Prescribing Information Important Safety Information Warnings and Precautions

• Hypertension reported in 73% of patients on LENVIMA vs 16% for placebo (44% vs 4% ≥grade 3). Blood pressure should be controlled prior to treatment. Withhold dose for grade 3 hypertension despite optimal antihypertensive therapy; resume at reduced dose when controlled at ≤grade 2. Discontinue for life-threatening hypertension
• Cardiac dysfunction reported in 7% of patients on LENVIMA vs 2% for placebo (2% vs 0% ≥grade 3). Monitor for signs/symptoms of cardiac decompensation. Withhold for grade 3 cardiac dysfunction. Resume at reduced dose or discontinue based on severity and persistence of cardiac dysfunction. Discontinue for grade 4 cardiac dysfunction
• Arterial thromboembolic events reported in 5% of patients on LENVIMA vs 2% for placebo (3% vs 1% ≥grade 3). Discontinue following an arterial thrombotic event. The safety of resuming LENVIMA after an arterial thromboembolic event has not been established, and LENVIMA has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months
• ALT and AST increases (≥grade 3) occurred in 4% and 5% of patients on LENVIMA vs 0% for placebo. Across clinical studies in which 1108 patients received LENVIMA, hepatic failure (including fatal events) was reported in 3 patients and acute hepatitis in 1 patient. Monitor liver function before initiation, then every 2 weeks for first 2 months, and at least monthly thereafter during treatment. Withhold dose for liver impairment ≥grade 3. Resume at reduced dose or discontinue based on severity/persistence of hepatotoxicity. Discontinue for hepatic failure
• Proteinuria reported in 34% of patients on LENVIMA vs 3% for placebo (11% vs 0% ≥grade 3). Monitor for proteinuria before and during treatment. Withhold dose for ≥2 grams of proteinuria/24 hours. Resume at reduced dose when proteinuria is <2 gm/24 hours. Discontinue for nephrotic syndrome
• Events of renal impairment reported in 14% of patients on LENVIMA vs 2% for placebo (3% vs 1% ≥grade 3). Withhold LENVIMA for grade 3 or 4 renal failure/impairment. Resume at reduced dose or discontinue, depending on severity/persistence of renal impairment
• Events of gastrointestinal (GI) perforation or fistula reported in 2% of patients on LENVIMA vs 0.8% for placebo. Discontinue in patients who develop GI perforation or life-threatening fistula
• QT/QTc interval prolongation reported in 9% of patients on LENVIMA vs 2% for placebo (2% vs 0% ≥grade 3). Monitor ECG in patients with congenital long QT syndrome, CHF, bradyarrhythmias, or patients taking drugs known to prolong the QT interval. Monitor and correct electrolyte abnormalities in all patients. Withhold dose for ≥grade 3 QT interval prolongation. Resume at reduced dose when QT prolongation resolves to grade 0, 1, or baseline
• Hypocalcemia ≥grade 3 reported in 9% of patients on LENVIMA (2% for placebo). Monitor blood calcium levels at least monthly and replace calcium as necessary. Interrupt and adjust LENVIMA as necessary. In most cases, hypocalcemia responded to replacement and dose interruption/reduction
• Across clinical studies in which 1108 patients received LENVIMA, reversible posterior leukoencephalopathy syndrome (RPLS) was reported in 3 patients. Withhold LENVIMA for RPLS until fully resolved. Resume at reduced dose or discontinue based on the severity and persistence of neurologic symptoms
• Hemorrhagic events occurred in 35% of patients on LENVIMA vs 18% for placebo (2% vs 3% ≥grade 3). The most frequently reported hemorrhagic event was epistaxis (11% grade 1 and 1% grade 2). Discontinuation due to hemorrhagic events occurred in 1% of patients on LENVIMA. There was 1 fatal intracranial hemorrhage case among 16 patients who received LENVIMA and had CNS metastases at baseline. Withhold dose for grade 3 hemorrhage. Resume at reduced dose or discontinue, based on severity/persistence of hemorrhage. Discontinue for grade 4 hemorrhage
• LENVIMA impairs exogenous thyroid suppression. In patients with a normal baseline TSH, elevation of TSH level above 0.5 mU/L was observed post baseline in 57% of patients on LENVIMA (14% for placebo). Monitor TSH levels monthly and adjust thyroid replacement medication as needed in patients with DTC
• LENVIMA may cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 2 weeks following completion of therapy

Adverse Reactions

• The most common adverse reactions observed in LENVIMA-treated patients vs placebo-treated patients were hypertension (73% vs 16%), fatigue (67% vs 35%), diarrhea (67% vs 17%), arthralgia/myalgia (62% vs 28%), decreased appetite (54% vs 18%), weight decreased (51% vs 15%), nausea (47% vs 25%), stomatitis (41% vs 8%), headache (38% vs 11%), vomiting (36% vs 15%), proteinuria (34% vs 3%), palmar-plantar erythrodysesthesia syndrome (32% vs 1%), abdominal pain (31% vs 11%), and dysphonia (31% vs 5%)

Use in Specific Populations

• Because of the potential for serious adverse reactions in nursing infants, advise women to discontinue breastfeeding during treatment
• LENVIMA may result in reduced fertility in females of reproductive potential, and may result in damage to male reproductive tissues, leading to reduced fertility of unknown duration
  

Please see full Prescribing Information at LENVIMA.com/hcp.