Adult Dosing
Radioactive iodine-refractory, differentiated thyroid cancer
- Recommended dose: 24 mg (two 10 mg capsules and one 4 mg capsule) PO qd, with or without food
Note:
- The dose should be taken at the same time each day
- Do not take a missed dose within 12 hours; skip that dose and take the next dose at the usual time of administration
Recommended dose modifications for persistent and intolerable Grade 2 or Grade 3 adverse reactions or Grade 4 laboratory abnormalities:
- First occurrence: Interrupt therapy until resolved to Grade 0-1 or baseline; decrease dose to 20 mg (two 10 mg capsules) PO once daily
- Second occurrence: Interrupt therapy until resolved to Grade 0-1 or baseline; decrease dose to 14 mg (one 10 mg plus one 4 mg capsule) PO once daily
- Third occurrence: Interrupt therapy until resolved to Grade 0-1 or baseline; decrease dose to 10 mg (one 10 mg capsule) PO once daily
Note:
- Initiate medical management for nausea, vomiting, or diarrhea prior to interruption or dose reduction
- Adjust the dose by reducing it in succession based on the previous dose level (24 mg, 20 mg, or 14 mg per day)
- Second and third occurrence refers to the same or different adverse reaction that requires dose modification
Pediatric Dosing
- Safety and effectiveness in pediatric patients have not been established
[Outline]
Renal Dose Adjustment (Based on Cockroft-Gault equation)
- Mild renal impairment (CrCl 60-89 mL/min): No dose adjustment
- Moderate renal impairment (CrCl 30-59 mL/min): No dose adjustment
- Severe renal impairment (CrCl <30 mL/min): 14 mg PO once daily
- End-stage renal disease: Dose adjustment not defined
Hepatic Dose Adjustment
- Mild to moderate hepatic impairment (Child-Pugh A and B): No dose adjustment
- Severe hepatic impairment (Child-Pugh C): 14 mg PO once daily
- Hypertension has been reported with therapy. Initiate or adjust the antihypertensives as required to control blood pressure. Monitor blood pressure during treatment. Withhold therapy for Grade 3 hypertension that persists despite antihypertensive therapy. Resume therapy at a reduced dose when hypertension is controlled at
Grade 2. Discontinue lenvatinib for life-threatening hypertension - Cardiac dysfunction, defined as decreased left or right ventricular function, cardiac failure, or pulmonary edema, has been reported. Monitor for clinical signs/symptoms of cardiac decompensation. If Grade 3 cardiac dysfunction develops, withhold therapy until improved to Grade 0 or 1 or baseline. Resume therapy at a reduced dose or discontinue it depending on the severity and persistence of cardiac dysfunction. If Grade 4 cardiac dysfunction develops, discontinue therapy
- If an arterial thrombotic event occurs, discontinue therapy
- Hepatotoxicity indicated by elevated ALT and/or AST of
Grade 3 level has been reported. Monitor liver function prior to initiating lenvatinib and throughout the treatment. If Grade 3 liver impairment develops, withhold lenvatinib until resolved to Grade 0 to 1 or baseline. Resume therapy at a reduced dose or discontinue it depending on the severity and persistence of hepatotoxicity. If hepatic failure develops, discontinue therapy - Withhold lenvatinib if proteinuria of 2 g /24 hrs develops. Resume therapy when proteinuria is < 2 g/24 hrs. Discontinue therapy if nephrotic syndrome develops
- If Grade 3 or 4 renal failure/impairment develops, withhold lenvatinib until resolved to Grade 0 to 1 or baseline. Resume therapy at a reduced dose or discontinue it depending on the severity and persistence of renal impairment
- Discontinue lenvatinib if gastrointestinal perforation or life-threatening fistula develops
- QT prolongation has been reported with lenvatinib. Monitor ECG in patients with congenital long QT syndrome, CHF, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including class Ia and III antiarrhythmics. Monitor and correct electrolyte abnormalities in all patients. Withhold therapy if Grade 3 QT interval prolongation develops and resume it at a reduced dose when QT prolongation resolves to Grade 0 or 1 or baseline
- Hypocalcemia has been reported with lenvatinib. Monitor blood calcium levels during treatment. Interrupt and adjust the dose of lenvatinib according to the severity, presence of ECG changes, and persistence of hypocalcemia
- Rare case of reversible posterior leukoencephalopathy syndrome (RPLS) has been reported with lenvatinib treatment. Withhold therapy until RPLS is fully resolved. Resume therapy at a reduced dose or discontinue it depending on the severity and persistence of neurologic symptoms
- Hemorrhagic events have been reported. Withhold lenvatinib for the development of Grade 3 hemorrhage until resolved to Grade 0 to 1. Resume therapy at a reduced dose or discontinue it depending on the severity and persistence of hemorrhage. Discontinue therapy if Grade 4 hemorrhage develops
- Lenvatinib impairs exogenous thyroid suppression. Monitor TSH levels monthly and adjust thyroid replacement medication as needed in patients with DTC
- Lenvatinib can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during therapy and for at least 2 weeks following completion of therapy
Cautions: Use cautiously in
- Hypertension
- Cardiac dysfunction
- Electrolyte abnormalities
- Hepatic impairment
- Renal impairment
- Proteinuria
- Hx of QT interval prolongation
- Congenital long QT syndrome
- Congestive heart failure
- Bradycardia
- Patients using antiarrhythmic medication
Discontinue therapy if following events occur:
- Life-threatening hypertension
- Cardiac dysfunction or hemorrhage, Grade 4
- Arterial thrombotic event
- Hepatic failure
- Nephrotic syndrome
- Gastrointestinal perforation or life-threatening fistula
Pregnancy category: Not rated; however, based on its mechanism of action and data from animal reproduction studies, lenvatinib can cause fetal harm when administered to a pregnant woman; caution pregnant women of the potential risk to a fetus.
Breastfeeding: It is not known whether lenvatinib is excreted in human breast milk; advise lactating women to discontinue breastfeeding during therapy because of the potential for serious adverse reactions in nursing infants from lenvatinib.
