Lenvima (lenvatinib)

Lenvima is a prescription medicine that is used to treat certain kinds of cancer.

• Lenvima is used by itself to treat differentiated thyroid cancer (DTC), a type of thyroid cancer that can no longer be treated with radioactive iodine and is progressing.
• Lenvima is used along with another medicine called everolimus to treat advanced renal cell carcinoma (RCC), a type of kidney cancer, after one course of treatment with another anticancer medicine.
• 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 along with another medicine called pembrolizumab to treat advanced endometrial carcinoma, a type of uterine cancer:
  • that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), and
  • that has progressed after treatment with anti-cancer medicine, and
  • that cannot be treated with surgery or radiation.

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

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. Your healthcare provider should check your blood pressure regularly during treatment with Lenvima. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure.
• heart problems. Lenvima can cause serious heart problems that may lead to death. Call your healthcare provider right away if you get symptoms of heart problems, such as shortness of breath or swelling of your ankles.
• problem with blood clots in your blood vessels (arteries). Get emergency medical help right away if you get any of the following symptoms:
  • 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. Lenvima may cause liver problems that may lead to liver failure and death. Your healthcare provider will check your liver function before and during treatment with Lenvima. Tell your healthcare provider right away if you have any of the following symptoms:
  • your skin or the white part of your eyes turns yellow (jaundice)
  • dark “tea colored” urine
  • light-colored bowel movements (stools)
  • feeling drowsy, confused or loss of consciousness
• kidney problems. Kidney failure, which can lead to death, has happened with Lenvima treatment. Your healthcare provider should do regular blood tests to check your kidneys.
• 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 your treatment with Lenvima.
• diarrhea. Diarrhea is a common side effect of Lenvima and can be serious. If you get diarrhea, ask your healthcare provider about what medicines you can take to treat your diarrhea. It is important to drink more water when you get diarrhea. Tell your healthcare provider or go to the emergency room, if you are unable to drink enough liquids and your diarrhea is not able to be controlled.
• an opening in the wall of your stomach or intestines (perforation) or an abnormalconnection between two or more body parts (fistula). Get emergency medical help right away if you have severe stomach (abdomen) pain.
• changes in the electrical activity of your heart called QT prolongation. QT prolongation can cause irregular heartbeats that can be life threatening. Your healthcare provider will do blood tests before and during your treatment with Lenvima to check the levels of potassium, magnesium, and calcium in your blood, and may check the electrical activity of your heart with an ECG.
• low levels of blood calcium (hypocalcemia). Your healthcare provider will check your blood calcium levels during treatment with Lenvima and may tell you to take a calcium supplement if your calcium levels are low.
• a condition called Reversible Posterior Leukoencephalopathy Syndrome (RPLS). Call your healthcare provider right away if you get severe headache, seizures, weakness, confusion, or blindness or change in vision.
• bleeding. Lenvima may cause serious bleeding problems that may lead to death. Tell your healthcare provider if you have any signs or symptoms of bleeding during treatment with Lenvima, including:
  • severe and persistent nose bleeds
  • vomiting blood
  • red or black (looks like tar) stools
  • blood in your urine
  • coughing up blood or blood clots
  • 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. Wound healing problems have happened in some people who take Lenvima. Tell your healthcare provider if you plan to have any surgery before or during treatment with Lenvima.
  • You should stop taking Lenvima at least 1 week before planned surgery.
  • Your healthcare provider should tell you when you may start taking Lenvima again after surgery.

The most common side effects of Lenvima in people 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 (abdomen) pain
• hoarseness

The most common side effects of Lenvima in people treated for kidney cancer include:

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

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

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

The most common side effects of Lenvima when given with pembrolizumab in peopletreated for uterine cancer include:

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

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

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 1-800FDA-1088.

Important Dosage Information

• Reduce the dose for certain patients with renal or hepatic impairment.
• Take Lenvima 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 Lenvima is 24 mg orally once daily until disease progression or until unacceptable toxicity.

Recommended Dosage For Renal Cell Carcinoma (RCC)

• The recommended dosage of Lenvima is 18 mg in combination with 5 mg everolimus orally once daily until disease progression or until unacceptable toxicity.
• Refer to everolimus prescribing information for recommended everolimus dosing information.

Recommended Dosage For Hepatocellular Carcinoma (HCC)

The recommended dosage of Lenvima 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.

Take Lenvima orally once daily until disease progression or until unacceptable toxicity.

Recommended Dosage For Endometrial Carcinoma

• The recommended dosage of Lenvima 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.
• Refer to the pembrolizumab prescribing information for recommended pembrolizumab dosing information.

Dosage Modifications For Adverse Reactions

Recommendations for Lenvima dose interruption, reduction and discontinuation for adverse reactions are listed in Table 1. Table 2 lists the recommended dosage reductions of Lenvima for adverse reactions.

Table 1: Recommended Dosage Modifications for Lenvima for Adverse Reactions

Table 2: Recommended Dosage Reductions of Lenvima for Adverse Reactions

When administering Lenvima in combination with everolimus for the treatment of renal cell carcinoma, reduce the Lenvima dose first and then the everolimus dose for adverse reactions of both Lenvima and everolimus. Refer to the everolimus prescribing information for additional dose modification information.

When administering Lenvima in combination with pembrolizumab for the treatment of endometrial carcinoma, interrupt one or both drugs or dose reduce Lenvima as appropriate. No dose reductions are recommended for pembrolizumab. Withhold or discontinue pembrolizumab in accordance with the instructions in the pembrolizumab prescribing information.

Dosage Modifications For Severe Renal Impairment

The recommended dosage of Lenvima for patients with DTC, RCC, or endometrial carcinoma and severe renal impairment (creatinine clearance less than 30 mL/min calculated by Cockcroft-Gault equation using actual body weight) is:

• Differentiated thyroid cancer: 14 mg orally once daily
• Renal cell carcinoma: 10 mg orally once daily
• Endometrial carcinoma: 10 mg orally once daily

Dosage Modifications For Severe Hepatic Impairment

The recommended dosage of Lenvima for patients with DTC, RCC, or endometrial carcinoma and severe hepatic impairment (Child-Pugh C) is:

• Differentiated thyroid cancer: 14 mg taken orally once daily
• Renal cell carcinoma: 10 mg taken orally once daily
• Endometrial carcinoma: 10 mg orally once daily

Preparation And Administration

• Lenvima capsules can be swallowed whole or dissolved in a small glass of liquid.
• To dissolve in liquid, put capsules into 1 tablespoon of water or apple juice without breaking or crushing the capsules.
• Leave the capsules in the water or apple juice for at least 10 minutes. Stir for at least 3 minutes.
• After drinking the mixture, add 1 tablespoon of water or apple juice to the glass, swirl the contents a few times and swallow the water or apple juice.

Drugs That Prolong The QT Interval

• Lenvima has been reported to prolong the QT/QTc interval.
• Avoid coadministration of Lenvima with medicinal products with a known potential to prolong the QT/QTc interval.

• Based on its mechanism of action and data from animal reproduction studies, Lenvima can cause fetal harm when administered to a pregnant woman.
• It is not known whether Lenvima is present in human milk; however, lenvatinib and its metabolites are excreted in rat milk at concentrations higher than those in maternal plasma.
• Because of the potential for serious adverse reactions in breastfed infants, advise women to discontinue breastfeeding during treatment with Lenvima and for at least 1 week after the last dose.