Package leaflet: Information for the patient Capexion 0.5 mg hard capsules Capexion 1 mg hard capsules Capexion 5 mg hard capsules

tacrolimus

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

■    Keep this leaflet. You may need to read it again.

■    If you have any further questions, ask your doctor or pharmacist.

■    This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

■    If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1.    What Capexion is and what it is used for

2.    What you need to know before you take Capexion

3.    How to take Capexion

4.    Possible side effects

5.    How to store Capexion

6.    Contents of the pack and other information

1. What Capexion is and what it is used for

Capexion contains the active substance tacrolimus which is an immunosuppressant. Following your organ transplant (e.g. liver, kidney, heart), your body’s immune system will try to reject the new organ.

Capexion is used to control your body’s immune response enabling your body to accept the transplanted organ.

Capexion is often used in combination with other medicines that also suppress the immune system.

You may also be given Capexion for an ongoing rejection of your transplanted liver, kidney, heart or other organ when any previous treatment you were taking was unable to control this immune response after your transplantation.

2. What you need to know before you take Capexion

Do not take Capexion

■    If you are allergic to tacrolimus or any of the other ingredients of this medicine (listed in section 6)

■    If you are allergic to sirolimus or to any macrolide antibiotic (e.g. erythromycin, clarithromycin, j osamycin).

Warnings and precautions

Talk to your doctor or pharmacist before taking Capexion

-    if you are taking any medicines mentioned below under ‘Other medicines’ and Capexion.

-    if you have or have had liver problems

-    if you need to receive any vaccinations

-    if you or a family member have been diagnosed with heart problems (e.g. congestive heart failure, bradyarrhythmias)

-    if you have been diagnosed with a heart condition called “Congenital Long QT Syndorme” or “QT prolongation”.

Your doctor may need to adjust your dose of Capexion.

During treatment tell your doctor or pharmacist:

■    if you have diarrhoea for more than one day

■    if you feel strong abdominal pain accompanied with or without other symptoms, such as chills, fever, feeling sick (nausea) or being sick (vomiting)

■    if you have a change of the electrical activity of your heart called “QT prolongation”.

You should keep in regular contact with your doctor. From time to time, your doctor may need to do blood, urine, heart, eye and neurological tests, to set the right dose of Capexion.

Patients treated with tacrolimus have been reported to have an increased risk of developing lymphoproliferative disorders (see section 4). Ask your doctor for specific advice on these disorders.

You should limit your exposure to the sun and UV (ultraviolet) light whilst taking Capexion. This is because immunosuppressants could increase the risk of skin cancer. Wear appropriate protective clothing and use a sunscreen with a high sun protection factor.

Other medicines and Capexion

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription and herbal preparations.

Capexion must not be taken with ciclospoim

Capexion blood levels can be affected by other medicines you take, and blood levels of other medicines can be affected by taking Capexion which may require an increase or decrease in dose. In particular, you should tell your doctor if you are taking or have recently taken medicines like:

■    antifungal medicines and antibiotics, particularly so-called macrolide antibiotics, used to treat infections, such as ketoconazole, fluconazole, itraconazole, telithromycin, voriconazole, clotrimazole, erythromycin, clarithromycin, josamycin, rifabutin and rifampicin

■    HIV medicines ( e.g. ritonavir, nelfinavir, saquinavir), used to treat HIV infection

■ HCV protease inhibitors (e.g. telaprevir, boceprevir), used to treat hepatitis C infection

■ medicines for stomach ulcer and acid reflux (e.g. omeprazole, lansoprazole or cimetidine)

■    antiemetics, used to treat nausea and vomiting (e.g. metoclopramide)

■    cisapride or the antacid magnesium-aluminium-hydroxide, used to treat heartburn

■    the contraceptive pill or other hormone treatments with ethinylestradiol.

