For Patients and Caregivers

Dose modifications or interruptions can help manage select adverse reactions1

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Interrupt dosing or reduce dose for select adverse reactions

  • For patients having a dosage interruption lasting more than 1 week during the ramp-up phase, or more than 2 weeks after completion of ramp-up, reassess for risk of TLS to determine if reinitiation with a reduced dose is necessary (e.g., all or some levels of the dose ramp-up schedule)
Recommended VENCLEXTA dose modifications for adverse reactions*
TLS
Any occurrence:
Blood chemistry changes or symptoms suggestive of TLS		 Withhold the next day’s dose. If resolved within 24-48 hours of last dose, resume at same dose.
For any blood chemistry changes requiring more than 48 hours to resolve, resume at a reduced dose. See dose-reduction guidelines by scrolling down on current page.
For any events of clinical TLS,† resume at a reduced dose following resolution. Scroll down to see dose-reduction guidelines.
Non-hematologic adverse reactions
1st occurrence:
Grade 3 or 4 nonhematologic toxicities
 
2nd and subsequent occurrences:
Grade 3 or 4 nonhematologic toxicities		 Interrupt VENCLEXTA. Once the toxicity has resolved to Grade 1 or baseline level, VENCLEXTA therapy may be resumed at the same dose.
Interrupt VENCLEXTA. Follow dose-reduction guidelines when resuming VENCLEXTA treatment after resolution. A larger dose reduction may occur at the discretion of the physician. Scroll down to see dose-reduction guidelines.
Hematologic adverse reactions
1st occurrence:
Grade 3 neutropenia with infection or fever, or Grade 4 hematologic toxicities (except lymphopenia)
 
2nd and subsequent occurrences:
Grade 3 neutropenia with infection or fever, or Grade 4 hematologic toxicities (except lymphopenia)
 Interrupt VENCLEXTA. Once the toxicity has resolved to Grade 1 or baseline level, VENCLEXTA therapy may be resumed at the same dose.
Interrupt VENCLEXTA. Follow dose-reduction guidelines when resuming VENCLEXTA treatment after resolution. A larger dose reduction may occur at the discretion of the physician. Scroll down to see dose-reduction guidelines.

Consider discontinuing VENCLEXTA for patients who require dose reductions to less than 100 mg for more than 2 weeks

*Adverse reactions were graded using NCI CTCAE version 4.0.
†Clinical TLS was defined as laboratory TLS with clinical consequences such as acute renal failure, cardiac arrhythmias, or sudden death and/or seizures.

NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.

Dose reduction for adverse reactions during VENCLEXTA treatment

Dose at interruption, mg Restart dose, mg‡§
400 300
300 200
200 100
100 50
50 20
20 10

‡During the ramp-up phase, continue the reduced dose for 1 week before increasing the dose.
§If a dosage interruption lasts more than 1 week during the ramp-up phase or more than 2 weeks after completion of ramp-up, reassess the risk of TLS and determine if reinitiation at a reduced dosage is necessary.

Dosage modifications for use in severe hepatic impairment

  • Reduce the VENCLEXTA once-daily dose by 50% for patients with severe hepatic impairment (Child-Pugh C); monitor these patients more closely for signs of toxicity

For information on use with CYP3A and P-gp inhibitors as well as management of potential drug interactions, see VENCLEXTA drug interactions.

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Drug Interactions

Learn about the management of potential VENCLEXTA drug interactions

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Important Safety Information & Indication

Indication

  • VENCLEXTA is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Important Safety Information

Contraindication

  • Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome (TLS).

