Important Safety Information
Contraindication
• Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated 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 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 .
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
• In combination with rituximab , serious adverse reactions were reported in 46 % of patients , with the most frequent ( ≥5 %) being pneumonia ( 9 %). The most common adverse reactions ( ≥20 %) of any grade were neutropenia ( 65 %), diarrhea ( 40 %), upper respiratory tract infection ( 39 %), fatigue ( 22 %), cough ( 22 %), and nausea ( 21 %).
• As monotherapy , serious adverse reactions were reported in 52 % of patients , with the most frequent ( ≥5 %) being 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 %).
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 .
Neutropenia
• Avoid concomitant use of moderate CYP3A inhibitors or
• Grade 3 or 4 neutropenia developed in 64 % ( 124 / 194 ) of P-gp inhibitors . If an inhibitor must be used , reduce the
patients treated with VENCLEXTA in combination with Print-only content VENCLEXTA dose by at least 50 %. Monitor patients more rituximab and in 63 % ( 216 / 344 ) of patients treated with VENCLEXTA monotherapy . Febrile neutropenia occurred in 4 % of patients treated with VENCLEXTA in combination with rituximab and in 6 % of patients treated with VENCLEXTA monotherapy . 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 ).
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 .
References : 1 . Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology ( NCCN Guidelines ® ) for Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma V . 5.2018 . National Comprehensive Cancer Network , Inc . 2018 . All rights reserved . Accessed April 2 , 2018 . To view the most recent and complete version of the guideline , go online to NCCN . org . 2 . VENCLEXTA Prescribing Information . 3 . AbbVie ’ s Venetoclax receives breakthrough therapy designation from FDA in combination with rituximab for the treatment of patients with relapsed / refractory chronic lymphocytic leukemia [ press release ]. North Chicago , IL : AbbVie Inc . https :// news . abbvie . com / news / abbvies-venetoclax-receives-breakthrough-therapy-designationfrom-fda-in-combination-with-rituximab-for-treatment-patients-with-relapsedrefractory-chronic-lymphocyticleukemia . htm . Accessed March 21 , 2018 .
Please see Brief Summary of full Prescribing Information on the following pages .