InfoCons Consumer Protection informs you – Kisplyx – Package Leaflet

Before anything else

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 get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

ℹ️ 1. What Kisplyx is and what it is used for

What Kisplyx is Kisplyx is a medicine that contains the active substance lenvatinib. It is used in combination with pembrolizumab as the first treatment for adults with advanced kidney cancer (advanced renal cell carcinoma) . It is also used in combination with everolimus to treat adults with advanced kidney cancer where other treatments (so -called “VEGF -targeted therapy”) have not helped stop thedisease .

How Kisplyx works

Kisplyx blocks the action of proteins called receptor tyrosine kinases (RTKs), which are involved in the development of new blood vessels that supply oxygen and nutrients to cells and help them to grow .

These proteins can be present in high amounts in cancer cells, and by blocking their action Kisplyx may slow the rate at which the cancer cells multiply and the tumour grow sand help to cut off the blood supply that the cancer needs.

⚠️ 2. What you need to know before you take Kisplyx

Do not take Kisplyx if

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

Warnings and precautions

Talk to your doctor before taking Kisplyx if you:  have high blood pressure  are a woman able to become pregnant (see the section “Contraception, pregnancy and breast -feeding ” below )  have a history of heart problems or stroke  have liver or kidney problems  have had recent surgery or radiotherapy 48 need to have a surgical procedure .Your doctor may consider stopping Kisplyx if you will be undergoing a major surgical procedure as Kisplyx may affect wound healing. Kisplyx may be restarted once adequate wound healing is established.  are over 75 years old  belong to an ethnic group other than White or Asian  weigh less than 60 kg  have a history of abnormal passageways (known as a fistula) between different organs in the body or from an organ to the skin  If you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in a blood vessel wall.  have or have had pain in the mouth, teeth and/or jaw, swelling or sores inside 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 Kisplyx as bone damage in the jaw (osteonecrosis) has been reported in patients treated with Kisplyx. If you need to undergo an invasive dental treatment or dental surgery, tell your dentist that you are being treated with Kisplyx, particularly when you are also receiving or have received injections of bisphosphonates (used to treat or prevent bone disorders) .  are receiving or have received some medicines used to treat osteoporosis (antiresorptive medicines) or cancer medicines which alter formation of blood vessels (so called angiogenesis inhibitors), as the risk of bone damage in the jaw may be increased.

Before taking Kisplyx , your doctor may carry out some blood tests, for example to check your blood pressure and your liver or kidney function and to see if you have low levels of salt and high levels of thyroid stimulating hormone in your blood. Your doctor will discuss the results of these tests with you and decidewhether you can be given Kisplyx. You may need to have additional treatment with other medicines, to take a lower dose of Kisplyx , or to take extra care due to an increased risk of side effects.

If you are not sure talk to y our doctor before taking Kisplyx .

Conditions you need to look ou tfor During treatment of your cancer, the breakdown of tumour cells may leak substances into the blood which may lead to a group of complications called tumour lysis syndrome (TLS). This may lead to changes in your kidneys and can be life -threatening. Your doct or will observe and may give you a treatment to reduce the risk. Tell your doctor immediately if you experience signs of TLS (see section 4; Possible side effects) .

Children and adolescents

Kisplyx is not currently recommended for use in children and adolescents younger than 18 years old.

Other medicines and Kisplyx

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes herbal preparations and medicines 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.  Use highly effective contraception while taking this medicine, and for at least one month after you finish treatment.  Do not take Kisplyx if you are planning to become pregnant during your treatment. This is because it may seriously harm your baby.  If you become pregnant while being treated with Kisplyx , tell your doctor immediately. Your doctor will help you decide whether the treatment should be continued.  Do not brea st-feed if you are taking Kisplyx . This is because the medicine passes into breast milk andmay seriously harm your breastfed baby.

49Driving and using machines Kisplyx 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 Kisplyx

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

How much to take  The recommended daily dose of Kisplyx is 20 mg once a day (two 10 -mg capsules) in combination with pembrolizumab either 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 mgonce a day (one 10 mgcapsule and two 4 mg capsules) in combination with one5mgtablet of everolimus once a day .  If you have severe liver or kidney problems the recommended daily dose of Kisplyx is 10mg once a day (1capsule of 10 mg)in combination with one5mgtablet of everolimus once a day.

If you are receiving lenvatinib in combination with pembrolizumab, your doctor or pharmacist will check to see how much pembrolizumab you should receive.  Your doctor may reduce your dose if you experience side effects.

Taking this medicine  You can take the capsules with or without food.  Do not open the capsules to avoid exposure to the contents of the capsule.  Swallow the capsules whole with water. If you cannot swallow the capsules whole, a liquid mixture can be prepared using water, apple juice, or milk. The liquid mixture may be given by mouth or through a feeding tube. If given through a feeding tube, then the liquid mixture should be prepared us ing water. If not used at the time of preparation, the liquid mixture may be stored in a covered container and must be refrigerated at 2ºC to 8ºC for a maximum of 24 hours. Shake the liquid mixture for 30 seconds afte r removing from the refrigerator. If the liquid mixture is not used within 24 hours of preparation, it should be thrown away.

Preparation and administration of the liquid mixture: o Place the whole capsule(s) corresponding to the prescribed dose (up to 5 capsules) in a small container (approximately 20 mL (4 tsp) capacity) or oral syringe (20 mL); do not break or crush capsules. o Add 3 mL of liquid to the container or oral syringe. Wait 10 minutes for the capsule shell (outer surface) to dissolve, then stir or shake the mixture for 3 minutes until the capsules are fully dissolved.  If liquid mixture is prepared in an oral syringe, cap the syringe, remove plunger and use a second syringe or medicine dropper to add the liquid to the first syringe, then replace plunger prior to mixing. o Drink the liquid mixture from the container or use an oral syringe to take directly into the mouth or through a feeding tube. o Next, add an additional 2 mL of liquid to the container, or oral syringe using a second syringe or dropper , swirl or shake and take the liquid mixture. Repeat this step at least twice and until there is no visible sign of the mixture to make sure all of the medication is taken.  Take the capsules at about the same time each day.

How long to take Kisplyx You will usually carry on taking this medicine as long as you are getting benefit.

If you take more Kisplyx than you should

If you take more Kisplyx than you should, talk to a doctor or pharmacist straight away. Take the medicine pack with you.

If you forget to take Kisplyx

50Do not take a double dose (two doses at the same time) to make up for a forgotten dose.

What to do if you forget to take your dose depends on how long it is until your next dose.  If it is 12 hours or more until your next dose : take the missed dose as soon as you remember.

Then take the next dose at the normal time.  If it is less than 12 hours until your next dose : skip the missed dose. Then take the next dose at the normal time.

❗ 4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may happen with this medicine.

Tell your doctor straight away if you notice any of the following side effects -you may need urgent medical treatment:  feeling numb or weak on one side of your body, severe headache, seizure, confusion, difficulty talking, vision changes or feeling dizzy -these may be signs of a stroke, bleeding inyour brain, or the effect on your brain of a severe increase in blood pressure.  chest pain or pressure, pain in your arms, back, neck or jaw, being short of breath, rapid or irregular heart rate, coughing, bluish colour to lips or fingers, feeling very tired –these may be signs of a heart problem a blood clot in your lung or a leak of air from your lung into your chest so your lung cannot inflate .  severe pain in your belly (abdomen) -this may be due to a hole in the wall of your gut or a fistula (a hole in your gut which links through a tube -like passage to another part of your body or skin).  black, tarry, or bloody stools, or coughing up of blood -these may be signs of bleeding inside your body.  diarrhoea, feeling and being sick -these are very common side effects that can become serious if they cause you to become dehydrated, which can lead to kidney failure. Your doctor can give you medicine to reduce these side effects.  pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw, or loosening of a tooth -these could be signs of bone dama ge in the jaw (osteonecrosis) .  nausea, shortness of breath, irregular heartbeat, muscular cramps, seizure, clouding of urine and tiredness. These symptoms may be complications due to the breakdown products of dying cancer cells and known as tumour lysis syndrome (TLS).

Tell your doctor straight away if you notice any of the side effects below .

The following side effects may happen with this medicine when given 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 in wound healing  decrease in the number of white blood cells  underactive thyroid (tiredness, weight gain, constipation, feeling cold, dry skin) and changes in blood test results for thyroid stimulating hormone (high)  changes inblood test results for potassium levels (low) and calcium levels (low)  changes in blood test results for magnesium (low) and cholesterol (high)  loss of appetite or weight loss  trouble sleeping  feeling dizzy  headache  bleeding (most commonly nose bleeds, but also other types of bleeding such as blood in the urine, bruising, bleeding from the gums or gut wall)  high or low blood pressure 51 hoarse voice  feeling sick (nausea) and being sick (vomiting), constipation, diarrhoea, abdominal pain, indigestion  dry, sore, or inflamed mouth, odd taste sensation  increase in lipase and amylase (enzymes involved in digestion)  changes in blood test results for liver function  redness , soreness and swelling of the skin on the hands and feet (palmar -plantar erythrodysaesthesia)  rash  hairloss  back pain  joint or muscle pain  changes in urine tests for protein (high) and urinary infections (increased frequency in urination and pain in passing urine)  changes in blood test results for kidney function and kidney failure  feeling very tired or weak  swelling of the legs

Common (may affect up to 1 in 10 people)

 loss of body fluids (dehydration)  signs of a stroke, including feeling numb or weak on one side of your body, severe headache, seizure, confusion, difficulty talking, vision changes or feeling dizzy  heart palpitations  heart problems or blood clots in the lungs (difficulty breathing, chest pain) or other organs which may include chest pain or pressure, pain in your arms, back, neck or jaw, being short of breath, rapid or irregular heart rate, coughing, bluish colour to l ips or fingers, and feeling very tired  anal fistula (a small channel that forms between the anus and the surrounding skin)  feeling bloated or having excess wind  liver failure  drowsiness, confusion, poor concentration, loss of consciousness that may be signs of liver failure  inflammation of the gallbladder  dry skin, thickening and itching of the skin  feeling unwell  a hole (perforation) in the stomach or intestines

Uncommon (may affect up to 1 in 100 people)

 painful infection or irritation near the anus  severe pain in the upper left part of the belly (abdomen) which may be associated with fever, chills, nausea and vomiting (splenic infarction)  mini-stroke  severe difficulty breathing and chest pain, caused by a leak of air from your lung into your chest so your lung cannot inflate  inflammation of the pancreas  inflammation of the colon (colitis)  liver damage  bone damage in the jaw (osteonecrosis)  wound healing problems  decreased secretion of hormones produced by adrenal glands

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

 Tumour lysis syndrome (TLS) 52Not Known (the following side effects have been reported since the marketing of Kisplyx but the frequency for them to occur is not known)  an enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections).  other types of fistulae (an abnormal connection between different organs in the body or between the skin and an underlying structure such as throat and windpipe). Symptoms depend on where the fistula is located. Talk to your doctor if you experience any ne w or unsual symptoms such as coughing when swallowing.

The following side effects may happen with this medicine when given in combination 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 in wound healing  decrease in the number of white blood cells  underactive thyroid (tiredness, weight gain, constipation, feeling cold, dry skin) and changes in blood test results for thyroid stimulating hormone (high)  changes inblood test results for potassium levels (low) and calcium levels (low)  changes in blood test results for magnesium (low) and cholesterol (high)  loss of appetite or weight loss  trouble sleeping  headache  bleeding (most commonly nose bleeds, but also other types of bleeding such as blood in the urine, bruising, bleeding from the gums or gut wall)  high blood pressure  hoarse voice  feeling sick (nausea) and being sick (vomiting), constipation, diarrhoea, abdominal pain, indigestion  sore, or inflamed mouth, odd taste sensation  increase in lipase and amylase (enzymes involved in digestion)  changes in blood test results for liver function  redness , soreness and swelling of the skin on the hands and feet (palmar -plantar erythrodysaesthesia)  rash  back pain  joint or muscle pain  changes in urine tests for protein (high)  changes in blood test results for kidney function and kidney failure  feeling very tired or weak  swelling of the legs

Common (may affect up to 1 in 10 people)

 urinary infections (increased frequency in urination and pain in passing urine)  loss of body fluids (dehydration)  feeling dizzy  heart palpitations  heart problems or blood clots in the lungs (difficulty breathing, chest pain) or other organs which may include chest pain or pressure, pain in your arms, back, neck or jaw, being short of breath, rapid or irregular heart rate, coughing, bluish colour to l ips or fingers, and feeling very tired  low blood pressure  severe difficulty breathing and chest pain, caused by a leak of air from your lung into your chest so your lung cannot inflate  dry mouth  feeling bloated or having excess wind 53 inflammation of the gallbladder  hair loss  feeling unwell  a hole (perforation) in the stomach or intestines

Uncommon (may affect up to 1 in 100 people)

 painful infection or irritation near the anus  signs of a stroke, including feeling numb or weak on one side of your body, severe headache, seizure, confusion, difficulty talking, vision changes 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 yellow skin or yellowing of the whites of the eyes (jaundice) or drowsiness, confusion, poor concentration  bone damage in the jaw (osteonecrosis)  dry skin, thickening and itching of the skin  wound healing problems  other types of fistulae (an abnormal connection between different organs in the body or between the skin and an underlying structure such as throat and windpipe). Symptoms depend on where the fistula is located. Talk to your doctor if you experience any ne w or unsual symptoms such as coughing when swallowing.  decreased secretion of hormones produced by adrenal glands

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

 Tumour lysis syndrome (TLS) Not Known (the following side effects have been reported since the marketing of Kisplyx but the frequency for them to occur is not known)  an enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections).

The following side effects may happen with this medicine when given in combination 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 in wound healing  decrease in the number of white blood cells  underactive thyroid (tiredness, weight gain, constipation, feeling cold, dry skin) and changes in blood test results for thyroid stimulating hormone (high)  changes inblood test results for potassium levels (low) and calcium levels (low)  changes in blood test results for magnesium (low) and cholesterol (high)  loss of appetite or weight loss  trouble sleeping  feeling dizzy  headache  bleeding (most commonly nose bleeds, but also other types of bleeding such as blood in the urine, bruising, bleeding from the gums or gut wall)  high blood pressure  hoarse voice  feeling sick (nausea) and being sick (vomiting), constipation, diarrhoea, abdominal pain, indigestion  dry, sore, or inflamed mouth, odd taste sensation  increase in lipase and amylase (enzymes involved in digestion)  changes in blood test results for liver function 54 redness , soreness and swelling of the skin on the hands and feet (palmar -plantar erythrodysaesthesia)  rash  back pain  joint or muscle pain  changes in urine tests for protein (high)  changes in blood test results for kidney function and kidney failure  feeling very tired or weak  swelling of the legs

Common (may affect up to 1 in 10 people)

 urinary infections (increased frequency in urination and pain in passing urine)  loss of body fluids (dehydration)  heart palpitations  heart problems or blood clots in the lungs (difficulty breathing, chest pain) or other organs which may include chest pain or pressure, pain in your arms, back, neck or jaw, being short of breath, rapid or irregular heart rate, coughing, bluish colour to l ips or fingers, and feeling very tired  low blood pressure  inflammation of the pancreas  inflammation of the colon (colitis)  feeling bloated or having excess wind  inflammation of the gallbladder  dry skin, thickening and itching of the skin  hair loss  feeling unwell  decreased secretion of hormones produced by adrenal glands  a hole (perforation) in the stomach or intestines

