VENCLEXTA

Venetoclax mean (± standard deviation) steady state C max was 2.1 ± 1.1 mcg/mL and AUC 0-24h was 32.8 ± 16.9 mcg

• h/mL following administration of 400 mg once daily with a low-fat meal. Venetoclax steady state AUC increased proportionally over the dose range of 150 to 800 mg (0.25 to 1.33 times the maximum approved recommended dosage). The pharmacokinetics of venetoclax does not change over time.

AbsorptionMaximum plasma concentration of venetoclax was reached 5 to 8 hours following multiple ora...

Figure 1. Kaplan-Meier Curve of IRC-Assessed Progression-free Survival in AMPLIFY Figure 1 Figure 2 Figure 3 Figure 4 14.1 Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma In Combination with Acalabrutinib AMPLIFY (ACE-CL-311) was a randomized, multi-center, open-label study (NCT03836261) that evaluated the efficacy and safety of VENCLEXTA in combination with acalabrutinib (VEN+A). The study included patients previously untreated for CLL without del(17p) or TP53 mutation that were 18 years of age and older. Patients were randomized to receive: VENCLEXTA plus acalabrutinib (VEN+A): Acala...

The following clinically significant adverse reactions are described elsewhere in the labeling: Tumor Lysis Syndrome [see Warnings and Precautions ( 5.1 )] Neutropenia [see Warnings and Precautions ( 5.2 )] Infections [see Warnings and Precautions ( 5.3 )] In CLL/SLL, the most common adverse reactions (≥20%) for VENCLEXTA when given in combination with obinutuzumab or rituximab or as monotherapy are neutropenia, thrombocytopenia, anemia, diarrhea, nausea, upper respiratory tract infection, cough...

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 [see Dosage and Administration ( 2.6 ) and Drug Interactions ( 7.1 )] . Concomitant use with strong CYP3A inhibitors at initiation and during ramp-up phase in patients with CLL/SLL is contrai...

Tumor Lysis Syndrome (TLS): Anticipate TLS; assess risk in all patients. Premedicate with anti-hyperuricemics and ensure adequate hydration. Employ more intensive measures (intravenous hydration, frequent monitoring, hospitalization) as overall risk increases. ( 2.4 , 5.1 ) Neutropenia: Monitor blood counts. Interrupt dosing and resume at same or reduced dose. Consider supportive care measures. ( 2.5 , 5.2 ) Infections: Monitor for signs and symptoms of infection and treat promptly. Withhold for...

7 DRUG INTERACTIONS Strong or moderate CYP3A inhibitors or P-gp inhibitors: Adjust dosage of VENCLEXTA. ( 2.6 , 7.1 ) Strong or moderate CYP3A inducers: Avoid co-administration. ( 7.1 ) P-gp substrates: Take at least 6 hours before VENCLEXTA. ( 7.2 ) 7.1 Effects of Other Drugs on VENCLEXTA Strong or Moderate CYP3A Inhibitors or P-gp Inhibitors Concomitant use with a strong or moderate CYP3A inhibi...