Dose ramp-up is designed to allow patients to safely attain the recommended daily dose 1

  • 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 (venetoclax tablets) to reduce risk of TLS
  • Instruct patients to take VENCLEXTA tablets with a meal and water at approximately the same time each day. VENCLEXTA tablets should be swallowed whole and not chewed, crushed, or broken prior to swallowing

 

Pretreatment TLS risk assessment and prophylaxis 1

  • All patients should have white blood cell count less than 25 × 109/L prior to initiation of VENCLEXTA. Cytoreduction prior to treatment may be required
  • Prior to first VENCLEXTA dose, provide all patients with prophylactic measures including adequate hydration and anti-hyperuricemic agents and continue during ramp-up phase
  • Assess blood chemistry 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, consider additional measures, including increased laboratory monitoring and reducing VENCLEXTA starting dose

TLS in clinical trials 1,7

  • With implementation of dosing ramp-up plus standard TLS prophylaxis and monitoring:
    • In VIALE-A, the rate of TLS was 1.1% (3/283) in patients who received VENCLEXTA in combination with azacitidine. All events were laboratory TLS
    • In VIALE-C, the rate of TLS was 5.6% (8/142) in patients who received VENCLEXTA in combination with low-dose cytarabine. There were 4 events of laboratory TLS and 4 events of clinical TLS, which included 2 deaths and cases of renal failure

Dosing schedule for VENCLEXTA + azacitidine (AZA) 1

In the VIALE-A trial, which evaluated the efficacy and safety of VEN+AZA:

  • Azacitidine was administered in 28-day cycles, beginning on Day 1 of VENCLEXTA treatment, at a dosage of 75 mg/m2, intravenously or subcutaneously once daily on Days 1-7 of each cycle

Dosing schedule for VENCLEXTA + decitabine (DEC) or low-dose cytarabine (LDAC) 1

  • If using VENCLEXTA in combination with decitabine, follow the dose ramp-up schedule for VENCLEXTA 400 mg and administer decitabine at 20 mg/m2 intravenously once daily on Days 1-5 of each 28-day cycle beginning on Cycle 1, Day 1
  • If using VENCLEXTA in combination with low-dose cytarabine, follow the dose ramp-up schedule for VENCLEXTA 600 mg and administer cytarabine at 20 mg/m2 subcutaneously once daily on Days 1-10 of each 28-day cycle beginning on Cycle 1, Day 1. For more information, please refer to the full Prescribing Information

VENCLEXTA dose should be modified for concomitant use with certain medications 1,8,9

  • VENCLEXTA is metabolized by the CYP3A enzyme; the dose should be reduced when used with P-gp inhibitors or strong or moderate CYP3A inhibitors
Dose modifications for managing potential interactions
Coadministered drug
Initiation and ramp-up phase Steady daily dose after
ramp-up phase
Posaconazole Day 1: 10 mg
Day 2: 20 mg
Day 3: 50 mg
Day 4: 70 mg
Reduce the VENCLEXTA dose
to 70 mg
Other strong CYP3A inhibitor Day 1: 10 mg
Day 2: 20 mg
Day 3: 50 mg
Day 4: 100 mg
Reduce the VENCLEXTA dose
to 100 mg
Moderate CYP3A inhibitor Reduce the VENCLEXTA dose by at least 50%
P-gp inhibitor
Examples of other coadministered CYP3A and P-gp inhibitors
Other strong CYP3A inhibitors Clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, ritonavir, telaprevir, voriconazole*
Moderate CYP3A inhibitors Aprepitant, ciprofloxacin, conivaptan, cyclosporine, diltiazem, dronedarone, erythromycin, fluconazole, isavuconazole, verapamil*
P-gp inhibitors Amiodarone, carvedilol, clarithromycin, cyclosporine, dronedarone, itraconazole, ketoconazole, quinidine, ranolazine, ritonavir, verapamil*
  • Adjust the VENCLEXTA dose and monitor more frequently for adverse reactions. 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 1
  • Avoid grapefruit products, Seville oranges, and starfruit during treatment with VENCLEXTA, as they contain inhibitors of CYP3A 1
  • Concomitant use of VENCLEXTA with strong CYP3A inducers decreases VENCLEXTA exposure, which may decrease VENCLEXTA efficacy. Avoid concomitant use of VENCLEXTA with strong CYP3A inducers or moderate CYP3A inducers 1
  • Concomitant use of VENCLEXTA increases warfarin exposure, which may increase the risk of bleeding. Monitor international normalized ratio (INR) more frequently in patients using warfarin concomitantly with VENCLEXTA 1
  • Concomitant use of VENCLEXTA increases exposure of P-gp substrates, which may increase toxicities of these substrates. 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 1

Dose modifications for patients with severe hepatic impairment 1

  • Reduce the VENCLEXTA once-daily dose by 50% for patients with severe hepatic impairment (Child-Pugh C); monitor these patients more closely for adverse reactions 

*This is not an exhaustive list and is intended only to complement, not replace, clinical judgment during treatment of patients with VENCLEXTA. Please refer to the FDA website for more examples.

CYP3A=cytochrome P450 3A; P-gp=P-glycoprotein.
CRESEMBA® is a registered trademark of Astellas US LLC.