Prospecto: Information for the User

LENVIMA 4mg Hard Capsules

LENVIMA 10mg Hard Capsules

Lenvatinib

Read this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

1.What is LENVIMA and for what it is used

2.What you need to know before starting to take LENVIMA

3.How to take LENVIMA

4.Possible adverse effects

5.Storage of LENVIMA

6.Contents of the package and additional information

What is LENVIMA

LENVIMA is a medication that contains the active ingredient lenvatinib. It is used alone to treat progressive or advanced thyroid cancer in adults who have failed previous treatment with radioactive iodine.

LENVIMA can also be used alone to treat liver cancer (hepatocellular carcinoma) in adults who have not received previous treatment with another circulating antineoplastic agent.Patients take LENVIMA when their liver cancer has spread or cannot be removed through surgery.

LENVIMA can also be used in combination with another antineoplastic agent called pembrolizumab to treat advanced cancer in the tissue that covers the uterus (endometrial cancer) in adults when the cancer has spread after previous treatment with a circulating antineoplastic agent and when surgical or radiological treatment is not indicated.

How LENVIMA works

LENVIMAblocks the action of proteins called tyrosine kinase receptors (RTK), which are involved in the development of new blood vessels that supply oxygen and nutrients to cells and help them grow. These proteins may be present in large quantities in cancer cells, and by blocking their action,LENVIMAcan slow down the rate at which cancer cells multiply and tumors grow and help cut off the blood supply that cancer cells need.

Do not take LENVIMA:

• if you are allergic to lenvatinib or any of the other ingredients in this medicine (listed in section 6);
• if you are breastfeeding (see the section below on Contraception, Pregnancy and Breastfeeding).

Warnings and Precautions

Consult your doctor before starting to take LENVIMA if:

• you have high blood pressure;
• you are a fertile woman (see the section below on Contraception, Pregnancy and Breastfeeding);
• you have a history of heart problems or stroke;
• you have liver or kidney problems;
• you have recently undergone surgery or radiation therapy;
• you are scheduled to undergo surgery. Your doctor may consider suspending LENVIMA if you undergo major surgery, as LENVIMA may affect wound healing. LENVIMA treatment can be resumed once wound healing is deemed adequate.
• you are over 75 years old;
• you are not of white or Asian race;
• you weigh less than 60 kg;
• you have a history of abnormal connections (known as fistulas) between different organs of the body or between an organ and the skin.
• you have or have had an aneurysm (enlargement and weakening of the wall of a blood vessel) or a tear in the wall of a blood vessel.
• you have or have had mouth pain, tooth pain or jaw pain, inflammation or stomatitis, numbness or heaviness in the jaw or loosening of a tooth. You may be advised to undergo a dental examination before starting LENVIMA, as osteonecrosis of the jaw (bone death) has been reported in patients treated with LENVIMA. If you need to undergo invasive dental treatment or oral surgery, inform your dentist that you are being treated with LENVIMA, particularly if you are also receiving or have received bisphosphonate injections (used to treat or prevent bone disorders);
• if you are taking or have taken some medications used to treat osteoporosis (bone-thinning medications) or medications used to treat cancer that affect blood vessel formation (known as angiogenesis inhibitors), as this may increase the risk of bone damage.

Before starting to take LENVIMA, your doctor may perform some tests, for example, to check your blood pressure and liver or kidney function, and to check if you have low sodium levels and high thyroid-stimulating hormone levels in your blood. Your doctor will discuss the results of these tests with you and decide if you can take LENVIMA. You may need to receive additional treatment with other medications, reduce the dose of LENVIMA, or take extra precautions due to an increased risk of side effects.

Consult your doctor before taking LENVIMA if you are unsure.

Children and Adolescents

LENVIMA is not recommended for use in children and adolescents under 18 years of age.

Use of LENVIMA with other Medicines

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication. This includes herbal medicines and medicines obtained without a prescription.

Contraception, Pregnancy and Breastfeeding

Consult your doctor or pharmacist if you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant.

• Use highly effective contraceptive methods while taking this medicine and for at least one month after completing treatment. Since LENVIMA may reduce the effectiveness of oral contraceptives, if this is your usual method of contraception, you should also use a barrier method such as a cervical cap or condoms if you have sex during LENVIMA treatment.
• Do not take LENVIMA if you are planning to become pregnant during treatment, as it may severely harm your baby.
• If you become pregnant while receiving LENVIMA treatment, inform your doctor immediately. Your doctor will help you decide whether to continue treatment.
• Do not breastfeed while taking LENVIMA, as the medicine passes into breast milk and may severely harm your baby.

