Interrupt dosing or reduce for toxicities 

  • For patients who have had a dosing interruption greater than 1 week during the ramp-up phase or greater than 2 weeks after completing the 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 dose 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.

*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
.

During the ramp-up phase, continue the reduced dose for 1 week before increasing the dose.

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 due to the potential for increased risk of tumor lysis syndrome.

  • Monitor these patients more closely for signs of toxicities
  • Concomitant use of VENCLEXTA with strong CYP3A inhibitors increases VENCLEXTA 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

TLS=tumor lysis syndrome; NCI=National Cancer Institute; CTCAE=Common Terminology Criteria for Adverse Events; G-CSF=granulocyte colony stimulating factor; CYP3A=cytochrome P450, family 3, subfamily A; P-gp:P-glycoprotein.