Lenvatinib Accord

Lenvatinib Accord 4 mg hard capsules
Lenvatinib Accord 10 mg hard capsules
Lenvatinib
Equivalent medicine
Please read this leaflet carefully before 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 pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What Lenvatinib Accord is and what it is used for
2. What you need to know before taking Lenvatinib Accord
3. How to take Lenvatinib Accord
4. Possible side effects
5. How to store Lenvatinib Accord
6. Contents of the pack and other information

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

Lenvatinib Accord is a medicine that contains the active substance lenvatinib. It is used alone for the treatment of progressive or advanced thyroid cancer in adults when radioactive iodine treatment has not helped to stop the disease.

Lenvatinib Accord may also be used alone for the treatment of liver cancer (hepatocellular carcinoma) in adults who have not previously been treated with another anticancer medicine that spreads through the bloodstream. Lenvatinib Accord is given when the patient's liver cancer has spread or cannot be removed by surgery.

Lenvatinib Accord may also be used in combination with another anticancer medicine called pembrolizumab for the treatment of 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, or cannot be removed by surgery or radiotherapy.

How Lenvatinib Accord works
Lenvatinib Accord 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 Accord can slow down the rate at which cancer cells multiply and tumors grow, and help cut off the blood supply that the tumor needs.

2. What you should know before taking LENVATINIB ACCORD

Do not take Lenvatinib Accord

• 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 section “Pregnancy, breastfeeding and fertility”).

Warnings and precautions
Talk to your doctor before taking Lenvatinib Accord

• if you have high blood pressure
• if you are a woman of childbearing potential (see section “Pregnancy, breastfeeding and fertility”)
• 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 Lenvatinib Accord treatment, as the medicine may affect wound healing. Lenvatinib Accord 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 white or Asian
• if you weigh less than 60 kg
• if you have a history of abnormal connections (known as 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 ulcers in the mouth, numbness or a feeling of heaviness in the jaw, or loosening of a tooth. You may be advised to undergo a dental examination before starting Lenvatinib Accord, as jaw bone damage (osteonecrosis) has been reported in patients treated with Lenvatinib Accord. If you need invasive dental treatment or oral surgery, inform your dentist that you are being treated with Lenvatinib Accord, especially if you are or have also been treated with injectable bisphosphonates (used to prevent or treat bone diseases).
• If you are taking or have taken medicines used to treat osteoporosis (anti-resorptive bone agents) or anticancer medicines that affect blood vessel formation (so-called angiogenesis inhibitors), because the risk of jaw bone damage may be higher. Before taking Lenvatinib Accord, your doctor may perform certain tests, for example, to monitor blood pressure and liver or kidney function, and to check for low levels of salts and high levels of thyroid-stimulating hormone in the blood. Your doctor will discuss the results of these tests with you and decide whether you can receive treatment with Lenvatinib Accord. You may need additional treatment with other medicines, a lower dose of Lenvatinib Accord, or closer monitoring due to an increased risk of adverse effects.

If you have any doubts, talk to your doctor before taking Lenvatinib Accord.
Conditions requiring attention
Breakdown of tumour cells during cancer treatment may cause the release into the blood of substances that can lead to a series of complications known as tumour lysis syndrome (TLS). This condition may cause kidney problems that could potentially be fatal. 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
The use of Lenvatinib Accord is not currently recommended in children and adolescents under 18 years of age.
Other medicines and LENVATINIB ACCORD
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes herbal preparations and over-the-counter medicines.
Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.

• If you are a woman of childbearing age, 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 Accord may reduce the effectiveness of oral contraceptive pills; therefore, if this is your usual method of contraception, you should use an additional barrier method, such as a diaphragm or condom, if you have sexual intercourse during treatment with Lenvatinib Accord.
• Do not take Lenvatinib Accord if you are planning a pregnancy during treatment, as it may cause severe harm to the unborn child.
• If you become pregnant during treatment with Lenvatinib Accord, inform your doctor immediately. Your doctor will help you decide whether to continue treatment.
• Do not breastfeed while taking Lenvatinib Accord, as the medicine passes into breast milk and may cause severe harm to the breastfed infant.

