Lenvima 10 mg hard capsules

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

LENVIMA 4 mg hard capsules

LENVIMA 10 mg hard capsules

Lenvatinib

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

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

Contents of the leaflet:

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

1. What LENVIMA is and what it is used for

What LENVIMA is

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

LENVIMA may also be used alone to treat liver cancer (hepatocellular carcinoma) in adults who have not previously received systemic anticancer therapy. Patients take LENVIMA when their liver cancer has spread or cannot be removed by surgery.

LENVIMA may also be used in combination with another anticancer treatment called pembrolizumab to treat advanced cancer in the tissue lining the uterus (endometrial cancer) in adults when the cancer has spread after prior systemic anticancer therapy and when surgery or radiotherapy are not suitable options.

How LENVIMA works

LENVIMA blocks the action of proteins called tyrosine kinase receptors (TKRs), which 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 high amounts in cancer cells, and by blocking their activity, 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 taking LENVIMA

Do not take LENVIMA:

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

Warnings and precautions

Talk to your doctor before starting LENVIMA if:

• you have high blood pressure;
• you are a woman of childbearing potential (see the section below on Contraception, pregnancy and lactation);
• you have a history of heart problems or stroke;
• you have liver or kidney problems;
• you have recently undergone surgery or radiotherapy;
• you are scheduled for surgery. Your doctor may consider temporarily stopping LENVIMA, as it may affect wound healing. Treatment with LENVIMA may be resumed once adequate wound healing has been confirmed.
• you are over 75 years of age;
• 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 in the body or between an organ and the skin;
• you have or have had an aneurysm (a bulge and weakening in the wall of a blood vessel) or a tear in the wall of a blood vessel;
• you have or have had mouth, tooth, or jaw pain, inflammation or stomatitis, numbness or heaviness in the jaw, or loose teeth. You may be advised to have a dental examination before starting LENVIMA, as jaw bone damage (osteonecrosis) has been reported in patients treated with LENVIMA. If you need to undergo invasive dental procedures or dental surgery, inform your dentist that you are being treated with LENVIMA, especially if you are also receiving or have received bisphosphonate injections (used to treat or prevent bone disorders);
• if you are receiving or have received certain medications used to treat osteoporosis (anti-resorptive agents) or cancer treatments that affect blood vessel formation (called angiogenesis inhibitors), as the risk of bone damage may be increased.

Before starting LENVIMA, your doctor may perform tests, for example to monitor your blood pressure and liver or kidney function, and to check for low blood salt levels and high levels of thyroid-stimulating hormone in the blood. Your doctor will discuss the results of these tests with you and decide whether you can receive LENVIMA. You may need additional treatment with other medicines, a reduced dose of LENVIMA, or extra monitoring due to an increased risk of adverse effects.

If you are in any doubt, consult your doctor before taking LENVIMA.

Conditions to pay attention to

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

Children and adolescents

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

Use of LENVIMA with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This includes herbal medicines and over-the-counter medicines.

Contraception, pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

• If you are able to become pregnant, use highly effective contraceptive methods while taking this medicine and for at least one month after stopping treatment. Since it is not known whether LENVIMA may reduce the effectiveness of oral contraceptive pills, if this is your usual method of contraception, you must also use a barrier method such as a cervical cap or condoms if you have sexual intercourse 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 LENVIMA, 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 seriously harm your baby.

Driving and using machines

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

3. How to take LENVIMA

Follow exactly the instructions for using this medicine as given by your doctor. If you are unsure, consult your doctor or pharmacist again.

How much to take

Thyroid cancer

• The recommended dose of LENVIMA is normally 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 any problems with side effects.

Liver cancer

• The recommended dose of LENVIMA depends on body weight at the start of treatment. The usual dose is 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 administer pembrolizumab intravenously, at a dose 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.

