DAILY DOSING SCHEDULE INCLUDING RAMP-UP

Assess patient-specific factors for level of risk of tumor lysis syndrome (TLS) and provide prophylactic hydration and anti-hyperuricemics to patients prior to first dose of VENCLEXTA to reduce risk of TLS.

Instruct patients to take VENCLEXTA tablets with a meal and water at approximately the same time each day; tablets should be swallowed whole and not chewed, crushed, or broken prior to swallowing.

VEN + AZA OR DEC DOSING IN AML INCLUDES A 3-DAY RAMP-UP TO SAFELY ATTAIN THE RECOMMENDED DAILY DOSE 1

In clinical trials:

  • No reported events of laboratory or clinical TLS with implementation of dosing ramp-up plus standard TLS prophylaxis and monitoring 1
  • Azacitidine was administered in 28-day cycles, beginning on Day 1 of VENCLEXTA treatment, at a dosage of 75 mg/m2, IV or subcutaneous, on Days 1-7 of each cycle 1
  • Decitabine was administered in 28-day cycles, beginning on Day 1 of VENCLEXTA treatment, at a dosage of 20 mg/m2, IV, on Days 1-5 of each cycle 1

VEN + LDAC DOSING IN AML INCLUDES A 4-DAY RAMP-UP TO SAFELY ATTAIN THE RECOMMENDED DAILY DOSE 1

In clinical trials:

  • LDAC was administered in 28-day cycles, beginning on Day 1 of VENCLEXTA treatment, at a dosage of 20 mg/m2, subcutaneous, on Days 1-10 of each cycle 1
  • There were 2/61 (3%) reported events of TLS with implementation of dose ramp-up plus standard TLS prophylaxis and monitoring. All events were laboratory TLS, and all patients were able to reach the target dose 1

AZA=azacitidine; DEC=decitabine; LDAC=low-dose cytarabine; IV=intravenous; TLS=tumor lysis syndrome; VEN=VENCLEXTA; LDH=lactate dehydrogenase.

RISK ASSESSMENT AND PROPHYLAXIS FOR TLS

Patients treated with VENCLEXTA may develop tumor lysis syndrome (TLS) 1

  • Assess patient-specific factors for TLS risk level and provide prophylactic hydration and anti-hyperuricemics to patients prior to first dose of VENCLEXTA to reduce risk of TLS
  • All patients should have white blood cell count <25 x 109/L prior to initiation of VENCLEXTA. Cytoreduction prior to treatment may be required
  • Prior to first VENCLEXTA dose, all patients should receive prophylactic measures including adequate hydration and anti-hyperuricemic agents and continue during ramp-up phase
  • Assess blood chemistry (potassium, uric acid, phosphorus, calcium, and creatinine) and correct pre-existing abnormalities prior to initiation of treatment with VENCLEXTA
  • Monitor blood chemistries for TLS at pre-dose, 6 to 8 hours after each new dose during ramp-up, and 24 hours after reaching final dose
  • For patients with risk factors for TLS (eg, circulating blasts, high burden of leukemia involvement in bone marrow, elevated pretreatment LDH levels, or reduced renal function), additional measures should be considered, including increased laboratory monitoring and reducing VENCLEXTA starting dose

LDH=lactate dehydrogenase; TLS=tumor lysis syndrome.