Lenvatinib Capsule 10 mg (Lenvatinib Mesylate Dimethyl Sulfoxide)

Adult dose

Treatment with this drug should be initiated and supervised by a physician with sufficient knowledge and experience in cancer therapy. Treatment should continue until the patient no longer derives clinical benefit or develops unacceptable toxicity. Take this drug orally once daily at the same time each day, with or without food. If a dose is missed at the scheduled time, skip that dose if less than 12 hours remain until the next day's dose. Do not take a double dose the next day. Caregivers should not open the capsules to avoid repeated exposure to the contents. The capsules may be swallowed whole or dispersed in a small cup. To disperse in liquid, do not break or crush the capsule; place it in one tablespoon of water for at least 10 minutes and stir for at least 3 minutes. After drinking the suspension, add one tablespoon of water to the cup, swirl it several times to rinse, and drink the liquid. Differentiated thyroid cancer: The recommended dose of this drug in adults is 24mg once daily. The daily dose may be adjusted as needed to manage adverse reactions (see section ‘2) Dose adjustment’ below). Take this drug orally at the same time each day, with or without food. Hepatocellular carcinoma: The recommended dose of this drug is based on body weight. Continue treatment with this drug once daily until disease progression or unacceptable toxicity occurs. There is no clinical evidence supporting the use of the 10mg dose in hepatocellular carcinoma. Endometrial cancer: The recommended dose of this drug is 20mg orally once daily until disease progression or unacceptable toxicity occurs, in combination with pembrolizumab administered as an intravenous infusion of 200mg over 30 minutes every 3 weeks. Refer to the prescribing information for pembrolizumab for its recommended dosage information. Renal cell carcinoma: The recommended dose of this drug is 20mg orally once daily, in combination with pembrolizumab administered as an intravenous infusion of 200mg over 30 minutes every 3 weeks. Continue the combination treatment until disease progression or unacceptable toxicity occurs, or for a maximum of 2 years. After 2 years of combination therapy, this drug may be administered as a single agent until disease progression or unacceptable toxicity occurs. Refer to the prescribing information for pembrolizumab for its recommended dosage information. Temporary interruption, dose adjustment, or discontinuation of this drug may be required to manage adverse reactions. Mild to moderate adverse reactions (e.g., Grade 1 or Grade 2) generally do not warrant interruption of treatment with this drug, unless they are intolerable to the patient despite appropriate management. For severe adverse reactions (e.g., Grade 3) or intolerable adverse reactions, temporarily interrupt treatment with this drug until symptoms resolve or improve, then resume treatment at a reduced dose as presented in Tables 1 and 2. Optimal medical treatment for nausea, vomiting, and diarrhea should be provided before reducing the dose or temporarily interrupting this drug. Gastrointestinal toxicity should be actively managed to reduce the risk of developing renal impairment or renal failure (see Precautions for Use, 4. General Precautions, 4) Renal Impairment and Renal Failure). Table 1. Recommended dose modifications of this drug for adverse reactions Hypertension, Grade 3: Temporarily interrupt treatment for persistent Grade 3 hypertension despite appropriate antihypertensive treatment; resume treatment at a reduced dose if hypertension is controlled to Grade 2 or lower Hypertension, Grade 4: Permanently discontinue Cardiac dysfunction, Grade 3: Temporarily interrupt treatment until improved to Grade 0-1 or baseline; resume treatment at a reduced dose or discontinue, depending on the severity and persistence of the adverse reaction Cardiac dysfunction, Grade 4: Permanently discontinue Arterial thromboembolic events, all grades: Permanently discontinue Hepatotoxicity, Grade 3 or 4: Temporarily interrupt treatment until improved to Grade 0-1 or baseline; resume treatment at a reduced dose or discontinue, depending on the severity and persistence of hepatotoxicity; permanently discontinue for hepatic failure Renal failure or renal impairment, Grade 3 or 4: Temporarily interrupt treatment until improved to Grade 0-1 or baseline; resume treatment at a reduced dose or discontinue, depending on the severity and persistence of renal impairment Proteinuria ≥2g/24 hours: Temporarily interrupt treatment until reduced to ≤2g/24 hours; resume treatment at a reduced dose; permanently discontinue for nephrotic syndrome Gastrointestinal perforation, all grades: Permanently discontinue Fistula formation, Grade 3 or 4: Permanently discontinue QT prolongation >500 ms or increase >60 ms from baseline: Temporarily interrupt treatment until improved to ≤480 ms or baseline; resume treatment at a reduced dose Reversible posterior leukoencephalopathy syndrome (RPLS), all grades: Temporarily interrupt treatment until fully recovered; resume treatment at a reduced dose or discontinue, depending on the severity and persistence of neurological symptoms Other adverse reactions: Persistent or intolerable Grade 2-3 adverse