Dose modifications based on VENCLEXTA™ toxicities or drug interactions 1

Interrupt or reduce VENCLEXTA dose for toxicities

There are recommended dose modifications for TLS, non-hematologic, and hematologic toxicities. For patients who require an interruption longer than 1 week during the ramp-up phase or greater than 2 weeks at the recommended daily dose of 400 mg, reassess the risk of TLS to determine if reinitiation at a reduced dose is necessary (e.g., all or some levels of the dose ramp-up schedule). Consider discontinuing VENCLEXTA for patients who require dose reductions to less than 100 mg for more than 2 weeks.

Recommended dose modifications for toxicities

TLS

Non-hematologic toxicities

Hematologic toxicities

TLS=tumor lysis syndrome; G-CSF=granulocyte colony-stimulating factor.
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.

VENCLEXTA dose reduction guidelines

Dose modifications for use with CYP3A and P-gp inhibitors

Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated

  • Monitor these patients more closely for signs of toxicities
  • Concomitant use of VENCLEXTA with strong CYP3A inhibitors increases venetoclax exposure and may increase the risk for TLS at initiation and during the ramp-up phase
  • 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