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.
Neutropenia
• Grade 3 or 4 neutropenia developed in 64% (124/194) of
patients treated with VENCLEXTA in combination with
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).
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
FDA
BREAKTHROUGH
THERAPY
DESIGNATION 3
• 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.
• 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.
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-designation-
from-fda-in-combination-with-rituximab-for-treatment-patients-with-relapsedrefractory-chronic-lymphocytic-
leukemia.htm. Accessed March 21, 2018.
Please see Brief Summary of full Prescribing
Information on the following pages.