Artwork No.	-		Colours Used
	Customer	Accord	■	Pantone Black
	Description	Tacrolimus
	Market	UK
	Language	English
	Size	170 x 550 mm PIL
	Min. Font Size	9
	Version No.	3 (Page 1 of 2) (PIQ variation)
	Date	14.06.13 (Tacrolimus (PHA V-UK)NEW-PIL)

PACKAGE LEAFLET: INFORMATION FOR THE USER

Perixis 0.5 mg Hard Capsules Perixis 1 mg Hard Capsules Perixis 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.

What is in this leaflet:

1.    What Perixis is and what it is used for

2.    What you need to know before you take Perixis

3.    How to take Perixis

4.    Possible side effects

5.    How to store Perixis

6.    Contents of the pack and other information

1. What Perixis is and what it is used for

Tacrolimus belongs to a group of medicines called immunosuppressants. Following your organ transplant (e.g. liver, kidney or heart), your body's immune system will try to reject the new organ. Tacrolimus is used to control your body's immune response enabling your body to accept the transplanted organ.

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

You may also be given Tacrolimus 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. What you need to know before you take Perixis

Do not take Perixis:

•    if you are allergic (hypersensitive) to Tacrolimus or any of the other ingredients of this medicine (listed in section 6).

•    if you are allergic (hypersensitive) to macrolide types of antibiotics e.g. erythromycin, clarithromycin, josamycin.

Warnings and precautions:

Talk to your doctor or pharmacist before taking Perixis

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

•    During your treatment period of Perixis, your doctor may want to carry out a number of tests (including blood, urine, heart function, visual and neurological tests) from time to time. These investigations are normal and will help your doctor to decide on the most appropriate dose of Tacrolimus for you.

•    Do not take any herbal remedies, e.g. St.

John's wort (Hypericum perforatum) or other herbal medicines, as these can influence the action of tacrolimus and hence the dose you need to take. If in doubt, contact your doctor before taking any herbal medicine.

•    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 Perixis that you receive.

•    If you have had diarrhoea for more than one day, please tell your doctor, because it might be necessary to adjust the dose of Perixis that you receive.

•    Limit your exposure to sunlight and UV light while you are using Perixis by wearing protective clothing that gives full coverage and using sunscreen with a high protection factor. This is because of the possible risk of cancerous changes of the skin in immunosuppressive therapy.

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

Other medicines and Perixis:

Please tell your doctor or pharmacist if you are taking, or have recently taken or might take any other medicines including medicines obtained without a prescription and herbal remedies. Tacrolimus must not be taken with ciclosporin. Tacrolimus blood levels can be affected by other medicines you take, and blood levels of other medicines can be affected by taking Tacrolimus. Consequently it may be necessary to increase or reduce the dose of tacrolimus. In particular, you should tell your doctor if you are taking or have recently taken medicines with active substances like.

•    antifungal medicines and antibiotics (in particular those known as macrolide antibiotics) for the treatment of infections, such as ketoconazole, fluconazole, itraconazole, voriconazole, clotrimazole, erythromycin, clarithromycin, josamycin and rifampicin

•    HIV protease inhibitors, for example ritonavir

•    Omeprazole or lansoprazole, to treat stomach ulcers

•    hormone treatments with ethinylestradiol (such as the contraceptive pill) or danazol

•    medicines used to treat high blood pressure or heart problems such as nifedipine, nicardipine, diltiazem and verapamil

•    medicines known as 'statins' to treat high cholesterol and triglyceride levels

•    the anti-epilepsy medicines phenobarbital and phenytoin

•    the corticosteroids prednisolone and methylprednisolone

•    the anti-depressant nefadozone

•    St John's wort (Hypericum perforatum)

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

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

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

Tell your doctor if you have to use (or are currently using) ibuprofen, amphotericin B or anti-viral drugs (such as aciclovir). These medicines can worsen kidney and nervous system disorders if they are taken with Perixis.

While you are using Perixis, your doctor must also be informed if you are taking potassium supplements or potassium-sparing diuretics (certain water pill such as amiloride, triamterene or spironolactone), certain painkillers (known as NSAIDs, such as ibuprofen), anticoagulants or oral medicines to treat diabetes.

Perixis with food and drink:

You should generally take Perixis on an empty stomach or at least 1 hour before or 2 to 3 hours after a meal. Grapefruit and grapefruit juice must not be consumed while taking Perixis.

Pregnancy, breast-feeding and fertility:

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

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

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 Perixis. These effects are observed more frequently when Perixis is used together with alcohol.

Perixis contains Lactose monohydrate

Perixis 0.5/1/5 mg contains 0.050/0.102/0.098 g of lactose monohydrate respectively. When taken according to the dosage recommendations each dose supplies 0.050/0.102/0.098 g of lactose monohydrate respectively. If you have been told by your doctor that you have intolerance to some sugars, contact your doctor before taking this medicinal product. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

3. How to take Perixis

Always take this medicine exactly as your doctor 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 of Perixis to prevent rejection of your transplanted organ will be decided by your doctor and will be related to your body weight. The first dose directly after the transplant operation will usually be between 0.075 and 0.30 mg per kg body weight per day depending on the transplanted organ.

