Lenvatinib Mesylate - Uses, Dosage and Side Effects

What Is Lenvatinib Mesylate?

Lenvatinib mesylate is a medication for treating endometrial cancer as well as thyroid cancer. It acts by slowing the progression of cancer growth by interrupting cell functions. Lenvatinib mesylate is available as an oral capsule. It is also used to treat other cancers, including endometrial, liver, and kidney cancer.

Is Lenvatinib Mesylate FDA Approved?

The FDA (United States Food and Drug Administration) approved Lenvatinib mesylate for the treatment of endometrial and thyroid cancer in 2015. Patients are advised to inform the healthcare provider regarding any planned surgery before starting the therapy with Lenvatinib mesylate.

How Does Lenvatinib Mesylate Work?

Lenvatinib mesylate is a tyrosine kinase inhibitor whose action is by blocking the activity of specific proteins (tyrosine kinases) involved in the growth and spread of cancer cells. By inhibiting the activity of these proteins, Lenvatinib mesylate can slow down or stop the growth of cancer cells, leading to the shrinkage of the tumor or slowing its progression.

For Patients:

How Effective Is Lenvatinib Mesylate?

The benefit of lenvatinib mesylate in treating endometrial and thyroid cancers depends on several factors, including the cancer subtype, disease stage, and the patient’s overall health and prior treatments.

Treatment outcomes can differ from one individual to another based on these clinical considerations.

However, clinical studies have shown that Lenvatinib mesylate can act depending on treatment options for certain types of endometrial and thyroid cancer, particularly differentiated thyroid cancer that has spread to other body parts (metastatic disease).

In clinical trials, Lenvatinib mesylate has been shown to shrink and slow the tumor progression in patients with metastatic differentiated thyroid cancer. In some cases, the treatment has led to long-lasting remissions or disease control.

What Are the Guidelines to Inform the Doctor Before Taking Lenvatinib Mesylate?

Inform the doctor if any of the following conditions are present before taking Lenvatinib mesylate:

• Under treatment for high blood pressure.

• Have a history of heart conditions or strokes.

• Have liver or kidney issues.

• Have just undergone surgery or radiotherapy. If the patient is planning to have major surgery, the doctor might think about stopping Lenvatinib mesylate since it can interfere with wound healing. Once sufficient wound healing has occurred, the drug may be resumed.

• Weigh less than 60 kg.

• Have a history of abnormal vascular connections (called fistulas) between various body organs or from an organ to the skin.

• If jaw bone deterioration (osteonecrosis) has been documented in Lenvatinib mesylate patients, the patient should undergo a dental examination before starting Lenvatinib mesylate. In particular, if the patient has recently received bisphosphonate injections (used to treat or prevent bone diseases), the dentist should know if the patient needs any invasive dental work.

• The patient is using or has taken certain cancer medications that affect the growth of blood vessels (known as angiogenesis inhibitors) or antiresorptive medications used to treat osteoporosis, as these medications may raise the risk of jawbone damage.

What Are the Side Effects of Lenvatinib Mesylate?

Inform the doctor immediately if the patient experiences any of the following side effects of Lenvatinib mesylate:

• Sudden weakness on one side of the body, severe headache, seizures, confusion, difficulty speaking, vision changes, or dizziness. These may be signs of a stroke, brain bleeding, or very high blood pressure affecting the brain.

• Chest pain or tightness, pain spreading to the arms, back, neck, or jaw, shortness of breath, fast or irregular heartbeat, coughing, bluish lips or fingers, or extreme tiredness. These may indicate heart or lung problems.

• Severe stomach or abdominal pain, which may be caused by a hole in the intestine or an abnormal connection (fistula) in the digestive tract.

• Black or tar-colored stools, blood in stools, or coughing up blood can be signs of internal bleeding.

• Yellowing of the eyes, unusual tiredness, confusion, or difficulty concentrating, which may indicate liver problems.

