tablets: 10 mg, 50 mg, 100 mg; Starter Pack: 10/50/100 mg for 5-week ramp-up

Strong CYP3A inhibitors at initiation and during ramp-up phase in CLL/SLL.

• Tumor Lysis Syndrome (TLS): TLS, including fatal cases, has occurred. Assess TLS risk by tumor burden. Perform ramp-up dosing schedule. Provide TLS prophylaxis with hydration and anti-hyperuricemics. Monitor blood chemistries: CLL: before first dose, 6-8h and 24h after each ramp-up dose; AML: before first dose, 6-8h after each ramp-up dose.
• Neutropenia: Grade 3-4 in 40% (CLL) and 46% (AML). Monitor CBCs throughout treatment. Consider G-CSF.
• Infections: Fatal and serious infections including pneumonia and sepsis (46% AML). Monitor and treat promptly.
• Immunization: Do not administer live attenuated vaccines during and after treatment.
• Embryo-Fetal Toxicity

CLL/SLL: Neutropenia (40%), diarrhea (29%), nausea (25%), anemia (18%), fatigue (16%), upper respiratory tract infection (14%), cough (13%)
AML: Nausea (46%), diarrhea (44%), thrombocytopenia (45%), constipation (37%), neutropenia (46%), febrile neutropenia (42%), fatigue (38%), vomiting (33%), edema (32%), pneumonia (29%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Venetoclax is a selective inhibitor of B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL cells and AML blasts, where it mediates tumor cell survival and has been associated with resistance to chemotherapy. Venetoclax binds directly to the BH3-binding groove of BCL-2, displacing pro-apoptotic proteins (BIM), restoring apoptosis. This mechanism is independent of p53 function.

Tmax: 5-8 hours. Half-life: approximately 26 hours. Protein binding: >99.9%. Metabolized primarily by CYP3A4. Fecal excretion (>99.9%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• CLL14 — Venetoclax + obinutuzumab vs. chlorambucil + obinutuzumab in 1L CLL. Phase III, n=432.
  🔬 NCT02242942 ↗ 📄 Primary Publication ↗
• MURANO — Venetoclax + rituximab vs. bendamustine + rituximab in relapsed/refractory CLL. Phase III, n=389.
  🔬 NCT02005471 ↗ 📄 Primary Publication ↗

Venclexta has FDA-approved indications across the following cancer types covered on PipelineEvidence: