Tazemetostat Dose Adjustments in Special Populations
1. Renal Impairment
(1) Mild, moderate, severe, or end-stage renal impairment: No dose adjustment required.
(2) Dialysis patients: No data available.
2. Hepatic Impairment
(1) Mild hepatic impairment (total bilirubin >1-1.5 times upper limit of normal [ULN] or AST > ULN): No dose adjustment required.
(2) Moderate (total bilirubin >1.5-3 times ULN) or severe hepatic impairment (total bilirubin >3 times ULN): No data available.
General Principles of Tazemetostat Dose Adjustments
1. First dose reduction: 600 mg orally twice daily.
2. Second dose reduction: 400 mg orally twice daily.
3. Unable to tolerate 400 mg twice daily: Permanently discontinue.
Dose Adjustments for Adverse Reactions to Tazemetostat
1. Neutropenia
(1) Withhold until recovery to ≥1×10⁹/L or baseline.
(2) First occurrence: Resume at original dose.
(3) Second or third occurrence: Resume at reduced dose.
(4) Fourth occurrence: Permanently discontinue.
2. Thrombocytopenia
(1) Withhold until recovery to ≥75×10⁹/L or baseline.
(2) First or second occurrence: Resume at reduced dose.
(3) Third occurrence: Permanently discontinue.
3. Anemia
Withhold until improvement to Grade 1 or baseline, then resume at original dose or reduced dose.
4. Other Grade ≥3 adverse reactions
(1) Withhold until improvement to Grade 1 or baseline.
(2) First or second occurrence: Resume at reduced dose.
(3) Third occurrence: Permanently discontinue.
5. Grade ≥4 adverse reactions
(1) Withhold until improvement to Grade 1 or baseline.
(2) First occurrence: Resume at reduced dose.
(3) Second occurrence: Permanently discontinue.
