LENVIMA 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

Indications

• Hypertension
• Heart failure
• Chronic kidney disease

Dosage

Children: Refer to established guidelines for specific dosing recommendations.

Adults: Refer to established guidelines for specific dosing recommendations.

Mechanism of action

Mesilate acts as a selective inhibitor of certain pathways involved in the renin-angiotensin-aldosterone system (RAAS). By inhibiting angiotensin-converting enzyme (ACE), it reduces the formation of angiotensin II, a potent vasoconstrictor, leading to vasodilation and a decrease in blood pressure. This mechanism also promotes natriuresis, aiding in the reduction of blood volume and further contributing to its antihypertensive effects.

Pharmacodynamics

The pharmacodynamics of mesilate involve its influence on vascular smooth muscle tone and the modulation of renal function. By decreasing systemic vascular resistance, mesilate lowers both systolic and diastolic blood pressure without significantly affecting heart rate. Its effects can be observed within hours of administration, with peak antihypertensive effects typically seen within 24 hours.

Pharmacokinetics

Mesilate is absorbed well from the gastrointestinal tract, with peak plasma concentrations reached within 1 to 2 hours post-administration. It is metabolized in the liver through various pathways, and its metabolites are primarily excreted via the kidneys. The elimination half-life of mesilate generally ranges from 6 to 12 hours, allowing for once or twice daily dosing in clinical practice.

Contra-indications

• Hypersensitivity to mesilate or any component of the formulation
• Severe hepatic impairment
• Active gastrointestinal bleeding

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Dizziness
• Fatigue
• Skin rash

Interactions

• Anticoagulants may have their effects potentiated
• Caution with concomitant use of other medications that affect liver function

Precautions

• Use with caution in patients with liver disease
• Monitor for signs of gastrointestinal bleeding
• Assess renal function prior to use

Pregnancy

There is limited data on the safety of mesilate in pregnancy. It should be used only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether mesilate is excreted in human milk. Caution should be exercised when administering to a nursing mother.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Injectable solution

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.