• Severe or ongoing diarrhea, nausea, or vomiting can lead to dehydration and kidney failure if not treated promptly.

• Pain, swelling, sores, or numbness in the mouth or jaw, jaw heaviness, or loose teeth may be signs of jawbone damage (osteonecrosis of the jaw).

Some of the common side effects that may be countered during drug use include:

• Appetite loss or weight loss.

• Experiencing nausea and vomiting, as well as constipation, diarrhea, abdominal pain, and indigestion.

• Rash, feeling drained or weak, hoarse voice, swelling in the legs.

• Joint or muscular discomfort, feeling lightheaded, strange taste sensation, dry, painful, or inflamed mouth, and hair loss.

• Bleeding (most frequently nosebleeds, but sometimes blood in the urine, bruises, bleeding from the gums or gut wall).

• Difficulty in falling asleep.

• Backache, redness, discomfort, and swelling of the hands and feet.

• Underactive thyroid (tiredness, weight gain, constipation, feeling cold, dry skin).

• Alterations in calcium and potassium levels (low) were found in blood tests.

• A reduction in the white blood cell count and changes in liver function blood test results.

• Low platelet counts can cause bruising and make wound healing difficult; changes in magnesium, cholesterol, and thyroid-stimulating hormone blood test results; changes in kidney function and kidney failure blood test results; and low platelet counts.

• A rise in amylase and lipase (enzymes involved in digestion).

If these effects persist or do not resolve on their own, contact the doctor immediately.

Dietary Alterations:

Some of the dietary changes that may be recommended while taking Lenvatinib mesylate include:

1. Avoiding High-Fat Meals: Lenvatinib mesylate can be affected by the amount of fat in the digestive system, so high-fat meals should be avoided.

2. Staying Hydrated: Lenvatinib mesylate can cause dehydration, so it is important to drink plenty of water and other non-alcoholic beverages.

3. Avoid Grapefruit and Grapefruit Juice: Grapefruit and grapefruit juice can interact with Lenvatinib, increasing its blood levels and the risk of side effects.

4. Avoiding Alcohol: Alcohol can increase the risk of side effects while taking Lenvatinib mesylate, so it is best to avoid alcohol or limit the intake amount.

Follow the dietary recommendations provided by the healthcare provider or pharmacist to help ensure the safe and effective use of Lenvatinib mesylate. In case of any questions or concerns about dietary restrictions while taking Lenvatinib mesylate, make sure to discuss them with the healthcare provider.

What Should Be Done if a Dose Is Missed?

If a dose of Lenvatinib mesylate is missed:

• Take the missed dose as soon as you remember.

• If it is almost time for the next dose, skip the missed dose and take the next dose at the usual time.

• Do not take two doses at the same time to make up for a missed one.

• If more than one dose is missed, contact the doctor or healthcare provider as soon as possible.

• The healthcare provider may change the dosing schedule or give specific instructions based on the situation.

What Should Be Done to Treat Lenvatinib Mesylate Overdose?

Cases of overdose should be reported to the nearest poison control center or emergency department of the nearest hospital. The treatment will be based on the amount of drug ingested and the duration since the overdose.

How to Store Lenvatinib Mesylate?

• Lenvatinib mesylate should be stored at a temperature between 20°C and 25°C (68°F and 77°F) and protected from light and moisture.

• Keep the medication and all medications out of reach of children and pets.

• Store the medication away from sources of heat, such as a stove or radiator, and from cold sources, such as a freezer.

• Keep track of the expiration date of Lenvatinib and dispose of the expired medication properly.

Avoid Self-Medication:

Lenvatinib mesylate is prescribed only for certain cancers and is not suitable for everyone. A doctor must evaluate a person’s health and decide whether this medicine is appropriate. Taking lenvatinib without medical advice can lead to incorrect dosing and serious side effects, especially in people with other health problems, where the drug may not be safe.

