Lenvatinib Teva: detailed information

Patient Information Leaflet: Information for the User

Lenvatinib Teva 4 mg Hard Capsules, 10 mg Hard Capsules

lenvatinib
Generic Medicine
Please read all of 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

What Lenvatinib Teva is and what it is used for
What you need to know before taking Lenvatinib Teva
How to take Lenvatinib Teva
Possible side effects
How to store Lenvatinib Teva
Contents of the pack and other information

1. What Lenvatinib Teva is and what it is used for

Lenvatinib Teva is a medicine that contains the active substance lenvatinib. It is used on its own to treat advanced or progressive thyroid cancer in adults when radioactive iodine treatment has not helped stop the disease.
Lenvatinib Teva may also be used on its own to treat liver cancer (hepatocellular carcinoma) in adults who have not previously been treated with another anticancer medicine that spreads through the bloodstream. Lenvatinib Teva is administered when liver cancer has spread or cannot be removed by surgery.
Lenvatinib Teva can also be used in combination with another anticancer medicine called pembrolizumab to treat advanced cancer of the lining of the uterus (endometrial carcinoma) in adult women whose cancer has spread after prior treatment with another anticancer medicine that spreads through the bloodstream and that cannot be removed by surgery or radiotherapy.

How Lenvatinib Teva works
Lenvatinib Teva blocks the action of proteins called tyrosine kinase receptors (RTKs), which are involved in the development of new blood vessels that supply oxygen and nutrients to cells, helping them grow. These proteins may be present in high amounts in cancer cells. By blocking their action, Lenvatinib Teva can slow down the rate of cancer cell multiplication and tumor growth, and help stop the blood supply that the tumor needs.

2. What you need to know before taking Lenvatinib Teva

Do not take Lenvatinib Teva:

if you are allergic to lenvatinib or to any of the other ingredients of this medicine (listed in section 6);
if you are breastfeeding (see the section “Contraception, pregnancy and breastfeeding” below).

Warnings and precautions
Talk to your doctor before taking Lenvatinib Teva:

if you have high blood pressure;
if you are a woman of childbearing potential (see the section “Contraception, pregnancy and breastfeeding” below);
if you have previously had heart problems or stroke;
if you have liver or kidney problems;
if you have recently undergone surgery or radiotherapy;
if you are scheduled for a surgical procedure. If you are to undergo major surgery, your doctor may consider interrupting treatment with Lenvatinib Teva, as the medicine may affect wound healing. Lenvatinib Teva may be restarted once adequate wound healing has been established;
if you are over 75 years old;
if you belong to an ethnic group other than Caucasian or Asian;
if you weigh less than 60 kg;
if you have a history of abnormal connections (called fistulas) between different organs in the body or from an organ to the skin;
if you have or have had an aneurysm (dilation and weakening of a blood vessel wall) or a tear in the wall of a blood vessel;
if you have or have had mouth, tooth, and/or jaw pain, swelling or mouth ulcers, numbness or a feeling of heaviness in the jaw, or loosening of a tooth. You may be advised to have a dental examination before starting treatment with Lenvatinib Teva, as jawbone damage (osteonecrosis) has been reported in patients treated with Lenvatinib Teva. If you need invasive dental treatment or oral surgery, inform your dentist that you are being treated with Lenvatinib Teva, especially if you are receiving or have received bisphosphonate injections (used to treat or prevent bone disorders);
if you are receiving or have received certain medicines used to treat osteoporosis (anti-resorptive bone agents) or anticancer medicines that affect blood vessel formation (so-called angiogenesis inhibitors), as the risk of jawbone damage may be higher. Before taking Lenvatinib Teva, your doctor may perform certain tests, for example, to monitor blood pressure and liver or kidney function, and to check whether you have low levels of blood salts and high levels of thyroid-stimulating hormone. Your doctor will discuss the results of these tests with you and decide whether Lenvatinib Teva can be administered. You may need additional treatment with other medicines, a lower dose of Lenvatinib Teva, or closer monitoring due to an increased risk of adverse effects.

If you have any doubts, talk to your doctor before taking Lenvatinib Teva.
Conditions requiring attention
Breakdown of tumour cells during cancer treatment may cause the release of substances into the blood, leading to a series of complications known as tumour lysis syndrome (TLS). This condition may cause kidney problems and can be life-threatening. Your doctor will monitor you and may prescribe treatment to reduce this risk. Inform your doctor immediately if you notice signs of TLS (see section 4: “Possible side effects”).
Children and adolescents
Currently, the use of Lenvatinib Teva is not recommended in children and adolescents under 18 years of age.
Other medicines and Lenvatinib Teva
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including herbal preparations and non-prescription medicines.
Contraception, pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

If you are a woman of childbearing potential, use highly effective contraceptive methods during treatment with this medicine and for at least one month after the end of treatment. It is not known whether Lenvatinib Teva may reduce the effectiveness of oral contraceptive pills; therefore, if this is your usual method of contraception, you must also use an additional barrier method, such as a cervical cap or condom, if you have sexual intercourse during treatment with Lenvatinib Teva.
Do not take Lenvatinib Teva if you are planning a pregnancy during treatment, as it may cause severe harm to the unborn child.
If you become pregnant while taking Lenvatinib Teva, inform your doctor immediately. Your doctor will help you decide whether to continue treatment.
Do not breastfeed while taking Lenvatinib Teva, as the medicine passes into breast milk and may cause severe harm to the infant.

Driving and using machines
Lenvatinib Teva may cause side effects that could impair your ability to drive or operate machinery. Avoid driving or operating machinery if you experience dizziness or fatigue.
Lenvatinib Teva contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per hard capsule, i.e. essentially “sodium-free”.

3. How to take Lenvatinib Teva

Take this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Dosage
Thyroid cancer

The recommended dose of Lenvatinib Teva is usually 24 mg once daily (2 capsules of 10 mg and 1 capsule of 4 mg).
If you have severe liver or kidney problems, the recommended dose is 14 mg once daily (1 capsule of 10 mg and 1 capsule of 4 mg).
Your doctor may reduce the dose if you experience side effects.

Liver cancer

The recommended dose of Lenvatinib Teva depends on your body weight at the start of treatment. The dose is usually 12 mg once daily (3 capsules of 4 mg) if you weigh 60 kg or more, and 8 mg once daily (2 capsules of 4 mg) if you weigh less than 60 kg.
Your doctor may reduce the dose if you experience side effects.

Uterine cancer

The recommended dose of Lenvatinib Teva is 20 mg once daily (2 capsules of 10 mg) in combination with pembrolizumab. Pembrolizumab is administered by your doctor as an intravenous injection, at a dose of 200 mg every 3 weeks or 400 mg every 6 weeks.
Your doctor may reduce the dose if you experience side effects.

How to take this medicine

You may 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, alternative lenvatinib-containing medicines should be used instead of Lenvatinib Teva.
Take the capsules at approximately the same time each day.

How long to take Lenvatinib Teva
You will usually continue taking this medicine for as long as you are benefiting from it.
If you take more Lenvatinib Teva than you should
If you take more Lenvatinib Teva than you should, contact your doctor or pharmacist immediately. Take the medicine pack with you.
If you forget to take Lenvatinib Teva
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 a dose depends on how long it is until your next scheduled dose.

If 12 hours or more remain before your next dose: take the missed dose as soon as you remember. Then take your next dose at the usual time.
If less than 12 hours remain before your next dose: skip the missed dose. Then take your next dose at the usual time.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Immediately inform your doctor if you experience any of the following side effects, as you may
require urgent medical treatment:

numbness or weakness on one side of the body, severe headache, seizures, confusion, difficulty speaking, vision changes, or dizziness: these may be signs of a stroke, bleeding in the brain, or the effect on the brain of a severe increase in blood pressure;
chest pain or pressure, arm, back, neck, or jaw pain, shortness of breath, rapid or irregular heartbeat, cough, bluish discoloration of the lips or fingertips, or extreme fatigue: these may be signs of a heart problem, blood clot in the lung, or air leaking from the lung into the chest cavity, preventing the lung from expanding;
severe abdominal pain, which may be due to a hole in the intestinal wall or a fistula (an abnormal connection between the intestine and another part of the body or skin via a tubular passage);
black, tarry stools or blood in the stool, or coughing up blood: these may be signs of internal bleeding;
yellowing of the skin or whites of the eyes (jaundice), or drowsiness, confusion, poor concentration: these may be signs of liver problems;
diarrhoea, nausea, and vomiting: these are very common side effects, which may become severe if they lead to dehydration, possibly resulting in kidney failure. Your doctor may prescribe a medicine to reduce these side effects;
mouth, tooth, and/or jaw pain, mouth swelling or ulcers, numbness or heaviness in the jaw, or loose teeth: these could be signs of jaw bone damage (osteonecrosis);
nausea, shortness of breath, irregular heartbeat, muscle cramps, seizures, cloudy urine, and fatigue. These symptoms may be complications due to the breakdown products of dying tumour cells, known as tumour lysis syndrome (TLS).

