For Patients and Caregivers

VEN+DEC: Summary of safety data from Study M14-358

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A tolerable, manageable, and predictable safety profile1

No additional warnings or precautions for VENCLEXTA (venetoclax tablets) were observed in the AML trials.

Adverse reactions reported in ≥30% (any grade)

  • The most common adverse reactions (≥30%) were febrile neutropenia (69%), fatigue (62%), constipation (62%), musculoskeletal pain (54%), dizziness (54%), nausea (54%), abdominal pain (46%), diarrhea (46%), pneumonia (46%), sepsis (excluding fungal; 46%), cough (38%), pyrexia (31%), hypotension (31%), oropharyngeal pain (31%), edema (31%), and vomiting (31%)
  • The most common hematologic laboratory abnormalities (≥30%) were neutrophils decreased (100%), lymphocytes decreased (100%), white blood cells decreased (100%), platelets decreased (92%), hemoglobin decreased (69%)
  • The median duration of exposure for patients taking VEN+DEC was 8.4 months (range: 0.5-39.0 months)

Treatment events and occurrence rates1

  • Serious adverse reactions were reported in 85% of patients
  • The most frequent serious adverse reactions (≥10%) were sepsis (excluding fungal; 46%), febrile neutropenia (38%), and pneumonia (31%)
  • One (8%) fatal adverse reaction of bacteremia occurred within 30 days of starting treatment
  • Permanent discontinuations due to adverse reactions occurred in 38% of patients
  • The most frequent adverse reaction leading to permanent drug discontinuation (≥5%) was pneumonia (8%)
  • Dosage interruptions due to adverse reactions occurred in 69% of patients
  • The most frequent adverse reactions leading to dose interruption (≥10%) were neutropenia (38%), febrile neutropenia (23%), leukopenia (15%), and pneumonia (15%)
  • Dosage reductions due to adverse reactions occurred in 15% of patients
  • The most frequent adverse reaction leading to dose reduction (≥5%) was neutropenia (15%)

For dose modifications related to drug interactions and management of adverse reactions specific to VEN+DEC regimen, please see Section 2 of the full Prescribing Information.

AML=acute myeloid leukemia; DEC=decitabine; VEN=VENCLEXTA.

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Dosing & Administration

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Important Safety Information & Indication

Indication

VENCLEXTA is indicated 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.

Important Safety Information

Tumor Lysis Syndrome

  • Tumor lysis syndrome (TLS), including fatal events and renal failure requiring dialysis, has occurred in patients treated with VENCLEXTA.
  • 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. Changes in blood chemistries consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLEXTA and at each dose increase.
  • In patients with AML who followed the current 3-day ramp-up dosing schedule and the TLS prophylaxis and monitoring measures, the rate of TLS was 1.1% in patients who received VENCLEXTA in combination with azacitidine. In patients with AML who followed a 4-day ramp-up dosing schedule and the TLS prophylaxis and monitoring measures, the rate of TLS was 5.6% and included deaths and renal failure in patients who received VENCLEXTA in combination with low-dose cytarabine.
  • The risk of TLS is a continuum based on multiple factors, particularly reduced renal function, tumor burden, and type of malignancy.
  • Assess all patients for risk and provide appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Monitor blood chemistries and manage abnormalities promptly. Employ more intensive measures (IV hydration, frequent monitoring, hospitalization) as overall risk increases. Interrupt dosing if needed; when restarting VENCLEXTA follow dose modification guidance in the Prescribing Information.
  • Concomitant use of VENCLEXTA with P-gp inhibitors or strong or moderate CYP3A inhibitors increases venetoclax exposure, which may increase the risk of TLS at initiation and during the ramp-up phase, and requires VENCLEXTA dose reduction.

Neutropenia

  • In patients with AML, baseline neutrophil counts worsened in 95% to 100% of patients treated with VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine. Neutropenia can recur with subsequent cycles.
  • Monitor complete blood counts. Interrupt dosing for severe neutropenia. Resume at same dose then reduce duration based on remission status and first or subsequent occurrence of neutropenia. Consider supportive measures including antimicrobials and growth factors (e.g., G-CSF).

Infections

  • Fatal and serious infections such as pneumonia and sepsis have occurred in patients treated with VENCLEXTA. Monitor patients for signs and symptoms of infection and treat promptly. Withhold VENCLEXTA for Grade 3 and 4 infection until resolution and resume at same dose.

Immunization

  • Do not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-cell recovery occurs. Advise patients that vaccinations may be less effective. 

Embryo-Fetal Toxicity

  • VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with VENCLEXTA and for 30 days after the last dose.

Increased Mortality in Patients with Multiple Myeloma when VENCLEXTA is Added to Bortezomib and Dexamethasone

  • In a randomized trial (BELLINI; NCT02755597) in patients with relapsed or refractory multiple myeloma, the addition of VENCLEXTA to bortezomib plus dexamethasone, a use for which VENCLEXTA is not indicated, resulted in increased mortality. Treatment of patients with multiple myeloma with VENCLEXTA in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials. 