Driving and using machines
Lenvatinib Accord 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 Accord 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 Accord

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Dosage
Thyroid cancer

• The recommended dose of Lenvatinib Accord 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 problems due to side effects.

Liver cancer

• The recommended dose of Lenvatinib Accord 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 problems due to side effects.

Endometrial cancer

• The recommended dose of Lenvatinib Accord 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 problems due to 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, you may prepare a liquid mixture using water, apple juice, or milk. The liquid mixture can be administered orally or via a feeding tube. If administered via a feeding tube, the liquid mixture must be prepared with water only. If not used immediately after preparation, the liquid mixture may be stored in a covered container and refrigerated at a temperature between 2 °C and 8 °C for up to 24 hours. Shake the liquid mixture for 30 seconds after removing it from the refrigerator. If the liquid mixture is not used within 24 hours of preparation, it must be discarded.
  Preparation and administration of the liquid mixture:
  o Place the intact capsules corresponding to the prescribed dose (up to 5 capsules) into a small container (capacity of approximately 20 mL (4 teaspoons)) or into an oral dosing syringe (20 mL); do not break or crush the capsules.
  o Add 3 mL of liquid to the container or oral dosing syringe. Wait 10 minutes to allow the capsule coating (outer surface) to dissolve, then mix or shake the mixture for 3 minutes until the capsules are completely dissolved.
  o If the liquid mixture is prepared in an oral dosing syringe, cap the syringe, remove the plunger, and use a second syringe or medicine dropper to add the liquid into the first syringe, then reinsert the plunger before mixing.
  o Drink the liquid mixture directly from the container or use an oral dosing syringe to administer it directly into the mouth or via a feeding tube.
  o Then, add another 2 mL of liquid to the container or oral dosing syringe using a second syringe or medicine dropper, mix or shake, and administer the liquid mixture. Repeat this step at least twice, or until no visible residue remains, to ensure the entire dose is administered.
• Take the capsules at approximately the same time each day.

How long to take Lenvatinib Accord
You will usually continue taking this medicine for as long as you are benefiting from it.
If you take more Lenvatinib Accord than you should
If you take more LENVATINIB ACCORD than prescribed, contact your doctor or pharmacist immediately. Bring the medicine package with you.
If you forget to take Lenvatinib Accord
Do not take a double dose (two doses at the same time) to make up for a missed dose.
What you should do if you miss a dose depends on how long it is until your next scheduled dose.

• If there are 12 hours or more until your next dose: take the missed dose as soon as you remember. Then take your next dose at the usual time.
• If there are less than 12 hours until 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 everybody will get them.
Tell your doctor immediately if you notice any of the following side effects – urgent medical treatment may be needed:

• Numbness or weakness on one side of the body, severe headache, seizures, confusion, difficulty speaking, vision changes, or dizziness: these may be signs of stroke, bleeding in the brain, or the effect of a severe increase in blood pressure in the brain.
• Chest pain or pressure, pain in the arms, back, neck, or jaw, shortness of breath, rapid or irregular heartbeat, cough, bluish color of the lips or fingertips: these may be signs of a heart problem, blood clot in the lungs, or air leaking from the lungs into the chest cavity, preventing the lungs from expanding.
• Severe abdominal (belly) 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, or bloody stools, or coughing up blood: these may be signs of internal bleeding.
• Yellowing of the skin or whites of the eyes (jaundice), drowsiness, confusion, or poor concentration: these may be signs of liver problems.
• Diarrhea, nausea, and vomiting: these are very common side effects, which can become severe if they lead to dehydration, possibly resulting in kidney failure. Your doctor may prescribe medicines to reduce these side effects.
• Pain in the mouth, teeth, and/or jaw, swelling or ulcers in the mouth, numbness or heaviness in the jaw, or loosening of a tooth: these could be signs of damage to the jawbone (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 tumor cells, known as tumor lysis syndrome (TLS).