For Doctors:

Indication:

Lenvatinib mesylate is used for the treatment of the following conditions:

• Endometrial Carcinoma: This drug is used in combination with Pembrolizumab to treat endometrial carcinoma.

• Thyroid Carcinoma: Differentiated, metastatic, or locally recurrent, progressing, and resistant to radioactive iodine.

• Carcinoma of the Uterus: In patients with disease progression after prior systemic therapy in any setting who are not suitable for curative surgery or radiation, patients with advanced cancer that is mismatch repair proficient (pMMR) or not microsatellite instability-high (MSI-H) may be treated with Pembrolizumab in combination.

• Liver cancer is the first treatment for incurable conditions.

What Is the Dosing Schedule for Lenvatinib Mesylate?

• Lenvatinib Mesylate dosage in cases to treat thyroid carcinoma is given 24 mg (two 10 mg capsules and one 4 mg capsule) to be prescribed once daily at the same time each day.

• Lenvatinib Mesylate dosage in cases to treat endometrial carcinoma is given at 20 mg orally once daily.

Pharmacology:

Mechanism of Action:

• Lenvatinib mesylate is a type of cancer drug called a receptor tyrosine kinase (RTK) inhibitor.

• It blocks VEGF receptors (VEGFR-1, VEGFR-2, VEGFR-3), which are responsible for the formation of new blood vessels.

• It also inhibits other RTKs such as FGFR 1–4, PDGFR-α, KIT, and RET.

• These receptors normally help regulate cell growth, movement, survival, and specialization.

• In cancer, these receptors become overactive and contribute to tumor growth, spread of cancer, and abnormal blood and lymph vessel formation.

• RTKs are present on the cell surface and activate signaling pathways inside the cell.

• By blocking these pathways, Lenvatinib helps slow tumor growth and reduce blood supply to cancer cells.

• VEGF (vascular endothelial growth factor) controls both normal and abnormal blood vessel formation.

• High VEGF levels are linked to aggressive cancer and poorer prognosis.

Pharmacokinetics:

Absorption:

Lenvatinib mesylate is absorbed into the bloodstream after oral administration and reaches maximum plasma concentrations within one to four hours.

Distribution:

The distribution of Lenvatinib mesylate is not well characterized, but the drug has been shown to have a large volume of distribution in preclinical studies. Lenvatinib mesylate is highly protein-bound, with more than 99 percent bound to plasma proteins.

Metabolism:

Lenvatinib mesylate is primarily metabolized in the liver, with the primary active metabolite, E7080, and is extensively metabolized by CYP3A4 and CYP3A5.

Excretion:

The drug and its breakdown products are mainly eliminated through the stool, with only a small amount passing out in the urine.

Clinical Studies:

• A Phase 2 clinical trial studied Lenvatinib mesylate in patients with

  • Endometrial cancer, and

  • Advanced, treatment-resistant differentiated thyroid cancer (DTC).

• The study included 58 patients.

• Effectiveness Results:

  • Overall response rate (ORR): 31% of patients showed tumor shrinkage.

  • Disease control rate (DCR): 68.9% of patients had either tumor shrinkage or stable disease.

• Disease Progression:

  • Patients lived an average of 4.2 months without disease worsening.

• Duration of Response:

  • The typical treatment response lasted about 8.9 months.

• Common Side Effects:

  • Diarrhea.

  • Nausea.

  • Vomiting.

This shows that Lenvatinib can help control disease in some patients, with manageable side effects.

Warnings and Precautions:

• Hypertension: Blood pressure should be under control before and during treatment. Despite receiving the best antihypertensive care, the therapy is withheld for Grade 3 hypertension. For Grade 4 hypertension, the drug’s usage is stopped.

• Cardiac Dysfunction: Monitor for any indicators or clinical symptoms of cardiac dysfunction. For cardiac dysfunction in Grade 3, the therapy is withheld or stopped. For cardiac dysfunction Grade 4, it is discontinued.

• Arterial Thromboembolic Events: Using the medication is stopped immediately if thromboembolic events are experienced.

