Lenvatinib

Lenvatinib is a kinase inhibitor used to treat adults with certain kinds of cancer.

Lenvatinib is used by itself to treat differentiated thyroid cancer (DTC), a type of thyroid cancer that has come back or spread, can no longer be treated with radioactive iodine, and is progressing.

Lenvatinib is used to treat a type of kidney cancer called advanced renal cell carcinoma (RCC):

• in combination with pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) as your first treatment when your kidney cancer has spread or cannot be removed by surgery;
• in combination with belzutifan (Welireg) to treat advanced RCC with a clear cell component following treatment with a type of anticancer medicine called a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor; or
• in combination with everolimus (Afinitor) after one course of treatment with another anticancer medicine (anti-angiogenic therapy).

Lenvatinib is used by itself as the first treatment for a type of liver cancer called hepatocellular carcinoma (HCC) when it cannot be removed by surgery.

Lenvatinib is used in combination with pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) to treat advanced endometrial carcinoma (EC), a type of uterine cancer:

• when a laboratory test shows that your tumor is mismatch repair proficient (pMMR) or not microsatellite instability-high (MSI-H), and
• you have received anticancer treatment, and it is no longer working, and
• your cancer cannot be cured by surgery or radiation.

It is not known if lenvatinib is safe and effective in children.

Take lenvatinib exactly as prescribed by your doctor. Follow all directions on your prescription label and read all medication guides or instruction sheets.

Take lenvatinib 1 time each day at the same time each day, with or without food.

Your dose may be made up of more than one capsule. Follow your doctor's dosing instructions very carefully.

Swallow lenvatinib capsules whole. Do not crush or chew the capsules.

If you cannot swallow the capsules whole, they can be mixed with water or apple juice and taken by mouth, or mixed with water and given through a feeding tube. Do not break or crush the capsules.

How to take lenvatinib by mouth if you cannot swallow whole capsules

• Place your daily dose, up to 5 capsules, in a small container or oral syringe (approximately 20 mL capacity).
• Add 3 mL of water or apple juice to the container or oral syringe. Wait 10 minutes for the capsule shell (outer surface) to dissolve completely, then stir or shake the mixture for 3 minutes until the capsules are fully dissolved.
• Drink the liquid mixture or use an oral syringe to take it directly into the mouth.
• Next, using a second syringe, add an additional 2 mL of liquid to the container or oral syringe (cap the first oral syringe before adding the additional liquid), then swirl or shake and take the liquid mixture. Repeat this step at least one time and until you cannot see any of the mixture left in the container or oral syringe, to make sure all of the medicine is taken.
• If 6 capsules are needed for your daily dose, follow these instructions using 3 capsules at a time.

How to give lenvatinib through a feeding tube

• Lenvatinib should be given in feeding tubes of at least 5 French diameter (polyvinyl chloride or polyurethane tube) and at least 6 French diameter (silicone tube).
• Place your daily dose, up to 5 capsules, in a syringe (20 mL capacity).
• Add 3 mL of water to the syringe. Wait 10 minutes for the capsule shell to dissolve completely, then stir or shake the mixture for 3 minutes until the capsules are fully dissolved.
• Give the mixture through the feeding tube.
• Next, cap the syringe and remove the plunger. Use a second syringe to add an additional 2 mL of liquid to the syringe. Swirl or shake and give the mixture through the feeding tube. Repeat this step at least one time and until you cannot see any of the mixture left in the syringe.
• If 6 capsules are needed for your daily dose, follow these instructions using 3 capsules at a time.

If you get diarrhea, ask your doctor about medicines you can take to treat it. It is important to drink more water when you get diarrhea. Tell your doctor or go to the emergency room if you are unable to drink enough liquids and your diarrhea cannot be controlled. Loss of fluids (dehydration) can lead to kidney problems.

You will need frequent medical tests to check your blood pressure, heart, liver and kidney function, urine protein, blood salts (electrolytes) including calcium, and thyroid hormone levels. Your heart rhythm may also be checked with an electrocardiogram (ECG).

Practice good mouth care during treatment with lenvatinib, and tell your dentist that you are taking this medicine. Avoid invasive dental procedures if possible during treatment.

If you plan to have surgery or a dental procedure, tell the surgeon or dentist you use lenvatinib. You should stop taking lenvatinib at least 1 week before planned surgery, dental surgery, or an invasive dental procedure. Your doctor will tell you when you may start taking lenvatinib again.

Your doctor may reduce your dose, delay treatment, or stop treatment completely if you have certain side effects.

Store capsules at room temperature, between 68°F to 77°F (20°C to 25°C).

A lenvatinib mixture may be stored in a covered container in the refrigerator at 36°F to 46°F (2°C to 8°C) for up to 24 hours. Throw away the mixture if it is not used within 24 hours of mixing.

