reported in 3 patients and acute hepatitis was reported in 1 patient.
In Study 1 in DTC, 4% of LENVIMA-treated patients experienced an increase in alanine aminotransferase (ALT) and 5% experienced an increase in aspartate aminotransferase (AST) that was Grade 3 or greater. No patients in the placebo group experienced Grade 3 or greater increases in ALT or AST.
The incidence of ALT and AST elevation was similar in Study 2 in RCC. In Study 2, 3% of LENVIMA + everolimus-treated patients experienced an increase in ALT and 3% experienced an increase in AST that was Grade 3 or greater. Two percent of patients in the everolimus-treated group experienced an increase in ALT and none experienced an increase in AST that was Grade 3 or greater.
Monitor liver function before initiation of LENVIMA, then every 2 weeks for the first 2 months, and at least monthly thereafter during treatment. Withhold LENVIMA for the development of Grade 3 or greater liver impairment until resolved to Grade 0 to 1 or baseline. Either resume at a reduced dose or discontinue LENVIMA depending on the severity and persistence of hepatotoxicity. Discontinue LENVIMA for hepatic failure [see DOSAGE AND ADMINISTRATION (2.4)].
5.5 Proteinuria
In Study 1 in DTC, proteinuria was reported in 34% of LENVIMA-treated patients and 3% of patients in the placebo group [see ADVERSE REACTIONS (6.1)]. The incidence of Grade 3 proteinuria in LENVIMA-treated patients was 11% compared to none in the placebo group.
In Study 2 in RCC, proteinuria was reported in 31% of patients in the LENVIMA + everolimus-treated group and 14% of patients in the everolimus-treated group. The incidence of Grade 3 proteinuria in LENVIMA + everolimus-treated patients was 8% compared to 2% in everolimus-treated patients.
Monitor for proteinuria before initiation of, and periodically throughout treatment. If urine dipstick proteinuria greater than or equal to 2+ is detected, obtain a 24 hour urine protein. Withhold LENVIMA for ≥2 grams of proteinuria/24 hours and resume at a reduced dose when proteinuria is <2 gm/24 hours. Discontinue LENVIMA for nephrotic syndrome [see DOSAGE AND ADMINISTRATION (2.4)].
5.6 Diarrhea
In Study 2 in RCC, diarrhea was reported in 81% of LENVIMA + everolimus-treated patients and 34% of everolimus-treated patients. Grade 3 or 4 events occurred in 19% of LENVIMA + everolimus-treated patients and 2% of everolimus-treated patients. Diarrhea was te most frequent cause of dose interruption/reduction and recurred despite dose reduction. Diarrhea resulted in discontinuation in one patient [see ADVERSE REACTIONS (6.1)].
Initiate prompt medical management for the development of diarrhea. Monitor for dehydration. Interrupt LENVIMA for Grade 3 or 4 diarrhea. For Grade 3 diarrhea, resume at a reduced dose of LENVIMA when diarrhea resolves to Grade 1 or baseline. Permanently discontinue LENVIMA for Grade 4 diarrhea despite medical management.
5.7 Renal Failure and Impairment
In Study 1 in DTC, events of renal impairment were reported in 14% of LENVIMA-treated patients compared to 2% of patients in the placebo group. The incidence of Grade 3 or greater renal failure or impairment was 3% in LENVIMA-treated patients and 1% in the placebo group.
In Study 2 in RCC, renal impairment was reported in 18% of LENVIMA + everolimus-treated group and 12% in the everolimus-treated group. The incidence of Grade 3 or greater renal failure or impairment was 10% in the LENVIMA + everolimus-treated group and 2% |
