Lenvima 10 mg Capsules

It contains the active ingredient lenvatinib (as lenvatinib mesilate). LENVIMA 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 LENVIMA may slow the rate at which the cancer cells multiply, and the tumour grows and by helping to cut off the blood supply that the cancer needs.

• LENVIMA is used to treat thyroid cancer in adults (> 18 years of age) when radioactive iodine treatment has not helped to stop your disease.
• It is also used in combination with everolimus to treat adult patients (> 18 years of age) with advanced kidney cancer (advanced renal cell carcinoma):
  • LENVIMA may be used with the medicine pembrolizumab as your first treatment when your kidney cancer has spread or cannot be removed by surgery.
  • LENVIMA may be used with the medicine everolimus after one course of treatment with another anti-cancer medicine.
• It is also used to treat liver cancer (hepatocellular carcinoma) in adult patients (> 18 years of age).
• It is also used (along with another medicine called pembrolizumab) to treat a kind of uterine cancer called endometrial carcinoma, if laboratory tests show the cancer is not microsatellite instability - high (MSI - H) or mismatch repair deficient (dMMR) and other treatments have not helped stop the disease.

Do not take LENVIMA :

• if you are hypersensitive (allergic) to LENVIMA (lenvatinib mesilate), or any of the other ingredients of LENVIMA
• if you have a fistula(e) (abnormal connection between to two spaces such as blood vessels, intestines and other organs), or if you are at risk of developing a fistula(e), such as after major surgery
• if you suffer from severe and/or uncontrolled high blood pressure
• if you have a condition in which you have a low blood platelet count and/or active bleeding
• if you are due to undergo surgery or radiotherapy (cancer treatment also called radiation therapy).

Warnings and precautions

Take special care with LENVIMA

• if you develop diarrhoea, nausea and vomiting. Treatment thereof should be initiated immediately to reduce the risk of developing complications such as dehydration and possible liver and kidney problems.
• if you have kidney problems
• if you have high blood pressure (refer to “Do not take Lenvima”)
• if you have ever had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in a blood vessel wall.
• have a history of blood clots in your arteries (type of blood vessel), including stroke, heart attack, or change in vision
• if you have neurological symptoms such as headache, seizure, lethargy, confusion, altered mental function, blindness, and other visual disturbances
• if you have liver problems
• if you have bleeding problems (refer to “Do not take Lenvima”)
• if you have had recent surgery
• if you need to have a surgical procedure. Your doctor may consider stopping LENVIMA if you will be undergoing a major surgical procedure as LENVIMA may affect wound healing. LENVIMA may be restarted once adequate wound healing is established.
• if you 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 LENVIMA as bone damage in the jaw (osteonecrosis) has been reported in patients treated with LENVIMA. If you need to undergo an invasive dental treatment or dental surgery, tell your dentist that you are being treated with LENVIMA, particularly when you are also receiving or have received injections of bisphosphonates (used to treat or prevent bone disorders)
• if you have thyroid problems
• if you are from Asian origin
• if you are over 75 years of age
• if you are younger than 18 years old. LENVIMA should not be used in children and teenagers.

Before taking LENVIMA, 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 LENVIMA. You may need to have additional treatment with other medicines, to take a lower dose of LENVIMA or to take extra care due to an increased risk of side effects.

Other medicines and LENVIMA

Always tell your healthcare provider if you are taking any other medicine. (This includes complementary or traditional medicines.)

Your doctor and pharmacist have more information on medicines to be careful with or to avoid while taking LENVIMA.

LENVIMA with food and drink

LENVIMA can be taken with or without food.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, please consult your doctor, pharmacist or other healthcare provider for advice before taking LENVIMA. You should not take LENVIMA if you are pregnant or while breastfeeding your baby.

Driving and using machines

It is not always possible to predict to what extent LENVIMA may interfere with the daily activities of a patient. Patients should ensure that they do not engage in driving a vehicle or use machines until they are aware of the measure to which LENVIMA affects them. LENVIMA may make you feel dizzy or tired, particularly at the beginning of treatment. If this happens to you, do not drive or use any tools or machines.

