n (2.3)].
Non-Hematologic Toxicities
Grade 3 or 4 non-hematologic toxicities 1st occurrence 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 guidelines in Table 4 when resuming treatment with VENCLEXTA after resolution. A larger dose reduction may occur at the discretion of the physician.
Hematologic Toxicities
Grade 3 or 4 neutropenia with infection or fever; or Grade 4 hematologic toxicities (except lymphopenia) [see Warnings and Precautions (5.2)] 1st occurrence 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, VENCLEXTA therapy may be resumed at the same dose.
2nd and subsequent occurrences Interrupt VENCLEXTA.
Consider using G-CSF as clinically indicated.
Follow dose reduction guidelines in Table 4 when resuming treatment with VENCLEXTA 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.
aAdverse reactions were graded using NCI CTCAE version 4.0.
bClinical TLS was defined as laboratory TLS with clinical consequences such as acute renal failure, cardiac arrhythmias, or sudden death and/or seizures.
Table 4. Dose Modification for Toxicity During VENCLEXTA Treatment Dose at Interruption, mg Restart Dose, mga
400 300
300 200
200 100
100 50
50 20
20 10
aDuring the ramp-up phase, continue the reduced dose for 1 week before increasing the dose.
2.5 Dose Modifications for Use with CYP3A and P-gp InhibitorsConcomitant use of VENCLEXTA with strong CYP3A inhibitors at initiation and during ramp-up phase is contraindicated. Concomitant use of VENCLEXTA with strong CYP3A inhibitors increases venetoclax exposure (i.e., Cmax and AUC) and may increase the risk for TLS at initiation and during ramp-up phase [see Contraindications (4)]. For patients who have completed the ramp-up phase and are on a steady daily dose of VENCLEXTA, reduce the VENCLEXTA dose by at least 75% when strong CYP3A inhibitors must be used concomitantly.
Avoid concomitant use of VENCLEXTA with moderate CYP3A inhibitors or P-gp inhibitors. Consider alternative treatments. If a moderate CYP3A inhibitor or a P-gp inhibitor must be used, reduce the VENCLEXTA dose by at least 50%. Monitor these patients more closely for signs of toxicities [see Dosage and Administration (2.4)].
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 [see Dosage and Administration (2.4) and Drug Interactions (7.1)].
The recommendations for managing drug-drug interactions are summarized in Table 5.
Table 5. Management of Potential VENCLEXTA Interactions with CYP3A and P-gp Inhibitors Inhibitors Initiation and Ramp-Up
Phase Steady Daily Dose
(After Ramp-Up Phase)
Strong CYP3A inhibitor Contraindicated Avoid inhibitor use or reduce the VENCLEXTA dose by at least 75%
Moderate CYP3A inhibitor Avoid inhibitor use or reduce the VENCLEXTA dose by at least 50%
P-gp inhibitor
2.6 Missed DoseIf the patien |
