Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 13 April 2018

Indication(s)

1 INDICATIONS AND USAGE LENVIMA is a kinase inhibitor that is indicated for: Differentiated Thyroid Cancer (DTC): single agent for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC. (1.1) Renal Cell Cancer (RCC): in combination with everolimus, for patients with advanced RCC following one prior anti-angiogenic therapy. (1.2) 1.1 Differentiated Thyroid Cancer LENVIMA is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory DTC. 1.2 Renal Cell Carcinoma LENVIMA is indicated in combination with everolimus for the treatment of patients with advanced RCC following one prior anti-angiogenic therapy.

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Advisory information

contraindications
4 CONTRAINDICATIONS None. None. (4)
Adverse reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere in the label: Hypertension [see Warnings and Precautions (5.1) ] Cardiac Dysfunction [see Warnings and Precautions (5.2) ] Arterial Thromboembolic Events [see Warnings and Precautions (5.3) ] Hepatotoxicity [see Warnings and Precautions (5.4) ] Proteinuria [see Warnings and Precautions (5.5) ] Diarrhea [see Warnings and Precautions (5.6) ] Renal Failure and Impairment [see Warnings and Precautions (5.7) ] Gastrointestinal Perforation and Fistula Formation [see Warnings and Precautions (5.8) ] QT Interval Prolongation [see Warnings and Precautions (5.9) ] Hypocalcemia [see Warnings and Precautions (5.10) ] Reversible Posterior Leukoencephalopathy Syndrome [see Warnings and Precautions (5.11) ] Hemorrhagic Events [see Warnings and Precautions (5.12) ] Impairment of Thyroid Stimulating Hormone Suppression/Thyroid Dysfunction [see Warnings and Precautions (5.13) ] Wound Healing Complications [ see Warnings and Precautions (5.14) ] In DTC, the most common adverse reactions (incidence greater than or equal to 30%) for LENVIMA are hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia syndrome, abdominal pain, and dysphonia. (6.1) In RCC, the most common adverse reactions (greater than 30%) for LENVIMA + everolimus are diarrhea, fatigue, arthralgia/myalgia, decreased appetite, vomiting, nausea, stomatitis/oral inflammation, hypertension, peripheral edema, cough, abdominal pain, dyspnea, rash, weight decreased, hemorrhagic events, and proteinuria. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Eisai Inc. at 1-877-873-4724 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the Warnings and Precautions section reflect exposure to LENVIMA as a single agent in 261 DTC patients (Study 1) and LENVIMA + everolimus in 62 RCC patients (Study 2). Safety data obtained in 1160 patients with advanced solid tumors who received LENVIMA as a single agent across multiple clinical studies was used to further characterize the risks of serious adverse reactions [ see Warnings and Precautions ( 5.4 , 5.10 , 5.11 ) ]. In the entire single agent population, the median age was 60 years (range 21-89 years), the dose range was 0.2 mg to 32 mg, and the median duration of exposure was 5.5 months. Differentiated Thyroid Cance r The safety data described below are derived from Study 1 which randomized (2:1) patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) to LENVIMA (n=261) or placebo (n=131) [ see Clinical Studies (14.1) ]. The median treatment duration was 16.1 months for LENVIMA and 3.9 months for placebo. Among 261 patients who received LENVIMA in Study 1, median age was 64 years, 52% were women, 80% were White, 18% were Asian, and 2% were Black; 4% identified themselves as having Hispanic or Latino ethnicity. In Study 1, the most common adverse reactions observed in LENVIMA-treated patients (greater than or equal to 30%) were, in order of decreasing frequency, hypertension, fatigue, diarrhea, arthralgia/myalgia, decreased