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Prograf 0.5mg Capsules

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PACKAGE LEAFLET: INFORMATION FOR THE USER

PROGRAF® 0.5MG CAPSULES

(tacrolimus)

Your medicine is available using the name Prograf 0.5mg Capsules but will be referred to as Prograf throughout this leaflet.

Other strengths 1mg and 5mg are also available.

Read all of this leaflet carefully before you start taking this medicine.

■    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. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

■    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1.    What Prograf is and what it is used for

2.    Before you take Prograf

3.    How to take Prograf

4.    Possible side effects

5.    How to store Prograf

6.    Further information

1.    What Prograf is and what is it used for

Prograf belongs to a group of medicines called immunosuppressants. Following your organ transplant (e.g. liver, kidney, heart), your body's immune system will try to reject the new organ. Prograf is used to control your body's immune response enabling your body to accept the transplanted organ. Prograf is often used in combination with other medicines that also suppress the immune system.

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

2.    Before you take Prograf

Do not take Prograf

■    If you are allergic (hypersensitive) to tacrolimus or any of the other ingredients of Prograf.

■    If you are allergic (hypersensitive) to any antibiotic belonging to the subgroup of macrolide antibiotics (e.g. erythromycin, clarithromycin, josamycin).

Take special care with Prograf

■    You will need to take Prograf every day as long as you need immunosuppression to prevent rejection of your transplanted organ. You should keep in regular contact with your doctor.

■    Whilst you are taking Prograf your doctor may want to carry out a number of tests (including blood, urine, heart function, visual and neurological tests) from time to time. This is quite normal and will help your doctor to decide on the most appropriate dose of Prograf for you.

■    Please avoid taking any herbal remedies, e.g. St. John's wort (Hypericum perforatum) or any other herbal products as this may affect the effectiveness and the dose of Prograf that you need to receive. If in doubt please consult your doctor prior to taking any herbal products or remedies.

■    If you have liver problems or have had a disease which may have affected your liver, please tell your doctor as this may affect the dose of Prograf that you receive.

■    If you have diarrhoea for more than one day, please tell your doctor, because it might be necessary to adapt the dose of Prograf that you receive.

■    Limit your exposure to sunlight and UV light whilst taking Prograf by wearing appropriate protective clothing and using a sunscreen with a high sun protection factor. This is because of the potential risk of malignant skin changes with immunosuppressive therapy.

■    If you need to have any vaccinations, please inform your doctor beforehand. Your doctor will advise you on the best course of action.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription and herbal remedies.

Prograf must not be taken with ciclosporin.

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

■    antifungal medicines and antibiotics (particularly so-called macrolide antibiotics) used to treat infections e.g. ketoconazole, fluconazole, itraconazole, voriconazole, clotrimazole, erythromycin, clarithromycin, josamycin, and rifampicin

■    HIV protease inhibitors e.g. ritonavir

■    omeprazole or lansoprazole, used for treating stomach ulcers

■    hormone treatments with ethinylestradiol (e.g. the oral contraceptive pill) or danazol

■    medicines for high blood pressure or heart problems such as nifedipine, nicardipine, diltiazem and verapamil

■    medicines known as "statins" used to treat elevated cholesterol and triglycerides

■    the anti-epileptic medicines phenytoin or phenobarbital

■    the corticosteroids prednisolone and methylprednisolone

■    the anti-depressant nefazodone

■    St. John's Wort (hypericum perforatum)

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

Your doctor also needs to know if you are taking potassium supplements or potassium-sparing diuretics (e.g. amiloride, triamterene, or spironolactone), certain pain killers (so-called NSAIDs, e.g. ibuprofen), anticoagulants, or oral medication for diabetic treatment, while you take Prograf.

If you need to have any vaccinations, please inform your doctor beforehand.

Taking Prograf with food and drink

You should generally take Prograf on an empty stomach or at least 1 hour before or 2 to 3 hours after a meal. Grapefruit and grapefruit juice should be avoided while taking Prograf.

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.

Prograf is excreted into breast milk. Therefore you should not breast-feed whilst receiving Prograf.

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 Prograf.

These effects are more frequently observed if Prograf is taken in conjunction with alcohol use.

Important information about some of the ingredients of Prograf

■    Prograf contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. How to take Prograf

Always take Prograf exactly as your doctor has told you. You should 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 - 0.30mg 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 Prograf dose once your condition has stabilised. Your doctor will tell you exactly how many capsules to take and how often.

Prograf is taken orally twice daily, usually in the morning and evening. You should generally take Prograf 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. Take the capsules immediately following removal from the blister. Avoid grapefruit and grapefruit juice while taking Prograf. Do not swallow the desiccant contained in the foil wrapper.

If you take more Prograf than you should

If you have accidentally taken too much Prograf see your doctor or contact your nearest hospital emergency department immediately.

If you forget to take Prograf

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

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

If you stop taking Prograf

Stopping your treatment with Prograf 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, Prograf can cause side effects, although not everybody gets them.

Prograf 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 Prograf you may therefore catch more infections than usual such as infections of the skin, mouth, stomach and intestines, lungs and urinary tract.

Severe effects have been reported, including allergic and anaphylactic reactions. Benign and malignant tumours have been reported following Prograf treatment as a result of immunosuppression.

Possible side effects are listed according to the following categories:

Very common side effects are experienced in more than one in ten patients.

