Caprelsa

Package leaflet: Information for the patient

Caprelsa 100 mg film-coated tablets, 300 mg film-coated tablets

Vandetanib
In addition to this leaflet, you will be given a Patient Alert Card containing important safety information that you need to know before starting Caprelsa and during treatment with this medicine.
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet and the alert card. You may need to read it again.
• It is important to keep the Alert Card with you during treatment.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Never give it to other people, even if their symptoms are the same as yours, as it may be dangerous.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Caprelsa is and what it is used for

Caprelsa is a treatment for adults and children aged 5 years and older with:
a type of medullary thyroid carcinoma associated with a mutation in the RET (Rearranged during Transfection) gene, which cannot be surgically removed or has already spread to other parts of the body.
Caprelsa works by slowing down the growth of new blood vessels in the tumour (cancer), thereby cutting off the tumour's supply of nutrients and oxygen. Caprelsa may also act directly on tumour cells by killing them or slowing their growth.

2. What you should know before taking Caprelsa

Do not take Caprelsa:

• If you are allergic to vandetanib or to any of the excipients of this medicine (listed in section 6).
• If you have a congenital heart problem called “congenital long QTc syndrome”. This can be detected by an electrocardiogram (ECG).
• If you are breastfeeding.
• If you are taking any of the following medicines: arsenic, cisapride (used to treat heartburn), intravenous erythromycin and moxifloxacin (used to treat infections), toremifene (used to treat breast cancer), mizolastine (used to treat allergies), Class IA and III antiarrhythmics (used to control heart rhythm).

Do not take Caprelsa if any of the above apply to you. If in doubt, consult your doctor.

Warnings and precautions

Talk to your doctor or pharmacist before taking Caprelsa:

• If you are sensitive to sunlight. Some people taking Caprelsa become more sensitive to sunlight. This may cause sunburn. During treatment with Caprelsa, and to avoid sun exposure, you should always protect yourself before going outdoors by using sunscreen and wearing protective clothing.
• If you have high blood pressure.
• If you have or have had an aneurysm (a bulging and weakening of the wall of a blood vessel) or a tear in the wall of a blood vessel.
• If you need to undergo surgery. Your doctor may consider interrupting treatment with Caprelsa if you are scheduled for major surgery, as Caprelsa may affect wound healing. Treatment with Caprelsa may be resumed once adequate wound healing has been established.
• If you have kidney problems.

Severe Cutaneous Adverse Reactions (SCARs), including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported in association with vandetanib treatment. If you notice any symptoms related to these severe skin reactions described in section 4, stop treatment with Caprelsa and contact your doctor immediately.

Before starting treatment with Caprelsa, it will be necessary to determine the RET gene status of the tumor.

Blood and heart monitoring:

Your doctor or nurse must perform blood tests to monitor levels of potassium, calcium, magnesium, and thyroid-stimulating hormone (TSH), as well as the electrical activity of the heart using a test called an electrocardiogram (ECG). You must undergo these tests:

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

Children

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

Other medicines and Caprelsa

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription and herbal medicines. This is because Caprelsa may affect the action of certain medicines and some medicines may interfere with the action of Caprelsa.

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 motor tics and verbal aggression), and halofantrine and lumefantrine (used to treat malaria)
• methadone (used to treat addiction), haloperidol, chlorpromazine, sulpiride, amisulpride, and zuclopentixol (used to treat mental illnesses)
• pentamidine (used to treat infections)
• vitamin K antagonists, and dabigatran, commonly referred to as 'blood thinners'
• cyclosporine and tacrolimus (used to prevent transplant rejection), digoxin (used to treat irregular heart rate), and metformin (used to control blood sugar)
• proton pump inhibitors (used to treat heartburn)

This information is also included in the Patient Alert Card provided by your doctor. It is important that you keep this Alert Card and show it to your family members or healthcare providers.

Pregnancy and breastfeeding

If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor for advice before taking this medicine, as Caprelsa may harm the fetus. Your doctor will explain the benefits and risks associated with taking Caprelsa during pregnancy.

• If you are of childbearing age, you must use an effective method of contraception during treatment with Caprelsa and for at least four months after the last dose of Caprelsa.

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

Driving and using machines

Exercise caution when driving or operating machinery. Be aware that Caprelsa may cause fatigue, weakness, or blurred vision.

3. How to take Caprelsa

Use in adults
Always take this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist.

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

Use in children and adolescents
Your doctor will tell you how many Caprelsa tablets to give your child. The amount of Caprelsa will depend
on the child's height and weight. The total daily dose in children must not exceed 300 mg.
Treatment may be administered to the child either as a single daily dose, on alternate days, or according to
a repeating 7-day schedule, as indicated in the dosing guide provided to you by your doctor. It is important
that you keep the dosing guide and show it to anyone who cares for you.
If you have difficulty swallowing the tablet
If you have difficulty swallowing the tablet, you may mix it in water as described below:

• Take half a glass of still (non-carbonated) water. Use water only – do not use any other liquid.
• Place the tablet into the water.
• Stir the contents until the tablet has dispersed in the water. This may take about 10 minutes.
• Drink the liquid immediately.

