CAPRELSA 300 mg FILM-COATED TABLETS

Introduction

Patient Information: Summary of Product Characteristics

Caprelsa 100mg film-coated tablets

Caprelsa 300mg film-coated tablets

vandetanib

In addition to this summary, you will also be given a Patient Information Card, which contains important safety information that you need to know before you start taking Caprelsa and during treatment with Caprelsa.

Read the entire summary carefully before you start taking this medicine, as it contains important information for you.

• Keep this summary and the Patient Information Card, as you may need to read them again.
• It is important that you keep the Patient Information Card with you during treatment.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed to 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 side effects, ask your doctor or pharmacist, even if they are not listed in this summary. See section 4.

Contents of the summary

1. What is Caprelsa and what is it used for
2. What you need to know before you start taking Caprelsa
3. How to take Caprelsa
4. Possible side effects
5. Storage of Caprelsa
6. Package contents and further information

1. What is Caprelsa and what is it used for

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

A type of medullary thyroid cancer called RET mutation, which cannot be removed by surgery or has spread to other parts of the body.

Caprelsa works by slowing down the growth of new blood vessels in tumors (cancers). This disrupts the supply of nutrients and oxygen to the tumor. Caprelsa may also act directly on cancer cells, destroying them or slowing down their growth.

2. What you need to know before you start taking Caprelsa

Do not take Caprelsa:

• if you are allergic to vandetanib or any of the other ingredients of this medicine (listed in section 6).
• if you have a congenital heart condition called "long QTc syndrome". This can be seen on 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 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 applies to you, do not take Caprelsa. If you are unsure, ask your doctor.

Warnings and precautions

Ask your doctor or pharmacist before starting Caprelsa:

• If you are sensitive to the sun. Some people taking Caprelsa may become more sensitive to the sun, which can cause sunburn. While taking Caprelsa, protect yourself when going outside by always using sunscreen and wearing protective 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 surgery. Your doctor may consider stopping Caprelsa if you are to undergo a major surgical procedure, as Caprelsa may affect wound healing. Caprelsa may be restarted once the wound has healed adequately.
• If you have kidney problems.

Severe skin reactions (SSRs), including Stevens-Johnson syndrome (SJS) and 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.

It will be necessary to determine the RET status of your cancer before starting treatment with Caprelsa.

Blood and heart monitoring:

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

• Before you start taking Caprelsa
• Regularly during treatment with Caprelsa
• 1, 3, and 6 weeks after starting Caprelsa
• 12 weeks after starting Caprelsa
• After that, every 3 months
• If your doctor or pharmacist changes your dose of Caprelsa
• If you start taking medicines that affect the heart
• As directed by your doctor or pharmacist

Children

Caprelsa should not be given to children under 5 years of age.

Taking Caprelsa with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription and herbal medicines. This is because Caprelsa may affect the way some medicines work and some medicines may have an effect on Caprelsa.

Tell 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 uncontrolled 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 infection)
• vitamin K antagonists and dabigatran, often called "anticoagulants"
• cyclosporine 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 Card that your doctor has given you. It is important that you keep this Patient Information Card and show it to your partner or caregivers.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, ask your doctor before using this medicine. This is because Caprelsa may 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 when taking Caprelsa and for at least four months after the last dose of Caprelsa.

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

Driving and using machines

Be cautious before driving or using machines. Note that Caprelsa may make you feel tired, weak, or cause blurred vision.

3. How to take Caprelsa

Use in adults

Follow exactly the instructions for administration of this medicine given by your doctor. If you are unsure, ask your doctor or pharmacist again.

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

Use in children and adolescents

Your doctor will tell you how many Caprelsa tablets to give to your child. The amount of Caprelsa given will depend on your child's body weight and height. The daily total dose in children should not exceed 300 mg. The treatment can be given to your child as a single dose once daily, a single dose every other day, or a periodic regimen of 7 days as indicated in the dosing guide given by your doctor. It is important that you keep this dosing guide and show it to your caregiver.

If you have problems swallowing the tablet

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

• Take half a glass of water (still water). Use only water, do not use any other liquid.
• Place the tablet in the water.
• Stir the tablet until it has dissolved in the water. This may take about 10 minutes.
• Drink it immediately.

To ensure that no medicine is left, fill the glass with water to about half and drink it.

If you experience side effects

If you experience side 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 medicines to help control the side effects. The side effects of Caprelsa are listed in section 4.

If you take more Caprelsa than you should

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

If you forget to take Caprelsa

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

• If there are 12hours 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 12hours 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 the same time) to make up for missed doses.

