Lenvatinib Mesylate

Introduction

Lenvatinib mesylate is an oral tyrosine kinase inhibitor used primarily in the treatment of various types of cancer. It targets multiple receptor tyrosine kinases involved in tumor growth, angiogenesis (formation of new blood vessels), and cancer progression.

Uses

Lenvatinib is indicated for:

Advanced or metastatic thyroid cancer that is refractory to radioactive iodine treatment.
Unresectable hepatocellular carcinoma (liver cancer) in combination with pembrolizumab.
Advanced renal cell carcinoma, in combination with everolimus.

Brand Name	Lenvatinib Mesylate
Type
Weight
Generic	Lenvatinib Mesylate
Manufacturer
Available in	English বাংলা

Mechanism of Action

Lenvatinib works by inhibiting multiple receptor tyrosine kinases, including:

Vascular endothelial growth factor receptors (VEGFR 1, 2, and 3), which are crucial for angiogenesis.
Fibroblast growth factor receptors (FGFR 1, 2, 3, and 4), involved in cell proliferation and survival.
Platelet-derived growth factor receptors (PDGFR alpha) and c-KIT, which contribute to tumor growth and metastasis.

By blocking these pathways, lenvatinib impairs tumor growth and reduces blood supply to tumors.

How Long Does It Take to Work?

The time to observe clinical benefits varies depending on the type of cancer and the individual patient. For thyroid cancer, some patients may see improvement within 8 to 12 weeks of starting treatment. For other cancers, the response time may differ and requires regular monitoring.

Absorption

Lenvatinib is well-absorbed after oral administration, with peak plasma concentrations reached approximately 1-4 hours post-dose. Its absorption is not significantly affected by food intake.

Route of Elimination

Lenvatinib is primarily metabolized by the liver and excreted via feces. A small fraction is eliminated through the urine. The drug undergoes extensive hepatic metabolism.

Dosage

Important Dosage Information: The dose reduction is needed for certain patients with renal or hepatic impairment. Lenvatinib should be taken once daily, with or without food, 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.

Recommended Dosage for Differentiated Thyroid Cancer (DTC): The recommended dosage of Lenvatinib is 24 mg orally once daily until disease progression or until unacceptable toxicity.

Recommended Dosage for Renal Cell Carcinoma (RCC): The recommended dosage of Lenvatinib is 18 mg in combination with 5 mg Everolimus orally once daily until disease progression or until unacceptable toxicity.

Recommended Dosage for Hepatocellular Carcinoma (HCC): The recommended dosage of Lenvatinib is based on actual body weight: 12 mg for patients greater than or equal to 60 kg or 8 mg for patients less than 60 kg. Lenvatinib should be taken orally once daily until disease progression or until unacceptable toxicity.

Recommended Dosage for Endometrial Carcinoma: The recommended dosage of Lenvatinib is 20 mg orally once daily, in combination with Pembrolizumab 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks, until unacceptable toxicity or disease progression.

The dosage of lenvatinib depends on the type of cancer and patient-specific factors:

For thyroid cancer: 24 mg once daily.
For hepatocellular carcinoma: 8 mg once daily in combination with pembrolizumab.
For renal cell carcinoma: 20 mg once daily in combination with everolimus.

Dose adjustments may be necessary based on tolerability and side effects.

Administration

Lenvatinib is administered orally in the form of capsules. It should be taken at the same time each day, with or without food. The capsules should be swallowed whole, not chewed or crushed.

Side Effects

Common side effects include:

Hypertension (elevated blood pressure).
Diarrhea.
Fatigue.
Nausea and vomiting.
Loss of appetite and weight loss.
Hand-foot syndrome (pain, redness, or swelling of the hands and feet).

Serious side effects may include:

Severe bleeding.
Heart problems, including heart failure.
Severe liver toxicity.
Proteinuria (protein in the urine).

Toxicity

Symptoms of toxicity may include severe hypertension, heart failure, liver dysfunction, and significant bleeding. Immediate medical attention is required if severe symptoms occur, and dose adjustments or discontinuation may be necessary.

Precautions

Precautions include:

Regular monitoring of blood pressure and liver function during treatment.
Assessment of renal function due to the risk of proteinuria and other renal issues.
Monitoring for signs of bleeding or thromboembolic events.

Interaction

Lenvatinib may interact with:

Drugs that affect hepatic enzymes, potentially altering lenvatinib metabolism.
Anticoagulants and antiplatelet agents, increasing the risk of bleeding.

Disease Interaction

Use with caution in patients with:

Pre-existing cardiovascular conditions, due to the risk of hypertension and heart failure.
Liver impairment, as lenvatinib can exacerbate liver dysfunction.

Drug Interaction

Drug interactions may occur with:

Drugs that are strong inducers or inhibitors of hepatic cytochrome P450 enzymes, which can impact lenvatinib levels.
Other medications that can affect blood pressure or cause bleeding.

Food Interactions

Food does not significantly impact the absorption of lenvatinib. However, maintaining a consistent diet and avoiding excessive alcohol intake is advised during treatment.

Pregnancy Use

Lenvatinib is classified as Category D for pregnancy. It may cause harm to the fetus and is contraindicated in pregnant women. Effective contraception is required during treatment and for a period after discontinuation.

Lactation Use

It is not known if lenvatinib is excreted in breast milk. Due to potential serious adverse effects in a nursing infant, breastfeeding is generally not recommended during treatment.

Acute Overdose

Acute overdose symptoms may include severe hypertension, liver toxicity, and gastrointestinal symptoms. Treatment involves symptomatic management and supportive care, with immediate medical attention necessary.

Contraindication

Lenvatinib is contraindicated in:

Pregnant women due to the risk of fetal harm.
Patients with severe liver impairment or active liver disease without proper dose adjustment.
Patients with known hypersensitivity to lenvatinib or any component of the formulation.

Use Direction

Take lenvatinib at the same time each day, following the prescribed dosage regimen. The capsules should be swallowed whole and not altered. Regular monitoring and follow-up with healthcare providers are essential.

Storage Conditions

Store lenvatinib capsules at room temperature, away from moisture and heat. Keep out of reach of children and do not use beyond the expiration date on the packaging.

Volume of Distribution

The volume of distribution for lenvatinib is approximately 2.5 L/kg, indicating a significant distribution into body tissues.

Half Life

Lenvatinib has a terminal half-life of approximately 28 hours, which supports once-daily dosing.

Clearance

Lenvatinib is primarily cleared through the liver, with about 90% of the drug excreted in the feces. The clearance rate can be affected by hepatic function, necessitating dose adjustments in patients with liver impairment.

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