■    hormone treatments with danazol

■    medicines used to treat high blood pressure or heart problems (e.g. nifedipine, nicardipine, diltiazem and verapamil)

■    amiodarone, used to control arrhythmia (uneven beating of the heart)phenytoin, phenobarbital or carbamazepine, used to treat epilepsy

■    the corticosteroids prednisolone and methylprednisolone, belonging to the class of corticosteroids used to treat inflammations or suppress the immune system (e.g. in transplant rejection)

■    isoniazid, used to treat tuberculosis

■    nefazodone, used to treat depression

■    herbal preparations containing St. John’s wort (Hypericumperforatum) or extracts of

Schisandra sphenanthera.

Tell your doctor if you are taking or need to take ibuprofen, amphotericin B or antivirals (e.g. ganciclovir, aciclovir). These may worsen kidney or nervous system problems when taken together with Capexion.

Your doctor also needs to know if you are taking potassium supplements or certain diuretics used for heart failure, hypertension and kidney disease, (e.g. amiloride, triamterene, or spironolactone), non-steroidal anti-inflammatory drugs (NSAIDs, e.g. ibuprofen) used for fever, inflammation and pain, anticoagulants (blood thinners), or oral medicines for diabetes, while you take Capexion.

If you need vaccinations, tell your doctor in advance that you are taking this medicine.

Taking Capexion with food and drink

Avoid grapefruit (also as juice) while on treatment with Capexion since it can affect its levels. Pregnancy and breast-feeding

If you plan to become pregnant or think that you may be pregnant, ask your doctor or pharmacist for advice before taking any medicine.

Tacrolimus passes into breast milk. Therefore you should not breast-feed whilst using Capexion.

Driving and using machines

Do not drive or use any tools or machines if you feel dizzy or sleepy, or have problems seeing clearly after taking this medicine. These effects are more frequently observed if you also drink alcohol.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

3. How to take Capexion

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Make sure that you receive the same tacrolimus medicine every time you collect your prescription, unless your transplant specialist has agreed to change to a different tacrolimus medicine.

This medicine should be taken twice a day. If the appearance of this medicine is not the same as usual, or if dosage instructions have changed, speak to your doctor or pharmacist as soon as possible to make sure that you have the right medicine.

The starting dose to prevent the rejection of your transplanted organ will be determined by your doctor calculated according to your body weight. Initial doses just after transplantation will generally be in the range of 0.075 - 0.30 mg per kg body weight per day depending on the transplanted organ.

Your dose depends on your general condition and on which other immunosuppressive medication you are taking. Regular blood tests by your doctor will be required to define the correct dose and to adjust the dose from time to time. Your doctor will usually reduce your Capexion dose once your condition has stabilised. Your doctor will tell you exactly how many capsules to take and how often.

Capexion is taken orally twice daily, usually in the morning and evening. You should generally take Capexion on an empty stomach or at least 1 hour before or 2 to 3 hours after the meal The capsules should be swallowed whole with a glass of water. Avoid grapefruit and grapefruit juice while taking Capexion. Do not swallow the desiccant contained in the foil wrapper.

If you take more Capexion than you should

If you have accidentally taken too much see your doctor or contact your nearest hospital emergency department immediately. Someone who has taken an overdose of Capexion may have any of these symptoms: shaking, headache, feeling or being sick, itchy rash (hives), feeling tired and increased infections.

If you forget to take Capexion

Do not take a double dose to make up for forgotten individual doses.

If you have forgotten to take your capsules, wait until it is time for the next dose, and then continue as before.

If you stop taking Capexion

Stopping your treatment may increase the risk of rejection of your transplanted organ. Do not stop your treatment unless your doctor tells you to do so.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Capexion reduces your body's own defence mechanism to stop you rejecting your transplanted organ. Consequently, your body will not be as good as usual at fighting infections. So if you are taking Capexion you may therefore catch more infections than usual, such as infections of the skin, mouth, stomach and intestines, lungs and urinary tract.

