KISPLYX 4 мг Капсулы

Содержание инструкции

1. Kisplyx 4 mg hard capsules, 10 mg hard capsules
   1. What is Kisplyx and what is it used for
   2. What you need to know before taking Kisplyx
   3. How to take Kisplyx
   4. Possible side effects
   5. How to store Kisplyx
   6. Package contents and other information

Kisplyx 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 they have the same symptoms as you, as it may 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 Kisplyx is and what it is used for
• 2. What you need to know before you take Kisplyx
• 3. How to take Kisplyx
• 4. Possible side effects
• 5. How to store Kisplyx
• 6. Contents of the pack and other information

1. What is Kisplyx and what is it used for

What is Kisplyx
Kisplyx is a medicine that contains the active substance lenvatinib. It is used in association with
pembrolizumab as first-line treatment for adults with advanced renal cancer (advanced renal cell
carcinoma). It is also used in association with everolimus to treat adults with
advanced renal cancer, when other treatments (so-called “anti-VEGF therapy”) have not been helpful in
stopping the disease.

How Kisplyx works
Kisplyx blocks 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 high amounts in cancer cells and by blocking their action, Kisplyx
can slow down the rate at which cancer cells
multiply and the tumor grows and help to interrupt the blood supply that the tumor needs.

2. What you need to know before taking Kisplyx

Do not take Kisplyx

• if you are allergic to lenvatinib or 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 taking Kisplyx if:

• you have high blood pressure
• you are a woman who could become pregnant (see the “Contraception, pregnancy and breastfeeding” section below)
• you have had heart problems or stroke in the past
• you have problems with your liver or kidneys
• you have recently had surgery or radiotherapy
• you are going to have surgery. If you are going to have major surgery, your doctor may consider stopping Kisplyx, because Kisplyx can affect wound healing. Kisplyx can be restarted when adequate wound healing has been established.
• you are over 75 years of age
• you belong to an ethnic group other than white or Asian
• you weigh less than 60 kg
• you have a history of abnormal passages (known as fistulas) forming between different organs in the body or from an organ to the skin
• you have or have had an aneurysm (bulging and weakening of the wall of a blood vessel) or a tear in the wall of a blood vessel.
• you have or have had pain in the mouth, teeth and/or jaw, swelling or ulcers in the mouth, numbness or a feeling of heaviness in the jaw or loosening of a tooth. You may be advised to have a dental check-up before starting to take Kisplyx, because jaw bone damage (osteonecrosis) has been reported in patients treated with Kisplyx. If you need to have invasive dental treatment or dental surgery, tell your dentist that you are taking Kisplyx, especially if you are or have been also taking bisphosphonates by injection (used to prevent or treat bone diseases).
• you are taking or have taken medicines used to treat osteoporosis (bone anti-resorption 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 Kisplyx, your doctor may perform some blood tests, for example 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 Kisplyx. You may need additional treatment with other
medicines, to take a lower dose of Kisplyx or to pay particular attention due to an
increased risk of side effects.
If you have any doubts, ask your doctor before taking Kisplyx.

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

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

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

• Use highly effective contraceptive measures while taking this medicine and for at least one month after the end of treatment.
• Do not take Kisplyx if you are planning to become pregnant during treatment. This is because it can seriously harm the baby.
• If you become pregnant during treatment with Kisplyx, tell your doctor immediately. The doctor will help you decide whether to continue treatment.
• Do not breastfeed while taking Kisplyx. This is because the medicine passes into breast milk and can seriously harm the baby.

Driving and using machines
Kisplyx can cause side effects that may affect your ability to drive or operate
machinery. Avoid driving or operating machinery if you feel dizzy or tired.

3. How to take Kisplyx

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

Dosage to be taken

• The recommended daily dose of Kisplyx is 20 mg once a day (two 10 mg capsules) in combination with pembrolizumab 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes.
• The recommended daily dose of Kisplyx is 18 mg once a day (one 10 mg capsule and two 4 mg capsules) in combination with a 5 mg tablet of everolimus once a day.
• If you have severe liver or kidney problems, the recommended daily dose of Kisplyx is 10 mg once a day (1 10 mg capsule) in combination with a 5 mg tablet of everolimus once a day. If you receive lenvatinib in combination with pembrolizumab, your doctor or pharmacist will check the dose of pembrolizumab you need to take.
• Your doctor may reduce the dose if side effects occur.

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 administered orally or via a feeding tube. If administered via 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 administration syringe (20 mL); do not break or crush the capsules. o Add 3 mL of liquid to the container or oral administration 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 administration 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 administration syringe to take it directly into your mouth or via a feeding tube. o Afterwards, add another 2 mL of liquid to the container or oral administration 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 of the medicine is taken.
• Take the capsules every day at about the same time.

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

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

If you forget to take Kisplyx
Do not take a double dose (two doses at the same time) to make up for a forgotten 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 everyone will experience them. The following side effects may occur with this medicine.

Immediately inform your doctor if you notice any of the following side effects – urgent medical treatment may be needed:

• feeling of numbness or weakness on one side of the body, severe headache, seizures, confusion, difficulty speaking, changes in vision or feeling dizzy: these may be signs of stroke, bleeding in the brain or the effect on the brain of a severe increase in blood pressure.
• chest pain or pressure, pain in the arms, back, neck or jaw, shortness of breath, rapid or irregular heartbeat, coughing, bluish discoloration of the lips or fingers, feeling of great fatigue: these may be signs of a heart problem, a blood clot in the lungs or air leakage from the lungs into the chest, preventing the lungs from inflating.
• severe abdominal (stomach) pain - this may be due to a hole in the wall of the intestine or a fistula (a hole in the intestine that connects, through a tube-like passage, to another part of the body or the skin).
• black, tarry stools, or bleeding stools, or coughing up blood - these may be signs of internal bleeding.
• diarrhea, feeling unwell and malaise - these are very common side effects, which can become serious if they cause dehydration, which can lead to 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).

Immediately inform your doctor if any of the following side effects occur.

The following side effects may occur with this drug when administered alone:
Very common(may affect more than 1 in 10 people)

• low levels of platelets in the blood which may lead to bruising and difficulty healing wounds
• reduction in the number of white blood cells in the blood
• thyroid gland not functioning sufficiently (fatigue, weight gain, constipation, feeling cold, dry skin) and changes in blood test results for thyroid-stimulating hormone levels (high)
• changes in blood test results regarding potassium levels (low) and calcium levels (low)
• changes in blood test results regarding magnesium levels (low) and cholesterol levels (high)
• loss of appetite or weight loss
• difficulty sleeping
• feeling dizzy
• headache
• 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 or low blood pressure
• hoarse voice
• nausea and vomiting, constipation, diarrhea, abdominal pain, indigestion
• dry, painful or inflamed mouth, altered sense of taste
• increased levels of lipase and amylase (enzymes involved in digestion)
• changes in blood test results for liver function
• redness, pain and swelling of the skin of the hands and feet (palmo-plantar erythrodysesthesia)
• skin rash
• hair loss
• back pain
• joint or muscle pain
• changes in urine tests regarding protein levels (high) and urinary tract infections (urinating more often than usual and pain when passing urine)
• changes in blood test results for kidney function and kidney failure
• feeling of marked fatigue or weakness
• swelling of the legs

Common(may affect up to 1 in 10 people)

• loss of body fluids (dehydration)
• signs of a stroke, including feeling of numbness or weakness on one side of the body, severe headache, seizures, confusion, difficulty speaking, changes in vision or feeling dizzy
• heart palpitations
• heart problems or blood clots in the lungs (difficulty breathing, chest pain) or in other organs, may include chest pain or pressure, pain in the arms, back, neck or jaw, shortness of breath, rapid or irregular heartbeat, coughing, bluish discoloration of the lips or fingers and feeling of great fatigue
• anal fistula (a small channel that forms between the anus and the surrounding skin)
• feeling of bloating or excess air
• liver failure
• sleepiness, confusion, poor concentration, loss of consciousness which may be signs of liver failure
• inflammation of the gallbladder
• dry, thickened and itchy skin
• feeling unwell
• a hole (perforation) in the stomach or intestine

Uncommon(may affect up to 1 in 100 people)

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

Not known(the following side effects have been reported with the marketing of Kisplyx, but the frequency with which they occur is not known)

• dilation and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)
• other types of fistulas (an abnormal connection between different organs in the body or from the skin to an underlying structure, such as the throat and trachea). Symptoms depend on where the fistula is located. Inform your doctor if you experience new or unusual symptoms, such as coughing when swallowing.

The following side effects may occur with this drug when administered in association with everolimus:
Very common(may affect more than 1 in 10 people)

• low levels of platelets in the blood which may lead to bruising and difficulty healing wounds
• reduction in the number of white blood cells in the blood
• thyroid gland not functioning sufficiently (fatigue, weight gain, constipation, feeling cold, dry skin) and changes in blood test results for thyroid-stimulating hormone levels (high)
• changes in blood test results regarding potassium levels (low) and calcium levels (low)
• changes in blood test results regarding magnesium levels (low) and cholesterol levels (high)
• loss of appetite or weight loss
• difficulty sleeping
• headache
• 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
• hoarse voice
• nausea and vomiting, constipation, diarrhea, abdominal pain, indigestion
• painful or inflamed mouth, altered sense of taste
• increased levels of lipase and amylase (enzymes involved in digestion)
• changes in blood test results for liver function
• redness, pain and swelling of the skin of the hands and feet (palmo-plantar erythrodysesthesia)
• skin rash
• back pain
• joint or muscle pain
• changes in urine tests regarding protein levels (high)
• changes in blood test results for kidney function and kidney failure
• feeling of marked fatigue or weakness
• swelling of the legs

Common(may affect up to 1 in 10 people)

• urinary tract infections (urinating more often than usual and pain when passing urine)
• loss of body fluids (dehydration)
• feeling dizzy
• heart palpitations
• heart problems or blood clots in the lungs (difficulty breathing, chest pain) or in other organs, may include chest pain or pressure, pain in the arms, back, neck or jaw, shortness of breath, rapid or irregular heartbeat, coughing, bluish discoloration of the lips or fingers and feeling of great fatigue
• low blood pressure
• severe difficulty breathing and chest pain, caused by air leakage from the lung into the chest, preventing the lung from inflating
• dry mouth
• feeling of bloating or excess air
• inflammation of the gallbladder
• hair loss
• feeling unwell
• a hole (perforation) in the stomach or intestine

Uncommon(may affect up to 1 in 100 people)

• painful infection or irritation near the anus
• signs of a stroke, including feeling of numbness or weakness on one side of the body, severe headache, seizures, confusion, difficulty speaking, changes in vision or feeling dizzy
• mini-stroke
• inflammation of the pancreas
• anal fistula (a small channel that forms between the anus and the surrounding skin)
• inflammation of the colon (colitis)
• liver failure or signs of liver damage, including yellowing of the skin or whites of the eyes (jaundice) or sleepiness, confusion, poor concentration
• damage to the jawbone (osteonecrosis)
• dry, thickened and itchy skin
• problems with wound healing
• other types of fistulas (an abnormal connection between different organs in the body or from the skin to an underlying structure, such as the throat and trachea). Symptoms depend on where the fistula is located. Inform your doctor if you experience new or unusual symptoms, such as coughing when swallowing
• decreased secretion of hormones produced by the adrenal glands.

Not known(the following side effects have been reported with the marketing of Kisplyx, but the frequency with which they occur is not known)

• dilation and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)

The following side effects may occur with this drug when administered in association with pembrolizumab:
Very common(may affect more than 1 in 10 people)

• low levels of platelets in the blood which may lead to bruising and difficulty healing wounds
• reduction in the number of white blood cells in the blood
• thyroid gland not functioning sufficiently (fatigue, weight gain, constipation, feeling cold, dry skin) and changes in blood test results for thyroid-stimulating hormone levels (high)
• changes in blood test results regarding potassium levels (low) and calcium levels (low)
• changes in blood test results regarding magnesium levels (low) and cholesterol levels (high)
• loss of appetite or weight loss
• difficulty sleeping
• feeling dizzy
• headache
• 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
• hoarse voice
• nausea) and vomiting, constipation, diarrhea, abdominal pain, indigestion
• dry, painful or inflamed mouth, altered sense of taste
• increased levels of lipase and amylase (enzymes involved in digestion)
• changes in blood test results for liver function
• redness, pain and swelling of the skin of the hands and feet (palmo-plantar erythrodysesthesia)
• skin rash
• back pain
• joint or muscle pain
• changes in urine tests regarding protein levels (high)
• changes in blood test results for kidney function and kidney failure
• feeling of marked fatigue or weakness
• swelling of the legs

Common(may affect up to 1 in 10 people)

• urinary infections (urinating more often than usual and pain when passing urine)
• loss of body fluids (dehydration)
• heart palpitations
• heart problems or blood clots in the lungs (difficulty breathing, chest pain) or in other organs, may include chest pain or pressure, arm pain, back pain, neck pain or jaw pain, shortness of breath, rapid or irregular heartbeat, cough, bluish discoloration of the lips or fingers and feeling very tired
• low blood pressure
• pancreatitis (inflammation of the pancreas)
• colitis (inflammation of the colon)
• feeling of bloating or excess air
• inflammation of the gallbladder
• dry skin, thickening and itching of the skin
• hair loss
• feeling unwell
• 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)

• painful infection or irritation near the anus
• signs of a stroke, including numbness or weakness on one side of the body, severe headache, convulsions, confusion, difficulty speaking, changes in vision or feeling dizzy
• mini-stroke
• severe difficulty breathing and chest pain, caused by air leaking from the lung into the chest that prevents the lung from inflating
• 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
• problems with wound healing
• other types of fistulas (an abnormal connection between different organs in the body or from the skin to an underlying structure, such as the throat and trachea). Symptoms will depend on where the fistula is located. Tell your doctor if you experience new or unusual symptoms, such as coughing when swallowing.

Not known(the following adverse reactions have been reported from post-marketing of Kisplyx,
but their frequency is not known)

• widening and weakening of the wall of a blood vessel or a tear in the wall of a blood vessel (aneurysms and arterial dissections)

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or pharmacist. 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 Kisplyx

• 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 package after “Scad.” and on the 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 humidity.
• Do not dispose of any medicine in wastewater 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 Kisplyx contains

• The active ingredient is lenvatinib.
• Kisplyx 4 mg hard capsules: - each hard capsule contains 4 mg of lenvatinib (as mesylate).
• Kisplyx 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 substituted 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 Kisplyx and contents of the pack

• Kisplyx 4 mg hard capsule: body reddish-yellow and cap reddish-yellow, approximately 14.3 mm in length, with “Є” imprinted in black ink on the cap and “LENV 4 mg” on the body.
• Kisplyx 10 mg hard capsule: body yellow and cap reddish-yellow, approximately 14.3 mm in length, with “Є” imprinted in black ink on the cap and “LENV 10 mg” on the body.
• The capsules are supplied in blisters with an aluminum foil cover with push-through opening, in cardboard packs 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
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 authorization holder:

Lietuva
Ewopharma AG representation
Tel: + 370 5 2430444

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

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

Luxembourg/Luxemburg
Eisai SA/NV
Tél/Tel: +32 (0) 2 502 58 04
(Belgique/Belgien)

Česká republika
Eisai GesmbH organizational unit
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

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

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

Eesti
Ewopharma AG Estonian branch
Tel: + 372 6015540

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
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 organizational unit
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
(Germany)
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 Representation
Tel: + 371 67450497