CONTRAINDICATIONS / PRECAUTIONS
General Information
During the initial and dose titration phase, the concomitant use of venetoclax with a strong CYP3A inhibitor is contraindicated.
Electrolyte imbalance, renal failure, tumor lysis syndrome (TLS)
Tumor lysis syndrome (TLS) has occurred in previously treated chronic lymphocytic leukemia patients with a high tumor burden who received venetoclax therapy; fatal events and renal failure requiring dialysis have been reported as a result of TLS. Assess patient-specific factors for level of TLS risk (e.g., tumor burden using radiographic eva luation, blood chemistries, comorbidities). All patients require hydration and anti-hyperuricemic agents prior to the first venetoclax dose to reduce the risk of TLS; more intensive measures (e.g., IV hydration, increased monitoring, hospitalization) may be necessary as the overall risk increases. Prior to starting venetoclax, eva luate serum electrolytes (e.g., potassium, phosphorus, calcium), uric acid level, and serum creatinine concentration; correct any electrolyte imbalance. Monitor for laboratory signs of TLS at 6 to 8 hours after the first dose of 20 mg/day and 50 mg/day and then prior to subsequent dose titrations in patients with low or medium tumor burden. Consider hospitalization during the first dose of 20 mg/day and 50 mg/day in patients with a medium tumor burden who have a creatinine clearance less than 80 mL/min; monitor for signs of TLS at 6 to 8 hours and 24 hours after the subsequent dose titrations in these patients. In patients with a high tumor burden, administer the first dose of 20 mg/day and 50 mg/day in the hospital and monitor for laboratory signs of TLS at 4, 8, 12, and 24 hours. Monitor for signs of TLS at 6 to 8 hours and 24 hours after subsequent dose titrations in these patients in the outpatient setting. A dose reduction and/or therapy interruption may be necessary in patients who develop TLS.
Anemia, infection, neutropenia, thrombocytopenia
Hematologic toxicity (e.g., neutropenia, thrombocytopenia, and anemia) and infection have been reported with venetoclax therapy. Monitor patients for fever or other signs or symptoms of infection and obtain complete blood counts periodically during treatment. A dose reduction and/or therapy interruption may be necessary in patients who develop grade 3 or 4 neutropenia with infection or fever or other grade 4 hematologic toxicities (except lymphopenia). Consider the use of granulocyte-colony stimulating factors as indicated to reduce the infection risk associated with neutropenia.
Vaccination
Avoid vaccination with live attenuated vaccines prior to, during, and after venetoclax treatment because the antibody response may be suboptimal. Live vaccines may be administered after B-cell recovery.
Renal disease, renal impairment
Use venetoclax with caution in patients with renal disease; it has not been eva luated in patients with severe renal impairment (creatinine clearance (CrCl) < 30 mL/min) or in patients receiving dialysis. No venetoclax dosage adjustment is necessary in patients with mild or moderate renal impairment. Patients with decreased renal function (CrCl < 80 mL/min) may be at increased risk of developing tumor lysis syndrome (TLS) with venetoclax therapy; increased monitoring and more intensive TLS propylaxis may be necessary.
Hepatic disease
Use venetoclax with caution in patients with hepatic disease; it has not been eva luated in patients with severe hepatic impairme |
