Interrupt dosing or reduce for toxicities 

  • For patients who have had a dosing interruption greater than 1 week during the first 5 weeks of the ramp-up phase or greater than 2 weeks after completing the VENCLEXTA (venetoclax tablets) ramp-up phase, reassess the risk of TLS to determine if reinitiation with a reduced dose is necessary (eg, all or some levels of the ramp-up schedule)

Recommended VENCLEXTA dose modifications for toxicities*
 

Tumor lysis syndrome

Non-hematologic toxicities

Hematologic toxicities

Consider discontinuing VENCLEXTA for patients who require dose reductions to less than 100 mg for more than 2 weeks.

  • Monitor complete blood counts throughout the treatment period

*Adverse reactions were graded using NCI CTCAE version 4.0.
Clinical TLS was defined as laboratory TLS with clinical consequences such as acute renal failure, cardiac arrhythmias, or sudden death and/or seizures.

G-CSF=granulocyte colony-stimulating factor; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.

Dose modifications for use with CYP3A and P-gp inhibitors 1

Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during the ramp-up phase is contraindicated due to the potential for increased risk of TLS.

  • 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
  • Concomitant use of VENCLEXTA with a strong or moderate CY3PA inhibitor or a P-gp inhibitor increases venetoclax Cmax and AUCinf which may increase VENCLEXTA toxicities, including the risk of TLS 1

Dosage modifications for patients with severe hepatic impairment

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

CYP3A=cytochrome P450 3A; P-gp=P-glycoprotein.