Venetoclax

Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an anti-apoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL and AML cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics.

• VENCLEXTA is a BCL-2 inhibitor indicated: For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). ( 1.1 ) In combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.ICD-10: C85.90, C95.90

• Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during the ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome [see Dosage and Administration ( 2.6 ) and Drug Interactions ( 7.1 )] . Concomitant use with strong CYP3A inhibitors at initiation and during ramp-up phase in patients with CLL/SLL is contraindicated.contraindicated

See Full Prescribing Information for recommended VENCLEXTA dosages. ( 2.2 , 2.3 ) Take VENCLEXTA tablets orally once daily with a meal and water. ( 2.8 ) Provide prophylaxis for tumor lysis syndrome. ( 2.1 , 2.4 ) 2.1 Important Safety Information Assess patient-specific factors for level of risk of tumor lysis syndrome (TLS) and provide prophylactic hydration and anti-hyperuricemics to patients prior to first dose of VENCLEXTA to reduce risk of TLS [see Dosage and Administration ( 2.4 ) and Warnings and Precautions ( 5.1 )]. 2.2 Recommended Dosage for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma VENCLEXTA dosing begins with a 5-week ramp-up. The 5-week ramp-up dosing schedule is designed to gradually reduce tumor burden (debulk) and decrease the risk of TLS. VENCLEXTA 5-week Dose Ramp-Up Schedule Administer VENCLEXTA according to the 5-week ramp-up dosing schedule to the recommended dosage of 400 mg orally once daily as shown in Table 1 . Table 1. Dosing Schedule for 5-Week Ramp-up Phase for Patients with CLL/SLL VENCLEXTA Oral Daily Dose Week 1 20 mg Week 2 50 mg Week 3 100 mg Week 4 200 mg Week 5 and beyond 400 mg The CLL/SLL Starting Pack provides the first 4 weeks of VENCLEXTA according to the ramp-up schedule [see How Supplied/Storage and Handling ( 16 )] . In Combination with Acalabrutinib Cycle 1 Day 1: Start acalabrutinib 100 mg orally approximately every 12 hours until disease progression, unacceptable toxicity or completion of 14 cycles of treatment. Each cycle is 28 days.

Tumor Lysis Syndrome (TLS): Anticipate TLS; assess risk in all patients. Premedicate with anti-hyperuricemics and ensure adequate hydration. Employ more intensive measures (intravenous hydration, frequent monitoring, hospitalization) as overall risk increases. ( 2.4 , 5.1 ) Neutropenia: Monitor blood counts. Interrupt dosing and resume at same or reduced dose. Consider supportive care measures. ( 2.5 , 5.2 ) Infections: Monitor for signs and symptoms of infection and treat promptly. Withhold for Grade 3 and 4 infection until resolution and resume at same or reduced dose. ( 2.5 , 5.3 ) Immunization: Do not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-cell recovery. ( 5.4 ) Embryo-Fetal Toxicity: May cause embryo-fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.5 ) Treatment of patients with multiple myeloma with VENCLEXTA in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials. ( 5.6 ) 5.1 Tumor Lysis Syndrome Tumor lysis syndrome (TLS), including fatal events and renal failure requiring dialysis, has occurred in patients treated with VENCLEXTA [see Adverse Reactions ( 6.1 )]. VENCLEXTA can cause rapid reduction in tumor and thus poses a risk for TLS at initiation and during the ramp-up phase in all patients, and during reinitiation after dosage interruption in patients with CLL/SLL.

The following clinically significant adverse reactions are described elsewhere in the labeling: Tumor Lysis Syndrome [see Warnings and Precautions ( 5.1 )] Neutropenia [see Warnings and Precautions ( 5.2 )] Infections [see Warnings and Precautions ( 5.3 )] In CLL/SLL, the most common adverse reactions (≥20%) for VENCLEXTA when given in combination with obinutuzumab or rituximab or as monotherapy are neutropenia, thrombocytopenia, anemia, diarrhea, nausea, upper respiratory tract infection, cough, musculoskeletal pain, fatigue, and edema. ( 6.1 ) In CLL/SLL, the most common adverse reactions (≥20%) for VENCLEXTA when given in combination with acalabrutinib are neutropenia, headache, diarrhea, musculoskeletal pain, and COVID-19. ( 6.1 ) In AML, the most common adverse reactions (≥30%) in combination with azacitidine or decitabine or low-dose cytarabine are nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, edema, pyrexia, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, musculoskeletal pain, dizziness, cough, oropharyngeal pain, and hypotension. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely variable conditions, adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice.

Lactation: Advise women not to breastfeed. ( 8.2 ) Hepatic Impairment: Reduce the VENCLEXTA dose by 50% in patients with severe hepatic impairment. ( 2.7 , 8.7 ) 8.1 Pregnancy Risk Summary Based on findings in animals and its mechanism of action [see Clinical Pharmacology ( 12.1 )] , VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. There are no available data on VENCLEXTA use in pregnant women to inform a drug-associated risk. Administration of venetoclax to pregnant mice during the period of organogenesis was fetotoxic at exposures 1.2 times the human exposure at the recommended dose of 400 mg daily based on AUC. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal data In embryo-fetal development studies, venetoclax was administered to pregnant mice and rabbits during the period of organogenesis.

Metabolism

Venetoclax mean (± standard deviation) steady state C max was 2.1 ± 1.1 mcg/mL and AUC 0-24h was 32.8 ± 16.9 mcg•h/mL following administration of 400 mg once daily with a low-fat meal. Venetoclax steady state AUC increased proportionally over the dose range of 150 to 800 mg (0.25 to 1.33 times the maximum approved recommended dosage).