Tumor Lysis Syndrome

  • Tumor lysis syndrome, 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, and during reinitiation after dosage interruption in patients with CLL/SLL. 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. TLS, including fatal cases, has been reported after a single 20 mg dose.
  • In patients with CLL/SLL who followed the current (5 week) dose ramp-up and the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in the VENCLEXTA CLL/SLL monotherapy trials. The rate of TLS remained consistent with VENCLEXTA in combination with obinutuzumab or rituximab. With a 2- to 3-week dose ramp-up and higher starting dose in patients with CLL/SLL, the TLS rate was 13% and included deaths and renal failure.
  • The risk of TLS is a continuum based on multiple factors, particularly reduced renal function, tumor burden, and type of malignancy. Splenomegaly may also increase the risk of TLS in patients with CLL/SLL.
  • 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 CLL, Grade 3 or 4 neutropenia developed in 63% to 64% of patients and Grade 4 neutropenia developed in 31% to 33% of patients when treated with VENCLEXTA in combination and monotherapy studies. Febrile neutropenia occurred in 4% to 6% of patients.
  • Monitor complete blood counts. Interrupt dosing for severe neutropenia and resume at same or reduced dose. 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 or reduced 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 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 CLL receiving combination therapy with obinutuzumab, serious adverse reactions were most often due to febrile neutropenia and pneumonia (5% each). The most common adverse reactions (≥20%) of any grade were neutropenia (60%), diarrhea (28%), and fatigue (21%). Fatal adverse reactions that occurred in the absence of disease progression and with onset within 28 days of the last study treatment were reported in 2% (4/212) of patients, most often from infection.
  • In patients with CLL receiving combination therapy with rituximab, the most frequent serious adverse reaction (≥5%) was pneumonia (9%). The most common adverse reactions (≥20%) of any grade were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), and nausea (21%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of the last VENCLEXTA treatment and/or 90 days of the last rituximab were reported in 2% (4/194) of patients.
  • In patients with CLL/SLL receiving monotherapy, the most frequent serious adverse reactions (≥5%) were pneumonia (9%), febrile neutropenia (5%), and sepsis (5%). The most common adverse reactions (≥20%) of any grade were neutropenia (50%), diarrhea (43%), nausea (42%), upper respiratory tract infection (36%), anemia (33%), fatigue (32%), thrombocytopenia (29%), musculoskeletal pain (29%), edema (22%), and cough (22%). Fatal adverse reactions that occurred in the absence of disease progression and within 30 days of venetoclax treatment were reported in 2% of patients in the VENCLEXTA monotherapy studies, most often (2 patients) from septic shock.

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 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 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.
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    • VENCLEXTA Prescribing Information.

      VENCLEXTA Prescribing Information.

    • Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225​-2236.

      Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225​-2236.

    • GAZYVA Prescribing Information.

      GAZYVA Prescribing Information.

    • Data on file, AbbVie Inc. ABVRRTI69608.

      Data on file, AbbVie Inc. ABVRRTI69608.

    • Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23)(suppl):2225​​-2236.

      Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23)(suppl):2225​​-2236.

    • Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-1120.

      Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107-1120.

    • Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12)(suppl):1107-1120.

      Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12)(suppl):1107-1120.

    • Data on file, AbbVie Inc. ABVRRTI69609.

      Data on file, AbbVie Inc. ABVRRTI69609.

    • Seymour JF, Kipps TJ, Eichhorst B, et al. Four-year analysis of MURANO study confirms sustained benefit of time-limited venetoclax-rituximab (VenR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.

      Seymour JF, Kipps TJ, Eichhorst B, et al. Four-year analysis of MURANO study confirms sustained benefit of time-limited venetoclax-rituximab (VenR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.

    • Data on file, AbbVie Inc. ABVRRTI72219.

      Data on file, AbbVie Inc. ABVRRTI72219.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 12, 2023. To view the most recent and complete version of the guidelines, go online to NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma V.3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed June 12, 2023. To view the most recent and complete version of the guidelines, go online to NCCN.org.

    • Data on file, AbbVie Inc. ABVRRTI71322.

      Data on file, AbbVie Inc. ABVRRTI71322.

    • Owen C, Christofides A, Johnson N, Lawrence T, MacDonald D, Ward C. Use of minimal residual disease assessment in the treatment of chronic lymphocytic leukemia [published online ahead of print May 16, 2017]. Leuk Lymphoma. 2017;58(12):2777​​-2785.

