LENVIMA 4 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the User

LENVIMA 4mg hard capsules

LENVIMA 10mg hard capsules

Lenvatinib

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What is LENVIMA and what is it used for
2. What you need to know before you take LENVIMA
3. How to take LENVIMA
4. Possible side effects
5. Storage of LENVIMA
6. Contents of the pack and further information

1. What is LENVIMA and what is it used for

What is LENVIMA

LENVIMA is a medicine that contains the active substance lenvatinib. It is used on its own to treat advanced or progressive thyroid cancer in adults who have not responded to radioactive iodine treatment.

LENVIMA can also be used on its own to treat liver cancer (hepatocellular carcinoma) in adults who have not previously received another anti-cancer treatment that circulates in the bloodstream. Patients take LENVIMA when their liver cancer has spread or cannot be removed by surgery.

LENVIMA can also be used in combination with another anti-cancer treatment called pembrolizumab to treat advanced cancer in the tissue that lines the uterus (endometrial cancer) in adults when the cancer has spread after previous anti-cancer treatment that circulates in the bloodstream and when surgical or radiation treatment is not indicated.

How LENVIMA works

LENVIMA blocks the action of proteins called tyrosine kinase receptors (RTKs) that are involved in the development of new blood vessels that carry 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, LENVIMA can slow down the rate at which cancer cells multiply and tumors grow and help cut off the blood supply that cancer cells need.

2. What you need to know before you take LENVIMA

Do not take LENVIMA:

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

Warnings and precautions

Talk to your doctor before taking LENVIMA if:

• you have high blood pressure;
• you are a woman of childbearing age (see the section below on Contraception, pregnancy and breast-feeding);
• 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 stopping LENVIMA if you are undergoing major surgery, as LENVIMA may affect wound healing. Treatment with LENVIMA can be resumed once adequate wound healing has been determined.
• 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 or between an organ and the skin.
• you have had or have an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in the blood vessel wall.
• you have had or have jaw pain, toothache, or jaw swelling, inflammation or stomatitis, numbness or heaviness in the jaw or loosening of a tooth. You may be advised to have a dental examination before starting LENVIMA, as jawbone damage (osteonecrosis) has been reported in patients treated with LENVIMA. If you need to undergo invasive dental treatment or surgery, inform your dentist that you are being treated with LENVIMA, especially if you are also receiving or have received injections of bisphosphonates (used to treat or prevent bone disorders);
• if you are taking or have taken certain medications used to treat osteoporosis (anti-resorptive medications) or cancer medications that affect blood vessel formation (called angiogenesis inhibitors), as the risk of bone damage may be increased.

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

In case of doubt, consult your doctor before taking LENVIMA.

Conditions to be aware of

During cancer treatment, the breakdown of tumor cells can release substances into the blood, which can lead to a group of complications called tumor lysis syndrome (TLS). This can cause changes in the kidneys and be life-threatening. Your doctor will monitor you and may give you treatment to reduce the risk. Tell your doctor immediately if you experience signs of TLS (see section 4: Possible side effects).

Children and adolescents

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

Using LENVIMA with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes herbal medicines and medicines obtained without a prescription.

Contraception, pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

• In case you can become pregnant, use highly effective contraceptive methods while taking this medicine and for at least one month after finishing treatment. Since it is not known if LENVIMA can reduce the effect of the oral contraceptive pill, if this is your usual contraceptive method, you should also use a barrier method such as a cervical cap or condoms if you have sex during treatment with LENVIMA.
• Do not take LENVIMA if you are planning to become pregnant during treatment, as it may seriously harm your baby.
• If you become pregnant while receiving treatment with LENVIMA, tell your doctor immediately. Your doctor will help you decide if you should continue treatment.
• Do not breast-feed while taking LENVIMA, as the medicine passes into breast milk and may seriously harm your baby.

Driving and using machines

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

3. How to take LENVIMA

Follow exactly the administration instructions of this medicine given 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 24 mg once daily (2 capsules of 10 mg and 1 capsule of 4 mg).
• If you have severe liver or kidney problems, the recommended dose is 14 mg once daily (1 capsule of 10 mg and 1 capsule of 4 mg).
• Your doctor may reduce your dose if you experience problems with side effects.

Liver cancer

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

Uterine cancer

• The recommended dose of LENVIMA is 20 mg once daily (2 capsules of 10 mg) in combination with pembrolizumab. Your doctor will give you pembrolizumab by intravenous infusion, in doses of 200 mg every 3 weeks or 400 mg every 6 weeks.
• Your doctor may reduce the dose if you have problems with side effects.