appetite, weight decreased, nausea, stomatitis, headache, vomiting, proteinuria, palmar-plantar erythrodysesthesia (PPE) syndrome, abdominal pain, and dysphonia. The most common serious adverse reactions (at least 2%) were pneumonia (4%), hypertension (3%), and dehydration (3%). Adverse reactions led to dose reductions in 68% of patients receiving LENVIMA and 5% of patients receiving placebo; 18% of patients discontinued LENVIMA and 5% discontinued placebo for adverse reactions. The most common adverse reactions (at least 10%) resulting in dose reductions of LENVIMA were hypertension (13%), proteinuria (11%), decreased appetite (10%), and diarrhea (10%); the most common adverse reactions (at least 1%) resulting in discontinuation of LENVIMA were hypertension (1%) and asthenia (1%). Table 4 presents the percentage of patients in Study 1 experiencing adverse reactions at a higher rate in LENVIMA-treated patients than patients receiving placebo in the double-blind phase of the DTC study. Table 4: Adverse Reactions Occurring in Patients with a Between-Group Difference of Greater than or Equal to 5% in All Grades or Greater than or Equal to 2% in Grades 3 and 4 LENVIMA 24 mg N=261 Placebo N=131 Adverse Reaction All Grades (%) Grades 3-4 (%) All Grades (%) Grades 3- 4 (%) Vascular Disorders Hypertensiona 73 44 16 4 Hypotension 9 2 2 0 Gastrointestinal Disorders Diarrhea 67 9 17 0 Nausea 47 2 25 1 Stomatitisb 41 5 8 0 Vomiting 36 2 15 0 Abdominal painc 31 2 11 1 Constipation 29 0.4 15 1 Oral paind 25 1 2 0 Dry mouth 17 0.4 8 0 Dyspepsia 13 0.4 4 0 General Disorders and Administration Site Conditions Fatiguee 67 11 35 4 Edema peripheral 21 0.4 8 0 Musculoskeletal and Connective Tissue Disorders Arthralgia/Myalgiaf 62 5 28 3 Metabolism and Nutrition Disorders Weight decreased 51 13 15 1 Decreased appetite 54 7 18 1 Dehydration 9 2 2 1 Nervous System Disorders Headache 38 3 11 1 Dysgeusia 18 0 3 0 Dizziness 15 0.4 9 0 Renal and Urinary Disorders Proteinuria 34 11 3 0 Skin and Subcutaneous Tissue Disorders Palmar-plantar erythrodysesthesia 32 3 1 0 Rashg 21 0.4 3 0 Alopecia 12 0 5 0 Hyperkeratosis 7 0 2 0 Respiratory, Thoracic and Mediastinal Disorders Dysphonia 31 1 5 0 Cough 24 0 18 0 Epistaxis 12 0 1 0 Psychiatric Disorders Insomnia 12 0 3 0 Infections and Infestations Dental and oral infectionsh 10 1 1 0 Urinary tract infection 11 1 5 0 Cardiac Disorders Electrocardiogram QT prolonged 9 2 2 0 a Includes hypertension, hypertensive crisis, increased blood pressure diastolic, and increased blood pressure b Includes aphthous stomatitis, stomatitis, glossitis, mouth ulceration, and mucosal inflammation c Includes abdominal discomfort, abdominal pain, lower abdominal pain, upper abdominal pain, abdominal tenderness, epigastric discomfort, and gastrointestinal pain d Includes oral pain, glossodynia, and oropharyngeal pain e Includes asthenia, fatigue, and malaise f Includes musculoskeletal pain, back pain, pain in extremity, arthralgia, and myalgia g Includes macular rash, maculo-papular rash, generalized rash, and rash h Includes gingivitis, oral infection, parotitis, pericoronitis, periodontitis, sialoadenitis, tooth abscess, and tooth infection A clinically important adverse reaction occurring more frequently in LENVIMA-treated patients than patients receiving placebo, but with an incidence of less than 5% was pulmonary embolism (3%, including fatal reports vs 2%, respectively). Table 5: Laboratory Abnormalities with a Difference of at Least ≥2% in Grade 3 - 4 Events and at a Higher Incidence in LENVIMA-Treated Patientsa Laboratory Abnormality LENVIMA 24 mg N=258 b Placebo N=131 b Grades 3-4 (%) Grades 3-4 (%) Chemistry Creatinine increased 3 0 Alanine aminotransferase (ALT) increased 4 0 Aspartate aminotransferase (AST) increased 