Important Safety Information

Contraindication

  • Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated.a

Tumor Lysis Syndrome

  • Tumor lysis syndrome (TLS), including fatal events and renal failure requiring dialysis, has occurred in previously treated CLL patients with high tumor burden treated with VENCLEXTA.
  • VENCLEXTA poses a risk for TLS in the initial 5-week ramp-up phase. 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.
  • Patients should be assessed for TLS risk, including evaluation of tumor burden and comorbidities, and should receive appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics. Reduced renal function (CrCl <80 mL/min) further increases the risk. Monitor blood chemistries and manage abnormalities promptly. Interrupt dosing if needed. Employ more intensive measures (IV hydration, frequent monitoring, hospitalization) as overall risk increases.
  • Concomitant use of VENCLEXTA with strong or moderate CYP3A inhibitors and P-gp inhibitors may increase the risk of TLS at initiation and during the ramp-up phase, and may require dose adjustment due to increases in VENCLEXTA exposure.

Neutropenia

  • Grade 3 or 4 neutropenia occurred in 41% (98/240) of patients treated with VENCLEXTA. Monitor complete blood counts throughout treatment. Interrupt dosing or reduce dose for severe neutropenia. Consider supportive measures including antimicrobials for signs of infection and use of growth factors (e.g., G-CSF).

Immunization

  • Do not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-cell recovery. 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 avoid pregnancy during treatment.

Adverse Reactions

  • Serious adverse reactions were reported in 43.8% of patients. The most frequent serious adverse reactions (≥2%) were pneumonia (5%), febrile neutropenia (4.6%), pyrexia (3.3%), autoimmune hemolytic anemia (2.9%), anemia (2.1%), and TLS (2.1%).b
  • The most common adverse reactions (≥20%) of any grade were neutropenia (45%), diarrhea (35%), nausea (33%), anemia (29%), upper respiratory tract infection (22%), thrombocytopenia (22%), and fatigue (21%).a

Drug Interactions

  • For patients who have completed the ramp-up phase and are on a steady daily dose of VENCLEXTA, reduce the dose by at least 75% when used concomitantly with strong CYP3A inhibitors. Resume the VENCLEXTA dose that was used prior to initiating the CYP3A inhibitor 2 to 3 days after discontinuation of the inhibitor.
  • Avoid concomitant use of moderate CYP3A inhibitors or P-gp inhibitors. If an inhibitor must be used, reduce the VENCLEXTA dose by at least 50%. Monitor patients more closely for signs of VENCLEXTA toxicities. Resume the VENCLEXTA dose that was used prior to initiating the CYP3A inhibitor or P-gp 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.
  • Avoid concomitant use of narrow therapeutic index P-gp substrates. If these substrates must be used, they should be taken at least 6 hours before VENCLEXTA.
  • Monitor international normalized ratio (INR) closely in patients receiving warfarin.

Lactation

  • Advise nursing women to discontinue breastfeeding during treatment with VENCLEXTA.

Females and Males of Reproductive Potential

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


a
VENCLEXTA [package insert]. North Chicago, IL: AbbVie Inc.
bData on file, AbbVie Inc. ABVRRTI62926
 

Please see full Prescribing Information.


VENCLEXTA™ is a trademark of AbbVie, Inc.