Lenvatinib can cause an opening in the wall of your stomach or intestines (perforation) or an abnormal connection between two or more body parts (fistula). Get emergency medical help right away if you develop severe stomach area (abdomen) pain.

Lenvatinib can cause serious heart problems, including heart failure that may lead to death. Your doctor will check your heart function before and during treatment. Tell your doctor right away if you have shortness of breath, swelling of your ankles, unusual weight gain, chest pain, or feeling faint.

Get emergency medical help right away if you have signs of a blood clot in your arteries, such as severe chest pain or pressure, pain in your arms, back, neck or jaw, shortness of breath, numbness or weakness on one side of your body, trouble talking, sudden severe headache, or sudden vision changes.

Call your doctor at once if you have signs of other serious side effects, including high blood pressure, liver problems (jaundice, dark or tea colored urine, light-colored stools), kidney problems, severe diarrhea, serious bleeding, or a severe headache, seizures, confusion, or change in vision.

To make sure lenvatinib is safe for you, tell your doctor about all of your medical conditions, including if you:

• have high blood pressure;
• have heart problems, including heart failure;
• have long QT syndrome or a slow heart rhythm;
• have a history of blood clots in your arteries, including stroke, heart attack, or change in vision;
• have or have had liver or kidney problems;
• have a history of a tear (perforation) in your stomach or intestine, or an abnormal connection between two or more body parts (fistula);
• have headaches, seizures, or vision problems;
• have any bleeding problems;
• plan to have surgery, a dental procedure, or have had a recent surgery;
• are pregnant or plan to become pregnant; or
• are breastfeeding or plan to breastfeed.

Lenvatinib may cause severe jawbone problems (osteonecrosis). Certain risk factors such as taking a bisphosphonate medicine or the medicine denosumab, having dental disease, or an invasive dental procedure may increase your risk. Your doctor should examine your mouth before you start and during treatment with lenvatinib.

Lenvatinib can harm an unborn baby. If you are able to become pregnant, your doctor will do a pregnancy test before you start treatment. Use an effective method of birth control during treatment and for 30 days after your last dose. Tell your doctor right away if you become pregnant or think you are pregnant.

If you are taking lenvatinib in combination with another medicine, your doctor will tell you how long you should use birth control.

Lenvatinib may cause fertility problems in males and females. Talk to your doctor if this is a concern for you.

It is not known if lenvatinib passes into breast milk. Do not breastfeed during treatment and for 1 week after your last dose. If you are taking lenvatinib in combination with another medicine, your doctor will tell you how long you should not breastfeed.

Lenvatinib may cause serious side effects. Call your doctor at once if you have:

• high blood pressure - your blood pressure should be well controlled before you start taking lenvatinib and checked regularly during treatment;
• heart problems - shortness of breath, swelling of your ankles, unusual weight gain, chest pain, feeling faint;
• a blood clot in your arteries (get emergency medical help) - severe chest pain or pressure, pain in your arms, back, neck or jaw, shortness of breath, numbness or weakness on one side of your body, trouble talking, sudden severe headache, sudden vision changes;
• liver problems - yellowing of your skin or the white part of your eyes (jaundice), dark or tea colored urine, light-colored stools, nausea or vomiting, pain in your upper right stomach area, feeling drowsy, confused, or losing consciousness;
• kidney problems - changes in the amount or color of your urine, blood in your urine, swelling in your legs or ankles, loss of appetite;
• increased protein in your urine (proteinuria);
• severe diarrhea, or diarrhea that cannot be controlled when you are unable to drink enough liquids;
• a tear in your stomach or intestines, or a fistula (get emergency medical help) - severe stomach area pain;
• QTc prolongation (a change in the electrical activity of your heart) - irregular heartbeats that can cause you to faint;
• low blood calcium (hypocalcemia);
• reversible posterior leukoencephalopathy syndrome (RPLS) - new or worsening severe headache, seizures, weakness, confusion, change in vision;
• bleeding - severe and persistent nosebleeds, vomiting blood, red or black (tarry) stools, blood in your urine, coughing up blood or blood clots, heavy or new onset vaginal bleeding;
• changes in thyroid hormone levels - your doctor should check your thyroid hormone levels before you start and every month during treatment;
• wound healing problems; or
• severe jawbone problems (osteonecrosis) - jaw pain, toothache, or sores on your gums.

Your doctor may reduce your dose, delay treatment, or stop treatment completely if you have certain side effects.

Common lenvatinib side effects in adults treated for thyroid cancer may include:

• tiredness, headache;
• joint and muscle pain;
• decreased appetite, weight loss;
• nausea, vomiting, stomach area (abdomen) pain;
• mouth sores;
• rash, redness, itching, or peeling of the skin on your hands and feet; or
• hoarseness.

Common lenvatinib side effects in adults treated for liver cancer may include:

• tiredness;
• decreased appetite, weight loss;
• joint and muscle pain;
• stomach area (abdomen) pain, nausea;
• rash, redness, itching, or peeling of the skin on your hands and feet;
• hoarseness;
• bleeding; or
• decreased thyroid hormone levels (hypothyroidism).

