il resolved to
Grade 0-1 or baseline 10 mg (one 10 mg capsule) orally once daily
a Initiate medical management for nausea, vomiting, or diarrhea prior to interruption or dose reduction of LENVIMA
b Reduce dose in succession based on the previous dose level (24 mg, 20 mg, or 14 mg per day)
c Refers to the same or a different adverse reaction that requires dose modification
Severe Renal or Hepatic Impairment in DTC
For patients with DTC, the recommended dose of LENVIMA is 14 mg taken orally once daily in patients with severe renal impairment (creatinine clearance [CLcr] less than 30 mL/min calculated by the Cockcroft-Gault equation) or severe hepatic impairment (Child-Pugh C) [see Warnings and Precautions (5.4, 5.6), Use in Specific Populations (8.6, 8.7)].
Recommendations for Dose Modifications in RCC
Table 3: Dose Modifications for LENVIMA for Persistent and Intolerable Grade 2 or Grade 3 Adverse Reactions or Grade 4 Laboratory Abnormalities in RCCa
Adverse Reaction Modification Adjusted Doseb
First occurrence Interrupt until resolved to Grade 0-1 or baseline 14 mg (one 10 mg capsule plus one 4 mg capsule) orally once daily
Second occurrencec Interrupt until resolved to Grade 0-1 or baseline 10 mg (one 10 mg capsule) orally once daily
Third occurrencec Interrupt until resolved to Grade 0-1 or baseline 8 mg (two 4 mg capsules) orally once daily
a Initiate medical management for nausea, vomiting, or diarrhea prior to interruption or dose reduction of LENVIMA
b Reduce dose in succession based on the previous dose level (18 mg, 14 mg, 10 mg, or 8 mg per day)
c Refers to the same or a different adverse reaction that requires dose modification
Recommendations for Dose Modification of Everolimus in RCC
Review the Full Prescribing Information for everolimus for recommended dose modifications. For toxicities thought to be related to everolimus alone, discontinue, interrupt, or use alternate day dosing. For toxicities thought to be related to both LENVIMA and everolimus, first reduce LENVIMA and then everolimus.
Severe Renal or Hepatic Impairment in RCC
For patients with RCC, the recommended dose of LENVIMA is 10 mg taken orally once daily in patients with severe renal impairment (CLcr less than 30 mL/min calculated by the Cockcroft-Gault equation) or severe hepatic impairment (Child-Pugh C) [see Warnings and Precautions (5.4, 5.6), Use in Specific Populations (8.6, 8.7)].
3 DOSAGE FORMS AND STRENGTHS
4 mg hard capsule: A yellowish-red body and yellowish-red cap, marked in black ink with “Є” on the cap and “LENV 4 mg” on the body.
10 mg hard capsule: A yellow body and yellowish-red cap, marked in black ink with “Є” on the cap and “LENV 10 mg” on the body.
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Hypertension
In Study 1 in DTC, hypertension was reported in 73% of LENVIMA-treated patients and 16% of patients in the placebo group [see ADVERSE REACTIONS (6.1)]. The median time to onset of new or worsening hypertension was 16 days for LENVIMA-treated patients. The incidence of Grade 3 hypertension was 44% as compared to 4% for placebo, and the incidence of Grade 4 hypertension was less than 1% in LENVIMA-treated patients and none in the placebo group.
In Study 2 in RCC, hypertension was reported in 42% of patients in the LENVIMA + everolimus-treated group and 10% of patients in the everolimus-treated gr |