Driving and Operating Machines

LENVIMA may cause side effects that may affect your ability to drive or operate machines. Avoid driving or operating machines if you feel dizzy or tired.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

How much to take

Thyroid cancer

• The recommended dose of LENVIMA is usually 24mg once a day
  (2capsules of 10mg and 1capsule of 4mg).
• If you have severe liver or kidney problems, the recommended dose is 14mg once a day
  (1capsule of 10mg and 1capsule of 4mg).
• Your doctor may reduce your dose if you experience any side effects.

Liver cancer

• The recommended dose of LENVIMA depends on your body weight at the start of treatment. The usual dose is 12mg once a day (3capsules of 4mg) if you weigh 60kg or more and 8mg once a day (2capsules of 4mg) if you weigh less than 60kg.
• Your doctor may reduce your dose if you have problems with side effects.

Uterine cancer

• The recommended dose of LENVIMA is 20mg once a day (2capsules of 10mg) in combination with pembrolizumab. Your doctor will administer pembrolizumab intravenously, in doses of 200mg every 3weeks or 400mg every 6weeks.
• Your doctor may reduce your dose if you have problems with side effects.

Medication intake

• You can take the capsules with or without food.
• Do not open the capsules to avoid exposure to their contents.
• Swallow the capsules whole with water. If you cannot swallow the capsules whole, prepare a liquid mixture with water, apple juice, or milk. The liquid mixture can be administered orally or through a feeding tube. If administered through a feeding tube, the liquid mixture must be prepared with water. If the liquid mixture is not used at the time of preparation, it must be stored in a covered container and refrigerated at a temperature between2°C and 8°C for a maximum of 24hours. Once removed from the refrigerator, shake the liquid mixture for 30seconds. If not used within 24hours from preparation, the liquid mixture must be discarded.
  Preparation and administration of the liquid mixture:
• • Place the corresponding capsules for the prescribed dose (up to 5capsules) whole in a small container (approximately20ml in capacity) or in an oral syringe(20ml). Do not break or crush the capsules.
  • Add 3ml of liquid to the container or oral syringe. Wait 10minutes until the capsule coating (outer covering) dissolves. Then, remove or shake the mixture for 3minutes until the capsules havecompletely dissolved.
  • • If the liquid mixture is prepared in an oral syringe, cover the syringe, pull back the plunger, and use a second syringe or a calibrated dropper to add the liquid to the first syringe. Replace the plunger before shaking.
  • Drink the liquid from the container or use an oral syringe to administer it directly to the mouth or through a feeding tube.
  • Then, add 2ml more of liquid to the container or oral syringewith a second syringe or with the dropper,shakethe liquid mixture and administer it. Repeat this step at least twice to ensure that all the medication is administered.
• Take the capsules approximately at the same time every day.

For how long should you take LENVIMA

You will usually continue taking this medication as long as you continue to receive clinical benefits.

If you take more LENVIMA than you should

If you take more LENVIMA than you should, consult your doctor or pharmacist immediately. Bring the medication packaging with you.

If you forget to take LENVIMA

Do not take a double dose (two doses at the same time) to make up for the missed doses.

The schedule you should follow if you forget to take a dose will depend on how much time is left until your next dose.

• If there are 12hours or more until your next dose, take the missed dose as soon as you remember. Then take the next dose at the usual time.
• If there are less than 12hours until your next dose, omit the missed dose. Then take the next dose at the usual time.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Inform your doctor immediately if you experience any of the following side effects, you may need urgent medical attention:

• Numbness or weakness on one side of the body, severe headache, seizures, confusion, difficulty speaking, changes in vision or dizziness; these may be signs of a stroke, brain hemorrhage, or severe increase in blood pressure in the brain.
• Chest pain or pressure, arm, back, neck, or jaw pain, difficulty breathing, rapid or irregular heartbeat, cough, blue lips or fingers, feeling extremely tired; these effects may be signs of a heart problem, blood clot in the lung, or air leakage from the lung into the chest that prevents the lung from inflating.
• Severe stomach pain; this may be due to a hole in the intestinal wall or a fistula (an opening in the intestine that connects to another part of the body or skin through a tube-like structure).
• Black, sticky, or bloody stools, or coughing up blood; these may be signs of internal bleeding.
• Yellow or white skin, yellowish eyes (jaundice), or numbness, confusion, poor concentration – may be signs of liver problems.
• Diarrhea, feeling unwell (nausea and vomiting); these are very common side effects that can become severe if they cause dehydration, which in turn can cause kidney failure. Your doctor may give you a medication to reduce these side effects.
• Mouth, tooth, or jaw pain, inflammation, or stomatitis, numbness, or feeling heavy in the jaw, or loose teeth. These may be signs of jaw bone damage (osteonecrosis).

Inform your doctor immediately if you experience any of the side effects mentioned above.

The following side effects may occur when this medicine is taken alone:

Very common(may affect more than 1 in 10 people):

• High or low blood pressure.
• Weight loss or decreased appetite.
• Feeling unwell (nausea and vomiting), constipation, diarrhea, abdominal pain, indigestion.
• Feeling extremely tired or weak.
• Hoarse voice.
• Swelling of the legs.
• Rash on the skin.
• Dry, painful, or inflamed mouth, strange taste sensation.
• Joint or muscle pain.
• Dizziness.
• Hair loss.
• Bleeding (more often nosebleeds, but also other types of bleeding such as blood in the urine, bruises, gum bleeding, or intestinal wall bleeding).
• Difficulty sleeping.
• Changes in protein levels (high) in urine tests and urinary tract infections (increased frequency of urination and pain while urinating).
• Headache.
• Back pain.
• Redness, pain, and swelling of the skin on the hands and feet (erythromelalgia).
• Hypothyroidism (fatigue, weight gain, constipation, feeling cold, dry skin).
• Changes in potassium levels (low) and calcium levels (low) in blood tests.
• Low white blood cell count.
• Changes in liver function test results.
• Low platelet count in the blood that can cause bruises and difficulty healing wounds.
• Changes in blood test results for magnesium (low), cholesterol (high), and thyroid-stimulating hormone (high).
• Changes in kidney function test results and kidney failure.
• Increased levels of lipase and amylase (enzymes involved in digestion).

Common(may affect up to 1 in 10 people):

• Fluid loss (dehydration).
• Palpitations.
• Dry, thickened, and itchy skin.
• Feeling bloated and having excessive gas in the intestines.
• Cardiac problems or blood clots in the lungs (difficulty breathing, chest pain) or other organs.
• Liver failure
• Adormecimiento, confusión, concentración deficiente, pérdida de consciencia - pueden ser signos de insuficiencia hepática
• Feeling unwell.
• Inflammation of the gallbladder.
• Stroke.
• Fistula anal (a small channel that forms between the anus and the surrounding skin).
• Perforation (hole) in the stomach or intestine.

Rare(may affect up to 1 in 100 people):

• Infection or painful irritation near the anus.
• Transient ischemic attack.
• Liver damage.
• Severe pain in the upper left part of the stomach (abdomen) that may be associated with fever, chills, nausea, and vomiting (splenic infarction)
• Inflammation of the pancreas.
• Wound healing problems.
• Jaw bone damage (osteonecrosis).
• Inflammation of the colon (colitis).
• Reduction of hormone production by the adrenal glands.

Unknown frequency(the following side effects have been reported since the marketing of LENVIMA, but the frequency with which they occur is unknown):

• Other types of fistulas (an abnormal connection between different organs in the body or between the skin and a underlying structure such as the throat or airways). Symptoms depend on the location of the fistula.Consult your doctorif you experience any new or unusual symptoms such as difficulty swallowing.
• Increased and weakened wall of a blood vessel or tearing of the wall of a blood vessel (aneurysms and arterial dissections).