Immediately inform your doctor if you experience any of the above side effects.
When this medicine is given alone, the following side effects may occur:
Very common (may affect more than 1 in 10 people)

high or low blood pressure
loss of appetite or weight loss
nausea and vomiting, constipation, diarrhoea, abdominal pain, indigestion
extreme fatigue or weakness
hoarseness
swelling of the legs
skin rash
dry, sore, or inflamed mouth, altered taste sensation
joint or muscle pain
dizziness
hair loss
bleeding (most commonly nosebleeds, but also other types of bleeding, e.g. blood in urine, bruising, bleeding from gums or intestinal wall)
difficulty sleeping
changes in urine tests regarding protein (elevated) and urinary tract infections (increased frequency of urination and pain during urination)
headache
back pain
redness, pain, and swelling of the skin on the hands and feet (palmar-plantar erythrodysesthesia)
underactive thyroid (fatigue, weight gain, constipation, feeling cold, dry skin)
changes in blood test results regarding potassium levels (low) and calcium levels (low)
decrease in white blood cell count
changes in blood test results regarding liver function
low platelet count in the blood, which may cause bruising and impaired wound healing
changes in blood test results regarding magnesium (low), cholesterol (high), and thyroid-stimulating hormone (high)
changes in blood test results regarding kidney function and kidney failure
increased lipase and amylase levels (enzymes involved in digestion)

Common (may affect up to 1 in 10 people)

loss of body fluids (dehydration)
palpitations
dry skin, skin thickening, and itching
bloating or excessive gas
heart problems or blood clots in the lungs (difficulty breathing, chest pain) or in other organs
liver failure
drowsiness, confusion, poor concentration, loss of consciousness, which may be signs of liver failure
feeling unwell
inflammation of the gallbladder
stroke
anal fistula (a small channel forming between the anus and surrounding skin)
hole (perforation) in the stomach or intestine

Uncommon (may affect up to 1 in 100 people)

painful or irritated infection near the anus
mini-stroke
liver damage
severe pain in the upper left part of the abdomen, possibly associated with fever, chills, nausea, and vomiting (splenic infarction)
inflammation of the pancreas
impaired wound healing
jaw bone damage (osteonecrosis)
inflammation of the colon (colitis)
decreased secretion of hormones produced by the adrenal glands

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

tumour lysis syndrome (TLS)

Not known (frequency cannot be estimated from available data)

other types of fistulas (abnormal connections between different organs in the body or between the skin and an underlying structure, such as the throat and trachea). Symptoms depend on the location of the fistula. Inform your doctor if you experience new or unusual symptoms, such as coughing while swallowing.
dilation and weakening of a blood vessel wall or tearing of a blood vessel wall (aneurysms and arterial dissections)

When this medicine is given in combination with pembrolizumab, the following side effects may occur:
Very common (may affect more than 1 in 10 people)

changes in urine tests regarding protein (elevated) and urinary tract infections (increased frequency of urination and pain during urination)
low platelet count in the blood, which may cause bruising and impaired wound healing
decrease in white blood cell count
decrease in red blood cell count
underactive thyroid (fatigue, weight gain, constipation, feeling cold, dry skin) and changes in blood test results regarding thyroid-stimulating hormone (elevated)
overactive thyroid (symptoms may include rapid heartbeat, sweating, and weight loss)
changes in blood test results regarding calcium levels (low)
changes in blood test results regarding potassium levels (low)
changes in blood test results regarding cholesterol levels (high)
changes in blood test results regarding magnesium levels (low)
loss of appetite or weight loss
dizziness
headache
back pain
dry, sore, or inflamed mouth, altered taste sensation
bleeding (most commonly nosebleeds, but also other types of bleeding, e.g. blood in urine, bruising, bleeding from gums or intestinal wall)
high blood pressure
hoarseness
nausea and vomiting, constipation, diarrhoea, abdominal pain
increased amylase (digestive enzyme)
increased lipase (digestive enzyme)
changes in blood test results regarding liver function
changes in blood test results regarding kidney function
redness, pain, and swelling of the skin on the hands and feet (palmar-plantar erythrodysesthesia)
skin rash
joint or muscle pain
extreme fatigue or weakness
swelling of the legs

Common (may affect up to 1 in 10 people)

loss of body fluids (dehydration)
difficulty sleeping
palpitations
low blood pressure
blood clots in the lungs (difficulty breathing, chest pain)
inflammation of the pancreas
bloating or excessive gas
indigestion
inflammation of the gallbladder
hair loss
kidney failure
feeling unwell
inflammation of the colon (colitis)
decreased secretion of hormones produced by the adrenal glands
hole (perforation) in the stomach or intestine