Adverse Reactions

  • In patients with AML receiving combination therapy with azacitidine, the most frequent serious adverse reactions (≥5%) were febrile neutropenia (30%), pneumonia (22%), sepsis (excluding fungal; 19%), and hemorrhage (6%). The most common adverse reactions including hematological abnormalities (≥30%) of any grade were neutrophils decreased (98%), platelets decreased (94%), lymphocytes decreased (91%), hemoglobin decreased (61%), nausea (44%), diarrhea (43%), febrile neutropenia (42%), musculoskeletal pain (36%), pneumonia (33%), fatigue (31%), and vomiting (30%). Fatal adverse reactions occurred in 23% of patients who received VENCLEXTA in combination with azacitidine, with the most frequent (≥2%) being pneumonia (4%), sepsis (excluding fungal; 3%), and hemorrhage (2%).
  • In patients with AML receiving combination therapy with decitabine, the most frequent serious adverse reactions (≥10%) were sepsis (excluding fungal; 46%), febrile neutropenia (38%), and pneumonia (31%). The most common adverse reactions including hematological abnormalities (≥30%) of any grade were neutrophils decreased (100%), lymphocytes decreased (100%), white blood cells decreased (100%), platelets decreased (92%), hemoglobin decreased (69%), febrile neutropenia (69%), fatigue (62%), constipation (62%), musculoskeletal pain (54%), dizziness (54%), nausea (54%), abdominal pain (46%), diarrhea (46%), pneumonia (46%), sepsis (excluding fungal; 46%), cough (38%), pyrexia (31%), hypotension (31%), oropharyngeal pain (31%), edema (31%), and vomiting (31%). One (8%) fatal adverse reaction of bacteremia occurred within 30 days of starting treatment.
  • In patients with AML receiving combination therapy with low-dose cytarabine, the most frequent serious adverse reactions (≥10%) were pneumonia (17%), febrile neutropenia (16%), and sepsis (excluding fungal; 12%). The most common adverse reactions including hematological abnormalities (≥30%) of any grade were platelets decreased (97%), neutrophils decreased (95%), lymphocytes decreased (92%), hemoglobin decreased (63%), nausea (42%), and febrile neutropenia (32%). Fatal adverse reactions occurred in 23% of patients who received VENCLEXTA in combination with LDAC, with the most frequent (≥5%) being pneumonia (6%) and sepsis (excluding fungal; 7%).

Drug Interactions

  • Concomitant use with a P-gp inhibitor or a strong or moderate CYP3A inhibitor increases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including the risk of TLS. Consider alternative medications or adjust VENCLEXTA dosage and monitor more frequently for adverse reactions. Resume the VENCLEXTA dosage that was used prior to concomitant use of a P-gp inhibitor or a strong or moderate CYP3A inhibitor 2 to 3 days after discontinuation of the inhibitor.
  • Patients should avoid grapefruit products, Seville oranges, and starfruit during treatment as they contain inhibitors of CYP3A. 
  • Avoid concomitant use of strong or moderate CYP3A inducers.  
  • Monitor international normalized ratio (INR) more frequently in patients receiving warfarin.
  • Avoid concomitant use of VENCLEXTA with a P-gp substrate. If concomitant use is unavoidable, separate dosing of the P-gp substrate at least 6 hours before VENCLEXTA. 

Lactation

  • Advise nursing women not to breastfeed during treatment with VENCLEXTA and for 1 week after the last dose.

Females and Males of Reproductive Potential

  • Advise females of reproductive potential to use effective contraception during treatment with VENCLEXTA and for 30 days after the last dose.
  • Based on findings in animals, VENCLEXTA may impair male fertility.

Hepatic Impairment

  • Reduce the dose of VENCLEXTA for patients with severe hepatic impairment (Child-Pugh C); monitor these patients more frequently for signs of adverse reactions. No dose adjustment is recommended for patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment.

Please see full Prescribing Information.

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VENCLEXTA® and its design are registered trademarks of AbbVie Inc.

    • VENCLEXTA Prescribing Information.

      VENCLEXTA Prescribing Information.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed May 17, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed May 17, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

    • DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617-629.

      DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617-629.

    • Data on file, AbbVie Inc. ABVRRTI71211.

      Data on file, AbbVie Inc. ABVRRTI71211.

    • Data on file, AbbVie Inc. ABVRRTI71272.

      Data on file, AbbVie Inc. ABVRRTI71272.

    • Data on file, AbbVie Inc. ABVRRTI67697.

      Data on file, AbbVie Inc. ABVRRTI67697.

    • Data on file, AbbVie Inc. ABVRRTI71500.

      Data on file, AbbVie Inc. ABVRRTI71500.

    • CRESEMBA Prescribing Information.

      CRESEMBA Prescribing Information.