Do not share medicines prescribed for you with any other person. Always take LENVIMA exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

If you have thyroid cancer, the recommended dose for LENVIMA is 24 mg once a day (taken as 2 x 10 mg capsules and 1 x 4 mg capsule). If you have severe liver or kidney problems your doctor may prescribe a lower dose of 14 mg once a day (taken as 1 x 10 mg capsule and 1 x 4 mg capsule). If you have advanced kidney cancer and you have been prescribed LENVIMA in combination with pembrolizumab, the recommended dose for LENVIMA is 20 mg taken once a day (taken as 2 x 10 mg capsules). Your doctor will also give you an intravenous infusion of pembrolizumab for about 30 minutes every three weeks or every six weeks depending on the dose you are given. If you have advanced kidney cancer, the recommended dose for LENVIMA is 18 mg once a day (taken as 1 x 10 mg capsule and 2 x 4 mg capsules) in combination with one 5 mg tablet of everolimus once a day. If you have severe liver or kidney problems, your doctor may prescribe a lower dose of 10 mg once a day (taken as 1 x 10 mg capsule). Your doctor will check to see how much pembrolizumab or everolimus you should receive. If you have severe liver or kidney problems your doctor may prescribe a lower dose of 10 mg once a day (taken as 1 x 10 mg capsule) in combination with one 5 mg tablet of everolimus once a day. If you have endometrial carcinoma, the recommended dose for this medicine is 20 mg once a day (taken as 2 x 10 mg capsules). Your doctor will also give you an intravenous infusion of pembrolizumab for about 30 minutes every three weeks or every six weeks depending on the dose you are given. If you have severe liver or kidney problems your doctor may prescribe a lower dose of 10 mg once a day (taken as 1 x 10 mg capsule). Your doctor will check to see how much pembrolizumab you should receive.

How to take it

Swallow the capsules whole with a full glass of water. If unable to swallow the capsule whole, then place the capsule in a glass of about 25 mL of water or apple juice without breaking or crushing the capsules. Taking LENVIMA at the same time each day will have the best effect. It will also help you remember when to take it. Your doctor will tell you how long your treatment with LENVIMA will last. Do not stop treatment early. If you have the impression that the effect of LENVIMA is too strong or too weak, tell your doctor or pharmacist.

If you take more LENVIMA than you should

In the event of overdosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison centre.

If you forget to take LENVIMA

Do not take a double dose to make up for forgotten individual doses.

LENVIMA can have side effects. Not all side effects reported for LENVIMA are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking LENVIMA, please consult your doctor, pharmacist or other healthcare provider for advice.

If any of the following happens, stop taking LENVIMA and tell your doctor immediately or go to the casualty department at your nearest hospital:

• swelling of the hands, feet, ankles, face, lips and mouth or throat, which may cause difficulty in swallowing or breathing,
• rash or itching,
• fainting (dizziness).

These are all very serious side effects. If you have them, you may have had a serious reaction to LENVIMA. You may need urgent medical attention or hospitalisation.

Tell your doctor immediately or go to the casualty department at your nearest hospital if you notice any of the following:

• feeling numb or weak on one side of your body, severe headache, seizure or fit, confusion, difficulty talking, vision changes or feeling dizzy – these may be signs of a stroke, bleeding on your brain or the effect on your brain of a severe increase in blood pressure or posterior reversible encephalopathy syndrome (PRES);
• chest pain or pressure, pain in your arms, back, neck, jaw, being short of breath, rapid or irregular heart rate, coughing, bluish colour to the lips or fingers, feeling very tired – these may be signs of a heart problem or blood clot in your lungs;
• 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;
• severe pain in the back, chest or abdomen associated with tearing in the wall of the aorta and internal bleeding;
• yellow skin or yellowing of the whites of the eyes (jaundice) or drowsiness, confusion, poor concentration – these may be signs of liver problems and or failure;
• pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw loosening of a tooth – this may be a sign of osteonecrosis of the jaw;
• 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.