If you think you may have any of the following side effects, contact your doctor or go to your nearest hospital emergency room immediately:

Very common (may affect more than 1 in 10 people):

■    diabetes mellitus, you may notice increased thirst, needing to urinate more often than usual and increased hunger

■    kidney problems

Common (may affect up to 1 in 10 people):

■    yellowing of the skin due to liver problems, liver tissue damage and inflammation of the liver

■    insufficient function of the kidneys with reduced production of urine, impaired or painful urination

■    gastrointestinal perforation, you may have strong abdominal pain accompanied with other symptoms, such as chills, fever, feeling sick and being sick

■    inflammations or ulcers causing abdominal pain or diarrhoea, bleedings in the stomach

■    fits

Uncommon side effects (may affect up to 1 in 100 people):

■    bleeding in the brain, stroke

■    difficulties in breathing

■    reduction in the number of all types of blood cells

■    inflammation of the pancreas

■    partial or complete paralysis

■    obstruction of the gut

• haemolytic uraemic syndrome, a condition with the following symptoms: low or no urine output (acute renal failure), extreme tiredness, yellowing of the skin or eyes (jaundice) and abnormal bruising or bleeding and signs of infection.

■    inflammation of the membrane lining of the stomach wall

■    severe mental disorder that can cause abnormal thinking and perceptions

■    heart attack

■    insufficient function of your transplanted organ

■    coma, shock

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

■    Thrombotic Thrombocytopenic Purpura, a condition with the following symptoms: fever and bruising under the skin that may appear as red pinpoint dots, you may feel unexplained extreme tiredness, confusion, and notice yellowing of the skin or eyes (jaundice), with symptoms of kidney problems (low or no urine output).

■    Toxic epidermal necrolysis: erosion and blistering of skin or mucous membranes, red swollen skin that can detach in large parts of the body.

■    severe shortness of breath

■    blindness

■    collection of fluid around the heart

■    deafness

■    problems with blood flow in the liver

Very rare (may affect up to 1 in 10,000 people):

■    liver failure

■    Stevens-Johnson syndrome: unexplained widespread skin pain, facial swelling, serious illness with blistering of skin, mouth, eyes and genitals, hives, tongue swelling, red or purple skin rash that spreads, skin shedding

■    Torsades de Pointes: change in the heart frequency that can be accompanied by symptoms, such as chest pain (angina), fainting, dizziness or feeling sick (nausea), palpitations (feeling the heartbeat) and difficulty breathing.

■    painful urination with blood in the urine

■    abnormal heart scan

■    narrowing of the bile vessel

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

■    allergic and anaphylactic reactions with the following symptoms: a sudden itchy rash (hives), swelling of hands, feet, ankle, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing) and you may feel you are going to faint.

■    benign and malignant tumours have been reported following treatment as a result of immunosuppression

■    Posterior Reversible Encephalopathy Syndromes (PRES): headache, altered mental status, fits, and visual disturbances.

■    pure red cell aplasia (a very severe reduction in red blood cell counts) and haemolytic anaemia (decreased number of red blood cells due to abnormal breakdown accompanied with tiredness) have been reported. You may have no symptoms or depending on the severity of the condition, you may notice: fatigue, apathy, abnormal paleness of the skin, shortness of breath, dizziness, headache, chest pain and coldness in hands and feet.

■    agranulocytosis (a severely lowered number of white blood cells accompanied with ulcers in the mouth, fever and infections). You may have no symptoms or you may feel sudden fever, chills and sore throat.

Other possible side effects

Very common (may affect more than 1 in 10 people):

•    increased blood sugar, increased potassium in the blood

•    difficulty in sleeping

•    trembling, headache

•    diarrhoea, nausea

Common (may affect up to 1 in 10 people):

•    reduced magnesium, phosphate, potassium, calcium or sodium in the blood, fluid overload, increased uric acid or lipids in the blood, decreased appetite, increased acidity of the blood, other changes in the blood salts (seen in blood tests)

•    anxiety symptoms, confusion and disorientation, depression, mood changes, nightmares, hallucination, mental disorders

•    disturbances in consciousness, tingling and numbness (sometimes painful) in the hands and feet, dizziness, impaired writing ability, nervous system disorders

