Lenvatinib


Generic Medicine Info
Indications and Dosage
Oral
Locally advanced differentiated thyroid cancer, Locally recurrent differentiated thyroid cancer, Metastatic differentiated thyroid cancer, Progressive differentiated thyroid cancer
Adult: In the treatment of cases refractory to radioactive iodine: 24 mg once daily, continued until disease progression or unacceptable toxicity. Dose reduction and dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).

Oral
Unresectable hepatocellular carcinoma
Adult: 1st-line treatment: Based on actual body weight: Patient <60 kg: 8 mg once daily; ≥60kg: 12 mg once daily. Continued until disease progression or unacceptable toxicity. Dose reduction and dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).

Oral
Advanced renal cell carcinoma
Adult: In combination with everolimus for the treatment of patients with cases following 1 previous anti-angiogenic treatment such as VEGF-targeted therapy: 18 mg once daily, continued until disease progression or unacceptable toxicity. Dose reduction and dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).

Oral
Advanced endometrial carcinoma
Adult: In combination with pembrolizumab for treatment of patients with a case that is not microsatellite instability-high or mismatch repair deficient, who have disease progression following previous systemic therapy and are not candidates for curative surgery or radiation: 20 mg once daily, continued until disease progression or unacceptable toxicity. Dose reduction and dosing interruption or discontinuation may be required according to individual safety or tolerability (refer to detailed product guideline).
Renal Impairment
Locally advanced or locally recurrent or metastatic, progressive, refractory to radioactive iodine differentiated thyroid cancer:
CrCl (mL/min) Dosage
<30
14 mg once daily, further dose adjustment may be required according to individual safety and tolerability. Not recommended in ESRD.

Advanced renal cell carcinoma:
CrCl (mL/min) Dosage 
<30
In combination with everolimus: 10 mg once daily, further dose adjustment may be required according to individual safety and tolerability. Not recommended in ESRD.

Advanced endometrial carcinoma:
CrCl (mL/min) Dosage 
<30
10 mg once daily, further dose adjustment may be required according to individual safety and tolerability. Not recommended in ESRD.
Hepatic Impairment
Locally advanced or locally recurrent or metastatic, progressive, refractory to radioactive iodine differentiated thyroid cancer:
Severe (Child-Pugh class C): 14 mg once daily, further dose adjustment may be required according to individual safety and tolerability.

Advanced renal cell carcinoma:
Severe (Child-Pugh class C): In combination with everolimus at its recommended dose for severe impairment (refer to everolimus product guideline): 10 mg once daily, further dose adjustment may be required according to individual safety and tolerability. Combination treatment must be used only if the potential benefit outweighs the risk.