reactions; Grade 4 laboratory abnormalities: Temporarily interrupt treatment until improved to Grade 0-1 or baseline; resume treatment at a reduced dose Other adverse reactions, Grade 4 adverse reactions: Permanently discontinue a NCI CTCAE version 4.0 Table 2. Recommended dose reductions of this drug if adverse reactions occur Differentiated thyroid cancer: First dose reduction 20mg once daily; second dose reduction 14mg once daily; third dose reduction 10mg once daily Endometrial cancer: First dose reduction 14mg once daily; second dose reduction 10mg once daily; third dose reduction 8mg once daily Renal cell carcinoma: First dose reduction 14mg once daily; second dose reduction 10mg once daily; third dose reduction 8mg once daily When this drug is administered in combination with pembrolizumab, adjust the dose of one or both drugs as appropriate. Temporarily interrupt, reduce the dose of, or permanently discontinue this drug according to Tables 1 and 2. Refer to the prescribing information for pembrolizumab for additional dose adjustment information. For life-threatening adverse reactions (e.g., Grade 4), treatment should be permanently discontinued. This excludes laboratory abnormalities that are not considered life-threatening; in such cases, manage as severe adverse reactions (e.g., Grade 3). Patients aged 75 years or older, Asian patients, patients with comorbidities (such as hypertension, hepatic impairment, or renal impairment), and patients weighing less than 60kg showed a tendency toward reduced tolerability of this drug (see Precautions for Use, 3. Adverse Reactions, 3) Individual Adverse Reactions). Patients with hypertension: Blood pressure should be controlled before treatment with this drug is initiated, and should be monitored regularly during treatment. If necessary, manage hypertension as shown in Table 3 (see Precautions for Use, 4. General Precautions, 1) Hypertension). Table 3. Management of hypertension 140mmHg ≤ systolic blood pressure <160mmHg or 90mmHg ≤ diastolic blood pressure <100mmHg: If not receiving antihypertensive medication: initiate antihypertensive therapy while continuing this drug; if receiving antihypertensive medication: increase the dose of the current antihypertensive medication or initiate additional antihypertensive therapy while continuing this drug Systolic blood pressure ≥160mmHg or diastolic blood pressure ≥100mmHg despite appropriate antihypertensive therapy: 1. Withhold this drug 2. Resume treatment at one dose level lower in patients whose systolic blood pressure is ≤150mmHg and diastolic blood pressure is ≤95mmHg and who have been receiving stable antihypertensive therapy for at least 48 hours (see Table 1 in the Dosage and Administration section) If life-threatening consequences occur (malignant hypertension, neurological deficits, hypertensive crisis): Prompt intervention is required. Discontinue this drug and initiate appropriate medical management Patients with hepatic impairment Differentiated thyroid cancer: No initial dose adjustment based on hepatic function is required in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. An initial dose of 14mg daily is recommended for patients with severe (Child-Pugh C) hepatic impairment. Further dose adjustments may be needed depending on individual tolerability. Hepatocellular carcinoma: Dose adjustment is not recommended in patients with mild hepatic impairment. This drug has not been studied in patients with moderate or severe hepatic impairment. Endometrial cancer: Dose adjustment is not recommended in patients with mild or moderate (Child-Pugh A or B) hepatic impairment. The recommended dose of this drug in patients with severe (Child-Pugh C) hepatic impairment is 10mg orally once daily. Renal cell carcinoma: Dose adjustment is not recommended in patients with mild or moderate (Child-Pugh A or B) hepatic impairment. The recommended dose of this drug in patients with severe (Child-Pugh C) hepatic impairment is 10mg orally once daily. Patients with renal impairment Differentiated thyroid cancer: No initial dose adjustment based on renal function is required in patients with mild or moderate renal impairment. An initial dose of 14mg daily is recommended for patients with severe renal impairment. Further dose adjustments may be needed depending on individual tolerability. Patients with end-stage renal disease have not been studied, and use of this drug is not recommended. Hepatocellular carcinoma: Patients with severe renal impairment and end-stage renal disease have not been studied. Endometrial cancer: Dose adjustment is not recommended in patients with mild or moderate renal impairment. The recommended dose of this drug in patients with severe renal impairment is 10mg orally once daily. Renal cell carcinoma: Dose adjustment is not recommended in patients with mild or moderate renal impairment. The recommended dose of this drug in patients with severe renal impairment (creatinine clearance less than 30mL/min by the Cockcroft-Gault equation) is 10mg orally once daily. Elderly patients: No initial dose adjustment based on age is required. Available data in patients aged 75 years or older are limited. Race: No initial dose adjustment based on race is required. Available data in patients of races other than White and Asian are limited.

