or burden and comorbidities. Perform tumor burden assessments, including radiographic eva luation (e.g., CT scan), assess blood chemistry (potassium, uric acid, phosphorus, calcium, and creatinine) in all patients and correct pre-existing abnormalities prior to initiation of treatment with VENCLEXTA. Reduced renal function (creatinine clearance [CrCl] <80 mL/min) further increases the risk. The risk may decrease as tumor burden decreases [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6)].
Table 2 below describes the recommended TLS prophylaxis and monitoring during VENCLEXTA treatment based on tumor burden determination from clinical trial data.
Table 2. Recommended TLS Prophylaxis Based on Tumor Burden From Clinical Trial Data (consider all patient co-morbidities before final determination of prophylaxis and monitoring schedule) Tumor Burden Prophylaxis Blood Chemistry
Monitoringc,d
Hydrationa Anti-hyperuricemics Setting and
Frequency of
Assessments
Low All LN <5 cm AND
ALC <25 x109/L Oral
(1.5-2 L) Allopurinolb Outpatient
Pre-dose, 6 to 8 hours, 24 hours at first dose of 20 mg and 50 mg
Pre-dose at subsequent ramp-up doses
Medium Any LN 5 cm to <10 cm
OR
ALC ≥25 x109/L Oral
(1.5-2 L)
and consider additional intravenous Allopurinol Outpatient
Pre-dose, 6 to 8 hours, 24 hours at first dose of 20 mg and 50 mg
Pre-dose at subsequent ramp-up doses
Consider hospitalization for patients with CrCl <80ml/min at first dose of 20 mg and 50 mg; see below for monitoring in hospital
High Any LN ≥10 cm OR
ALC ≥25 x109/L AND
any LN ≥5 cm Oral (1.5-2L)
and intravenous
(150-200 mL/hr
as tolerated) Allopurinol; consider rasburicase if baseline uric acid is elevated In hospital at first dose of 20 mg and 50 mg
Pre-dose, 4, 8,12 and 24 hours
Outpatient at subsequent ramp-up doses
Pre-dose, 6 to 8 hours, 24 hours
ALC = absolute lymphocyte count; LN = lymph node.
aAdminister intravenous hydration for any patient who cannot tolerate oral hydration.
bStart allopurinol or xanthine oxidase inhibitor 2 to 3 days prior to initiation of VENCLEXTA.
ceva luate blood chemistries (potassium, uric acid, phosphorus, calcium, and creatinine); review in real time.
dFor patients at risk of TLS, monitor blood chemistries at 6 to 8 hours and at 24 hours at each subsequent ramp-up dose.
2.4 Dose Modifications Based on ToxicitiesInterrupt dosing or reduce dose for toxicities. See Table 3 for dose modifications for hematologic and other toxicities related to VENCLEXTA, and Table 4 for dose. For patients who have had a dosing interruption greater than 1 week during the first 5 weeks of ramp-up phase or greater than 2 weeks when at the daily dose of 400 mg, reassess for risk of TLS to determine if reinitiation with a reduced dose is necessary (e.g., all or some levels of the dose ramp-up schedule) [see Dosage and Administration (2.2, 2.3)].
Table 3. Recommended Dose Modifications for Toxicitiesa Event Occurrence Action
Tumor Lysis Syndrome
Blood chemistry changes or symptoms suggestive of TLS Any Withhold the next day’s dose. If resolved within 24 to 48 hours of last dose, resume at the same dose.
For any blood chemistry changes requiring more than 48 hours to resolve, resume at a reduced dose (see Table 4) [see Dosage and Administration (2.3)].
For any events of clinical TLS,b resume at a reduced dose following resolution (see Table 4) [see Dosage and Administratio |