To ensure that no medicine is left behind, refill the glass halfway with water and drink the contents.
If you experience side effects
If you experience any side effects, always inform your doctor. Your doctor may reduce or increase the dose
of Caprelsa (for example, two 100 mg tablets or one 100 mg tablet). They may also prescribe other
medicines to help manage the side effects. Caprelsa side effects are listed in section 4.
If you take more Caprelsa than you should
If you have taken more Caprelsa than prescribed, contact your doctor immediately or go to the nearest
hospital.
If you forget to take Caprelsa
What you should do if you forget to take a tablet depends on how long it is until your next dose.

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

Do not take a double dose (two tablets at the same time) to make up for a forgotten tablet.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. If you experience any side effects, your doctor may reduce your dose of Caprelsa. They may also prescribe other medicines to help manage the side effects.
Contact your doctor immediately if you notice any of the following side effects –
you may need urgent medical treatment:

• Fainting, dizziness, or changes in heart rhythm. These could be signs of a change in the electrical activity of your heart. These symptoms have been observed in 8% of patients treated with Caprelsa for medullary thyroid carcinoma. Your doctor may recommend a lower dose of Caprelsa or may discontinue treatment. Caprelsa has been associated, albeit infrequently, with life-threatening changes in heart rhythm.
• Stop taking Caprelsa and contact your doctor immediately if you notice any of the following symptoms: flat, reddish patches on the trunk, appearing target-like or circular, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These severe skin reactions may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome and toxic epidermal necrolysis).
• Severe diarrhoea.
• Severe shortness of breath or sudden worsening of breathlessness, possibly with cough or high temperature (fever). This could indicate a lung inflammation known as “interstitial lung disease”. This reaction is considered uncommon (occurring in fewer than 1 in 100 patients), but may be life-threatening.
• Seizures, headache, confusion, or difficulty concentrating. These may be signs of a condition called RPLS (Reversible Posterior Leukoencephalopathy Syndrome). These symptoms usually resolve when Caprelsa treatment is stopped. RPLS is considered an uncommon side effect (occurring in fewer than 1 in 100 patients).

Contact your doctor immediately if you notice any of the side effects listed above.
Other side effects include:
Very common (occur in more than 1 in 10 patients):

• Diarrhoea. Your doctor may prescribe medication to control diarrhoea. If it worsens, contact your doctor immediately.
• Abdominal pain.
• Skin rash or acne.
• Depression.
• Tiredness.
• Feeling unwell (nausea).
• Stomach discomfort (dyspepsia).
• Nail disorders.
• Feeling unwell (vomiting).
• Loss of appetite (anorexia).
• Weakness (asthenia).
• High blood pressure (arterial hypertension). Your doctor may prescribe medication to control your blood pressure.
• Headache.
• Tiredness.
• Sleep disturbances (insomnia).
• Inflammation of the nasal passages.
• Inflammation of the main airways of the lungs.
• Upper respiratory tract infections.
• Urinary tract infections.
• Numbness or tingling of the skin.
• Abnormal skin sensation.
• Dizziness.
• Pain.
• Swelling due to fluid retention (oedema).
• Kidney stones or calcium deposits in the urinary tract (nephrolithiasis).
• Blurred vision, including mild eye disorders that may cause blurred vision (corneal opacity).
• Skin sensitivity to sunlight. During treatment with Caprelsa, you must always protect yourself before going outdoors by using sunscreen and wearing appropriate clothing to avoid sun exposure.

Common (occur in fewer than 1 in 10 patients):

• Dehydration.
• Severe arterial hypertension.
• Weight loss.
• Stroke or other conditions in which the brain does not receive enough blood.
• A type of skin rash affecting the hands and feet (hand-foot syndrome).
• Painful mouth (stomatitis).
• Dry mouth.
• Lung infection.
• Toxins in the blood as a complication of infection.
• Influenza.
• Inflammation of the urinary bladder.
• Inflammation of the paranasal sinuses.
• Inflammation of the throat (laryngitis).
• Inflammation of a follicle, especially a hair follicle.
• Pimples.
• Fungal infection.
• Kidney infection.
• Fluid loss (dehydration).
• Anxiety.
• Tremor.
• Drowsiness.
• Fainting.
• Feeling of instability.
• Increased pressure inside the eye (glaucoma).
• Coughing up blood.
• Inflammation of lung tissue.
• Difficulty swallowing.
• Constipation.
• Inflammation of the stomach lining (gastritis).
• Gastrointestinal bleeding.
• Gallstones (cholelithiasis).
• Painful urination.
• Kidney failure.
• Frequent urination.
• Urgent need to urinate.
• Fever.
• Nosebleeds (epistaxis).
• Dry eye.
• Eye irritation (conjunctivitis).
• Vision changes.
• Seeing halos around lights.
• Perception of flashes of light (photopsia).
• Corneal disorder (keratopathy).
• Diarrhoea (colitis).
• Hair loss (alopecia).
• Changes in taste (dysgeusia).

