Label: information for the patient

Caprelsa 100mg film-coated tablets

Caprelsa 300mg film-coated tablets

vandetanib

In addition to this label, you will be provided with the Patient Information Leaflet, which contains important safety information that you need to know before you are given Caprelsa and during treatment with Caprelsa.

Read this label carefully before starting to take this medicine, because it contains important information for you.

• Keep this label and the patient information leaflet, as you may need to refer to them again.
• It is important to keep the Patient Information Leaflet with you during treatment.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist,even if they are not listed in this label. See section4.

1.What is Caprelsa and what it is used for

2.What you need to knowabefore starting to take Caprelsa

3.How to take Caprelsa

4.Possible side effects

5.Storage of Caprelsa

6. Contents of the pack and additional information

Caprelsa is a treatment for adults and children aged 5 years and older with:

A type of medullary thyroid cancer known as RET rearranged during transfection (RET) mutation that cannot be removed by surgery or has spread to other parts of the body.

Caprelsa works by reducing the growth rate of new blood vessels in tumors (cancers). This interrupts the supply of food and oxygen to the tumor. Caprelsa may also act directly on cancerous cells by destroying them or slowing their growth.

Do not take Caprelsa:

• if you are allergic to vandetanib or any of the other ingredients in this medicine (listed in section6).
• if you have a heart birth defect called “long QTc congenital syndrome”. This is observed in an electrocardiogram (ECG).
• if you are breastfeeding.
• if you are taking any of the following medicines: arsenic, cisapride (used for heartburn), intravenous erythromycin and moxifloxacin (used to treat an infection), toremifene (used to treat breast cancer), mizolastine (used to treat allergies), Class IA and III antiarrhythmics (used to control heart rhythm).

If any of the above cases apply to you, do not takeCaprelsa. If you are unsure, consult your doctor.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Caprelsa:

• if you are sensitive to the sun.Some people who take Caprelsa become more sensitive to the sun. This can cause sunburn. While taking Caprelsa, protect yourself when going outside by always using sunscreen and wearing clothing to avoid sun exposure.
• if you have high blood pressure.
• if you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in the wall of a blood vessel.
• if you need to undergo a surgical procedure. Your doctor may consider stopping Caprelsa if you undergo a major surgical procedure, as Caprelsa may affect wound healing. Caprelsa may be restarted once adequate wound healing has occurred.
• if you have kidney problems.

Severe skin reactions (SRSs), including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported in association with vandetanib treatment. Stop using Caprelsa and seek medical attention immediately if you notice any symptoms related to these severe skin reactions described in section 4.

Your doctor will need to determine the status of your RET cancer before starting treatment with Caprelsa.

Blood and heart monitoring:

Your doctor or nurse should perform tests to check your potassium, calcium, magnesium, and thyroid-stimulating hormone (TSH) levels in the blood, as well as the electrical activity of your heart with an electrocardiogram (ECG). These tests should be performed:

• before starting to take Caprelsa
• regularly during treatment with Caprelsa
• 1, 3, and 6weeks after starting Caprelsa
• 12weeks after starting Caprelsa
• then every 3months
• if your doctor or pharmacist change your Caprelsa dose
• if you start taking medicines that affect the heart
• as instructed by your doctor or pharmacist

Children

Caprelsa should not be administered to children under 5 years old.

Caprelsa with other medicines

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine, including those purchased without a prescription and herbal remedies. This is becauseCaprelsamay affect the way some medicines work and some medicines may affectCaprelsa.

Inform your doctor or pharmacist if you are taking any of the following medicines:

• itraconazole, ketoconazole, ritonavir, clarithromycin, rifampicin, and moxifloxacin (medicines used to treat infections)
• carbamazepine and phenobarbital (used to control seizures)
• ondansetron (used to treat nausea and vomiting)
• cisapride (used to treat heartburn), pimozide (used to treat involuntary and repetitive body movements and verbal outbursts), and halofantrine and lumefantrine (used to treat malaria)
• methadone (used to treat addiction), haloperidol, chlorpromazine, sulpiride, amisulpride, and zuclopenthixol (used to treat mental illnesses)
• pentamidine (used to treat an infection)
• anticoagulants (often called “blood thinners”)
• ciclosporin and tacrolimus (used to treat transplant rejection), digoxin (used to treat irregular heart rhythm), and metformin (used to control blood sugar)
• proton pump inhibitors (used to treat heartburn)

You will also find this information in the Patient Information Leaflet that your doctor has given you. It is essential to keep this leaflet and show it to your partner or caregivers.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. This is becauseCaprelsamay harm your baby. Your doctor will discuss the benefits and risks of taking Caprelsa during this period.

• If you could become pregnant, you must use an effective contraceptive method while takingCaprelsaand for at least four months after your last dose ofCaprelsa.

For the safety of your baby, do not breastfeed during treatment withCaprelsa.

Driving and operating machinery

Be cautious before driving or operating machinery. Note thatCaprelsamay make you feel tired, weak, or cause blurred vision.

Use in Adults

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

• The recommended dose is 300 mg per day.
• Take Caprelsa approximately at the same time every day.
• Caprelsa can be taken with or without food.

Use in Children and Adolescents

Your doctor will inform you how many Caprelsa tablets to administer to your child. The amount of Caprelsa administered will depend on your child's body weight and height. The total daily dose in children should not exceed 300 mg. Your child's treatment can be given as a single dose per day, a dose every two days, or a 7-day periodic program as indicated in the dosing guide provided by your doctor. It is essential to keep this dosing guide and teach it to your caregiver.

If You Have Difficulty Swallowing the Tablet

If you have difficulty swallowing the tablet, you can mix it with water as follows:

• Take half a glass of water (without gas). Use only water, do not use any other liquid.
• Place the tablet in the water.
• Remove the tablet until it has dissolved in the water. This may take about 10 minutes.
• Drink it immediately then.

To ensure no medication remains, fill the glass with water up to the middle and drink it.

If You Experience Adverse Effects

If you experience adverse effects, always inform your doctor. Your doctor may tell you to take Caprelsa at a higher or lower dose (such as two 100 mg tablets or one 100 mg tablet). Your doctor may also prescribe other medications to help control adverse effects. Adverse effects of Caprelsa are listed in section 4.

If You Take More Caprelsa Than Prescribed

If you have taken more Caprelsa than prescribed, consult a doctor or go to the hospital immediately.

If You Forget to Take Caprelsa

What to do if you forget to take a tablet depends on how much time is left until your next dose:

• If there are 12 hours or more until your next dose:Take the missed tablet as soon as you remember. Then take the next dose at the usual time.
• If there are less than 12 hours until your next dose:Do not take the missed dose. Then take the next dose at the usual time.

Do not take a double dose (two doses at once) to compensate for missed doses.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. If you experience side effects, your doctor may tell you to take Caprelsa at a lower dose. Your doctor may also prescribe other medicines to help control the side effects.

Inform your doctor immediately if you notice any of the following side effects - you may need urgent medical treatment:

• Weakness, dizziness, or changes in heart rhythm. These may be signs of a change in heart electrical activity. These are seen in 8% of people taking Caprelsa for medullary thyroid cancer. Your doctor may recommend that you take Caprelsa at a lower dose or stop taking it. Caprelsa has been associated with rare but potentially life-threatening changes in heart rhythm.
• Stop using Caprelsa and seek medical attention immediately if you notice any of the following symptoms: flat red spots, in the shape of a target or circles on the trunk, often with central blisters, skin peeling, mouth ulcers, throat, nose, genital, and eye ulcers. These severe skin eruptions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Severe diarrhea.
• Severe difficulty breathing, or sudden worsening of breathing difficulty, possibly with cough or high fever (pneumonitis). This may mean you have an inflammation of the lungs called "interstitial lung disease". This is rare (affects less than 1 in 100 people) but can be life-threatening.
• Seizures, headaches, confusion, or difficulty concentrating. These may be signs of a condition called SLPR (Posterior Reversible Leukoencephalopathy Syndrome). These usually stop when Caprelsa is stopped. SLPR is rare (affects less than 1 in 100 people).

Inform your doctor immediately if you notice any of the above side effects.

Other side effects include:

Very common (affects more than 1 in 10 people):

• Diarrhea. Your doctor may prescribe a medicine to treat it. If it worsens, inform your doctor immediately.
• Abdominal pain.
• Skin rash or acne.
• Depression.
• Fatigue.
• Nausea.
• Indigestion (dyspepsia).
• Nail changes.

• Vomiting.
• Loss of appetite (anorexia).
• Weakness (asthenia).
• High blood pressure. Your doctor may prescribe a medicine to treat it.
• Headache.
• Fatigue.
• Insomnia (difficulty sleeping).
• Nasal congestion.
• Bronchitis.
• Upper respiratory tract infections.
• Urinary tract infections.
• Insensitivity or numbness of the skin.
• Abnormal skin sensation.
• Dizziness.
• Pain.
• Swelling caused by excess fluid (edema).
• Calcium deposits or stones in the urinary tract (nephrolithiasis).
• Blurred vision, including mild changes in the eye that may cause blurred vision (corneal opacity).
• Sensitivity of the skin to sunlight. While taking Caprelsa, protect yourself when going outside by always using sunscreen and wearing clothing to avoid sun exposure.