Common side effects are experienced in less than one in ten patients but in more than one per one hundred patients. Uncommon side effects are experienced in less than one in one hundred patients but more than one per one thousand patients. Rare side effects are experienced in less than one per one thousand patients but more than one per ten thousand patients. Very rare side effects are experienced in less than one per ten thousand patients.

Very common    side effects:

■    Increased    blood sugar, diabetes    mellitus,    increased

potassium in the blood

■    Difficulty in sleeping

■    Trembling, headache

■    Increased    blood pressure

■    Diarrhoea, nausea

■    Kidney problems

Common side effects:

■    Reduction in blood cell counts (platelets, red or white blood cells), increase in white blood cell counts, changes in red blood cell counts

■    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

■    Anxiety symptoms, confusion    and    disorientation,    depression,

mood changes, nightmare, hallucination, mental disorders

■    Fits, 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 pharynx, cough, flu-like symptoms

■    Inflammations or ulcers causing abdominal pain or diarrhoea, bleeds in the stomach, inflammations or ulcers in the mouth, collection of fluid in the belly, vomiting, abdominal pains, indigestion, constipation, flatulence, bloating, loose stools, stomach problems

■    Changes in liver enzymes and function, yellowing of the skin due to liver problems, liver tissue damage and inflammation of the liver

■    Itching, rash, hair loss, acne, increased sweating

■    Pain in joints, limbs or back, muscle cramps

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

■    General weakness, fever, collection of fluid in your body, pain and discomfort, increase of the enzyme alkaline phosphatase in your blood, weight gain, feeling of temperature disturbed

■    Insufficient function of your transplanted organ

Uncommon side effects:

■    Changes in blood clotting, reduction in all blood cell counts

■    Dehydration, reduced protein or sugar in the blood, increased phosphate in the blood

■    Coma, bleeding in the brain, stroke, paralysis, brain disorder, speech and language abnormalities, memory problems

■    Blurring of the vision due to abnormality in the lens of the eye

■    Impaired hearing

■    Irregular heartbeat,    stop    of heartbeat,    reduced    performance

of your heart, disorder of the heart muscle, enlargement of the heart muscle, stronger heartbeat, abnormal ECG, heart rate and pulse abnormal

■    Blood clot in a vein of a limb, shock

■    Difficulties in breathing, respiratory tract disorders, asthma

■    Obstruction of the gut, 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

■    Inability to urinate,    painful    menstruation    and    abnormal

menstrual bleeding

■    Failure of some organs, 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 side effects:

■    Small bleeds in your skin due to blood clots

■    Increased muscle stiffness

■    Blindness

■    Deafness

■    Collection of fluid around the heart

■    Acute breathlessness

■    Cyst formation in your pancreas

■    Problems with blood flow in the liver

■    Serious illness with blistering of skin, mouth, eyes and genitals, increased hairiness

■    Thirst, fall, feeling of tightness in your chest, decreased mobility, ulcer

Very rare side effects:

■    Muscular weakness

■    Echocardiogram abnormal

■    Liver failure, narrowing of the    bile vessel

■    Painful urination with blood    in the urine

■    Increase of fat tissue

Cases of pure red cell aplasia (a very severe reduction in red blood cell counts) have been reported.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5.    How to store Prograf

■    Store the capsules in the original package (aluminium-wrapped blister pack). Once the aluminium wrapper is opened: keep the capsules in the original blister pack, do not store above 25°C.

■    Remove the capsules from the blister pack only when it is time to take your medicine.

■    Use all capsules within 12 months of opening the aluminium wrapping. Do not use Prograf after the expiry date which is stated on the carton after (EXP). The expiry date refers to the last day of the month.

■    Keep out of the reach and sight of children.

■    If your capsules appear to be discoloured or show any other signs of deterioration, please return to your pharmacist who will advise you.

■    If your doctor tells you to stop taking the capsules, please take them back to the pharmacist for safe disposal. Only keep the capsules if your doctor tells you to.

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

6.    Further Information

What Prograf contains

Each capsule contains 0.5mg of the active ingredient tacrolimus. Also contains: hypromellose, croscarmellose sodium, lactose monohydrate, magnesium stearate, titanium dioxide (E171), yellow iron oxide (E172), gelatin, shellac, lecithin (soy), hydroxypropylcellulose, simethicone and red iron oxide (E172).

What Prograf looks like and contents of the pack

Prograf are pale yellow, hard gelatin capsules marked with '0.5 mg' in red on the cap, and the 'Fujisawa logo' and '607' also in red on the body. The capsule blister strips are packed in a sealed aluminium pouch also containing a desiccant. The aluminium wrapper is contained in a carton.

Prograf are available in blister packs of 30 capsules.

Manufacturer

Your medicine is manufactured by: Astellas Ireland Co. Ltd., Killorgin, County Kerry, Ireland.

Procured from within the EU and repackaged by: Doncaster Pharmaceuticals Group Ltd., Kirk Sandall, Doncaster, DN3 1QR.

Product Licence holder: BR Lewis Pharmaceuticals Ltd.,

Kirk Sandall, Doncaster, DN3 1QR.

PL No: 08929/0234    POM

Leaflet revision and issue date (Ref): 23.01.12 Prograf® is a registered trademark of Astellas Pharma Inc.

Free Information Service

Dear Patient,

Your doctor has prescribed you Prograf to help treat your organ transplant.

To help ensure you have as much information as possible about your condition, Astellas Pharma Ltd has produced a selection of booklets called the PA Transplantation Support Service. The information service is free and has been produced with the help of transplant nurses and transplant coordinators.

If you would like more information about this information service, please talk to your transplant team.

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