• Hepatotoxicity: Prior to and occasionally during therapy, liver function is monitored. In the case of Grade 3 or 4 hepatotoxicities, the therapy is withheld or stopped. For hepatic failure, it is stopped.

• Renal Failure or Impairment: The therapy is discontinued or paused if renal failure or impairment occurs.

• Proteinuria: Monitoring for proteinuria should be done both before and during the treatment. The drug is withheld if proteinuria of 2 grams every 24 hours is detected. For nephrotic syndrome, it is stopped.

• Diarrhea: This condition can be severe and recurrent. Supportive treatment is started for severe diarrhea right away, depending on the intensity.

• Gastrointestinal: Patients who develop Grade 3 or 4 fistulas or any Grade gastrointestinal perforations should stop the treatment.

• QT Prolongation: Electrolyte imbalances to prevent QT interval prolongation are monitored and treated. The therapy is withheld if the baseline QT interval increases by at least 60 ms or if the QT interval is more than 500 ms.

• Hypocalcemia: Monitor blood calcium levels at least once a month, and provide calcium as needed depending on the intensity.

• Hematologic: Depending on the severity, the treatment is modified for hemorrhagic events.

• Impaired Thyroid-Stimulating Hormone Suppression or Thyroid Dysfunction: Prior to treatment and once a month while receiving it, thyroid function should be monitored.

• Impaired Wound Healing: Elective surgery is avoided for at least one week after stopping Lenvatinib mesylate. Also, after major surgery and for at least two weeks, the administration is avoided to allow for proper wound healing. The safety of continuing Lenvatinib mesylate after wound healing issues have been resolved has not been proven.

• Osteonecrosis of the Jaw: Before receiving Lenvatinib mesylate treatment, consider preventive dentistry. Invasive dental operations are avoided, especially for individuals who are more vulnerable.

• Embryo-Fetal Toxicity: The drug may be harmful to the fetus. Mention the use of effective contraception and possible risks to an unborn child.

Contraindications:

Specific contraindications are not yet determined for Lenvatinib mesylate.

Specific population:

Lenvatinib Mesylate in Pregnant Women:

The use of Lenvatinib mesylate in pregnant women has not been studied and is not recommended. Lenvatinib mesylate can cause harm to a developing fetus, and there is a potential risk for birth defects. Women receiving Lenvatinib mesylate should use reliable birth control during treatment and continue it for at least four weeks after stopping the medication to avoid pregnancy.

Lenvatinib Mesylate in Lactating Women:

The use of Lenvatinib mesylate in lactating women has not been studied, and it is unknown whether the drug is excreted in human milk. It is recommended that women avoid breastfeeding while taking Lenvatinib mesylate, as there is a potential risk of harm to a nursing infant.

Lenvatinib Mesylate in Pediatrics:

Lenvatinib mesylate is not currently approved by the FDA for use in pediatric patients.

Lenvatinib Mesylate in Patients With Renal Impairment:

• Lenvatinib mesylate can affect kidney function.

• Patients who already have kidney problems are at higher risk of worsening renal function during treatment.

• In clinical studies, some patients showed a decrease in eGFR, indicating reduced kidney function.

• Who should avoid or adjust treatment:

  • Patients with moderate to severe kidney impairment should not use Lenvatinib.

  • Patients with mild kidney impairment (eGFR 50–80 mL/min) may be treated with Lenvatinib at a lower dose.

• Monitoring is important:

  • Kidney function should be checked regularly during treatment.

  • Dose changes or treatment interruption may be needed if kidney function worsens.

This helps reduce the risk of kidney-related side effects while using Lenvatinib.

Lenvatinib Mesylate in Patients With Hepatic Impairment:

The usual dose of Lenvatinib mesylate may need to be changed in patients who have liver problems. Patients with moderate to severe impairment in hepatic function (Child-Pugh class B or C) should not receive Lenvatinib mesylate.