How to take the medicine

• You may 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 using water, apple juice, or milk. The liquid mixture may be administered orally or through a feeding tube. If administered via a feeding tube, the liquid mixture must be prepared with water. If the liquid mixture is not used immediately after preparation, it should be stored in a covered container and refrigerated at a temperature between 2 °C and 8 °C for up to 24 hours. After removal from the refrigerator, shake the liquid mixture for 30 seconds. If 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 into a small container (approximately 20 ml capacity) or into an oral syringe (20 ml). Do not break or crush the capsules.
• Add 3 ml of liquid to the container or oral syringe. Wait 10 minutes until the capsule coating (outer layer) dissolves. Then stir or shake the mixture for 3 minutes until the capsules have completely dissolved.
  • If the liquid mixture is prepared in an oral syringe, cap the syringe, pull out 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 into the mouth or through a feeding tube.
• Then add an additional 2 ml of liquid to the container or oral syringe using a second syringe or dropper, stir or shake the mixture, and administer it. Repeat this step at least twice until no visible residue remains, to ensure that all the medicine is administered.

• Take the capsules at approximately the same time each day.

How long to take LENVIMA

You will generally continue taking this medicine for as long as you continue to obtain clinical benefit.

If you take more LENVIMA than you should

If you take more LENVIMA than you should, contact your doctor or pharmacist immediately. Take the medicine 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 missed doses.

The instructions you should follow if you forget a dose depend on how much time remains until your next dose.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everybody will experience them.

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

• 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 affecting the brain.
• Chest pain or pressure, pain in the arms, back, neck, or jaw, difficulty breathing, rapid or irregular heartbeat, cough, bluish color of the lips or fingers, or extreme tiredness; these effects may indicate a heart problem, a blood clot in the lung, or a leak of air from the lung into the chest cavity, preventing the lung from inflating properly.
• Severe stomach (abdominal) pain; this may be due to a perforation in the intestinal wall or a fistula (an abnormal connection between the intestine and another part of the body or the skin via a tube-like passage).
• Black, tarry, or bloody stools, or coughing up blood; these may be signs of internal bleeding.
• Yellowing of the skin or yellowing of the whites of the eyes (jaundice), or numbness, confusion, poor concentration – these may be signs of liver problems.
• Diarrhea, feeling unwell (nausea and vomiting); these are very common adverse effects which may become serious if they lead to dehydration, which in turn may cause kidney failure. Your doctor may prescribe a medicine to reduce these adverse effects.
• Mouth, tooth, or jaw pain, swelling or stomatitis, numbness or heaviness in the jaw, or loose teeth. These could be signs of bone damage in the jaw (osteonecrosis).
• Nausea, difficulty breathing, irregular heartbeat, muscle cramps, seizures, cloudy urine, and fatigue. These symptoms may be complications due to breakdown products from dying cancer cells, known as tumor lysis syndrome (TLS).

Contact your doctor immediately if you experience any of the adverse effects listed above.

The following adverse effects may occur when this medicine is used 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.
• Extreme tiredness or weakness.
• Hoarseness.
• Swelling of the legs.
• Skin rash.
• Dry, sore, or inflamed mouth, altered taste sensation.
• Joint or muscle pain.
• Dizziness.
• Hair loss.
• Bleeding (most commonly nosebleeds, but also other types such as blood in the urine, bruising, bleeding from the gums, or bleeding from the intestinal wall).
• Difficulty sleeping.
• Changes in protein levels (elevated) 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 cold, dry skin).
• Changes in blood test results showing low potassium and low calcium levels.
• Low white blood cell count.
• Changes in blood test results indicating liver function abnormalities.
• Low platelet count in the blood, which may lead to bruising and impaired wound healing.
• Changes in blood test results showing low magnesium, high cholesterol, and high thyroid-stimulating hormone levels.
• Changes in blood test results indicating kidney function abnormalities and kidney failure.
• Increased levels of lipase and amylase (enzymes involved in digestion).

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

• Loss of body fluids (dehydration).
• Heart palpitations.
• Dry skin, skin thickening, and itching.
• Feeling bloated and 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 – these may be signs of liver failure.
• Malaise.
• Inflammation of the gallbladder.
• Stroke.
• Anal fistula (a small channel forming between the anus and surrounding skin).
• Hole (perforation) in the stomach or intestine.

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

• Painful infection or irritation near the anus.
• Transient ischaemic attack.
• Liver injury.
• Severe pain in the upper left part of the abdomen, possibly accompanied by fever, chills, nausea, and vomiting (splenic infarction).
• Inflammation of the pancreas.
• Impaired wound healing.
• Bone damage in the jaw (osteonecrosis).
• Inflammation of the colon (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 LENVIMA was marketed, but their frequency is unknown):

• Other types of fistulas (an abnormal connection between different organs in 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.
• Enlargement and weakening of a blood vessel wall or a tear in the blood vessel wall (aneurysms and arterial dissections).