5 0 Hypocalcemia 9 2 Hypokalemia 6 1 Lipase increased 4 1 Hematology Platelet count decreased 2 0 a With at least 1 grade increase from baseline b Subject with at least 1 post baseline laboratory value In addition the following laboratory abnormalities (all Grades) occurred in greater than 5% of LENVIMA-treated patients and at a rate that was two-fold or higher than in patients who received placebo: hypoalbuminemia, increased alkaline phosphatase, hypomagnesemia, hypoglycemia, hyperbilirubinemia, hypercalcemia, hypercholesterolemia, increased serum amylase, and hyperkalemia. Renal Cell Carcinoma The data described below are derived from Study 2 which randomized (1:1:1) patients with unresectable advanced or metastatic renal cell carcinoma (RCC) to LENVIMA 18 mg + everolimus 5 mg (n=51), LENVIMA 24 mg (n=52), or everolimus 10 mg (n=50) once daily [ see Clinical Studies (14.2) ]. This data also includes patients on the dose escalation portion of the study who received LENVIMA 18 mg + everolimus 5 mg (n=11). The median treatment duration was 8.1 months for LENVIMA + everolimus and 4.1 months for everolimus. Among 62 patients who received LENVIMA + everolimus in Study 2, the median age was 61 years, 71% were men, and 98% were White. The most common adverse reactions observed in the LENVIMA + everolimus-treated group (> 30%) were, in order of decreasing frequency, diarrhea, fatigue, arthralgia/myalgia, decreased appetite, vomiting, nausea, stomatitis/oral inflammation, hypertension, peripheral edema, cough, abdominal pain, dyspnea, rash, weight decreased, hemorrhagic events, and proteinuria. The most common serious adverse reactions (≥ 5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%). Adverse reactions led to dose reductions or interruption in 89% of patients receiving LENVIMA + everolimus and 54% in patients receiving everolimus. The most common adverse reactions (≥ 5%) resulting in dose reductions in the LENVIMA + everolimus-treated group were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%). Treatment discontinuation due to an adverse reaction occurred in 29% of patients in the LENVIMA + everolimus-treated group and 12% of patients in the everolimus-treated group. Table 6 presents the adverse reactions in > 15% of patients in the LENVIMA + Everolimus arm. Table 6: Grades 1-4 Adverse Reactions in > 15% of Patients in the LENVIMA + Everolimus Arm LENVIMA 18 mg + E verolimus 5 mg (N=62) E verolimus 10 mg (N=50) System Organ Class Preferred Term Grade 1-4 (%) Grade 3-4 (%) Grade 1-4 (%) Grade 3-4 (%) Endocrine Disorders Hypothyroidism 24 0 2 0 Gastrointestinal Disorders Constipation 16 0 18 0 Diarrhea 81 19 34 2 Dyspepsia/Gastro-esophageal reflux 21 0 12 0 Abdominal paina 37 3 8 0 Nausea 45 5 16 0 Oral painb 23 2 4 0 Stomatitis/Oral inflammationc 44 2 50 4 Vomiting 48 7 12 0 General Disorders and Administration Site Conditions Fatigued 73 18 40 2 Peripheral edema 42 2 20 0 Pyrexia/Increased body temperature 21 2 10 2 Investigations Weight decreased 34 3 8 0 Metabolism and Nutrition Disorders Decreased appetite 53 5 18 0 Musculoskeletal and Connective Tissue Disorders Arthralgia/Myalgiae 55 5 32 0 Musculoskeletal chest pain 18 2 4 0 Nervous System Disorders Headache 19 2 10 2 Psychiatric Disorders Insomnia 16 2 2 0 Renal and Urinary Disorders Proteinuria/Urine protein present 31 8 14 2 Renal failure eventf 18 10 12 2 Respiratory, Thoracic and Mediastinal Disorders Cough 37 0 30 0 Dysphonia 18 0 4 0 Dyspnea/Exertional dyspnea 35 5 28 8 Skin and Subcutaneous Tissue Disorders Rashg 35 0 40 0 Vascular Disorders Hemorrhagic eventsh 32 6 26 2 Hypertension/Increased blood pressure 42 13 10 2 a Includes abdominal discomfort, gastrointestinal pain, lower abdominal pain, and upper abdominal pain b Includes gingival pain, glossodynia, and oropharyngeal