MEDICATION INTERACTIONS TRIAL
MEDICATION INTERACTIONS PLUS

The most common adverse reactions (≥20%) of any grade were neutropenia (65%), diarrhea (40%), upper respiratory tract infection (39%), fatigue (22%), and nausea (21%).

In patients with CLL receiving combination therapy with rituximab, the most frequent serious adverse reaction (≥5%) was pneumonia (9%).

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. 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 obinutuzumab, serious adverse reactions were most often due to febrile neutropenia and pneumonia (5% each).

MEDICATION INTERACTIONS PLUS

Treatment of patients with multiple myeloma with VENCLEXTA in combination with bortezomib plus dexamethasone is not recommended outside of controlled clinical trials.

MEDICATION INTERACTIONS TRIAL

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.Increased Mortality in Patients with Multiple Myeloma when VENCLEXTA is Added to Bortezomib and Dexamethasone Advise females of reproductive potential to use effective contraception during treatment and for 30 days after the last dose. VENCLEXTA may cause embryo-fetal harm when administered to a pregnant woman.Advise patients that vaccinations may be less effective. Do not administer live attenuated vaccines prior to, during, or after treatment with VENCLEXTA until B-cell recovery occurs.Withhold VENCLEXTA for Grade 3 and 4 infection until resolution and resume at same or reduced dose. Monitor patients for signs and symptoms of infection and treat promptly. Fatal and serious infections such as pneumonia and sepsis have occurred in patients treated with VENCLEXTA.Consider supportive measures including antimicrobials and growth factors (e.g., G-CSF).

Interrupt dosing for severe neutropenia and resume at same or reduced dose. Febrile neutropenia occurred in 4% to 6% of patients.

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.

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.

Interrupt dosing if needed when restarting VENCLEXTA follow dose modification guidance in the Prescribing Information. Employ more intensive measures (IV hydration, frequent monitoring, hospitalization) as overall risk increases. Monitor blood chemistries and manage abnormalities promptly.

Assess all patients for risk and provide appropriate prophylaxis for TLS, including hydration and anti-hyperuricemics.Splenomegaly may also increase the risk of TLS in patients with CLL/SLL. The risk of TLS is a continuum based on multiple factors, particularly reduced renal function, tumor burden, and type of malignancy.

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 rate of TLS remained consistent with VENCLEXTA in combination with obinutuzumab or rituximab.

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.

TLS, including fatal cases, has been reported after a single 20 mg dose. 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.

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.

Tumor lysis syndrome, including fatal events and renal failure requiring dialysis, has occurred in patients treated with VENCLEXTA.

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).

Important Safety Information Contraindication

Medication interactions