LENVIMA 4 mg Hard Capsules

Зміст інструкції

1. LENVIMA 4 mg hard capsules, 10 mg hard capsules
   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. How to store LENVIMA
   6. Package contents and other information

LENVIMA 4 mg hard capsules, 10 mg hard capsules

Lenvatinib

Read this leaflet carefully before you start taking this medicine as it contains
important information for you.

• Keep this leaflet. 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

• 1. What LENVIMA is and what it is used for
• 2. What you need to know before you take 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 is LENVIMA and what is it used for

What is LENVIMA
LENVIMA is a medicine that contains the active substance lenvatinib. It is used for the treatment of progressive or advanced thyroid cancer in adults, when treatment with radioactive iodine has not been helpful in stopping the disease.
LENVIMA can also be used alone for the treatment of liver cancer (hepatocellular carcinoma)in adults who have not previously been treated with another anticancer medicine that spreads through the bloodstream. LENVIMA is administered when the patient's liver cancer has spread or cannot be removed by surgery.
LENVIMA can also be used together with another anticancer medicine called pembrolizumab for the treatment of advanced cancer of the uterine lining (endometrial carcinoma) in adult women whose cancer has spread after being previously treated with another anticancer medicine that spreads through the bloodstream or cannot be removed by surgery or radiotherapy.

How LENVIMA works
LENVIMA blocks the action of proteins called tyrosine kinase receptors (RTK), involved in the development of new blood vessels that supply oxygen and nutrients to cells, helping them to grow. These proteins may be present in high quantities in cancer cells.
By blocking their action, LENVIMA can then slow down the rate of cancer cell multiplication and tumor growth and help to interrupt the blood supply that the tumor needs.

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 breastfeeding (see section “Contraception, pregnancy and breastfeeding”).

Warnings and precautions
Talk to your doctor before taking LENVIMA

• if you have high blood pressure
• if you are a woman who could become pregnant (see section “Contraception, pregnancy and breastfeeding”)
• if you have had heart problems or stroke in the past
• if you have problems with your liver or kidneys
• if you have recently had surgery or radiotherapy
• if you are going to have surgery. If you are going to have major surgery, your doctor may consider stopping LENVIMA, because the medicine can affect wound healing. LENVIMA can be restarted when adequate wound healing has been established.
• if you are over 75 years old
• if you are of non-white or Asian ethnicity
• if you weigh less than 60 kg
• if you have a history of abnormal connections (known as fistulas) forming between different organs in the body or from an organ to the skin
• if you have or have had an aneurysm (a bulge and weakening of a blood vessel wall) or a tear in a blood vessel wall.
• if you have or have had pain in your mouth, teeth and/or jaw, swelling or ulcers in your mouth, numbness or a feeling of heaviness in your jaw or a loose tooth. You may be advised to have a dental check-up before starting to take LENVIMA, because jaw bone damage (osteonecrosis) has been reported in patients treated with LENVIMA. If you need to have invasive dental treatment or dental surgery, tell your dentist that you are taking LENVIMA, especially if you are or have been also taking bisphosphonates by injection (used to prevent or treat bone diseases).
• if you are taking or have taken medicines used to treat osteoporosis (anti-resorptive medicines) or cancer medicines that alter the formation of blood vessels (so-called angiogenesis inhibitors), because the risk of jaw bone damage may be greater. Before taking LENVIMA, your doctor may perform some tests, e.g. to check your blood pressure and liver or kidney function and to check if you have low levels of salts 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 treatment with LENVIMA. You may need to have additional treatment with other medicines, take a lower dose of LENVIMA or pay particular attention because of an increased risk of side effects.

If you are unsure, talk to your doctor before taking LENVIMA.

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

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

Contraception, pregnancy and breastfeeding
If you are pregnant, suspect you might be pregnant, are planning to become pregnant or are breastfeeding
ask your doctor or pharmacist for advice before taking this medicine.

• If you are a woman of childbearing potential, use highly effective contraceptive measures during treatment with this medicine and for at least one month after the end of treatment. It is not known whether LENVIMA can reduce the effect of oral contraceptive pills; therefore, if this is your usual method of contraception, you should use an additional barrier method, such as a cervical cap or condom, if you have sexual intercourse during treatment with LENVIMA.
• Do not take LENVIMA if you are planning a pregnancy during treatment, because it can cause serious harm to the baby.
• If you become pregnant during treatment with LENVIMA, tell your doctor immediately. The doctor will help you decide whether to continue treatment.
• Do not breastfeed while taking LENVIMA, because the medicine passes into breast milk and can cause serious harm to the infant.

Driving and using machines
LENVIMA can 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

Take this medicine following the instructions of your doctor exactly. If you have any doubts, ask your
doctor or pharmacist.

Dosage
Thyroid cancer

• The recommended dose of LENVIMA is usually 24 mg once a day (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 a day (1 capsule of 10 mg and 1 capsule of 4 mg).
• Your doctor may reduce the dose if you experience problems with side effects.

Liver cancer

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

Uterine cancer

• The recommended dose of LENVIMA is 20 mg once a day (2 capsules of 10 mg) in combination with pembrolizumab. Pembrolizumab is given by your doctor as an injection into a vein, 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.

Taking the medicine

• You can take the capsules with or without food.
• Do not open the capsules to avoid exposure to the capsule contents.
• Swallow the capsules whole with water. If you are unable to swallow the capsules whole, you can prepare a liquid mixture with water, apple juice or milk. The liquid mixture can be given by mouth or through a feeding tube. If given through a feeding tube, the liquid mixture must be prepared with water. If not used at the time of preparation, the liquid mixture can be stored in a covered container and must be refrigerated at a temperature between 2 °C and 8 °C for a maximum of 24 hours. Shake the liquid mixture for 30 seconds after taking it out of the refrigerator. If the

liquid mixture is not used within 24 hours of preparation, it must be discarded.
Preparation and administration of the liquid mixture:
o Place the whole capsules corresponding to the prescribed dose (up to 5 capsules) in a
small container (capacity of approximately 20 mL (4 teaspoons)) or in an
oral syringe (20 mL); do not break or crush the capsules.
o Add 3 mL of liquid to the container or oral syringe.
Wait 10 minutes to allow the capsule shell (outer surface) to dissolve, then mix or shake the mixture for 3 minutes until the capsules are
completely dissolved.

• If the liquid mixture is prepared in an oral syringe, cap the syringe, remove the plunger and use a second syringe or a medicine dropper to add the liquid into the first syringe, then reposition the plunger before mixing. o Drink the liquid mixture from the container or use an oral syringe to take it directly into your mouth or through a feeding tube. o Afterwards, add another 2 mL of liquid to the container or oral syringe using a second syringe or a medicine dropper, mix or shake, then take the liquid mixture. Repeat this step at least twice and until there is no visible sign of the mixture to ensure that all the medicine is taken.
• Take the capsules every day at about the same time.

How long to take LENVIMA
You will usually continue to take this medicine as long as you are benefiting from it.

If you take more LENVIMA than you should
If you take more LENVIMA than you should, consult your doctor or pharmacist immediately. Bring the
package of the medicine with you.

If you forget to take LENVIMA
Do not take a double dose (two doses at the same time) to make up for a missed dose.
What you should do if you forget to take the dose depends on how much time is left until the
next dose.

• If there are 12 hours or more until the 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 the next dose: skip the forgotten dose. Then take the next dose at the usual time.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediately if you notice any of the following side effects – medical treatment may
be urgently needed:

• feeling of 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 stroke, bleeding in the brain or the effect of a serious increase in blood pressure in the brain.
• chest pain or pressure, pain in the arms, back, neck or jaw, shortness of breath, rapid or irregular heartbeat, cough, bluish discoloration of the lips or fingertips, feeling of great fatigue: these may be signs of a heart problem, of

a blood clot in the lungs or air leaking from the lungs into the chest cavity, preventing
the lungs from inflating.

• severe abdominal (stomach) pain, which may be due to a hole in the wall of the intestine or a fistula (a hole in the intestine that connects, through a tubular passage, another part of the body or the skin).
• black, tarry or bloody stools, or coughing up blood: these may be signs of internal bleeding
• yellowing of the skin or whites of the eyes (jaundice) or drowsiness, confusion, poor concentration: these may be signs of liver problems.
• diarrhea, nausea and vomiting: these are very common side effects, which can become serious if they cause dehydration with possible subsequent kidney failure. Your doctor may prescribe medicines to reduce these side effects.
• pain in the mouth, teeth and/or jaw, swelling or ulcers in the mouth, numbness or heaviness in the jaw or loosening of a tooth; these could be signs of damage to the jawbone (osteonecrosis).

Tell your doctor immediately if any of the above-listed side effects occur.

With this medicine, when given alone, the following side effects may occur:
Very common(may affect more than 1 in 10 people)

• high or low blood pressure
• loss of appetite or weight loss
• nausea and vomiting, constipation, diarrhea, abdominal pain, indigestion
• feeling of marked fatigue or weakness
• hoarseness
• swelling of the legs
• skin rash
• dry, sore or inflamed mouth, altered sense of taste
• joint or muscle pain
• dizziness
• hair loss
• bleeding (most commonly nosebleeds, but also other types of bleeding, such as blood in the urine, bruising, bleeding from the gums or from the intestinal wall)
• difficulty sleeping
• changes in urine test results regarding proteins (elevated) and urinary tract infections (increased frequency of urination and/or pain when urinating)
• headache
• back pain
• redness, pain and swelling of the skin of the hands and feet (palmo-plantar erythrodysesthesia)
• underactive thyroid (fatigue, weight gain, constipation, feeling cold, dry skin)
• changes in blood test results regarding potassium levels (low) and calcium levels (low)
• decreased number of white blood cells
• changes in blood test results regarding liver function
• low platelet counts in the blood, which can cause bruising and difficulty healing wounds
• changes in blood test results regarding magnesium in the blood (low), cholesterol (high) and thyroid stimulating hormone (high)
• changes in blood test results regarding kidney function and kidney failure
• increased 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, thickening of the skin and itching
• feeling of fullness or excess gas
• heart problems or blood clots in the lungs (difficulty breathing, chest pain) or in other organs
• liver failure
• drowsiness, confusion, poor concentration, loss of consciousness, which may be signs of liver failure
• feeling unwell
• inflammation of the gallbladder
• stroke
• anal fistula (a small channel that forms between the anus and the surrounding skin)
• a hole (perforation) in the stomach or intestine

Uncommon(may affect up to 1 in 100 people)

• painful infection or irritation near the anus
• mini-stroke
• liver damage
• severe pain in the upper left side of the abdomen (stomach), which may be associated with fever, chills, nausea and vomiting (splenic infarction)
• inflammation of the pancreas (pancreatitis)
• problems with wound healing
• damage to the jawbone (osteonecrosis)
• inflammation of the colon (colitis)
• decreased secretion of hormones produced by the adrenal glands

Not known(the following side effects have been reported after marketing of
LENVIMA, but their frequency is not known):

• 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 and trachea). Symptoms depend on where the fistula is located. Tell your doctor if you develop new or unusual symptoms, such as coughing when swallowing.
• dilation and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections).

When this medicine is given in combination with pembrolizumab, the following side
effects may occur:
Very common(may affect more than 1 in 10 people)

• changes in urine test results regarding proteins (elevated) and urinary tract infections (increased frequency of urination and pain when urinating)
• low platelet counts in the blood, which can cause bruising and difficulty healing wounds
• decreased number of white blood cells
• decreased number of red blood cells
• underactive thyroid (fatigue, weight gain, constipation, feeling cold, dry skin) and changes in blood test results regarding levels of thyroid stimulating hormone (elevated)
• overactive thyroid (symptoms may include rapid heartbeat, sweating and weight loss)
• changes in blood test results regarding calcium levels (low)
• changes in blood test results regarding potassium levels (low)
• changes in blood test results regarding cholesterol levels (high)
• changes in blood test results regarding magnesium levels (low)
• loss of appetite or weight loss
• dizziness
• headache
• back pain
• dry, sore or inflamed mouth, altered sense of taste
• bleeding (most commonly nosebleeds, but also other types of bleeding, such as blood in the urine, bruising, bleeding from the gums or from the intestinal wall)
• high blood pressure
• hoarseness
• nausea and vomiting, constipation, diarrhea, abdominal pain
• increased amylase (enzyme involved in digestion)
• increased lipase (enzyme involved in digestion)
• changes in blood test results regarding liver function
• changes in blood test results regarding kidney function
• redness, pain and swelling of the skin of the hands and feet (palmo-plantar erythrodysesthesia)
• skin rash
• joint or muscle pain
• feeling of marked 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 fullness or excess gas
• indigestion
• inflammation of the gallbladder
• hair loss
• kidney failure
• feeling unwell
• inflammation of the colon (colitis)
• decreased secretion of hormones produced by the adrenal glands
• a hole (perforation) in the stomach or intestine

Uncommon(may affect up to 1 in 100 people)

• headache, feeling of confusion, seizures and changes in vision
• signs of stroke, including feeling of numbness or weakness on one side of the body, severe headache, seizures, confusion, difficulty speaking, changes in vision or dizziness
• mini-stroke
• signs of a heart problem, including chest pain or pressure, pain in the arms, back, neck or jaw, shortness of breath, rapid or irregular heartbeat, cough, bluish discoloration of the lips or fingertips, feeling of great fatigue
• severe difficulty breathing and chest pain caused by air leaking from the lungs into the chest cavity, preventing the lungs from inflating
• painful infection or irritation near the anus
• anal fistula (a small channel that forms between the anus and the surrounding skin)
• liver failure or signs of liver damage, including yellowing of the skin or whites of the eyes (jaundice) or drowsiness, confusion, poor concentration
• dry skin, thickening and itching of the skin
• difficulty healing wounds

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed
in this leaflet. You can also report side effects directly through
the national reporting system listed in Annex V. By reporting side effects you can help provide more
information on the safety of this medicine.

5. How to store 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 pack after “Scad.” and on each blister after “EXP”. The expiry date refers to the last day of that month.
• Do not store at a temperature above 25ºC. Store in the original blister to protect the medicine from moisture.
• Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What LENVIMA contains

• The active ingredient is lenvatinib.
• LENVIMA 4 mg hard capsules: - Each hard capsule contains 4 mg of lenvatinib (as mesylate).
• LENVIMA 10 mg hard capsules: - Each hard capsule contains 10 mg of lenvatinib (as mesylate).
• The other ingredients are calcium carbonate, mannitol, microcrystalline cellulose, hydroxypropylcellulose, low substitution hydroxypropylcellulose, talc. The capsule shell contains hypromellose, titanium dioxide (E171), yellow iron oxide (E172) and red iron oxide (E172). The printing ink contains shellac, black iron oxide (E172), potassium hydroxide and propylene glycol.

Description of the appearance of LENVIMA and package contents

• The 4 mg capsule has a reddish-yellow body and a reddish-yellow cap, approximately 14.3 mm in length, with “Є” printed in black ink on the cap and “LENV 4 mg” on the body.
• The 10 mg capsule has a yellow body and a reddish-yellow cap, approximately 14.3 mm in length, with “Є” printed in black ink on the cap and “LENV 10 mg” on the body.
• The capsules are provided in polyamide/aluminum/PVC blister packs with an aluminum push-through foil, in cardboard boxes containing 30, 60 or 90 hard capsules. Not all pack sizes may be marketed.

Marketing authorisation 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 on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Eisai SA/NV
Tél/Tel: +32 (0) 800 158 58

Lietuva
Ewopharma AG atstovybė
Tel: +370 5 2430444

България
Ewopharma AG
Teл.: +359 2 962 12 00

Luxembourg/Luxemburg
Eisai SA/NV
Tél/Tel: +32 (0) 800 158 58
(Belgique/Belgien)

Česká republika
Eisai GesmbH organizačni složka
Tel.: + 420 242 485 839

Magyarország
Ewopharma Hungary Ltd.
Tel.: +36 1 200 46 50

Danmark
Eisai AB
Tlf: + 46 (0) 8 501 01 600
(Sverige)

Malta
Cherubino LTD
Tel: +356 21343270
[email protected]

Nederland
Eisai B.V.
Tel: + 31 (0) 900 575 3340

Eesti
Ewopharma AG Eesti filiaal
Tel: +372 6015540

Deutschland
Eisai GmbH
Tel: + 49 (0) 69 66 58 50

Norge
Eisai AB
Tlf: + 46 (0) 8 501 01 600
(Sverige)

Ελλάδα
Arriani Pharmaceutical S.A.
Τηλ: + 30 210 668 3000

Österreich
Eisai GesmbH
Tel: + 43 (0) 1 535 1980-0

España
Eisai Farmacéutica, S.A.
Tel: + (34) 91 455 94 55

Polska
Ewopharma AG Sp. z o.o
Tel.: +48 (22) 620 11 71

France
Eisai SAS
Tél: + (33) 1 47 67 00 05

Portugal
Eisai Farmacêutica, Unipessoal Lda
Tel: + 351 214 875 540

Hrvatska
Ewopharma d.o.o
[email protected]
Tel: +385 (0) 1 6646 563

România
Ewopharma AG
Tel:+40 21 260 13 44

Ireland
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Germany)

Slovenija
Ewopharma d.o.o.
Tel: +386 590 848 40

Ísland
Eisai AB
Sími: + 46 (0) 8 501 01 600
(Svíþjóð)

Slovenská republika
Eisai GesmbH organizační složka
Tel.: +420 242 485 839
(Česká republika)

Italia
Eisai S.r.l.
Tel: + 39 02 5181401

Suomi/Finland
Eisai AB
Puh/Tel: + 46 (0) 8 501 01 600
(Ruotsi/Sverige)

Κύπρος
Arriani Pharmaceuticals S.A.
Τηλ: + 30 210 668 3000
(Ελλάδα)

Sverige
Eisai AB
Tel: + 46 (0) 8 501 01 600

United Kingdom (Northern Ireland)
Eisai GmbH
Tel: + 49 (0) 69 66 58 50
(Germania)
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu.

Latvija
Ewopharma AG Pārstāvniecība
Tel: +371 67450497