Child dose

Hepatocellular carcinoma, patients weighing 60kg or more: 12mg Hepatocellular carcinoma, patients weighing less than 60kg: 8mg Must not be administered to children under 2 years of age. No data are available for children aged 2 years to under 18 years, and safety and efficacy have not been established.

This drug should not be used in patients with allergies to the active ingredient or excipients and in breastfeeding patients. Caution is advised in patients with hypertension or a history of thromboembolic disease, patients with brain metastases, patients with incompletely healing surgical wounds, and patients with tumors infiltrating the carotid or jugular veins. This drug contains pigments such as Yellow No. 5, Red No. 40, and Yellow No. 203, so patients with allergies or hypersensitivity to these components should be careful. During administration, various adverse reactions may occur, including hypertension, blood abnormalities (thrombocytopenia, leukopenia, etc.), hypothyroidism, electrolyte abnormalities (hypocalcemia, hypokalemia, etc.), weight loss, appetite loss, dehydration, fatigue, insomnia, dizziness, headache, heart problems (myocardial infarction, heart failure, etc.), bleeding, pulmonary embolism, gastrointestinal symptoms (diarrhea, vomiting, stomatitis, etc.), skin rashes, musculoskeletal pain, renal function impairment, and proteinuria, so careful monitoring is required. Especially, hypertension and proteinuria may occur frequently during the initial administration, so regular blood pressure and urine tests should be conducted, and if symptoms are severe, dose adjustment or discontinuation should be considered. Additionally, this drug may delay wound healing, so administration should be stopped for a certain period before and after surgery, and there is a possibility of serious side effects such as gastrointestinal perforation or fistula formation, hepatotoxicity, renal failure, heart failure, arterial thromboembolism, so immediate consultation with medical personnel is required if symptoms occur. Women of childbearing potential should use effective contraception during and for at least one month after treatment, and the QT interval should be monitored via electrocardiogram, and electrolyte abnormalities should also be checked periodically. Elderly patients or those with liver or kidney impairment may have a higher risk of adverse reactions, so careful monitoring is needed. It is important to conduct regular blood tests, liver function tests, kidney function tests, and thyroid function tests during the use of this drug to detect and manage adverse reactions early.

Urinary tract infection, perineal abscess, thrombocytopenia, leukopenia, neutropenia, lymphopenia, splenic infarction, hypothyroidism, increased serum thyroid-stimulating hormone, hypocalcemia, hypokalemia, weight loss, decreased appetite, dehydration, hypomagnesemia, hypercholesterolemia, tumor lysis syndrome, insomnia, dizziness, headache, dysgeusia, cerebrovascular accident, reversible posterior leukoencephalopathy syndrome, unilateral incomplete paralysis, transient cerebral ischemic attack, myocardial infarction, heart failure, prolonged QT interval on ECG, reduced ejection fraction, hemorrhage, hypertension, hypotension, aneurysm and arterial dissection, dysphonia, pulmonary embolism, pneumothorax, diarrhea, gastrointestinal and abdominal pain, vomiting, nausea, oral inflammation, oral pain, constipation, dyspepsia, dry mouth, anal perforation, distension, increased lipase, increased amylase, pancreatitis, increased serum bilirubin, hypoalbuminemia, increased alanine aminotransferase, increased aspartate aminotransferase, liver failure, hepatic encephalopathy, increased serum alkaline phosphatase, abnormal liver function, increased gamma-glutamyl transferase, cholecystitis, hepatocellular damage/hepatitis, hand-foot erythema syndrome, rash, hair loss, hyperkeratosis, back pain, arthralgia, myalgia, limb pain, musculoskeletal pain, osteonecrosis of the jaw, proteinuria, cases of renal failure, renal impairment, elevated serum creatinine, elevated urea nitrogen, nephrotic syndrome, fatigue, asthenia, peripheral edema, malaise, impaired wound healing, gastrointestinal fistula, lymph node abscess, folliculitis, urethritis, seizures, sensory loss, peripheral sensory neuropathy, deterioration of general health status, generalized edema, dermatitis, dry skin, perioral dermatitis, urticaria, dysphagia, gastritis, anal fissure, gingival edema, flank pain, atelectasis, progression of malignant neoplasm, eye discharge, eyelid edema, periorbital edema, delirium, sleep disorders, frequent menstruation, ureteral calculi, palpitations, hyperthyroidism, gastroesophageal reflux disease, pruritus, muscle weakness, abdominal pain, ascites, epigastric pain, abdominal distension, melena, esophageal variceal bleeding, duodenal ulcer, gastritis, duodenal perforation, rectal bleeding, fecal incontinence, gastrointestinal disorder, odynophagia, elevated body temperature, fever, weight loss, asthenia, death, decreased performance ability, chest discomfort, influenza-like illness, facial swelling, skin peeling, acne, hyperhidrosis, skin ulcer, hypertensive crisis, increased serum creatinine, multiple organ dysfunction syndrome, myelodysplastic syndrome, right ventricular dysfunction, cardiac arrest, sepsis, arrhythmia, autoimmune hepatitis, dyspnea, increased serum creatinine, myasthenic syndrome, myocarditis, nephritis, pulmonary inflammation, aneurysm rupture, subarachnoid hemorrhage, pneumonia, acute kidney injury, acute myocardial infarction, colitis, intestinal perforation, lower gastrointestinal bleeding, malignant gastrointestinal obstruction, pulmonary embolism, right ventricular dysfunction, acute cholecystitis, interstitial lung disease, hearing loss, necrotizing pneumonia, sudden death, tinnitus, hearing impairment

This medicine should be stored in a tightly closed container to prevent exposure to air or moisture. Additionally, it is recommended to store the medicine at room temperature between 1 to 30 degrees Celsius, avoiding extremely hot or cold places.

Appearance

Capsules filled with white to light yellow granules; upper orange and lower yellow.

Package unit

30 capsules per box [10 capsules/Alu-Alu x 3]