Effect of other drugs on VENCLEXTA

These tables provide recommendations for management and potential interactions with CYP3A and P-gp inhibitors and examples of drugs that interact with VENCLEXTA.
 

  • VENCLEXTA is predominantly metabolized by CYP3A in vitro 1
  • P-gp is a transmembrane efflux pump that affects uptake of drugs such as VENCLEXTA from the gut 21
  • Avoid grapefruit products, Seville oranges, and starfruit during treatment with VENCLEXTA, as they contain inhibitors of CYP3A 1

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.
Coadministered drug Initiation and ramp-up phase Steady daily dose*
(after ramp-up phase)
Posaconazole Contraindicated Reduce the VENCLEXTA dose to 70 mg
Other strong CYP3A inhibitor Contraindicated Reduce the VENCLEXTA dose to 100 mg
Moderate CYP3A inhibitor Reduce the VENCLEXTA dose by at least 50%
P-gp inhibitor

*Consider alternative medications or reduce the VENCLEXTA dose as described in this table.
 

  • 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
  • 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; P-gp=P-glycoprotein.

Examples of CYP3A and P-gp inhibitors/inducers 22-24

Coadministered drug Name
Other strong CYP3A inhibitor Clarithromycin, Conivaptan, Diltiazem, Indinavir, Itraconazole, Ketoconazole, Lopinavir, Ritonavir, Telaprevir, Voriconazole
Moderate CYP3A inhibitor
Aprepitant, Cimetidine, Ciprofloxacin, Cyclosporine, Dronedarone, Erythromycin, Fluconazole, Isavuconazole, Verapamil
P-gp inhibitor
Amiodarone, Carvedilol, Clarithromycin, Cyclosporine, Dronedarone, Itraconazole, Ketoconazole, Quinidine, Ranolazine, Ritonavir, Verapamil
Strong CYP3A inducer Carbamazepine, Phenytoin, Rifampin, St. John’s wort
Moderate CYP3A inducer Bosentan, Efavirenz, Etravirine, Modafinil

This is not an exhaustive list and is intended only to complement, not replace, clinical judgment during treatment of patients with VENCLEXTA. Please refer to the FDA website for more examples.