There is no specific antidote for VENCLEXTA. For patients who experience overdose, closely monitor and provide appropriate supportive treatment; during ramp-up phase interrupt VENCLEXTA and monitor carefully for signs and symptoms of TLS along with other toxicities [see Dosage and Administration ( 2.2 , 2.3 , 2.4 , 2.5 )] . Based on venetoclax large volume of distribution and extensive protein binding, dialysis is unlikely to result in significant removal of venetoclax.

• Apr 11, 2016NDANDA208573Abbvie

1. 1Death9,99617%
2. 2Off Label Use6,65511%
3. 3Neutropenia3,3395.6%
4. 4Febrile Neutropenia3,0335.1%
5. 5Platelet Count Decreased2,7234.6%
6. 6Pyrexia2,6584.5%
7. 7Pneumonia2,6054.4%
8. 8Fatigue2,5464.3%
9. 9Myelosuppression2,4384.1%
10. 10Diarrhoea2,3083.9%
11. 11White Blood Cell Count Decreased2,1943.7%
12. 12Nausea2,0603.5%
13. 13Thrombocytopenia2,0433.4%
14. 14Infection1,9263.2%
15. 15Anaemia1,8813.2%

The 10 most recently updated of 848 ClinicalTrials.gov registrations naming Venetoclax as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study to Evaluate Adverse Events, Change in Disease Activity, and How Oral ABBV-101 Moves Through the Body in Adult Participants With B-Cell Malignancies
  Active not recruiting · Phase 1 · Interventional · 135 enrolled · AbbVie
  NCT05753501updated 2026-06-12
• Testing Early Treatment for Patients With High-Risk Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Leukemia (SLL), EVOLVE CLL/SLL Study
  Recruiting · Phase 3 · Interventional · 247 enrolled · National Cancer Institute (NCI)
  NCT04269902updated 2026-06-12
• A Phase I Study Investigating the Combination of the Menin Inhibitor Ziftomenib With Venetoclax and Gemtuzumab in Pediatric Patients With Acute Myeloid Leukemia
  Recruiting · Phase 1 · Interventional · 22 enrolled · M.D. Anderson Cancer Center
  NCT06448013updated 2026-06-12
• A Phase Ib Trial of Azacitidine, Venetoclax and Allogeneic NK Cells for Acute Myeloid Leukemia (ADVENT-AML)
  Recruiting · Phase 1 · Interventional · 32 enrolled · M.D. Anderson Cancer Center
  NCT05834244updated 2026-06-12
• Venetoclax, MLN9708 (Ixazomib Citrate) and Dexamethasone for the Treatment of Relapsed or Refractory Light Chain Amyloidosis
  Active not recruiting · Phase 1 · Interventional · 24 enrolled · National Cancer Institute (NCI)
  NCT04847453updated 2026-06-11
• Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
  Recruiting · Phase 2 · Interventional · 92 enrolled · National Cancer Institute (NCI)
  NCT04840602updated 2026-06-11
• Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)
  Recruiting · Phase 2 · Interventional · 153 enrolled · National Cancer Institute (NCI)
  NCT05554393updated 2026-06-11
• A Phase Ia/Ib Open-label, Multiple Dose, Study to Determine the Recommended Dose, Evaluate PKs, PDs, Safety, and Activity of Venetoclax in Combination With Oral Decitabine/Cedazuridine (ASTX727) in Pediatric Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
  Recruiting · Phase 1 · Interventional · 40 enrolled · M.D. Anderson Cancer Center
  NCT06191978updated 2026-06-11
• Testing a New Chemotherapy Drug, KRT-232 (AMG-232) in Combination With Decitabine and Venetoclax in Patients With Acute Myeloid Leukemia
  Active not recruiting · Phase 1 · Interventional · 58 enrolled · National Cancer Institute (NCI)
  NCT03041688updated 2026-06-11
• Testing the Addition of Venetoclax or Gemtuzumab Ozogamicin (GO) to Usual Treatment Regimen (Cytarabine and Daunorubicin, "7+3") for Core Binding Factor Acute Myeloid Leukemia (CBF-AML) to Improve Response (A MYELOMATCH Treatment Trial)
  Recruiting · Phase 2 · Interventional · 162 enrolled · National Cancer Institute (NCI)
  NCT06917911updated 2026-06-11

Frequently asked questions

How does Venetoclax work?

Venetoclax is a selective and orally bioavailable small-molecule inhibitor of BCL-2, an anti-apoptotic protein. Overexpression of BCL-2 has been demonstrated in CLL and AML cells where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics.

What is Venetoclax used for?

According to FDA labeling, Venetoclax carries indications including: VENCLEXTA is a BCL-2 inhibitor indicated: For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). ( 1.1 ) In combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Venetoclax?

Venetoclax is classified as Other antineoplastic agents, BCL-2 Inhibitor, Cytochrome P450 3A Inhibitors, P-Glycoprotein Inhibitors, Increased Cellular Death.

What are the brand names for Venetoclax?

Venetoclax is marketed under brand names including Venclexta.

What are the contraindications for Venetoclax?

Venetoclax labeling lists contraindications including: Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during the ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome [see Dosage and Administration ( 2.6 ) and Drug Interactions ( 7.1 )] . Concomitant use with strong CYP3A inhibitors at initiation and during ramp-up phase in patients with CLL/SLL is contraindicated.. Always consult the full prescribing information and a clinician.