Lenvima

Lenvima (lenvatinib) is a kinase inhibitor used to treat adults with certain kinds of cancer. Kinase inhibitors block the action of one or more protein kinases, which interferes with the growth and spread of cancer cells in the body.

• Lenvima 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.
• Lenvima is used to treat a type of kidney cancer called advanced renal cell carcinoma (RCC): in combination with the medicine pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph as your first treatment when your kidney cancer has spread or cannot be removed by surgery. in combination with the medicine 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. in combination with the medicine everolimus (Afinitor) after one course of treatment with another anti-cancer medicine (anti-angiogenic therapy).
• Lenvima 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.
• Lenvima is used in combination with the medicine pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph 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 anti-cancer treatment, and it is no longer working, and your cancer cannot be cured by surgery or radiation.

The safety and efficacy of Lenvima have not been established in children.

• Take Lenvima exactly as your healthcare provider tells you to take it.
• Your healthcare provider will tell you how much Lenvima to take and when to take it. To get a full dose, you may need to take a combination of capsules with different strengths.
• Take Lenvima 1 time each day at the same time each day, with or without food.
• Swallow Lenvima capsules whole. Do not crush or chew the Lenvima capsules.
• If you cannot swallow Lenvima capsules whole, Lenvima capsules can be mixed with water or apple juice, then taken by mouth, or mixed with water and given through a feeding tube.

How to take Lenvima 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 capsules are fully dissolved. Do not break or crush the capsules.
• Drink the liquid mixture or use an oral syringe to take 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 water), then swirl or shake and take the liquid mixture. Repeat this step at least one time and until you cannot see any of the Lenvima mixture left in the container or oral syringe to make sure all of the medicine is taken.
• If 6 capsules are required for your daily dose, follow the above instructions using 3 capsules at a time.

How to give Lenvima through a feeding tube

Lenvima 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 (outer surface) to dissolve completely, then stir or shake the mixture for 3 minutes until capsules are fully dissolved. Do not break or crush the capsules.
• Give the mixture through a feeding tube.
• Next, cap the syringe and remove the plunger. Use a second syringe and add an additional 2 mL of liquid to the syringe. Swirl or shake and give the mixture in the feeding tube. Repeat this step at least one time and until you cannot see any of the Lenvima mixture left in the syringe to make sure all of the medicine is taken.
• If 6 capsules are required for your daily dose, follow the above instructions using 3 capsules at a time.

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

While you are taking Lenvima

• Your healthcare provider will check your blood pressure, heart function, liver and kidney function, urine protein, blood salts (electrolytes), calcium, and thyroid hormone levels before and during treatment.
• If you get diarrhea, ask your healthcare provider about medicines you can take to treat it, and drink more water. Tell your healthcare provider or go to the emergency room if you are unable to drink enough liquids and your diarrhea cannot be controlled.
• Practice good mouth care during treatment and tell your dentist that you are taking Lenvima.
• If you plan to have surgery or a dental procedure, you should stop taking Lenvima at least 1 week before planned surgery, dental surgery, or invasive dental procedures. Your healthcare provider should tell you when you may start taking Lenvima again.

Lenvima can cause serious side effects, including high blood pressure, heart problems such as heart failure, blood clots in the arteries, liver problems, kidney problems, and serious bleeding. Some of these may lead to death.

Some people taking Lenvima have developed an opening in the wall of the 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.

Get emergency medical help right away if you have symptoms of a blood clot in an artery, 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.

Tell your healthcare provider right away if you have signs of heart problems (shortness of breath, swelling of your ankles, unusual weight gain, chest pain, or feeling faint), liver problems (yellowing of your skin or eyes, dark or tea colored urine, light-colored stools), or bleeding.

Before you take Lenvima, tell your healthcare provider about all of your medical conditions, including if you:

• have high blood pressure
• have heart problems
• have a history of blood clots in your arteries (type of blood vessel), 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. You should stop taking Lenvima at least 1 week before planned surgery
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed.

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

Pregnancy

Lenvima can harm your unborn baby. If you can become pregnant:

• Your healthcare provider will do a pregnancy test before you start treatment with Lenvima.
• Use an effective method of birth control (contraception) during treatment with Lenvima and for 30 days after the last dose. Talk with your healthcare provider about birth control methods you can use during this time.
• Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with Lenvima.
• If you are taking Lenvima in combination with another medicine, your healthcare provider will tell you how long you should use birth control.

Fertility

Lenvima may cause fertility problems in males and females. Talk to your healthcare provider if this is a concern for you.

Breastfeeding

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

Lenvima may cause serious side effects, including:

• High blood pressure (hypertension). High blood pressure is a common side effect of Lenvima and can be serious. Your blood pressure should be well controlled before you start taking Lenvima, and your healthcare provider should check it regularly during treatment. Tell your healthcare provider if you get high blood pressure during treatment.
• Heart problems. Lenvima can cause serious heart problems, including heart failure that may lead to death. Your healthcare provider will check your heart function before and during treatment with Lenvima. Tell your healthcare provider right away if you get any signs or symptoms of heart problems, including shortness of breath, swelling of your ankles, unusual weight gain, chest pain, or feeling faint.
• Problem with blood clots in your blood vessels (arteries). Get emergency medical help right away if you get 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.
• Liver problems. Lenvima may cause liver problems that may lead to liver failure and death. Tell your healthcare provider right away if your skin or the white part of your eyes turns yellow (jaundice), or if you have dark or tea colored urine, light-colored stools, nausea or vomiting, pain in your upper right stomach area, or feel drowsy, confused, or lose consciousness.
• Kidney problems. Kidney failure, which can lead to death, has happened with Lenvima treatment. Tell your healthcare provider if you have changes in the amount or color of your urine, blood in your urine, swelling in your legs or ankles, or loss of appetite.
• Increased protein in your urine (proteinuria). Proteinuria is a common side effect of Lenvima and can be serious. Your healthcare provider should check your urine for protein before and during treatment.
• Diarrhea. Diarrhea is a common side effect of Lenvima and can be serious. Tell your healthcare provider or go to the emergency room if you are unable to drink enough liquids and your diarrhea cannot be controlled.
• 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.
• Changes in the electrical activity of your heart called QTc prolongation. QTc prolongation can cause irregular heartbeats that can cause you to faint and may be life threatening. Your healthcare provider will check the salts (electrolytes) in your blood, including potassium, magnesium, and calcium, and may check your heart with an electrocardiogram (ECG).
• Low levels of blood calcium (hypocalcemia). Your healthcare provider will check your blood calcium levels and may tell you to take a calcium supplement if your levels are low.
• Reversible Posterior Leukoencephalopathy Syndrome (RPLS). Tell your healthcare provider right away if you get new or worsening severe headache, seizures, weakness, confusion, or change in vision.
• Bleeding. Lenvima can cause serious bleeding problems that may lead to death. Tell your healthcare provider right away if you have severe and persistent nose bleeds, vomiting blood, red or black (looks like tar) stools, blood in your urine, coughing up blood or blood clots, or heavy or new onset vaginal bleeding.
• Change in thyroid hormone levels. Your healthcare provider should check your thyroid hormone levels before starting and every month during treatment with Lenvima.
• Wound healing problems. Tell your healthcare provider if you plan to have any surgery before or during treatment with Lenvima.
• Severe jawbone problems (osteonecrosis). Tell your healthcare provider right away if you get jaw pain, toothache, or sores on your gums during treatment with Lenvima.

Your healthcare provider may reduce your dose of Lenvima, delay, or completely stop treatment if you have certain side effects.

Common Lenvima side effects

The most common side effects of Lenvima in adults treated for thyroid cancer include:

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

The most common side effects of Lenvima in adults treated for liver cancer include:

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

The most common side effects of Lenvima in adults treated for kidney cancer in combination with pembrolizumab include:

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

The most common side effects of Lenvima in adults treated for kidney cancer in combination with belzutifan include:

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

The most common side effects of Lenvima in adults treated for kidney cancer in combination with everolimus include:

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

The most common side effects of Lenvima in adults treated for endometrial cancer in combination with pembrolizumab include:

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

These are not all the possible side effects of Lenvima. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose of Lenvima 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 of Lenvima for Renal Cell Carcinoma

First-line treatment of advanced renal cell carcinoma:20 mg orally once a day in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph

Advanced renal cell carcinoma with a clear cell component following a PD-1 or PD-L1 inhibitor:20 mg orally once a day in combination with belzutifan

Advanced renal cell carcinoma 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, belzutifan, and everolimus prescribing information for recommended dosing information for those medicines.-Treatment should be continued until disease progression or unacceptable toxicity.-After completing 2 years of combination therapy with pembrolizumab, this drug may be administered 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 of Lenvima for Hepatocellular Carcinoma

-Actual body weight less than 60 kg: 8 mg orally once a day-Actual body weight 60 kg or greater: 12 mg orally once a day

Comment:-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 of Lenvima for Endometrial Carcinoma

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

Comments:-Refer to the pembrolizumab prescribing information for recommended dosing information.-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

Dose adjustments for severe kidney or liver problems

For patients with severe renal impairment (creatinine clearance less than 30 mL/min) or severe hepatic impairment (Child-Pugh C):-Thyroid cancer (DTC): 14 mg orally once a day-Renal cell carcinoma and endometrial carcinoma: 10 mg orally once a day

If you miss a dose of Lenvima, take it 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.

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

Avoid having invasive dental procedures, if possible, during treatment with Lenvima. Follow your doctor's instructions about any other restrictions on food, beverages, or activity.

Lenvima can cause changes in the electrical activity of your heart (QTc prolongation). Your risk may be higher if you also use other medicines that can affect heart rhythm, including certain medicines for infections, asthma, heart problems, high blood pressure, depression, mental illness, cancer, malaria, or HIV.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you are taking, or have taken, an osteoporosis medicine.

Know the medicines you take. Keep a list of your medicines to show to your healthcare provider and pharmacist when you get a new medicine.

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

Keep Lenvima and all medicines out of the reach of children.

Active ingredient: lenvatinib

Inactive ingredients: calcium carbonate, hydroxypropyl cellulose, low-substituted hydroxypropylcellulose, mannitol, microcrystalline cellulose, and talc.

The capsule shell contains ferric oxide red, ferric oxide yellow, hypromellose, and titanium dioxide. The printing ink contains black iron oxide, potassium hydroxide, propylene glycol and shellac.

Lenvima is distributed by Eisai Inc., Nutley, NJ 07110, and is a registered trademark of Eisai R&D Management Co., Ltd. and is licensed to Eisai Inc. For more information, call 1-877-873-4724 or go to www.LENVIMA.com.