Advanced endometrial carcinoma:
Severe (Child-Pugh class C): 10 mg once daily, further dose adjustment may be required according to individual safety and tolerability.
Administration
May be taken with or without food.
Contraindications
Fistulae. Lactation.
Special Precautions
Patient with hypertension, history of aneurysm, arterial thromboembolic event within the past 6 months; congenital long QT syndrome, CHF, bradyarrhythmias; risk factors for renal failure (e.g. dehydration, hypovolaemia due to gastrointestinal toxicity), QT prolongation (e.g. hypokalaemia, hypocalcaemia, hypomagnesaemia), or gastrointestinal perforation and fistula formation (e.g. previous surgery, radiotherapy); greater liver tumour burden (at baseline), liver cirrhosis. Patient undergoing or following major surgery/invasive dental procedure. Concomitant or previous antiresorptive bone therapy and/or other angiogenesis inhibitors. Treatment guidelines may vary among individual products or between countries (refer to product-specific recommendations). Not recommended for use in ESRD. Severe renal and hepatic impairment. Elderly (≥75 years). Pregnancy.
Adverse Reactions
Significant: Hypertension, QT/QTc prolongation, gastrointestinal toxicity (e.g. emesis, diarrhoea), fistula formation (gastrointestinal or non-gastrointestinal), gastrointestinal perforation, pneumothorax, epistaxis, haematuria, hepatic encephalopathy, encephalopathy, metabolic encephalopathy, hepatic coma; increased ALT/AST and blood bilirubin; hypocalcaemia, hypothyroidism, palmar-plantar erythrodysaesthesia; proteinuria, nephrotic syndrome; arterial thromboembolic events (e.g. cerebrovascular accident, TIA, MI), impaired wound healing; osteonecrosis of the jaw. Rarely, reversible posterior leucoencephalopathy syndrome (RPLS).
Blood and lymphatic system disorders: Thrombocytopenia, leucopenia, neutropenia, lymphopenia.
Gastrointestinal disorders: Nausea, oral pain or inflammation, dry mouth, dysgeusia, gastrointestinal and abdominal pain, constipation, dyspepsia, flatulence; pancreatitis.
General disorders and administration site conditions: Fatigue, asthenia, peripheral oedema, malaise.
Hepatobiliary disorders: Hypoalbuminaemia, cholecystitis.
Investigations: Increased blood TSH, amylase, lipase, blood alkaline phosphatase, gamma-glutamyl transferase, blood creatinine and urea; decreased weight.
Metabolism and nutrition disorders: Decreased appetite, hypokalaemia, hypomagnesaemia, hypercholesterolaemia, dehydration.
Musculoskeletal and connective tissue disorders: Musculoskeletal pain, back pain, arthralgia, myalgia, pain in extremity.
Nervous system disorders: Headache, dizziness.
Psychiatric disorders: Insomnia.
Renal and urinary disorders: UTI.
Respiratory, thoracic and mediastinal disorders: Dysphonia, pulmonary embolism.
Skin and subcutaneous tissue disorders: Rash, alopecia, palmar erythema, hyperkeratosis.
Vascular disorders: Hypotension.
Potentially Fatal: Cardiac dysfunction (e.g. cardiomyopathy, left or right ventricular dysfunction, decreased left or right ejection fraction, cardiac failure, ventricular hypokinesia), aortic aneurysm rupture, aortic dissection, haemorrhagic events (e.g. intracranial, cerebral, and carotid artery haemorrhage), hepatotoxicity (e.g. hepatic failure, acute hepatitis, hepatorenal syndrome), renal failure.
Patient Counseling Information
This drug may cause dizziness and fatigue; if affected, do not drive or operate machinery.
MonitoringParameters
Evaluate pregnancy status and perform a dental exam before treatment initiation. Monitor blood pressure at baseline, after 1 week, every 2 weeks for 2 months, then at least monthly thereafter; ECG at baseline and regularly particularly in patients with congenital long QT syndrome, CHF, bradyarrhythmias, or those with medications that may prolong the QT interval; renal function; LFTs prior to initiation, every 2 weeks for 2 months, then monthly thereafter; electrolytes (e.g. K, Mg), thyroid function (e.g. TSH levels), and proteinuria at baseline and as necessary; serum Ca levels at least every month. Assess for signs and symptoms of cardiac dysfunction, arterial thrombosis, RPLS, fistula formation, gastrointestinal perforation, haemorrhagic events, diarrhoea, wound healing complications, hepatic failure, and hepatic encephalopathy.
Overdosage
Symptoms: Hypertension, headache, fatigue, nausea, diarrhoea, stomatitis, proteinuria, and palmar-plantar erythrodysaesthesia aggravation. Management: Supportive treatment.
Drug Interactions
May increase the risk of QT interval prolongation with class Ia (e.g. quinidine, procainamide) and III antiarrhythmics (e.g. amiodarone, sotalol). May cause osteonecrosis of the jaw if used simultaneously or sequentially with other angiogenesis inhibitors (e.g. bevacizumab) and/or antiresorptive bone therapy.
Food Interaction
Food may decrease the rate but not the extent of absorption of lenvatinib.
Action
Description: Lenvatinib is a multitargeted tyrosine kinase inhibitor. It inhibits the activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), VEGFR3 (FLT4), fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4, platelet-derived growth factor receptor alpha (PDGFRα), stem cell factor receptor (c-KIT), and ret proto-oncogene (RET), which causes reduced tumour growth and slowed cancer progression.
Pharmacokinetics:
Absorption: Rapidly absorbed from the gastrointestinal tract. Decreased rate but not the extent of absorption with food. Time to peak plasma concentration: 1-4 hours.
Distribution: Plasma protein binding: 98-99%, mainly to albumin.
Metabolism: Metabolised in the liver primarily by the CYP3A4 isoenzyme, aldehyde oxidase, and by non-enzymatic processes.
Excretion: Via faeces (approx 64%); urine (approx 25%). Elimination half-life: Approx 28 hours.
Chemical Structure

Chemical Structure Image
Lenvatinib

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 9823820, Lenvatinib. https://pubchem.ncbi.nlm.nih.gov/compound/Lenvatinib. Accessed Jan. 26, 2021.

Storage
Store between 15-30°C. Protect from moisture. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
ATC Classification
L01EX08 - lenvatinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.
References
Anon. Lenvatinib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 02/12/2020.

Anon. Lenvatinib. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/12/2020.

Buckingham R (ed). Lenvatinib. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/12/2020.

Joint Formulary Committee. Lenvatinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/12/2020.

Kisplyx 4 mg and 10 mg Hard Capsules (Eisai GmbH). European Medicines Agency [online]. Accessed 11/12/2020.

Lenvima (Eisai [HK] Co. Ltd.). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 11/12/2020.

Lenvima (Eisai Co., Ltd. Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my/. Accessed 02/12/2020.

Lenvima 4 mg and 10 mg Hard Capsules (Eisai GmbH). European Medicines Agency [online]. Accessed 11/12/2020.

Lenvima Capsule (Eisai Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 02/12/2020.

Disclaimer: This information is independently developed by MIMS based on Lenvatinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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