Taking the medicine

• 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 given orally or through a feeding tube. If the liquid mixture is given through a feeding tube, it must be prepared with water. If the liquid mixture is not used immediately, it must be stored in a closed container and refrigerated at a temperature between 2°C and 8°C for a maximum of 24 hours. Once removed from the refrigerator, shake the liquid mixture for 30 seconds. If it is not used within 24 hours of preparation, the liquid mixture must be discarded. Preparation and administration of the liquid mixture:
• • Place the capsules corresponding to the prescribed dose (up to 5 capsules) whole in a small container (approximately 20 ml capacity) or in an oral syringe (20 ml). Do not crush or break the capsules.
  • Add 3 ml of liquid to the container or oral syringe. Wait 10 minutes until the capsule coating (outer covering) dissolves. Then stir or shake the mixture for 3 minutes until the capsules are completely dissolved.
  • • If the liquid mixture is prepared in an oral syringe, close the syringe, remove 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 2 ml more of liquid to the container or oral syringe with a second syringe or calibrated dropper, stir or shake the liquid mixture, and administer it. Repeat this step at least two times until no visible remnants are left to ensure that all the medicine is administered.
• Take the capsules approximately at the same time every day.

How long to take LENVIMA

You will usually continue taking this medicine while you are still benefiting from it clinically.

If you take more LENVIMA than you should

If you take more LENVIMA than you should, talk to your doctor or pharmacist immediately. Bring the medicine pack with you.

If you forget to take LENVIMA

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

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

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

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

• Feeling of numbness or weakness on one side of the body, severe headache, epileptic seizures, confusion, difficulty speaking, changes in vision or dizziness; these may be signs of a stroke, bleeding in the brain or the effect of a severe increase in blood pressure in the brain.
• Chest pain or pressure, pain in the arms, back, neck or jaw, difficulty breathing, rapid or irregular heartbeats, cough, bluish color on the lips or fingers, feeling of extreme fatigue; these effects may be signs of a heart problem, a blood clot in the lung or air leakage from the lung to the chest that prevents the lung from inflating.
• Severe stomach pain (abdomen); this may be due to a hole in the intestinal wall or a fistula (a hole in the intestine that connects through a tube-like conduit to another part of the body or skin).
• Black, sticky, or bloody stools, or coughing up blood; these may be signs of internal bleeding.
• Yellowish skin or yellowish eyes (jaundice) or numbness, confusion, poor concentration - may be signs of liver problems.
• Diarrhea, feeling of discomfort (nausea and vomiting); these are very frequent adverse effects that can become severe if they cause dehydration, which in turn can cause kidney failure. Your doctor may give you a medicine to reduce these adverse effects.
• Mouth pain, tooth or jaw pain, inflammation or stomatitis, numbness or feeling of heaviness in the jaw or loosening of a tooth. These could be indicative signs of bone damage in the jaw (osteonecrosis).
• Nausea, difficulty breathing, irregular heartbeats, muscle cramps, convulsions, cloudy urine, and fatigue. These symptoms can be complications due to the breakdown products of dying cancer cells, and are known as tumor lysis syndrome (TLS).

Tell your doctor immediately if you suffer from any of the above-mentioned adverse effects.

The following adverse effects may occur when this medicine is administered alone:

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

• High or low blood pressure.
• Weight loss or decreased appetite.
• Feeling of discomfort (nausea and vomiting), constipation, diarrhea, abdominal pain, indigestion.
• Feeling of extreme fatigue or weakness.
• Hoarse voice.
• Swelling of the legs.
• Skin rash.
• Dry, painful, or inflamed mouth, strange taste sensation.
• Pain in the joints or muscles.
• Feeling of dizziness.
• Hair loss.
• Bleeding (most frequently nosebleeds, although other bleeding such as blood in the urine, bruising, bleeding from the gums or intestinal wall).
• Difficulty sleeping.
• Changes in protein levels (high) in urine tests and urinary tract infections (increased frequency of urination and pain when urinating).
• Headache.
• Back pain.
• Redness, pain, and swelling of the skin on the hands and feet (palmar-plantar erythrodysesthesia).
• Underactive thyroid (fatigue, weight gain, constipation, feeling of 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 lead to bruising and difficulty healing wounds.
• Changes in magnesium levels (low), cholesterol levels (high), and thyroid-stimulating hormone levels (high) in blood tests.
• Changes in kidney function test results and kidney failure.
• Increased lipase and amylase values (enzymes involved in digestion).