The following side effects may occur when this medicine is taken in combination with pembrolizumab:

Very common(may affect more than 1 in 10 people):

• Changes in protein levels (high) in urine tests and urinary tract infections (increased frequency of urination and pain while urinating).
• Low platelet count in the blood that can cause bruises and difficulty healing wounds.
• Low white blood cell count.
• Low red blood cell count.
• Hypothyroidism (fatigue, weight gain, constipation, feeling cold, dry skin) and changes in thyroid-stimulating hormone levels (high) in blood tests.
• Hyperthyroidism (symptoms may include rapid heartbeat, sweating, and weight loss).
• Changes in calcium levels (low) in blood tests.
• Changes in potassium levels (low) in blood tests.
• Changes in cholesterol levels (high) in blood tests.
• Changes in magnesium levels (low) in blood tests.
• Weight loss or decreased appetite.
• Dizziness.
• Headache.
• Back pain.
• Dry, painful, or inflamed mouth, strange taste sensation.
• Bleeding (more often nosebleeds, but also other types of bleeding such as blood in the urine, bruises, gum bleeding, or intestinal wall bleeding).
• Hypertension.
• Hoarse voice.
• Feeling unwell (nausea and vomiting), constipation, diarrhea, abdominal pain.
• Increased levels of amylase (enzyme involved in digestion).
• Increased levels of lipase (enzyme involved in digestion).
• Changes in liver function test results.
• Changes in kidney function test results.
• Redness, pain, and swelling of the skin on the hands and feet (erythromelalgia).
• Rash on the skin.
• Joint or muscle pain.
• Feeling extremely tired or weak.
• Swelling of the legs.

Common(may affect up to 1 in 10 people):

• Fluid loss (dehydration).
• Difficulty sleeping.
• Palpitations.
• Hypotension.
• Blood clots in the lungs (difficulty breathing, chest pain).
• Inflammation of the pancreas.
• Feeling bloated and having excessive gas in the intestines.
• Indigestion.
• Inflammation of the gallbladder.
• Hair loss.
• Kidney failure.
• Feeling unwell.
• Inflammation of the colon (colitis).
• Reduction of hormone production by the adrenal glands.
• Perforation (hole) in the stomach or intestine.

Rare(may affect up to 1 in 100 people):

• Headache, dizziness, convulsions, and changes in vision.
• Signs of stroke, including numbness or weakness on one side of the body, severe headache, convulsions, dizziness, difficulty speaking, changes in vision, or dizziness.
• Transient ischemic attack.
• Signs of cardiac problem, including chest pain or pressure, arm, back, neck, or jaw pain, difficulty breathing, rapid or irregular heartbeat, cough, blue lips or fingers, and feeling tired.
• Difficulty breathing and chest pain caused by air leakage from the lung into the chest cavity that prevents the lung from inflating.
• Infection or painful irritation near the anus.
• Fistula anal (formation of a small channel that connects the anus to the surrounding skin).
• Liver damage or signs of liver damage, including yellowish skin or white of the eyes (jaundice), orsleepiness, confusion, and poor concentration.
• Dry, thickened, and itchy skin.
• Wound healing problems.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendixV.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the box and on each blister after “CAD”. The expiration date is the last day of the month indicated.
• Do not store at a temperature above 25°C. Store in the original blister to protect it from moisture.
• Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of LENVIMA

• The active ingredient is lenvatinib.
• • LENVIMA 4mg hard capsules: each hard capsule contains 4mg of lenvatinib (as mesylate).
  • LENVIMA 10mg hard capsules: each hard capsule contains 10mg of lenvatinib (as mesylate).

• The other components are calcium carbonate, mannitol, microcrystalline cellulose, hydroxypropyl cellulose, hydroxypropyl cellulose partially substituted, talc. The capsule coating contains hypromellose, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172). The printing ink contains shellac, black iron oxide (E172), potassium hydroxide, propylene glycol.

Appearance of the product and contents of the pack

• The 4mg capsule has a red-yellow cap and a yellow body, approximately 14.3mm in length, with black ink inscription “?” on the cap and “LENV 4mg” on the body.
• The 10mg capsule has a red-yellow cap and a yellow body, approximately 14.3mm in length, with black ink inscription “?” on the cap and “LENV 10mg” on the body.
• PVC/aluminium/polyamide blisters with an aluminium foil that breaks when pressed, in cartons of 30, 60 or 90hard capsules.
• Only some pack sizes may be marketed.

Marketing authorisation holder

Eisai GmbH

Edmund-Rumpler-Straße 3

60549 Frankfurt am Main

Germany

Email: [email protected]

Responsible person for the manufacture

Eisai GmbH

Edmund-Rumpler-Straße 3

60549 Frankfurt am Main

Germany

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Date of the last revision of this leaflet

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu.