• 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.

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

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 the disease.

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 grows and help to cut off the blood supply that the cancer needs.

• 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).

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
• 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 decide whether 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 your doctor before taking Kisplyx.

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

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.

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 breast-feed if you are taking Kisplyx. This is because the medicine passes into breast milk and may seriously harm your breastfed baby.

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.

• 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 mg once a day (one 10 mg capsule and two 4 mg capsules) in combination with one 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 capsule of 10 mg) in combination with one 5 mg tablet 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.

• 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 using 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 of24 hours. Shake the liquid mixture for 30 seconds after 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:
  • 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.
  • 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.
  • Drink the liquid mixture from the container or use an oral syringe to take directly into the mouth or through a feeding tube.
  • 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.

You will usually carry on taking this medicine as long as you are getting benefit.

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

Do 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.

• 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 in your 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 damage in the jaw (osteonecrosis).

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 in blood 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
• 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
• hair loss
• 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 lips 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

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).
• 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 new or unsual symptoms such as coughing when swallowing.

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 in blood 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 lips 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
• 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 new or unsual symptoms such as coughing when swallowing.
• decreased secretion of hormones produced by adrenal glands

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).

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 in blood 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
• 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 lips 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.

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).

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 Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play and Apple App store. By reporting side effects you can help provide more information on the safety of this medicine.

• 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.

• Kisplyx 4 mg hard capsule: 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 capsule: 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 .