      Owen C, Christofides A, Johnson N, Lawrence T, MacDonald D, Ward C. Use of minimal residual disease assessment in the treatment of chronic lymphocytic leukemia [published online ahead of print May 16, 2017]. Leuk Lymphoma. 2017;58(12):2777​​-2785.

    • Thompson PA, Wierda WG. Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL. Blood. 2016;127(3):279​-286.

      Thompson PA, Wierda WG. Eliminating minimal residual disease as a therapeutic end point: working toward cure for patients with CLL. Blood. 2016;127(3):279​-286.

    • US Food and Drug Administration. Hematologic malignancies: regulatory considerations for use of minimal residual disease in development of drug and biological products for treatment. Guidance for industry. https://www.fda.gov/media/134605/download. January 2020. Accessed April 7, 2023.

      US Food and Drug Administration. Hematologic malignancies: regulatory considerations for use of minimal residual disease in development of drug and biological products for treatment. Guidance for industry. https://www.fda.gov/media/134605/download. January 2020. Accessed April 7, 2023.

    • Seymour JF, Kipps TJ, Eichhorst B, et al. Four-year analysis of MURANO study confirms sustained benefit of time-limited venetoclax–rituximab (VenR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.

      Seymour JF, Kipps TJ, Eichhorst B, et al. Four-year analysis of MURANO study confirms sustained benefit of time-limited venetoclax–rituximab (VenR) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). Presented at: 61st American Society of Hematology Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.

    • Greer JA, Amoyal N, Nisotel L, et al. A systematic review of adherence to oral antineoplastic therapies. Oncologist. 2016;21(3):354​-376.

      Greer JA, Amoyal N, Nisotel L, et al. A systematic review of adherence to oral antineoplastic therapies. Oncologist. 2016;21(3):354​-376.

    • Ruddy K, Mayer E, Partridge A. Patient adherence and persistence with oral anticancer treatment. CA Cancer J Clin. 2009;59(1):56-66.

      Ruddy K, Mayer E, Partridge A. Patient adherence and persistence with oral anticancer treatment. CA Cancer J Clin. 2009;59(1):56-66.

    • Giacomini KM, Huang S-M, Tweedie DJ, et al. Membrane transporters in drug development. Nat Rev Drug Discov. 2010;9(3):215​-236.

      Giacomini KM, Huang S-M, Tweedie DJ, et al. Membrane transporters in drug development. Nat Rev Drug Discov. 2010;9(3):215​-236.

    • Wessler JD, Grip LT, Mendell J, Giugliano RP. The P-glycoprotein transport system and cardiovascular drugs. J Am Coll Cardiol. 2013;61(25):2495​-2502.

      Wessler JD, Grip LT, Mendell J, Giugliano RP. The P-glycoprotein transport system and cardiovascular drugs. J Am Coll Cardiol. 2013;61(25):2495​-2502.

    • CRESEMBA Prescribing Information. December 2019.

      CRESEMBA Prescribing Information. December 2019.

    • Drug development and drug interactions: table of substrates, inhibitors and inducers. US Food and Drug Administration website.
      https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers#cypEnzymes. Updated November 14, 2017. Accessed March 11, 2021.

      Drug development and drug interactions: table of substrates, inhibitors and inducers. US Food and Drug Administration website.
      https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers#cypEnzymes. Updated November 14, 2017. Accessed March 11, 2021.

    • RITUXAN Prescribing Information.

      RITUXAN Prescribing Information.

    • Souers AJ, Leverson JD, Doghaert ER, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19(2):202​-203.

      Souers AJ, Leverson JD, Doghaert ER, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19(2):202​-203.

    • Al-Sawaf O, Zhang C, Tandon M, et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukemia (CLL14); follow-up results from a multicentre, open-label, randomized, phase 3 trial. Lancet Oncol. 2020;21:1188​-1200.

