lenvatinib

Actions and Spectrum:

Actions:

• Inhibition of angiogenesis: lenvatinib blocks the formation of new blood vessels that tumors need to grow and spread.
• Inhibition of tumor cell growth: lenvatinib blocks the activity of certain proteins that help cancer cells grow and divide.
• Inhibition of metastasis: lenvatinib can help prevent cancer from spreading to other parts of the body.

Spectrum:

• Thyroid cancer: lenvatinib is approved for the treatment of advanced or metastatic thyroid cancer.
• Kidney cancer: lenvatinib, in combination with another medication called everolimus, is approved for the treatment of advanced renal cell carcinoma.
• Liver cancer: lenvatinib is approved for the treatment of hepatocellular carcinoma, the most common type of liver cancer.
• Endometrial cancer: lenvatinib, in combination with another medication called pembrolizumab, is approved for the treatment of advanced endometrial cancer that has certain genetic characteristics.

 

 

DRUG INTERACTION

Contraindicated  

Serious Use Alternative  

Monitor Closely  

Minor  

Adverse drug reactions:    

Frequency defined:    

>10%  

Urinary tract infection (11%) 

Insomnia (12%) 

Epistaxis (12%) 

Alopecia (12%) 

Dyspepsia (13%) 

Dizziness (15%) 

Dry mouth (17%) 

Dysgeusia (18%) 

Rash (21%) 

Peripheral edema (21%) 

Cough (24%) 

Oral pain (25%) 

Constipation (29%) 

Dysphonia (31%) 

Abdominal pain (31%) 

Palmar-plantar erythrodysesthesia (32%) 

Proteinuria (34%) 

Vomiting (36%) 

Headache (38%) 

Stomatitis (41%) 

Hypertension, grades 3-4 (44%) 

Nausea (47%) 

Weight decreased (51%) 

Decreased appetite (54%) 

Arthralgia/myalgia (62%) 

Fatigue (67%) 

Diarrhea (67%) 

Hypertension (73%) 

1-10% 

Decreased platelet count (2%) 

Nausea, grades 3-4 (2%) 

Creatinine increased (3%) 

Lipase increased (4%) 

ALT increased (4%) 

AST increased (5%) 

Hypokalemia (6%) 

Hyperkeratosis (7%) 

Decreased appetite, grades 3-4 (7%) 

Hypocalcemia (9%) 

Prolonged QT interval (9%) 

Dehydration (9%) 

Diarrhea, grades 3-4 (9%) 

Hypotension (9%) 

Dental infections (10%) 

 

 

 

 

 

 

Contraindication/Caution:

Contraindications:

• Pregnancy: lenvatinib can cause harm to a developing fetus and is contraindicated during pregnancy. Women of childbearing age should use effective contraception while taking lenvatinib.
• Breastfeeding: It is not known if lenvatinib is excreted in breast milk, and as such, it is not recommended for breastfeeding mothers.
• Hypersensitivity: lenvatinib should not be used in patients with a known hypersensitivity to the drug or any of its components.
• Liver function: lenvatinib is metabolized by the liver, and caution should be taken when using this drug in patients with impaired liver function.
• Blood clotting disorders: lenvatinib can increase the risk of bleeding, and as such, it should be used with caution in patients with bleeding disorders or those taking anticoagulant medications.
• Gastrointestinal perforation/fistula: lenvatinib can increase the risk of gastrointestinal perforation or fistula formation and is contraindicated in patients with a history of these conditions.
• Cardiovascular disease: lenvatinib can cause hypertension and cardiac events such as heart attack, heart failure, or stroke. Caution should be taken when using this drug in patients with a history of cardiovascular disease or hypertension.

 

 

Pregnancy  

Animal studies reveal data about the mechanism of action; wherein lenvatinib can cause harm to an ingrowing fetus. 

Breastfeeding warnings:    

It is advised to discontinue lactation during and after the treatment up to 1 week later the last dose. The drug distribution in breast milk is unknown but shows some adverse reactions. 

Pregnancy Categories: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus.  
• Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women      
• Category C: No adequate evidence for a result in humans must take care of potential risks in pregnant women. It is advised to use the drug with caution as the benefits outweigh the risks. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases of life threat for potential benefits      
• Category X: Drugs listed in this category outweigh risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. Apart from this medication, pregnant women can prefer better alternatives. 
• Category N: There is no data available for the drug under this category

 

 

Pharmacology:

lenvatinib is a multi-targeted tyrosine kinase inhibitor that is used to treat various types of cancer. Its pharmacology involves the inhibition of multiple receptor tyrosine kinases that are involved in tumor growth, angiogenesis, and metastasis. Some of the receptors that lenvatinib targets include the fibroblast growth factor receptor (FGFR), vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and epidermal growth factor receptor (EGFR).

Pharmacodynamics:

The pharmacodynamics of lenvatinib include inhibition of angiogenesis, which is the formation of new blood vessels, and tumor growth. Lenvatinib inhibits the signaling pathways of various growth factors and receptors that are responsible for tumor cell proliferation, survival, and migration. By blocking these pathways, lenvatinib can prevent the growth and spread of cancer cells.

Pharmacokinetics:

The pharmacokinetics of lenvatinib are as follows

Absorption

Peak plasma is achieved 1-4 hours after oral administration

Distribution

Protein-bound is 98-99%

Metabolism

The drug is metabolized by CYP3A enzymes and aldehyde oxidase

Elimination

The half-life is 28 hours

The drug is excreted 64% in feces and 25% in urine (10 days later the single dose)

 

 

Administration:

lenvatinib is an oral medication that is usually taken once a day, at the same time each day, with or without food. The dosage of lenvatinib varies depending on the type of cancer being treated, the patient’s weight, and other medical conditions.

It is important to take lenvatinib exactly as prescribed by the healthcare provider. Patients should not alter the dose or stop taking the medication without first consulting their doctor. If a patient misses a dose of lenvatinib, they should take it as soon as they remember. If it is within 12 hours of the next dose, the missed dose should be skipped, and the regular dosing schedule should be resumed.

lenvatinib is available as capsules and tablets, and patients should swallow the medication whole with a glass of water without chewing or crushing it. Patients should not consume grapefruit or grapefruit juice while taking lenvatinib, as it can increase the level of the medication in the blood and lead to an increased risk of side effects.

 

 

Patient information leaflet

Generic Name: lenvatinib

Pronounced: len-VA-ti-nib

Why do we use lenvatinib?

lenvatinib is used to treat various types of cancer, including:

• Thyroid cancer: lenvatinib is used in the treatment of advanced or metastatic thyroid cancer that is refractory to radioactive iodine therapy. It is used either as a single agent or in combination with another medication, such as pembrolizumab.
• Renal cell carcinoma: lenvatinib, in combination with another medication, everolimus, is used in the treatment of advanced renal cell carcinoma that has already been treated with another medication.
• Hepatocellular carcinoma: lenvatinib is used as a first-line treatment in patients with advanced or unresectable hepatocellular carcinoma, which is the most common form of liver cancer.