Common side effects in adults treated for kidney cancer with lenvatinib plus pembrolizumab may include:

• tiredness, headache;
• joint and muscle pain;
• decrease in thyroid hormone levels;
• mouth sores, hoarseness;
• decreased appetite, weight loss;
• rash, or redness, itching, or peeling of the skin on your hands and feet;
• nausea, vomiting, constipation, stomach area (abdomen) pain;
• bleeding;
• liver problems; or
• sudden kidney injury.

Common side effects in adults treated for endometrial cancer with lenvatinib plus pembrolizumab may include:

• decrease in thyroid hormone levels;
• tiredness, headache;
• joint and muscle pain;
• nausea, vomiting, constipation, stomach area (abdomen) pain;
• decreased appetite, weight loss;
• mouth sores, hoarseness;
• urinary tract infection;
• bleeding; or
• rash, or redness, itching, or peeling of the skin on your hands and feet.

Common side effects in adults treated for kidney cancer with lenvatinib plus belzutifan may include:

• decreased red blood cell counts;
• tiredness;
• muscle and joint pain;
• nausea, vomiting, constipation, stomach area (abdomen) pain;
• decrease in thyroid hormone levels;
• decreased appetite, weight loss;
• rash; or
• mouth sores.

Common side effects in adults treated for kidney cancer with lenvatinib plus everolimus may include:

• tiredness;
• joint and muscle pain;
• decreased appetite, weight loss;
• nausea, vomiting, stomach area (abdomen) pain;
• mouth sores;
• swelling in your arms and legs;
• cough, trouble breathing;
• rash; or
• bleeding.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Thyroid Cancer:

24 mg orally once a day

Comment:-Treatment should be continued until disease progression or unacceptable toxicity.

Use: For the treatment of adult patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)

Usual Adult Dose for Renal Cell Carcinoma:

First-line treatment of advanced RCC: 20 mg orally once a day in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmphAdvanced RCC with a clear cell component (ccRCC): 20 mg orally once a day in combination with belzutifanAdvanced RCC following one prior anti-angiogenic therapy: 18 mg orally once a day in combination with everolimus 5 mg orally once a day

Comments:-Refer to the pembrolizumab, pembrolizumab and berahyaluronidase alfa-pmph, belzutifan, or everolimus prescribing information for recommended dosing information.-Treatment should be continued until disease progression or unacceptable toxicity.-First-line RCC: after completing 2 years of combination therapy, this drug may be given as a single agent until disease progression or unacceptable toxicity.

Uses:-In combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC)-In combination with belzutifan, for the treatment of adult patients with advanced renal cell carcinoma with a clear cell component (ccRCC) following a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor-In combination with everolimus, for the treatment of adult patients with advanced RCC following one prior anti-angiogenic therapy

Usual Adult Dose for Hepatocellular Carcinoma:

-Weight less than 60 kg: 8 mg orally once a day-Weight 60 kg or greater: 12 mg orally once a day

Comments:-Dosage is based on actual body weight.-Treatment should be continued until disease progression or unacceptable toxicity.

Use: For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC)

Usual Adult Dose for Endometrial Carcinoma:

20 mg orally once a day in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph

Comments:-Refer to the pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph prescribing information for recommended dosing information.-Select patients based on MMR or MSI status in tumor specimens.-Treatment should be continued until disease progression or unacceptable toxicity.

Use: In combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, for the treatment of patients with advanced endometrial carcinoma (EC) that is mismatch repair proficient (pMMR) or not microsatellite instability-high (MSI-H), as determined by an FDA-authorized test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation

Renal Dose Adjustments

Severe renal impairment (CrCl less than 30 mL/min, Cockcroft-Gault using actual body weight):-DTC: 14 mg orally once a day-RCC and EC: 10 mg orally once a day

Liver Dose Adjustments

Severe hepatic impairment (Child-Pugh C):-DTC: 14 mg orally once a day-RCC and EC: 10 mg orally once a day

Take the medicine as soon as you remember. If your next dose is due within 12 hours, skip the missed dose and take the next dose at your regular time. Do not take two doses at one time.

If you take too much lenvatinib, call your doctor or go to the nearest hospital emergency room right away. You may also call the Poison Help line at 1-800-222-1222.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Lenvatinib can cause a serious heart rhythm problem (QTc prolongation). Your risk may be higher if you also use certain other medicines that affect heart rhythm, including some medicines for infections, asthma, heart problems, high blood pressure, depression, mental illness, cancer, malaria, or HIV.

Tell your doctor if you are taking, or have taken, an osteoporosis medicine. Bisphosphonates and denosumab may increase the risk of jawbone problems.

Other drugs may interact with lenvatinib, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medicines you use.