    • US Food and Drug Administration. For healthcare professionals | FDA’s examples of drugs that interact with CYP enzymes and transporter systems. Updated March 8, 2024. Accessed April 17, 2024. https://www.fda.gov/drugs/drug-interactions-labeling/healthcare-professionals-fdas-examples-drugs-interact-cyp-enzymes-and-transporter-systems

      US Food and Drug Administration. For healthcare professionals | FDA’s examples of drugs that interact with CYP enzymes and transporter systems. Updated March 8, 2024. Accessed April 17, 2024. https://www.fda.gov/drugs/drug-interactions-labeling/healthcare-professionals-fdas-examples-drugs-interact-cyp-enzymes-and-transporter-systems

    • Perl AE. The role of targeted therapy in the management of patients with AML. Blood Adv. 2017;1(24):2281-2294.

      Perl AE. The role of targeted therapy in the management of patients with AML. Blood Adv. 2017;1(24):2281-2294.

    • Karakas T, Maurer U, Weidmann E, Miething CC, Hoelzer D, Bergmann L. High expression of bcl-2 mRNA as a determinant of poor prognosis in acute myeloid leukemia. Ann Oncol. 1998;9(2):159-165.

      Karakas T, Maurer U, Weidmann E, Miething CC, Hoelzer D, Bergmann L. High expression of bcl-2 mRNA as a determinant of poor prognosis in acute myeloid leukemia. Ann Oncol. 1998;9(2):159-165.

    • Mehta SV, Shukla SN, Vora HH. Overexpression of Bcl2 protein predicts chemoresistance in acute myeloid leukemia: its correlation with FLT3. Neoplasma. 2013;60(6):666-675.

      Mehta SV, Shukla SN, Vora HH. Overexpression of Bcl2 protein predicts chemoresistance in acute myeloid leukemia: its correlation with FLT3. Neoplasma. 2013;60(6):666-675.

    • Tzifi F, Economopoulou C, Gourgiotis D, Ardavanis A, Papageorgiou S, Scorilas A. The role of BCL2 family of apoptosis regulator proteins in acute and chronic leukemias. Adv Hematol. 2012;2012:524308.

      Tzifi F, Economopoulou C, Gourgiotis D, Ardavanis A, Papageorgiou S, Scorilas A. The role of BCL2 family of apoptosis regulator proteins in acute and chronic leukemias. Adv Hematol. 2012;2012:524308.

    • Banker DE, Groudine M, Norwood T, Appelbaum FR. Measurement of spontaneous and therapeutic agent-induced apoptosis with BCL-2 protein expression in acute myeloid leukemia. Blood. 1997;89(1):243-255.

      Banker DE, Groudine M, Norwood T, Appelbaum FR. Measurement of spontaneous and therapeutic agent-induced apoptosis with BCL-2 protein expression in acute myeloid leukemia. Blood. 1997;89(1):243-255.

    • Data on file, Genentech, Inc. 07/2022.

      Data on file, Genentech, Inc. 07/2022.

    • Data on file, AbbVie Inc. ABVRRTI73540.

      Data on file, AbbVie Inc. ABVRRTI73540.

    • Pratz KW, Jonas BA, Pullarkat V, et al. Long-term follow-up of VIALE-A: venetoclax and azacitidine in chemotherapy-ineligible untreated acute myeloid leukemia. Am J Hematol. 2024;99(4):615-624.

      Pratz KW, Jonas BA, Pullarkat V, et al. Long-term follow-up of VIALE-A: venetoclax and azacitidine in chemotherapy-ineligible untreated acute myeloid leukemia. Am J Hematol. 2024;99(4):615-624.

    • Data on file, AbbVie Inc. ABVRRTI74719.

      Data on file, AbbVie Inc. ABVRRTI74719.

    • Ferrara F, Barosi G, Venditti A, et al. Consensus-based definition of unfitness to intensive and non-intensive chemotherapy in acute myeloid leukemia: a project of SIE, SIES and GITMO group on a new tool for therapy decision making. Leukemia. 2013;27(5):997-999.

      Ferrara F, Barosi G, Venditti A, et al. Consensus-based definition of unfitness to intensive and non-intensive chemotherapy in acute myeloid leukemia: a project of SIE, SIES and GITMO group on a new tool for therapy decision making. Leukemia. 2013;27(5):997-999.

    • Pratz KW, Jonas BA, Pullarkat V, et al. Long-term follow-up of the phase 3 VIALE-A clinical trial of venetoclax plus azacitidine for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Oral abstract presented at: 64th ASH Annual Meeting and Exposition; December 10, 2022; New Orleans, Louisiana. https://clin.larvol.com/abstract-detail/ASH%202022/61249960

      Pratz KW, Jonas BA, Pullarkat V, et al. Long-term follow-up of the phase 3 VIALE-A clinical trial of venetoclax plus azacitidine for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Oral abstract presented at: 64th ASH Annual Meeting and Exposition; December 10, 2022; New Orleans, Louisiana. https://clin.larvol.com/abstract-detail/ASH%202022/61249960