•    blurred vision, increased sensitivity to light, eye disorders

•    ringing sound in your ears

•    reduced blood flow in the heart vessels, faster heartbeat

•    bleeding, partial or complete blocking of blood vessels, reduced blood pressure

•    shortness in breath, changes in the lung tissue, collection of liquid around the lung, inflammation of the throat, cough, flu-like symptoms inflammation or ulcers in the mouth, collection of fluid in the belly, vomiting, abdominal pains, indigestion, constipation, passing wind, bloating, loose stools, stomach problems

•    changes in liver enzymes and function

•    itching, rash, hair loss, acne, increased sweating

•    pain in joints, limbs or back, muscle cramps

•    general weakness, fever, collection of fluid in your body, pain and discomfort, increase of the enzyme alkaline phosphatase in your blood, weight gain, feeling feverish

•    insufficient function of your transplanted organ.

Uncommon (may affect up to 1 in 100 people):

•    changes in blood clotting

•    dehydration, reduced protein or sugar in the blood, increased phosphate in the blood

•    brain disorder, speech and language abnormalities, memory problems

•    clouding of the eyes (cataracts)

•    impaired hearing

•    irregular heartbeat, skipped heartbeat, reduced performance of your heart, enlargement of the heart muscle, stronger heartbeat, abnormal ECG, heart rate and pulse abnormal

•    blood clot in a vein of a limb

•    respiratory tract disorders, asthma

•    increased blood level of the enzyme amylase, reflux of stomach content in your throat, delayed emptying of the stomach

•    dermatitis, burning sensation in the sunlight

•    joint disorders

•    painful menstruation and abnormal menstrual bleedings

•    influenza like illness, increased sensitivity to heat and cold

•    feeling of pressure on your chest, jittery or abnormal feeling

•    increase of the enzyme lactate dehydrogenase in your blood

•    weight loss.

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

•    increased muscle stiffness

•    cyst formation in your pancreas

•    increased hairiness

•    thirst, fall

•    feeling of tightness in your chest

•    decreased mobility

•    ulcer

Very rare (may affect up to 1 in 10,000 people):

•    muscular weakness

•    increase of fat tissue.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Capexion

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

■    Store below 30°C

■    Store in the original package (within the foil pouch) in order to protect from moisture and light.

■    Do not use Capexion after the expiry date which is stated on the carton and blister after {EXP}. Once the foil pouch is opened, the product should be used within 1 year. The expiry date refers to the last day of that month.

■    Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Capexion contains

Capexion 0.5 mg hard capsules -The active substance is tacrolimus.

For 0.5mg: Each capsule contains 0.5mg of tacrolimus The other ingredients are:

■    Capsule content: Povidone K-30, Croscarmellose Sodium (E 468), Lactose anhydrous, Magnesium stearate.

■    Capsule shell: Titanium dioxide (E-171), Yellow Iron Oxide (E-172), Gelatin

■ Capsule shell: Titanium dioxide (E-171), Red Iron Oxide (E-172), Gelatin

What Capexion looks like and contents of the pack

Capexion 0.5 mg hard capsules

Ivory cap and ivory body hard shell capsules with white powder.

Capexion 0.5 mg hard capsules are supplied as blister strips containing 10 capsules within a protective foil wrapper, including a desiccant protecting the capsules from moisture. The desiccant should not be swallowed.

Capexion is available in blister packs containing blister strips of 10 capsules each. 0.5 mg: 10, 30, 50, 60, 90 and 100 capsules 1 mg: 10, 30, 50, 60, 90 and 100 capsules 5 mg: 10, 30, 50, 60, 90 and 100 capsules

Not all pack sizes may be marketed

Marketing Authorisation Holder

Mylan, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom.

Manufacturer Laboratorios Cinfa, S.A.

Olaz-Chipi, 10-Polig Areta 31620 Huarte-Pamplona, Navarra,

Spain

This leaflet was last revised in: January 2016

9