2.1 Recommended Dose
The recommended daily dose of LENVIMA is 24 mg (two 10 mg capsules and one 4 mg capsule) orally taken once daily with or without food [see Clinical Pharmacology (12.3)]. Continue LENVIMA until disease progression or until unacceptable toxicity occurs.
Take LENVIMA at the same time each day. If a dose is missed and cannot be taken within 12 hours, skip that dose and take the next dose at the usual time of administration.
Severe Renal or Hepatic Impairment
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 Cockroft-Gault equation) or severe hepatic impairment (Child-Pugh C) [see Warning and Precaution (5.3), Use in Specific Populations (8.6, 8.7)].
2.2 Dose Modifications
Hypertension
Assess blood pressure prior to and periodically during treatment. Initiate or adjust medical management to control blood pressure prior to and during treatment.
Withhold LENVIMA for Grade 3 hypertension that persists despite optimal antihypertensive therapy; resume at a reduced dose (see Table 1) when hypertension is controlled at less than or equal to Grade 2.
Discontinue LENVIMA for life-threatening hypertension.
Cardiac dysfunction or hemorrhage
Discontinue for a Grade 4 event.
Withhold LENVIMA for development of Grade 3 event until improved to Grade 0 or 1 or baseline.
Either resume at a reduced dose (see Table 1) or discontinue LENVIMA depending on the severity and persistence of the adverse event.
Arterial thrombotic event
Discontinue LENVIMA following an arterial thrombotic event.
Renal failure and impairment or hepatotoxicity
Withhold LENVIMA for development of Grade 3 or 4 renal failure/impairment or hepatotoxicity until resolved to Grade 0 to 1 or baseline.
Either resume at a reduced dose (see Table 1) or discontinue LENVIMA depending on the severity and persistence of renal impairment or hepatotoxicity.
Discontinue LENVIMA for hepatic failure.
Proteinuria
Withhold LENVIMA for ≥2 grams of proteinuria/24 hours.
Resume at a reduced dose (see Table 1) when proteinuria is <2 gm/24 hours.
Discontinue LENVIMA for nephrotic syndrome.
Gastrointestinal perforation or fistula formation
Discontinue LENVIMA in patients who develop gastrointestinal perforation or life-threatening fistula.
QT prolongation
Withhold LENVIMA for the development of Grade 3 or greater QT interval prolongation.
Resume LENVIMA at a reduced dose (see Table 1) when QT prolongation resolves to Grade 0 or 1 or baseline.
Reversible posterior leukoencephalopathy syndrome (RPLS)
Withhold for RPLS until fully resolved.
Upon resolution, resume at a reduced dose or discontinue LENVIMA depending on the severity and persistence of neurologic symptoms.
Manage other adverse reactions according to the instructions in Table 1. Based on the absence of clinical experience, there are no recommendations on resumption of dosing in patients with Grade 4 clinical adverse reactions that resolve.
Table 1 Recommended Dose Modifications for Persistent and Intolerable Grade 2 or Grade 3 Adverse Reactions or Grade 4 Laboratory Abnormalitiesa
Adverse Reaction
Modification
Adjusted Doseb
First occurrence
Interrupt until resolved to
Grade 0-1 or baseline
20 mg (two 10 mg capsules)
orally once daily
Second occurrencec
Interrupt until resolved to
Grade 0-1 or baseline
14 mg (one 10 mg capsule plus
one 4 mg capsule) orally once
daily
Third occurrencec
Interrupt until 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