pain c Includes aphthous stomatitis, gingival inflammation, glossitis, and mouth ulceration d Includes asthenia, fatigue, lethargy and malaise e Includes arthralgia, back pain, extremity pain, musculoskeletal pain, and myalgia f Includes blood creatinine increased, blood urea increased, creatinine renal clearance decreased, nephropathy toxic, renal failure, renal failure acute, and renal impairment g Includes erythema, erythematous rash, genital rash, macular rash, maculo-papular rash, , papular rash, pruritic rash, pustular rash, and septic rash h Includes hemorrhagic diarrhea, epistaxis, gastric hemorrhage, hemarthrosis, hematoma, hematuria, hemoptysis, lip hemorrhage, renal hematoma, and scrotal hematocele Table 7: Grade 3-4 Laboratory Abnormalities in ≥ 3% of Patients in the LENVIMA + Everolimus Arma,b Laboratory Abnormality LENVIMA 18 mg + Everolimus 5 mg N=62 Everolimus 10 mg N=50 Grades 3-4 (%) Grades 3-4 (%) Chemistry Aspartate aminotransferase (AST) increased 3 0 Alanine aminotransferase (ALT) increased 3 2 Alkaline phosphatase increased 3 0 Hyperkalemia 6 2 Hypokalemia 6 2 Hyponatremia 11 6 Hypocalcemia 6 2 Hypophosphatemia 11 6 Hyperglycemia 3 16 Hypertriglyceridemia 18 18 Elevated cholesterol 11 0 Creatine kinase increased 3 4 Lipase increased 13 12 Hematology Hemoglobin decreased 8 16 Platelet count decreased 5 0 Lymphocyte count decreased 10 20 a With at least 1 grade increase from baseline b Subject with at least 1 post baseline laboratory value 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of LENVIMA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal Disorders: pancreatitis, amylase increased General Disorders: impaired healing Hepatobiliary Disorders: cholecystitis Musculoskeletal and Connective Tissue Disorders: fistula Vascular Disorders: aortic dissection

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Recommended dose (DTC): 24 mg orally, once daily. (2.1) Recommended dose (RCC): 18 mg LENVIMA + 5 mg everolimus, orally, once daily. (2.2) Administration Instructions. (2.3) Dose Modifications for DTC and RCC. (2.4) In patients with severe renal or hepatic impairment, the dose is 14 mg once daily in DTC and 10 mg once daily in RCC. (2.4) 2.1 Recommended Dose for DTC 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. 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. 2.2 Recommended Dose for RCC The recommended daily dose of LENVIMA is 18 mg (one 10 mg capsule and two 4 mg capsules) in combination with 5 mg everolimus orally taken once daily with or without food [see Clinical Pharmacology (12.3) ]. Continue LENVIMA plus everolimus until disease progression or until unacceptable toxicity. Take LENVIMA and everolimus 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. 2.3 Administration Instructions LENVIMA capsules should be swallowed whole. Alternatively, the capsules can be dissolved in a small glass of liquid. Measure 1 tablespoon of water or apple juice and put the capsules into the liquid without breaking or crushing them. Leave the capsules in the liquid for at least 10 minutes. Stir for at least 3 minutes. Drink the mixture. After drinking, add the same amount (1 tablespoon) of water or apple juice to the glass. Swirl the contents a few times and swallow the additional liquid. 