Tell your doctor immediately if any of the above side effects occur.
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, diarrhea, abdominal pain, indigestion
• Marked feeling of fatigue or weakness
• Hoarseness
• Swelling of the legs
• 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 test results regarding protein (elevated) and urinary tract infections (increased frequency of urination and pain when urinating)
• 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)
• Decreased number of white blood cells
• Changes in blood test results regarding liver function
• Low platelet count in the blood, which may cause bruising and delayed 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 (enzymes involved in digestion)

Common (may affect up to 1 in 10 people)

• Loss of body fluids (dehydration)
• Palpitations
• Dry skin, thickening of the skin, and itching
• Feeling of bloating or excess 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)
• A 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 (transient ischemic attack)
• Liver damage
• Severe pain in the upper left side of the abdomen, which may be associated with fever, chills, nausea, and vomiting (splenic infarction)
• Inflammation of the pancreas
• Wound healing problems
• Jawbone 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):

• Tumor lysis syndrome (TLS)

Not known (frequency cannot be estimated from available data):

• Other types of fistulas (an abnormal connection between different organs in the body or between the skin and an underlying structure, such as the throat and trachea). Symptoms depend on where the fistula is located. Inform your doctor if you experience new or unusual symptoms, e.g., coughing while swallowing.
• Widening and weakening of the wall of a blood vessel or a tear in the 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 test results regarding protein (elevated) and urinary tract infections (increased frequency of urination and pain when urinating)
• Low platelet count in the blood, which may cause bruising and delayed wound healing
• Decreased number of white blood cells
• Decreased number of red blood cells
• Underactive thyroid (fatigue, weight gain, constipation, feeling cold, dry skin) and changes in blood test results regarding thyroid-stimulating hormone levels (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 (elevated)
• 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, diarrhea, 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)
• Rash
• Joint or muscle pain
• Marked feeling of 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
• Feeling of bloating or excess 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
• A 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, pain in the arms, back, neck, or jaw, shortness of breath, rapid or irregular heartbeat, cough, bluish color of the lips or fingertips, marked fatigue
• Severe breathing difficulty and chest pain caused by air leaking from the lungs into the chest cavity, preventing the lungs 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
• Wound healing problems

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

• Tumor lysis syndrome (TLS)

Reporting of side effects
If you get any side effects, 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. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Lenvatinib Accord

• 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 after “Exp.” and on the 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 no longer required. This will help protect the environment.

6. Package contents and other information

What Lenvatinib Accord contains

• The active substance is lenvatinib.
  • Lenvatinib Accord 4 mg hard capsules: - Each hard capsule contains lenvatinib besylate equivalent to 4 mg of lenvatinib.
  • Lenvatinib Accord 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, yellow iron oxide (E172).
• The cap of the capsule 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), potassium hydroxide.

Description of the appearance of Lenvatinib Accord and package contents

• 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" over "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" over "10".
• Each box contains 30, 60 or 90 hard capsules in blisters made of oPA/Al/PVC/Al or 30x1, 60x1 or 90x1 hard capsules in unit-dose divisible blisters made of oPA/Al/PVC/Al.
• Each box contains 30, 60 or 90 hard capsules in blisters made of oPA/Al/PVC/PE/Al with desiccant or 30x1, 60x1 or 90x1 hard capsules in unit-dose divisible blisters made of oPA/Al/PVC/PE/Al with desiccant.

Not all pack sizes may be marketed.
Marketing Authorization Holder
Accord Healthcare S.L.U.
World Trade Center, Moll de Barcelona, s/n,
Edifici Est 6ª planta,
08039 Barcelona,
Spain
Manufacturer
Synthon B.V.
Microweg 22
6545 CM Nijmegen
Gelderland
The Netherlands
Synthon Hispania S.L.
Calle De Castello 1
Sant Boi De Llobregat
08830 Barcelona
Spain
This medicinal product is authorized in the European Economic Area Member States under the following names:
4 mg

10 mg