      Al-Sawaf O, Zhang C, Tandon M, et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukemia (CLL14); follow-up results from a multicentre, open-label, randomized, phase 3 trial. Lancet Oncol. 2020;21:1188​-1200.

    • Al-Sawaf O, Robrecht S, Zhang C, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized CLL14 study. Abstract presented at the European Hematology Association Congress 2023; June 8-11, 2023.

      Al-Sawaf O, Robrecht S, Zhang C, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized CLL14 study. Abstract presented at the European Hematology Association Congress 2023; June 8-11, 2023.

    • Data on file, AbbVie Inc. 6-year data ABVRRTI76226.

      Data on file, AbbVie Inc. 6-year data ABVRRTI76226.

    • Kater AP, Harrup R, Kipps TJ, et al. Final 7-year (yr) follow up and retreatment substudy analysis of MURANO: venetoclax-rituximab (VENR)-treated patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Abstract presented at the European Hematology Association Conference 2023; June 8-11, 2023.

      Kater AP, Harrup R, Kipps TJ, et al. Final 7-year (yr) follow up and retreatment substudy analysis of MURANO: venetoclax-rituximab (VENR)-treated patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL). Abstract presented at the European Hematology Association Conference 2023; June 8-11, 2023.

    • Data on file, AbbVie Inc. 7-year MURANO ABVRRTI76236.

      Data on file, AbbVie Inc. 7-year MURANO ABVRRTI76236.

    • Koffman B, Stewart C, Avruch L, et al. Awareness, knowledge, and preferences of United States (US) patient with chronic lymphocytic leukemia (CLL) and their caregivers related to finite duration (FD) therapy and minimal (measurable) residual disease (MRD). Blood. 2021;138(Suppl 1):1927​-1929.

      Koffman B, Stewart C, Avruch L, et al. Awareness, knowledge, and preferences of United States (US) patient with chronic lymphocytic leukemia (CLL) and their caregivers related to finite duration (FD) therapy and minimal (measurable) residual disease (MRD). Blood. 2021;138(Suppl 1):1927​-1929.

    • Koffman B, Stewart C, Avruch L, et al. Awareness, knowledge, and preferences of United States (US) patient with chronic lymphocytic leukemia (CLL) and their caregivers related to finite duration (FD) therapy and minimal (measurable) residual disease (MRD). Poster presented at: 63rd ASH Annual Meeting and Exposition; December 11-14, 2021.
      REF-104946

      Koffman B, Stewart C, Avruch L, et al. Awareness, knowledge, and preferences of United States (US) patient with chronic lymphocytic leukemia (CLL) and their caregivers related to finite duration (FD) therapy and minimal (measurable) residual disease (MRD). Poster presented at: 63rd ASH Annual Meeting and Exposition; December 11-14, 2021.
      REF-104946

    • Seymour JF, Kipps TJ, Eichhorst B, et al. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022;140(8)(suppl):839​-850.

      Seymour JF, Kipps TJ, Eichhorst B, et al. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022;140(8)(suppl):839​-850.

    • Data on file, AbbVie Inc. ABVRRTI74115.

      Data on file, AbbVie Inc. ABVRRTI74115.

    • Seymour JF, Kipps TJ, Eichhorst B, et al. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022;140(8):839​-850.

      Seymour JF, Kipps TJ, Eichhorst B, et al. Enduring undetectable MRD and updated outcomes in relapsed/refractory CLL after fixed-duration venetoclax-rituximab. Blood. 2022;140(8):839​-850.

    • Al-Sawaf O, Zhang C, Tandon M, et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukemia (CLL14); follow-up results from a multicentre, open-label, randomized, phase 3 trial. Lancet Oncol 2020;21(9)(suppl):1188​-1200.

      Al-Sawaf O, Zhang C, Tandon M, et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukemia (CLL14); follow-up results from a multicentre, open-label, randomized, phase 3 trial. Lancet Oncol 2020;21(9)(suppl):1188​-1200.