Common (affects less than 1 in 10 people):

• Dehydration.
• Severe high blood pressure.
• Weight loss.
• Stroke or other conditions where the brain may not receive enough blood.
• A type of rash that affects the hands and feet (hand-foot syndrome).
• Mouth irritation (stomatitis).
• Dry mouth.
• Pneumonia.
• Toxins in the blood as a complication of infection.
• Influenza.
• Urinary tract inflammation.
• Mastitis.
• Laryngitis.
• Folliculitis, especially a hair follicle.
• Boil.
• Fungal infection.
• Renal infection.
• Fluid loss (dehydration).
• Anxiety.
• Tremor.
• Numbness.
• Loss of consciousness.
• Unsteadiness.
• Increased eye pressure (glaucoma).
• Coughing up blood.
• Pulmonary inflammation.
• Difficulty swallowing.
• Constipation.
• Gastritis.
• Gastrointestinal bleeding.
• Bile stones (cholelithiasis).
• Painful urination.
• Renal insufficiency.
• Frequent urination.
• Urgent need to urinate.
• Fever.
• Nasal bleeding (epistaxis).
• Dry eyes.
• Eye irritation (conjunctivitis).
• Visual disturbances.
• Halos around lights.
• Seeing flashes of light (photopsia).
• Corneal changes (keratopathy).
• A type of diarrhea (colitis).
• Head or body hair loss (alopecia).
• Changes in the taste of food (dysgeusia).

Rare (affects less than 1 in 100 people):

• Heart failure.
• Appendicitis.
• Bacterial infection.
• Diverticulitis (inflammation of small pouches in the digestive system).
• Bacterial skin infection.
• Abdominal wall abscesses.
• Malnutrition.
• Uncontrolled muscle contractions (seizures).
• Rapid, alternating muscle contractions (clonus).
• Brain swelling.
• Clouding of the lens of the eye.
• Changes in heart rhythm and frequency.
• Loss of heart function.
• Lung failure.
• Pneumonia caused by inhaling foreign material into the lungs.
• Intestinal obstruction.
• Intestinal perforation.
• Loss of control over bowel movements.
• Abnormal urine color.
• Urinary incontinence.
• Inability to heal properly.
• Pancreatitis.
• Dermatitis bullosa (formation of blisters on the skin).

Unknown (frequency cannot be estimated from available data):

• Increased and weakened blood vessel wall or tearing of the blood vessel wall (aneurysms and arterial dissections).
• Flat red spots, in the shape of a target or circles on the trunk, often with central blisters, skin peeling, mouth ulcers, throat, nose, genital, and eye ulcers, which may be preceded by fever and flu-like symptoms. These severe skin eruptions may be potentially life-threatening (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• A skin reaction that causes red spots or patches on the skin, which may appear as a white or "bull's-eye" target with a dark red center surrounded by lighter red rings (erythema multiforme).

You may see the following side effects in tests that your doctor may perform:

• Proteins or blood in the urine (checked in a urine test).
• Changes in heart rhythm (checked in an ECG). Your doctor may ask you to stop taking Caprelsa or take it at lower doses.
• Anomalies in the liver or pancreas (checked in blood tests). This usually does not cause symptoms, but your doctor may want to monitor them.
• Low calcium levels in the blood. Your doctor may need to prescribe or change your thyroid hormone treatment.
• Low potassium levels in the blood.
• High calcium levels in the blood.
• High glucose levels in the blood.
• Low sodium levels in the blood.
• Decreased thyroid function.
• High red blood cell counts in the blood.

If you consider any of the side effects you are experiencing to be severe or if you notice any side effect not mentioned in this leaflet, inform your doctor or pharmacist immediately.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears on the blister pack and on the container after EXP. The expiration date is the last day of the month indicated.

Do not store at a temperature above 30°C.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Caprelsa

• The active ingredient is vandetanib. Each tablet contains 100or 300 mg of vandetanib.
• The other components are calcium dihydrogen phosphate, microcrystalline cellulose, crospovidone (type A), povidone (K29‑32), magnesium stearate, hypromellose, macrogol, and titanium dioxide (E171).

Appearance of the product and contents of the package

Caprelsa 100mg is a film-coated, round, white tablet, marked with “Z100” on one side.

Caprelsa 300mg is a film-coated, oval, white tablet, marked with “Z300” on one side.

Caprelsa is presented in blister packs of 30tablets.

Marketing authorization holder

Sanofi B.V.

Paasheuvelweg 25
1105 BP Amsterdam

Netherlands

Responsible for manufacturing

Genzyme Ireland Ltd., IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland

Sanofi Winthrop Industrie, 30-36 avenue Gustave Eiffel, 37100 Tours, France

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet:

Other sources of information

For more detailed information about this medicine, please visit the website of the European Medicines Agency:http://www.ema.europa.eu.