2.4 Dose Modifications for DTC and RCC Table 1: Adverse Reactions Requiring Dose Modification of LENVIMA in DTC and RCC Adverse Reaction CTCAE Grade Action Dose Reduce and Resume LENVIMA Hypertension Grade 31 Hold Resolves to Grade 0, 1, or 2 Grade 4 Discontinue Do Not Resume Cardiac Dysfunction Grade 3 Hold Resolves to Grade 0, 1, or baseline Grade 4 Discontinue Do Not Resume Arterial Thrombotic Event Any Grade Discontinue Do Not Resume Hepatotoxicity Grade 3 or 4 Hold OR Discontinue Consider resuming at reduced dose if resolves to Grade 0-1 or baseline Hepatic Failure Grade 3 or 4 Discontinue Do Not Resume Proteinuria Greater than or equal to 2 gm/24 hours Hold Resolves to less than 2 gm/24 hours Nephrotic Syndrome ------- Discontinue Do Not Resume Nausea, Vomiting, and Diarrhea2 Grade 3 Hold Resolves to Grade 0, 1, or baseline Vomiting and Diarrhea2 Grade 4 Discontinue Do Not Resume Renal Failure or Impairment Grade 3 or 4 Hold OR Discontinue Consider resuming at reduced dose if resolves to Grade 0-1 or baseline GI Perforation Any Grade Discontinue Do Not Resume Fistula Grade 3 or 4 Discontinue Do Not Resume QTc Prolongation Greater than 500 ms Hold Resolves to less than 480 ms or baseline RPLS Any Grade Hold OR Discontinue Consider resuming at reduced dose if resolves to Grade 0 to 1 Hemorrhage Grade 3 Hold Resolves to Grade 0 to 1 Grade 4 Discontinue Do Not Resume 1 Grade 3 despite optimal anti-hypertensive therapy 2 Initiate prompt medical management for nausea, vomiting or diarrhea. Permanently discontinue for Grade 4 vomiting and diarrhea despite medical management Manage other adverse reactions according to the instructions in Table 2 for DTC or Table 3 for RCC. Recommendations for Dose Modifications in DTC Table 2: Dose Modifications for LENVIMA for Persistent and Intolerable Grade 2 or Grade 3 Adverse Reactions or Grade 4 Laboratory Abnormalities in DTCa Adverse Reaction Modification Adjusted Dose b 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 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 Dose b 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 Recommend ations 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 )].
Use in special populations
8 USE IN SPECIFIC POPULATIONS Lactation: Discontinue breastfeeding. (8.2) 8.1 Pregnancy Risk Summary Based on its mechanism of action and data from animal reproduction studies, LENVIMA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ]. In animal reproduction studies, oral administration of lenvatinib during organogenesis at doses below the recommended human dose resulted in embryotoxicity, fetotoxicity, and teratogenicity in rats and rabbits [see Data ]. There are no available human data informing the drug-associated risk. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. Data Animal Data In an embryofetal development study, daily oral administration of lenvatinib mesylate at doses greater than or equal to 0.3 mg/kg [approximately 0.14 times the recommended human dose based on body surface area (BSA)] to pregnant rats during organogenesis resulted in dose-related decreases in mean fetal body weight, delayed fetal ossifications, and dose-related increases in fetal external (parietal edema and tail abnormalities), visceral, and skeletal anomalies. Greater than 80% postimplantation loss was observed at 1.0 mg/kg/day (approximately 0.5 times the recommended human dose based on BSA). Daily oral administration of lenvatinib mesylate to pregnant rabbits during organogenesis resulted in fetal external (short tail), visceral (retroesophageal subclavian artery), and skeletal anomalies at doses greater than or equal to 0.03 mg/kg (approximately 0.03 times the human dose of 24 mg based on body surface area). At the 0.03 mg/kg dose, increased post-implantation loss, including 1 fetal death, was also observed. Lenvatinib was abortifacient in rabbits, resulting in late abortions in approximately one-third of the rabbits treated at a dose level of 0.5 mg/kg/day (approximately 0.5 times the recommended clinical dose of 24 mg based on BSA). 