Uncommon (may affect up to 1 in 100 people)

headache, confusion, seizures, and vision changes
signs of stroke, including numbness or weakness on one side of the body, severe headache, seizures, confusion, difficulty speaking, vision changes, or dizziness
mini-stroke
signs of a heart problem, including chest pain or pressure, arm, back, neck, or jaw pain, shortness of breath, rapid or irregular heartbeat, cough, bluish discoloration of the lips or fingertips, and extreme fatigue
severe difficulty breathing and chest pain caused by air leaking from the lung into the chest cavity, preventing the lung from expanding
painful or irritated infection near the anus
anal fistula (a small channel forming between the anus and surrounding skin)
liver failure or signs of liver damage, including yellowing of the skin or whites of the eyes (jaundice), drowsiness, confusion, poor concentration
dry skin, skin thickening, and itching
impaired wound healing

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

tumour lysis syndrome (TLS)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Lenvatinib Teva

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.
Store in the original packaging to protect the medicine from moisture.
Do not dispose of any medicine via 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 Lenvatinib Teva contains

The active substance is lenvatinib.
Lenvatinib Teva 4 mg hard capsules: - Each hard capsule contains lenvatinib besylate equivalent to 4 mg of lenvatinib.
Lenvatinib Teva 10 mg hard capsules: - Each hard capsule contains lenvatinib besylate equivalent to 10 mg of lenvatinib.
The other components are sodium bicarbonate, mannitol, microcrystalline cellulose, hydroxypropylcellulose, low-substituted hydroxypropylcellulose, talc.
The capsule shell of the 4 mg capsules contains hypromellose, titanium dioxide, yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172).
The capsule shell of the 10 mg capsules contains hypromellose, titanium dioxide, and yellow iron oxide (E172).
The capsule cap contains hypromellose, titanium dioxide, yellow iron oxide (E172), red iron oxide (E172), black iron oxide (E172).
The printing ink contains shellac, black iron oxide (E172), and potassium hydroxide.

Description of the appearance of Lenvatinib Teva and contents of the pack

The 4 mg hard capsule (capsule) has an opaque caramel-colored body and an opaque caramel-colored cap (approximately 14.3 mm in length), printed with “L7VB” above “4”.
The 10 mg hard capsule (capsule) has an opaque yellow body and an opaque caramel-colored cap (approximately 14.3 mm in length), printed with “L7VB” above “10”.
Each box contains 30, 60, or 90 hard capsules in blisters oPA/Al/PVC/Al or 30 x 1, 60 x 1, or 90 x 1 hard capsules in unit-dose divisible blisters oPA/Al/PVC/Al.
Each box contains 30, 60, or 90 hard capsules in blisters oPA/Al/PVC/PE/Al with desiccant or 30 x 1, 60 x 1, or 90 x 1 hard capsules in unit-dose divisible blisters oPA/Al/PVC/PE/Al with desiccant.

Not all pack sizes may be marketed.
Marketing Authorization Holder
Teva Italia S.r.l. – Piazzale Luigi Cadorna, 4 – 20123 Milan, Italy
Manufacturers
Synthon Hispania S.L., Calle De Castello 1, Sant Boi De Llobregat, Barcelona 08830, Spain
Synthon B.V., Microweg 22, Nijmegen, Gelderland 6545 CM, Netherlands

This medicinal product is authorized in the European Economic Area countries under the following names:

4 mg
Netherlands: Lenvatinib Teva 4 mg, harde capsules
Austria: Lenvatinib Teva 4 mg Hartkapseln
Czech Republic: Lenvatinib Teva
Denmark: Lenvatinib Teva
Finland: Lenvatinib ratiopharm 4 mg kapseli, kova
France: LENVATINIB TEVA 4 mg, gélule
Germany: Lenvatinib-ratiopharm 4 mg Hartkapseln
Greece: Lenvatinib/Teva
Italy: Lenvatinib Teva
Norway: Lenvatinib Teva
Portugal: Lenvatinib Teva
Spain: Lenvatinib Teva 4 mg cápsulas duras EFG
Sweden: Lenvatinib Teva

10 mg
Netherlands: Lenvatinib Teva 10 mg, harde capsules
Austria: Lenvatinib Teva 10 mg Hartkapseln
Czech Republic: Lenvatinib Teva
Denmark: Lenvatinib Teva
Finland: Lenvatinib ratiopharm 10 mg kapseli, kova
France: LENVATINIB TEVA 10 mg, gélule
Germany: Lenvatinib-ratiopharm 10 mg Hartkapseln
Greece: Lenvatinib/Teva
Italy: Lenvatinib Teva
Norway: Lenvatinib Teva
Portugal: Lenvatinib Teva
Spain: Lenvatinib Teva 10 mg cápsulas duras EFG
Sweden: Lenvatinib Teva