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*
|Withhold the next day's dose. If resolved within 24-48 hours of last dose, resume at same dose.|
|For any blood chemistry changes requiring more than 48 hours to resolve, resume at a reduced dose.|
|For any events of clinical TLS,† resume at a reduced dose following resolution.|
|Interrupt VENCLEXTA. Once the toxicity has resolved to grade 1 or baseline level, VENCLEXTA therapy may be resumed at the same dose. No dose modification is required.|
2nd and subsequent occurrences
|Interrupt VENCLEXTA. Follow dose reduction recommendations when resuming treatment with VENCLEXTA after resolution. A larger dose reduction may occur at the discretion of the physician.|
Interrupt VENCLEXTA. To reduce the infection risks associated with neutropenia, granulocyte-colony stimulating factor (G-CSF) may be administered with VENCLEXTA if clinically indicated. Once the toxicity has resolved to grade 1 or baseline level, therapy may be resumed at the same dose.
2nd and subsequent occurrences
Interrupt VENCLEXTA. Consider using G-CSF as clinically indicated. Follow dose reduction recommendations when resuming treatment after resolution. A larger dose reduction may occur at the discretion of the physician.
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
†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.
Dosage modifications for concomitant use with strong or moderate CYP3A inhibitors or P-gp inhibitors
Concomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during the ramp-up phase is contraindicated in patients with CLL/SLL due to the potential for increased risk of tumor lysis syndrome.
- Concomitant use of VENCLEXTA with strong or moderate CYP3A inhibitors or P-gp inhibitors may increase the risk of TLS at initiation and during the ramp-up phase, and requires dose adjustment due to increases in VENCLEXTA exposure
- Resume the VENCLEXTA dose 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
§Consider alternative medications or reduce the VENCLEXTA dose as described in this table.
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.