Uncommon (occur in fewer than 1 in 100 patients):

• Heart failure.
• Inflammation of the appendix (appendicitis).
• Bacterial infection.
• Inflammation of diverticula (small pouch-like bulges that can form in the digestive tract).
• Bacterial skin infection.
• Abdominal wall abscess.
• Malnutrition.
• Involuntary muscle contractions (seizures).
• Rapid alternation of muscle contraction and relaxation (clonus).
• Brain swelling.
• Clouding of the eye's lens.
• Disturbances in heart rate and rhythm.
• Loss of heart function.
• Inadequate lung function.
• Pneumonia occurring when foreign bodies are inhaled into the lungs.
• Intestinal obstruction.
• Intestinal perforation.
• Inability to control bowel movements.
• Abnormal urine colour.
• Lack of urine.
• Impaired wound healing.
• Inflammation of the pancreas (pancreatitis).
• Blistering skin rash (bullous dermatitis).

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

• Widening and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and arterial dissections).
• Flat, reddish patches on the trunk, appearing target-like or circular, often with central blisters, skin peeling, mouth, throat, nose, genital or eye ulcers. These severe skin reactions may be preceded by fever and flu-like symptoms. These potentially life-threatening skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis) have not been assigned a frequency.
• Skin reaction causing red spots or patches on the skin, which may appear as targets or "bull's-eye" lesions with a dark red center surrounded by lighter red rings (erythema multiforme).

The following side effects may be detected during tests carried out by your doctor:

• Protein or blood in the urine (detected through a urine test).
• Changes in heart rhythm (detected on ECG). Your doctor may stop treatment with Caprelsa or prescribe a lower dose.
• Abnormalities of the liver or pancreas (detected through blood tests). These usually do not cause symptoms, but your doctor may decide to monitor them.
• Decreased levels of calcium in the blood. Your doctor may consider adjusting or changing your thyroid hormone therapy.
• Decreased levels of potassium in the blood.
• Increased levels of calcium in the blood.
• Increased levels of glucose in the blood.
• Decreased levels of sodium in the blood.
• Reduced thyroid function.
• Increased levels of red blood cells in the blood. If any of these side effects worsen, or if you notice any side effects not listed in this leaflet, contact your doctor or pharmacist immediately.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 pack and outer packaging following the word "EXP". The expiry date refers to the last day of that month.
Do not store above 30°C.
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 Caprelsa contains

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

Description of the appearance of Caprelsa and package contents
Caprelsa 100 mg is a white, round, film-coated tablet, marked with 'Z100' on one side.
Caprelsa 300 mg is a white, oval, film-coated tablet, marked with 'Z300' on one side.
Caprelsa is available in blisters in packages of 30 tablets.

Marketing Authorization Holder
Sanofi B.V.
Paasheuvelweg 25
1105 BP Amsterdam
The Netherlands

Manufacturer
Genzyme Ireland Ltd, IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland.
Sanofi Winthrop Industrie, 30-36 avenue Gustave Eiffel, 37100 Tours, France

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien / Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0) 2 710 54 00

България / Malta
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480
Sanofi S.r.l.
Tel: +39 02 3939 4275

Česká republika / Nederland
sanofi-aventis, s.r.o.
Tel: +420 233 086 111
Sanofi B.V.
Tel: +31 20 245 4000

Danmark / Norge
sanofi A/S
Tlf: +45 45 16 70 00
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Deutschland / Österreich
Sanofi-Aventis Deutschland GmbH
Tel.: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131
sanofi-aventis GmbH
Tel: +43 1 80 185 - 0

Eesti / Polska
Swixx Biopharma OÜ
Tel: +372 640 10 30
sanofi-aventis Sp. z o.o.
Tel.: +48 22 280 00 00

Ελλάδα / Portugal
Sanofi-Aventis Μονοπρόσωπη AEBE
Τηλ: +30 210 900 1600
Sanofi – Produtos Farmacêuticos, Lda.
Tel: +351 21 35 89 400

España / România
sanofi-aventis, S.A.
Tel: +34 93 485 94 00
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

France / Slovenija
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger: +33 1 57 63 23 23
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Hrvatska / Slovenská republika
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Ireland
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Ísland / Suomi/Finland
Vistor hf.
Sími: +354 535 7000
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Italia / Sverige
Sanofi S.r.l.
Tel: 800 536 389
Sanofi AB
Tel: +46 (0)8 634 50 00

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Latvija / United Kingdom (Northern Ireland)
Swixx Biopharma SIA
Tel: +371 6 616 47 50
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu