LENVANIX 10

Indications

• Advanced renal cell carcinoma
• Other malignancies responsive to targeted therapy

Dosage

Adults: 20 mg once daily, taken at the same time every day. For dose adjustments, treatment interruptions, or discontinuation due to side effects, consult product literature.

Mechanism of action

Lenvatinib inhibits the kinase activities of vascular endothelial growth factor receptors (VEGFR1, VEGFR2, VEGFR3) and other receptor tyrosine kinases (RTKs) involved in angiogenesis and tumor progression. It binds to the adenosine 5'-triphosphate binding site of VEGFR2, inhibiting tyrosine kinase activity and associated signaling pathways, thereby disrupting the processes that lead to tumor growth and metastasis.

Pharmacodynamics

Lenvatinib has a potent inhibitory effect on tumor angiogenesis and growth by blocking the signaling pathways activated by various RTKs. It is effective in reducing tumor size and progression by targeting multiple pathways that are crucial for tumor survival and growth.

Pharmacokinetics

Lenvatinib is administered orally and has a bioavailability that allows it to be absorbed effectively. It is extensively metabolized in the liver, primarily via cytochrome P450 enzymes, and has a half-life that supports once-daily dosing. The drug should be stored in a refrigerator and monitored for potential interactions and side effects, particularly with regards to blood pressure and other cardiovascular risks.

Contra-indications

• Fistulae
• Arterial thromboembolism within the previous 6 months
• Risk factors for aneurysm or artery dissection

Adverse effects

• Alopecia
• Appetite decreased
• Arthralgia
• Asthenia
• Cerebrovascular insufficiency
• Cholecystitis
• Constipation
• Dehydration
• Diarrhoea
• Dizziness
• Dry mouth
• Dysphonia
• Encephalopathy
• Gastrointestinal discomfort
• Gastrointestinal disorders
• Haemorrhage
• Headache
• Heart failure
• Hepatic coma
• Hepatic disorders
• Hyperbilirubinaemia
• Hypercholesterolaemia
• Hypertension
• Hypoalbuminaemia
• Hypotension
• Hypothyroidism
• Increased risk of infection
• Insomnia

Precautions

• Monitor blood pressure regularly during treatment
• Counsel patients on risks of dizziness and fatigue affecting driving and skilled tasks
• Consider modifiable risk factors for aneurysm and artery dissection such as smoking and hypertension

Pregnancy

There is limited data on the use of lenvatinib during pregnancy. It is recommended to avoid use unless the potential benefits outweigh the risks.

Breast-feeding

It is unknown whether lenvatinib is excreted in human milk. Caution is advised when administering to breastfeeding women.

Storage

For oral solution, store in a refrigerator at 2–8°C.

Formulations

• Oral solution: 20 mg per 1 ml
• Capsules: 25 mg

Mechanism of action

Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.

Pharmacodynamics

Based on x-ray crystallography and kinetic interaction studies, lenvatinib binds to the adenosine 5'-triphosphate binding site of VEGFR2 and to a neighbouring region via a cyclopropane ring and thereby inhibits tyrosine kinase activity and associated signalling pathways.