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

4. Possible Adverse Effects

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

Report immediately to your doctor if you notice any of the following adverse effects - you may need urgent medical treatment:

• Weakness, dizziness, or changes in heart rhythm. These can be signs of a change in the electrical activity of the heart. They occur 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 rarely associated with changes in heart rhythm that can be life-threatening.
• Stop using Caprelsa and seek immediate medical attention if you notice any of the following symptoms: reddish, non-raised, target-like, or circular patches on the trunk, often with central blisters, skin peeling, ulcers in the mouth, throat, nose, genitals, and eyes. These severe skin reactions can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Severe diarrhea.
• Severe difficulty breathing or sudden worsening of breathing difficulties, possibly with cough or elevated temperature (fever). This may mean you have a lung inflammation called "interstitial lung disease". This is rare (affects less than 1 in 100 people) but can be life-threatening.
• Seizures, headache, confusion, or difficulty concentrating. These can be signs of a disease called Posterior Reversible Leukoencephalopathy Syndrome (PRLS). These usually stop when Caprelsa is discontinued. PRLS is rare (affects less than 1 in 100 people).

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

Other adverse effects include:

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

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

• Vomiting.
• Lack of appetite (anorexia).
• Weakness (asthenia).
• High blood pressure. Your doctor may prescribe a medication to treat it.
• Headache.
• Fatigue.
• Sleeping problems (insomnia).
• Inflammation of the nasal passages.
• Inflammation of the main airways to the lungs.
• Upper respiratory tract infections.
• Urinary tract infections.
• Numbness or tingling of the skin.
• Abnormal skin sensation.
• Dizziness.
• Pain.
• Swelling caused by excess fluid (edema).
• Kidney stones or calcium deposits in the urinary tract (nephrolithiasis).
• Blurred vision, including mild changes in the eye that can lead to blurred vision (corneal opacity).
• Skin sensitivity to sunlight. While taking Caprelsa, protect yourself when going outside by always using sunscreen and wearing clothing to avoid sun exposure.

Common (affecting 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.
• Flu.
• Inflammation of the urinary bladder.
• Inflammation of the breasts.
• Inflammation of the voice box (larynx).
• Inflammation of a follicle, especially a hair follicle.
• Boil.
• Fungal infection.
• Kidney infection.
• Loss of body fluid (dehydration).
• Anxiety.
• Tremor.
• Numbness.
• Fainting.
• Feeling of instability.
• Increased pressure in the eye (glaucoma).
• Coughing up blood.
• Inflammation of lung tissue.
• Difficulty swallowing.
• Constipation.
• Inflammation of the stomach lining (gastritis).
• Gastrointestinal bleeding.
• Gallstones (cholelithiasis).
• Pain while urinating.
• Kidney failure.
• Frequent urination.
• Urgent need to urinate.
• Fever.
• Nosebleed (epistaxis).
• Dry eyes.
• Eyelid irritation (conjunctivitis).
• Visual disturbance.
• Seeing halos.
• Seeing flashes of light (photopsia).
• Abnormality of the cornea (keratopathy).
• A type of diarrhea (colitis).
• Loss of hair from the head or body (alopecia).
• Changes in the taste of food (dysgeusia).

Uncommon (affecting less than 1 in 100 people):

• Heart failure.
• Inflammation of the appendix (appendicitis).
• Bacterial infection.
• Inflammation of the diverticula (small bulging pouches that can form in the digestive system).
• Bacterial skin infection.
• Abscesses in the abdominal wall.
• Malnutrition.
• Involuntary muscle contraction (convulsions).
• Rapid alternating muscle contraction and relaxation (clonus).
• Brain swelling.
• Clouding of the eye lens.
• Abnormalities in heart rate and rhythm.
• Loss of heart function.
• Lung failure.
• Pneumonia that occurs when foreign material is inhaled into the lungs.
• Intestinal obstruction.
• Intestinal perforation.
• Inability to control bowel movements.
• Abnormal urine color.
• Lack of urine.
• Inability to heal properly.
• Inflammation of the pancreas (pancreatitis).
• Blistering skin condition (bullous dermatitis).

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

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

The following adverse effects may be observed in the tests that your doctor may perform:

• Protein 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 a lower dose.
• Abnormalities in the liver or pancreas (checked in blood tests). This usually does not cause symptoms, but your doctor may want to monitor them.
• Decreased calcium levels in the blood. Your doctor may need to prescribe or change your thyroid hormone treatment.
• Decreased potassium levels in the blood.
• Increased calcium levels in the blood.
• Increased glucose levels in the blood.
• Decreased sodium levels in the blood.
• Decreased thyroid function.
• Increased red blood cell count in the blood.

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

Reporting of adverse effects

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

5. Storage of Caprelsa

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

Do not use this medicine after the expiry date stated on the blister and carton after EXP. The expiry date is the last day of the month indicated.

Do not store above 30°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and further information

Composition of Caprelsa

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

Appearance and pack contents

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

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

Caprelsa is available in blister packs of 30 tablets.

Marketing authorisation holder

Sanofi B.V.

Paasheuvelweg 25 1105 BP Amsterdam

Netherlands

Manufacturer

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

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

You can obtain further information on this medicine by contacting the local representative of the marketing authorisation holder:

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.