Your dose will depend on your general condition and any other immunosuppressive drugs you are using. Your doctor should carry out regular blood tests in order to find the correct dose and occasionally in order to adjust it. Your doctor will normally reduce the dose of Perixis when your condition has stabilised. Your doctor will tell you exactly how many Perixis you must take and how often.

Perixis is taken orally twice daily, usually in the morning and evening. You should generally take tacrolimus 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 capsule immediately following removal from the blister. Avoid grapefruit juice while taking tacrolimus.

If you take more Perixis then you should

If you take too many capsules by accident, see your doctor immediately or contact the accident and emergency department of the nearest hospital.

If you forget to take Perixis

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

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

If you stop taking Perixis

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

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

4. Possible side effects

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

If any of the following happen, stop taking Perixis and contact a doctor or go to the nearest hospital straight away, as you may need urgent medical attention:

•    Severe allergic reaction that may include difficulty in breathing, dizziness and collapse

•    Allergic reactions that may include raised lumps (weals), swelling of the skin and swelling around the mouth.

•    Serious illness with blistering of skin, mouth, eyes and genitals (Rare)

•    Small bleedings in your skin due to blood clots (Rare)

•    Acute breathlessness (Rare)

•    Feeling of tightness in your chest (Rare)

•    Fits, disturbances in consciousness, tingling and numbness (sometimes painful) in the hands and feet (Common)

•    Benign and malignant tumours have been reported following Tacrolimus treatment as a result of immunosuppression.

Other side effects include:

•    ulcer

•    fall

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

•    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), agranulocytosis (a severely lowered number of white blood cells) and haemolytic anaemia (decreased number of red blood cells due to abnormal breakdown) have been reported.

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

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

5. How to store Perixis

Very common (may affect more than 1 in 10

people):

•    increased blood sugar

•    diabetes mellitus

•    increased potassium in the blood

•    difficulty in sleeping

•    trembling

•    Headache

•    increased blood pressure

•    diarrhoea

•    Nausea

•    kidney problems

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

•    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, hallucinations, mental disorders

•    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, bleedings 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 (may affect up to 1 in 100 people):

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

•    increased muscle stiffness

•    collection of fluid around the heart

•    blindness

•    deafness (hearing impaired)

•    cyst formation in your pancreas

•    problems with blood flow in the liver

•    increased hairiness

•    thirst

•    decreased mobility

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

•    Do not use this medicine after the expiry date which is stated on the carton and blister after EXP. The expiry date refers to the last day of that month.

•    Store below 25°C. Store in the original package in order to protect from moisture and light.

•    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 Perixis contains:

The active substance is Tacrolimus.

For 0.5 mg: Each hard capsule contains 0.5 mg tacrolimus(as tacrolimus monohydrate).

For 1 mg: Each hard capsule contains 1 mg tacrolimus(as tacrolimus monohydrate).

For 5 mg: Each hard capsule contains 5 mg tacrolimus(as tacrolimus monohydrate).

The other ingredients for Tacrolimus 0.5 mg, &

1 mg & 5 mg are: lactose monohydrate, croscarmellose sodium (E468), hypromellose (E464), magnesium stearate (E 470b).

Capsule Shell composition for Tacrolimus 0.5 mg: Gelatin, titanium dioxide (E 171) iron oxide yellow (E 172), sodium laurilsulfate.

Capsule Shell composition for Tacrolimus 1 mg: Gelatin, titanium dioxide (E 171), sodium laurilsulfate.

Capsule Shell composition for Tacrolimus 5 mg: Gelatin, titanium dioxide (E 171), iron oxide red (E 172), sodium laurilsulfate.

Printing ink of capsule shell: Shellac, propylene glycol, potassium hydroxide, black iron oxide (E172).

What Perixis looks like and contents of the pack:

Perixis 0.5 mg: Light yellow / Light yellow hard gelatin capsules, size "5" imprinted with “TCR” on cap & “0.5” on body containing white to off white granular powder.

Perixis 1 mg: White / White hard gelatin capsules, size "4" imprinted with “TCR” on cap & “1” on body containing white to off white granular powder

Perixis 5 mg: Pink/Pink hard gelatin capsules size “4” imprinted with “TCR” on cap & “5” on body containing white to off white granular powder.

Perixis are available in blisters packs of

Tacrolimus 0.5 mg capsules

Packs of 20, 30, 50, 60 and 100 hard capsules.

Tacrolimus 1 mg capsules

Packs of 20, 30, 50, 60, 90 and 100 hard

capsules.

Tacrolimus 5 mg capsules

Packs of 30, 50, 60 and 100 hard capsules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder:

Accord Healthcare Limited Sage House, 319, Pinner Road,

North Harrow, Middlesex,

HA1 4HF,

United Kingdom

Manufacturer:

Accord Healthcare Limited Sage House, 319, Pinner Road,

North Harrow, Middlesex,

HA1 4HF,

United Kingdom

The leaflet was last revised in 06/2013.