Tell your doctor if you notice any of the following:

The following side effects may happen with this medicine given alone:

Very Common (may affect more than 1 in 10 people):

• decreases in the number of white blood cells
• bruising and difficulty in wound healing – signs of low level of platelets in the blood
• underactive thyroid (tiredness, weight gain, constipation, feeling cold, dry skin)
• feeling sick and being sick, constipation, diarrhoea, stomach pain, indigestion
• dry, sore or inflamed mouth, odd taste sensation
• feeling tired or weak
• fever
• swelling of the legs
• inflammation of the liver
• urinary infections (increased frequency in urination and difficult or painful passing of urine)
• painful infection or irritation near the anus
• weight loss
• electrical disturbance in your heart rhythm
• increased liver enzyme levels
• high levels of thyroid stimulating hormone in blood tests
• increased urea in blood
• abnormal liver function
• loss of appetite
• low levels of sodium, magnesium, potassium and calcium in blood tests, loss of body fluids (dehydration)
• high levels of cholesterol
• swelling and inflammation of the joints, and stiff muscles, bones and joints
• pain – muscle, joint, headache, back, legs
• headache
• weakness limited to one limb without sensory disturbance
• trouble sleeping
• increased protein in the urine
• changes in blood test results for kidney function and kidney failure
• cough or hoarse voice
• redness, soreness and swelling of the skin on the hands and feet (hand-foot syndrome)
• hair loss
• bleeding (most commonly nose bleeds, but may include bleeding from other sites such as blood in the urine, bruising, bleeding from the gums or gut wall)
• high or low blood pressure
• high levels of potassium
• rash
• increase in lipase and amylase (enzymes involved in digestion)
• back pain
• feeling dizzy

Common (may affect up to 1 in 10 people):

• feeling bloated or gas in the bowel, abdominal swelling
• anal fistula (a small channel that forms between the anus and the surrounding skin)
• anal pain, constipation and fever (perineal abscess)
• heart problem or blood clots in the lungs (difficulty breathing, chest pain) or other organs
• dry skin, thickening and itching of skin
• liver failure
• shortness of breath or severe chest pain which may be signs of a collapsed lung
• drowsiness, confusion, poor concentration, loss of consciousness that may be signs of liver failure
• loss of body fluids (dehydration)
• heart palpitations
• feeling unwell
• inflammation of the gallbladder
• stroke

Uncommon

• mini-stroke
• anal pain, constipation and fever (perineal abscess)
• severe pain in the upper left part of the belly (abdomen) which may be associated with fever, chills, nausea and vomiting (splenic infarction)
• inflammation of the pancreas
• liver damage
• wound healing problems
• bone damage in the jaw (osteonecrosis)
• inflammation of the colon (colitis)

Not known

(the following side effects have been reported since the marketing of LENVIMA but the frequency for them to occur is not known)

• severe pain in the back, chest or abdomen associated with tearing in the wall of the aorta and internal bleeding.
• 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 unusual symptoms such as coughing when swallowing.

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):

• changes in urine tests for protein (high) and urinary infections (increased frequency in urination and pain in passing urine)
• 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
• decrease in the number of red blood cells
• underactive thyroid (tiredness, weight gain, constipation, feeling cold, dry skin) and changes in blood test results for thyroid stimulating hormone (high)
• overactive thyroid (symptoms can include rapid heart rate, sweating and weight loss)
• changes in blood test results for calcium levels (low)
• changes in blood test results for potassium levels (low)
• changes in blood test results for cholesterol levels (high)
• changes in blood test results for magnesium levels (low)
• loss of appetite or weight loss
• feeling dizzy
• headache
• back pain
• dry, sore, or inflamed mouth, odd taste sensation
• 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
• increase in amylase (enzyme involved in digestion)
• increase in lipase (enzyme involved in digestion)
• changes in blood test results for liver function
• changes in blood test results for kidney function
• redness, soreness and swelling of the skin on the hands and feet (palmar-plantar erythrodysaesthesia)
• rash
• joint or muscle pain
• 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

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

Not Known

• 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 unusual symptoms such as coughing when swallowing.
• decreased secretion of hormones produced by adrenal glands

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor, pharmacist or nurse. You can also report side effects to SAHPRA via the MedSafety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. By reporting side effects, you can help provide more information on the safety of LENVIMA.

STORE ALL MEDICINES OUT OF REACH OF CHILDREN.

Store at or below 30 °C.

Store in the original container until required for use.

Do not use after the expiry date stated on the label / carton / bottle.

Return all unused medicine to your pharmacist.

Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).