8.2 Lactation Risk Summary It is not known whether LENVIMA is present in human milk. However, lenvatinib and its metabolites are excreted in rat milk at concentrations higher than in maternal plasma [see Data ]. Because of the potential for serious adverse reactions in nursing infants from LENVIMA, advise women to discontinue breastfeeding during treatment with LENVIMA. Data Animal Data Following administration of radiolabeled lenvatinib to lactating Sprague Dawley rats, lenvatinib-related radioactivity was approximately 2 times higher (based on AUC) in milk compared to maternal plasma. 8.3 Females and Males of Reproductive Potential Contraception Based on its mechanism of action, LENVIMA can cause fetal harm when administered to a pregnant woman [ see Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective contraception during treatment with LENVIMA and for at least 2 weeks following completion of therapy. Inf ertility Females LENVIMA may result in reduced fertility in females of reproductive potential [ see Nonclinical Toxicology (13.1) ]. Males LENVIMA may result in damage to male reproductive tissues leading to reduced fertility of unknown duration [ see Nonclinical Toxicology (13.1) ]. 8.4 Pediatric Use The safety and effectiveness of LENVIMA in pediatric patients have not been established. Juvenile Animal Data Daily oral administration of lenvatinib mesylate to juvenile rats for 8 weeks starting on postnatal day 21 (approximately equal to a human pediatric age of 2 years) resulted in growth retardation (decreased body weight gain, decreased food consumption, and decreases in the width and/or length of the femur and tibia) and secondary delays in physical development and reproductive organ immaturity at doses greater than or equal to 2 mg/kg (approximately 1.2 to 5 times the clinical exposure by AUC at the recommended human dose). Decreased length of the femur and tibia persisted following 4 weeks of recovery. In general, the toxicologic profile of lenvatinib was similar between juvenile and adult rats, though toxicities including broken teeth at all dose levels and mortality at the 10 mg/kg/day dose level (attributed to primary duodenal lesions) occurred at earlier treatment time-points in juvenile rats. 8.5 Geriatric Use Of 261 patients who received LENVIMA in Study 1, 118 (45.2%) were greater than or equal to 65 years of age and 29 (11.1%) were greater than or equal to 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Of the 62 patients who received LENVIMA + everolimus in Study 2, 22 (35.5%) were greater than or equal to 65 years of age. Conclusions are limited due to the small sample size, but there appeared to be no overall differences in safety or effectiveness between these subjects and younger subjects. 8.6 Renal Impairment No dose adjustment is recommended in patients with mild or moderate renal impairment. In patients with severe renal impairment, the recommended dose is 14 mg in the treatment of DTC and 10 mg in the treatment of RCC, either taken orally once daily. Patients with end stage renal disease were not studied [ see Dosage and Administration (2.4) , Warnings and Precautions (5.6) , and Clinical Pharmacology (12.3) ]. 8.7 Hepatic Impairment No dose adjustment is recommended in patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, the recommended dose is 14 mg in the treatment of DTC and 10 mg in the treatment of RCC, either taken orally once daily [ see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ].

Interactions

7 DRUG INTERACTIONS 7.1 Effect of Other D rugs on Lenvatinib No dose adjustment of LENVIMA is recommended when co-administered with CYP3A, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) inhibitors and CYP3A and P-gp inducers [ see Clinical Pharmacology (12.3) ].

More information

Category Value
Authorisation number NDA206947
Agency product number EE083865G2
Orphan designation No
Product NDC 62856-724,62856-720,62856-718,62856-708,62856-710,62856-714
Date Last Revised 06-11-2017
Type HUMAN PRESCRIPTION DRUG
Marketing authorisation holder Eisai Inc.