KISPLYX 4 MG HARD CAPSULES - patient leaflet, side effects, dosage

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 the disease.

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 grows and 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 breastfeeding” 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 checkup 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.

Children and adolescents

Kisplyx is not recommended for use in children and adolescents. The effects of Kisplyx in people younger than 18 years old are not known.

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

Driving 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 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.

Taking this medicine

• You can take the capsules with or without food.
• Swallow the capsules whole with water or dissolved. To dissolve them, pour a tablespoon of water or apple juice into a small glass and put the capsules into the liquid without breaking or crushing them. Leave for at least 10 minutes then stir for at least 3 minutes to dissolve the capsule shells. Drink the mixture. After drinking, add the same amount of water or apple juice, swirl and swallow.
• Take the capsules at about the same time each day.
• Caregivers should not open capsules to avoid exposure to the contents of the capsule.

How long to takeKisplyx

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

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.

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 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).

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

Other side effects include:

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

• high or low blood pressure
• loss of appetite or weight loss
• feeling sick (nausea) and being sick (vomiting), constipation, diarrhoea, abdominal pain, indigestion
• feeling very tired or weak
• hoarse voice
• swelling of the legs
• rash
• dry, sore, or inflamed mouth, odd taste sensation
• joint or muscle pain
• feeling dizzy
• hair loss
• 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)
• trouble sleeping
• high levels of protein in the urine and urinary infections (increased frequency in urination and pain in passing urine)
• headache and back pain
• redness, soreness and swelling of the skin on the hands and feet (palmar-plantar erythrodysesthesia)
• changes in blood test results for potassium levels (low), calcium levels (low), cholesterol (high) and thyroid stimulating hormone (high), high lipase and amylase levels (enzymes involved in digestion), high creatinine levels (blood test results for kidney function).
• underactive thyroid (tiredness, weight gain, constipation, feeling cold, dry skin)
• 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
• changes in blood test results for liver function

Common (may affect up to 1 in 10 people)

• loss of body fluids (dehydration)
• heart palpitations
• dry skin, thickening and itching of the skin
• feeling bloated or having gas in the bowel
• heart problems or blood clots in the lungs (difficulty breathing, chest pain) or other organs
• liver failure
• drowsiness, confusion, poor concentration, loss of consciousness that may be signs of liver failure
• feeling unwell
• stroke
• inflammation of the gallbladder
• inflammation of the pancreas
• anal fistula (a small channel that forms between the anus and the surrounding skin)
• changes in blood test results for blood magnesium (low)
• changes in blood test results for kidney function (high blood urea levels) and kidney failure

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 part of the belly (abdomen) which may be associated with fever, chills, nausea and vomiting
• wound healing problems
• bone damage in the jaw (osteonecrosis)
• 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 lenvatinib 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).

Reporting 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 Yellow Card Scheme at: 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.

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 capsule: yellowish red body and yellowish red cap, approximately 14.3 mm in length, marked in black ink with „£“ 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 „£“ 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 Europe Limited

European Knowledge Centre

Mosquito Way

Hatfield

AL10 9SN

United Kingdom

Manufacturer

Eisai Manufacturing Limited,

European Knowledge Centre, MosquitoWay, Hatfield, AL10 9SN, United Kingdom

Company Contact Address: For further information on your medicine contact Medical Information at Eisai Europe Limited in Hatfield.

Tel: + 44 (0) 208 600 1400.

This leaflet was last revised in 10/2021

VARIABLE DATA

(e.g. Lot, Exp, Mfg, 2D code, serialisation etc.)

All Variable data is managed on the Market Specific Requirement Form, and is printed online at the time of packaging.

It does not appear on the artwork, and is not managed by the Artwork Department.

For all queries or requests to change the information please email the mailbox:

Please do not request changes to variable data on the Artwork.