On May 15, 2019, VENCLEXTA® (venetoclax tablets) was approved by the US Food and Drug Administration (FDA) for the first-line treatment of adult patie

5/24/2019

On May 15, 2019, VENCLEXTA® (venetoclax tablets) was approved by the US Food and Drug Administration (FDA) for the first-line treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).


VENCLEXTA is also approved in combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.


This indication is approved under accelerated approval based on response rates. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.


VENCLEXTA Access Solutions is your resource for access and reimbursement support after VENCLEXTA is prescribed. We can help your patients and practice by providing:

· Benefitsinvestigations (BIs)

· Priorauthorization(PA)resources

· Informationaboutauthorized specialtypharmacies (SPs) andspecialtydistributors

· Sample billingandcodinginformation

· Resources fordenialsandappeals

· Patientassistanceoptions


A list of authorized SPs and specialty distributors is available at Genentech-Access.com/VENCLEXTA.



FormoreinformationaboutVENCLEXTAAccessSolutions, please contactmedirectly,visit

Genentech-Access.com/VENCLEXTAorcall(888)249-4918.


Indicationsand ImportantSafetyInformation

Indications

 

VENCLEXTA is indicated:

· For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

· In combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of
newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that precludeuse of intensive induction chemotherapy.


This indication is approved under accelerated approval based on response rates. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.


Important Safety Information

 

Contraindication

· Concomitant use of VENCLEXTA with strongCYP3A 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 with high tumor burden when treated with VENCLEXTA.

· In patients with CLL 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 monotherapy studies. 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.

· VENCLEXTA poses a risk for TLS at initiation and during the 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 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 or P-gp inhibitors may increase the risk of TLS at initiation and during the ramp-up phase, and requires dose adjustment due to increases in VENCLEXTA exposure.


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 treated with VENCLEXTA in combination and monotherapy studies. Febrile neutropenia occurred in 4% to 6% of patients treated with VENCLEXTA in combination and monotherapy studies.

· In patients with AML, baseline neutrophil counts worsened in 97% to 100% of patients treated with VENCLEXTA in combination with azacitidine or decitabine or low-dose cytarabine. Neutropenia can recur with subsequent cycles of therapy.

· Monitor complete blood counts throughout the treatment period. 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).


Infections

· Fatal and serious infections such as pneumonia and sepsis have occurred in patients treated with VENCLEXTA. Monitor patients closely for signs and symptoms of infection and treat promptly. Withhold VENCLEXTA for Grade 3 and higher infection.


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 avoid pregnancy during treatment.


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%).

· In patients with CLL receiving combination therapy with rituximab, the most frequent seriousadverse 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%), cough (22%), and nausea (21%).

· 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%).

· In patients with AML receiving combination therapy with azacitidine, the most frequent serious adverse reactions (≥5%) were febrile neutropenia, pneumonia (excluding fungal), sepsis (excludingfungal), respiratory failure, and multiple organ dysfunction syndrome. The most common adverse reactions (≥30%) of any grade were nausea (58%), diarrhea (54%), constipation (49%), neutropenia (49%), thrombocytopenia (49%), hemorrhage (46%), peripheral edema (46%), vomiting (40%), fatigue (36%), febrile neutropenia (36%), rash (33%), and anemia (30%).

· In patients with AML receiving combination therapy with decitabine, the most frequent serious adverse reactions (≥5%) were febrile neutropenia, sepsis (excluding fungal), pneumonia (excluding fungal), diarrhea, fatigue, cellulitis, and localized infection. The most common adverse reactions (≥30%) of any grade were febrile neutropenia (69%), constipation (62%), fatigue (62%), thrombocytopenia (54%), abdominal pain (46%), dizziness (46%), hemorrhage (46%), nausea (46%), pneumonia (excluding fungal) (46%), sepsis (excluding fungal) (46%), cough (38%), diarrhea (38%), neutropenia (38%), back pain (31%), hypotension (31%), myalgia (31%), oropharyngeal pain (31%), peripheral edema (31%), pyrexia (31%), and rash (31%).

· Inpatients with AML receiving combination therapy with low-dose cytarabine, the most frequent serious adverse reactions (≥5%) were febrile neutropenia, sepsis (excluding fungal), hemorrhage, pneumonia (excluding fungal), and device-related infection. The most common adverse reactions (≥30%) of any grade were nausea (64%), thrombocytopenia (59%), hemorrhage (49%), febrile neutropenia (46%), neutropenia (46%), diarrhea (44%), fatigue (44%), constipation (33%), and dyspnea (31%).


Drug Interactions

· Concomitant use with a strong or moderate CYP3A inhibitor or a P-gp inhibitor increases VENCLEXTA exposure, which may increase VENCLEXTA toxicities, including the risk of TLS.
Adjust VENCLEXTA dosage and closely monitor patients for signs of VENCLEXTA toxicities.
Resume the VENCLEXTA dosage that was used prior to concomitant use of a strong or moderate CYP3A inhibitor or a 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 VENCLEXTA with a P-gp substrate. If concomitant use is unavoidable, separate dosing of the P-gp substrate at least 6 hours before VENCLEXTA.

· Monitorinternational 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.

Please see full Prescribing Informationfor Indication and additional Important Safety Information.

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