The following adverse effects may occur when this medicine is used in combination with pembrolizumab:

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

• Changes in protein levels (elevated) in urine tests and urinary tract infections (increased frequency of urination and pain when urinating).
• Low platelet count in the blood, which may lead to bruising and impaired wound healing.
• Low white blood cell count.
• Low red blood cell count.
• Underactive thyroid (fatigue, weight gain, constipation, feeling cold, dry skin) and changes in blood test results showing elevated thyroid-stimulating hormone levels.
• Overactive thyroid (symptoms may include rapid heartbeat, sweating, and weight loss).
• Changes in blood test results showing low calcium levels.
• Changes in blood test results showing low potassium levels.
• Changes in blood test results showing high cholesterol levels.
• Changes in blood test results showing low magnesium levels.
• Weight loss or decreased appetite.
• Dizziness.
• Headache.
• Back pain.
• Dry, sore, or inflamed mouth, altered taste sensation.
• Bleeding (most commonly nosebleeds, but also other types such as blood in the urine, bruising, bleeding from the gums, or bleeding from the intestinal wall).
• High blood pressure.
• Hoarseness.
• Feeling unwell (nausea and vomiting), constipation, diarrhea, abdominal pain.
• Increased amylase levels (an enzyme involved in digestion).
• Increased lipase levels (an enzyme involved in digestion).
• Changes in blood test results indicating liver function abnormalities.
• Changes in blood test results indicating kidney function abnormalities.
• Redness, pain, and swelling of the skin on the hands and feet (palmar-plantar erythrodysesthesia).
• Skin rash.
• Joint or muscle pain.
• Extreme tiredness or weakness.
• Swelling of the legs.

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

• Loss of body fluids (dehydration).
• Sleep disturbances.
• Heart palpitations.
• Low blood pressure.
• Blood clots in the lungs (difficulty breathing, chest pain).
• Inflammation of the pancreas.
• Feeling bloated and excessive gas in the intestines.
• Indigestion.
• Inflammation of the gallbladder.
• Hair loss.
• Kidney failure.
• Malaise.
• Inflammation of the colon (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, seizures, and changes in vision.
• Signs of stroke, including tingling or weakness on one side of the body, severe headache, seizures, dizziness, difficulty speaking, changes in vision, or dizziness.
• Transient ischaemic attack.
• Signs of heart problems, including chest pain or pressure, pain in the arms, back, neck, or jaw, difficulty breathing, rapid or irregular heartbeat, cough, bluish discoloration of the lips or fingers, and feeling tired.
• Severe difficulty breathing and chest pain caused by air leaking from the lung into the chest cavity, preventing the lungs from inflating.
• Painful infection or irritation near the anus.
• Anal fistula (formation of a small channel connecting the anus to the surrounding skin).
• Liver injury or signs of liver damage, including yellowing of the skin or whites of the eyes (jaundice), drowsiness, confusion, and poor concentration.
• Dry skin, skin thickening, and itching.
• Impaired wound healing.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide 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 expiry date which is stated on the carton and on each blister pack after “EXP”. The expiry date refers to the last day of the month indicated.
• Do not store above 25 °C. Store in the original blister pack to protect from moisture.
• Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This helps protect the environment.

6. Contents of the pack and other information

Composition of LENVIMA

• The active substance 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 components 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 contents of the pack

• The 4 mg capsule has a yellowish-red cap and body, approximately 14.3 mm in length, with the imprint in black ink “?” on the cap and “LENV 4 mg” on the body.
• The 10 mg capsule has a yellowish-red cap and yellow body, approximately 14.3 mm in length, with the imprint in black ink “?” on the cap and “LENV 10 mg” on the body.
• PVC/aluminum/polyamide blisters with an aluminum breakable foil, in cardboard boxes containing 30, 60 or 90 hard capsules.
• Only some pack sizes may be marketed.

Marketing Authorization Holder

Eisai GmbH

Edmund-Rumpler-Straße 3

60549 Frankfurt am Main

Germany

E-mail: [email protected]

Manufacturer

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 authorization holder:

Date of the most recent review of this leaflet

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