-gp) and Breast Cancer Resistance Protein (BCRP) and may be a P-gp inhibitor at therapeutic dose levels in the gut; vemurafenib is an inhibitor of P-gp and BCRP and a P-gp substrate. Consider alternative agents. If concomitant use of these drugs is required, reduce the venetoclax dosage by at least 50% (maximum dose of 200 mg/day) and consider administering vemurafenib at least 6 hours before venetoclax. If vemurafenib is discontinued, wait 2 to 3 days and then resume the recommended venetoclax dosage (or prior dosage if less). Monitor patients for signs and symptoms of venetoclax toxicity such as hematologic toxicity, GI toxicity, and tumor lysis syndrome. In a drug interaction study (n = 11), the venetoclax Cmax and AUC values were increased by 106% and 78%, respectively, when a P-gp inhibitor was co-administered in healthy subjects.
Verapamil: Avoid the concomitant use of venetoclax and verapamil; venetoclax is a substrate of CYP3A4 and P-glycoprotein (P-gp) and verapamil is a CYP3A4 (moderate) and P-gp inhibitor. Consider alternative agents. If concomitant use of these drugs is required, reduce the venetoclax dosage by at least 50% (maximum dose of 200 mg/day). If verapamil is discontinued, wait 2 to 3 days and then resume the recommended venetoclax dosage (or prior dosage if less). Monitor patients for signs and symptoms of venetoclax toxicity such as hematologic toxicity, GI toxicity, and tumor lysis syndrome. In a drug interaction study (n = 11), the venetoclax Cmax and AUC values were increased by 106% and 78%, respectively, when a P-gp inhibitor was co-administered in healthy subjects.
Voriconazole: Avoid the concomitant use of venetoclax and voriconazole; venetoclax is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. The concomitant use of these agents together is contraindicated during the initial and dose titration phase of venetoclax. If concomitant use of these drugs is required when the patient is on a steady venetoclax dose (after the titration phase), reduce the venetoclax dosage by at least 75% (maximum dose of 100 mg/day). If voriconazole is discontinued, wait 2 to 3 days and then resume the recommended venetoclax dosage (or prior dosage if less). Monitor patients for signs and symptoms of venetoclax toxicity such as hematologic toxicity, GI toxicity, and tumor lysis syndrome. In a drug interaction study, the venetoclax Cmax and AUC values were increased by 2.3-fold and 6.4-fold, respectively, when a strong CYP3A4 inhibitor was co-administered in NHL patients.
Warfarin: Use venetoclax and warfarin together with caution; warfarin levels may be increased. If these agents are used together, monitor the international normalized ratio (INR) closely and adjust the dosage of warfarin as necessary. In a drug-drug interaction study in healthy subjects (n = 3), the R- and S-warfarin Cmax and AUC values increased by 18% to 28% when a single 400-mg dose of venetoclax was co-administered with a single 5-mg dose of warfarin.
PREGNANCY AND LACTATION
Pregnancy
Venetoclax may cause fetal harm if administered during pregnancy based on its mechanism of action and data from animal studies. Females of reproductive potential should be advised to avoid becoming pregnant while receiving venetoclax. If a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus. In an embryo-fetal study in pregnant mice, post-implantation loss and decreased fetal weight were observed following venetoclax doses that resulted in drug e |