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

• Loss of body fluids (dehydration).
• Heart palpitations.
• Dry, thickened, and itchy skin.
• Feeling of bloating and having excessive gas in the intestines.
• Heart problems or blood clots in the lungs (difficulty breathing, chest pain) or other organs.
• Liver failure.
• Numbness, confusion, poor concentration, loss of consciousness - may be signs of liver failure.
• Discomfort.
• Inflammation of the gallbladder.
• Stroke.
• Anal fistula (a small channel that forms between the anus and surrounding skin).
• Hole (perforation) in the stomach or intestine.

Uncommon(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).
• Pancreatitis.
• Wound healing problems.
• Bone damage in the jaw (osteonecrosis).
• Colon inflammation (colitis).
• Reduced secretion of hormones produced by the adrenal glands.

Rare(may affect up to 1 in 1,000 patients)

Tumor lysis syndrome (TLS)

Frequency Not Known(the following adverse 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 of the body or between the skin and an underlying structure such as the throat or airways). Symptoms depend on the location of the fistula. Consult your doctor if you experience any new or unusual symptoms such as coughing when swallowing.
• Increased and weakened blood vessel wall or tear in the blood vessel wall (aneurysms and arterial dissections).

The following adverse effects may occur when this medicine is administered 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 when urinating).
• Low platelet count in the blood that can lead to bruising and difficulty healing wounds.
• Low white blood cell count.
• Low red blood cell count.
• Underactive thyroid (fatigue, weight gain, constipation, feeling of cold, dry skin) and changes in thyroid-stimulating hormone levels (high) in blood tests.
• Overactive thyroid (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.
• Feeling of dizziness.
• Headache.
• Back pain.
• Dry, painful, or inflamed mouth, strange taste sensation.
• Bleeding (most frequently nosebleeds, although other bleeding such as blood in the urine, bruising, bleeding from the gums or intestinal wall).
• High blood pressure.
• Hoarse voice.
• Feeling of discomfort (nausea and vomiting), constipation, diarrhea, abdominal pain.
• Increased amylase values (enzyme involved in digestion).
• Increased lipase values (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 (palmar-plantar erythrodysesthesia).
• Skin rash.
• Pain in the joints or muscles.
• Feeling of extreme fatigue or weakness.
• Swelling of the legs.

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

• Loss of body fluids (dehydration).
• Difficulty sleeping.
• Heart palpitations.
• Low blood pressure.
• Blood clots in the lungs (difficulty breathing, chest pain).
• Pancreatitis.
• Feeling of bloating and having excessive gas in the intestines.
• Indigestion.
• Inflammation of the gallbladder.
• Hair loss.
• Kidney failure.
• Discomfort.
• Colon inflammation (colitis).
• Reduced secretion of hormones produced by the adrenal glands.
• Hole (perforation) in the stomach or intestine.

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

• Headache, dizziness, convulsions, and changes in vision.
• Signs of stroke, including feeling of 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 heart problems, including chest pain or pressure, pain in the arms, back, neck or jaw, difficulty breathing, rapid or irregular heartbeats, cough, bluish color on the lips or fingers, and feeling of fatigue.
• Severe difficulty breathing and chest pain caused by air leakage from the lung to the chest cavity that prevents the lungs from inflating.
• Infection or painful irritation near the anus.
• Anal fistula (formation of a small channel that connects the anus to the surrounding skin).
• Liver damage or signs of liver damage, including yellowish skin or eyes (jaundice), or numbness, confusion, and poor concentration.
• Dry, thickened, and itchy skin.
• Wound healing problems.

Reporting of Adverse Effects

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

5. Storage of LENVIMA

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiration date that appears on the box and on each blister after "EXP". The expiration date is the last day of the month indicated.
• Do not store above 25°C. Store in the original blister to protect from moisture.
• Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of LENVIMA

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

• The other ingredients are calcium carbonate, mannitol, microcrystalline cellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, talc. The capsule shell 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 Package Contents

• The 4 mg capsule has a cap and body of yellowish-red color, approximately 14.3 mm in length, with black ink printing "?" on the cap and "LENV 4 mg" on the body.
• The 10 mg capsule has a cap of yellowish-red color and a body of yellow color, approximately 14.3 mm in length, with black ink printing "?" on the cap and "LENV 10 mg" on the body.
• PVC/aluminum/polyamide blisters with a breakable aluminum foil in cardboard boxes of 30, 60, or 90 hard capsules.
• Not all pack sizes may be marketed.

Marketing Authorization Holder

Eisai GmbH

Edmund-Rumpler-Straße 3

60549 Frankfurt am Main

Germany

Email: medinfo_de@eisai.net

Manufacturer

Eisai GmbH

Edmund-Rumpler-Straße 3

60549 Frankfurt am Main

Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.