Uncommon (may affect up to 1 in 100 people)

 painful infection or irritation near the anus  signs of a stroke, including feeling numb or weak on one side of your body, severe headache, seizure, confusion, difficulty talking, vision changes or feeling dizzy  mini-stroke  severe difficulty breathing and chest pain, caused by a leak of air from your lung into your chest so your lung cannot inflate  anal fistula (a small channel that forms between the anus and the surrounding skin)  liver failure or signs of liver damage, including yellow skin or yellowing of the whites of the eyes (jaundice) or drowsiness, confusion, poor concentration  wound healing problems  other types of fistulae (an abnormal connection between different organs in the body or from the skin to an underlying structure such as throat and windpipe). Symptoms would depend on where the fistula is located. Talk to your doctor if you experience any new or unsual symptoms such as coughing when swallowing.

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

 Tumour lysis syndrome (TLS) Not Known (the following side effects have been reported since the marketing of Kisplyx but the frequency for them to occur is not known)  an enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections).

55Reporting of side effects If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix 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 carton and blister after ‘EXP’. The expiry date refers to the last day of that month.  Do not store above 25°C. Store in the original blister in order to protect from moisture.  Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

📦 6. Contents of the pack and other information

What Kisplyx contains

 The active substance is lenvatinib.  Kisplyx 4 mg hard capsules: -Each hard capsule contains 4 mg of lenvatinib (as mesilate ).  Kisplyx 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 hydroxypropyl cellulose, 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.

What Kisplyx looks like and contents of the pack

 Kisplyx 4 mg hard c apsule :yellowish red body and yellowish red cap, approximately 14.3 mm in length, marked in black ink with “Є” on the cap, and “LENV 4 mg” on the body.  Kisplyx 10 mg hard c apsule: yellow body and yellowish red cap, approximately 14.3 mm in length, marked in black ink with “Є” on the cap, and “LENV 10 mg” on the body.  The capsules come in blisters with a push through aluminium foil lidding in cartons of 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 any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

56België/Belgique/Belgien Eisai SA/NV Tél/Tel: + 32 (0) 2 502 58 04Lietuva Ewopharma AG atstovybė Tel: + 370 5 2430444 България Ewopharma AGTeл.: + Teл.: + 359 2 962 12 00Luxembourg/Luxemburg Eisai SA/NV Tél/Tel: + 32 (0) 2 502 58 04 (Belgique/Belgien) Česká republika Eisai GesmbH organizačni složka Tel.: + 420 242 485 839Magyarország 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 50Nederland Eisai B.V.

Tel: + 31 (0) 900 575 3340 Eesti Ewopharma AG Eesti filiaal Tel: + 372 6015540Norge Eisai AB Tlf: + 46 (0) 8 501 01 600 (Sverige) Ελλάδα Arriani Pharmaceutica l S.A.

Τηλ: + 30 210 668 3000Österreich Eisai GesmbH Tel: + 43 (0) 1 535 1980 -0 España Eisai Farmacéutica, S.A.

Tel: + (34) 91 455 94 55Polska Ewopharma AG Sp. z o.o Tel: + 48 (22) 620 11 71 France Eisai SAS Tél: + (33) 1 47 67 00 05Portugal Eisai Farmacêutica, Unipessoal Lda Tel: + 351 214 875 540 Hrvatska Ewopharma d.o.o Tel: + 385 (0) 1 6646 563România 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) 57Italia Eisai S.r.l.

Tel: + 39 02 5181401Suomi/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 Latvija Ewopharma AG Pārstāvniecība Tel: + 371 67450497

This leaflet was last revised in {MM/YYYY}

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

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Kisplyx (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/16/1128).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.