How does it work?

Prograf capsules and infusion contain the active ingredient tacrolimus, which is a type of medicine called an immunosuppressant. Immunosuppressants are used to dampen down the activity of cells in the immune system.

When you receive an organ transplant the donor cells, although matched as closely as possible to yours, will not be identical to yours. This means that your immune system will recognise the tissue as foreign and try to attack the transplanted organ. This can result in the transplant being rejected.

Tacrolimus is used to prevent transplant rejection because it suppresses the activity of the cells in your immune system that would normally attack the transplanted tissue.

Tacrolimus acts on the white blood cells. It works by blocking the action of a substance called calcineurin that is found in white blood cells called T-lymphocytes. This action prevents the T-lymphocytes from producing substances called lymphokines.

Lymphokines are normally produced by the T-lymphocytes when a foreign substance is detected in the body. The purpose of the lymphokines is to stimulate the production of more T and B lymphocytes, the white blood cells responsible for regulating and triggering immune responses. The T and B lymphocytes attack foreign invadors and defend the body against infection and foreign cells.

By preventing the production of lymphokines, tacrolimus suppresses the action of the T and B lymphocytes. This stops these cells from attacking foreign invadors and triggering other responses by the immune system.

Tacrolimus is used to prevent rejection of kidney, liver and heart transplants. It is used in combination with other immunosuppressant medicines, such as corticosteroids.

What is it used for?

• Preventing the body rejecting a transplanted kidney, liver or heart.
• Treating transplant rejection when other immunosuppressants have failed to control the rejection.

How do I take it?

• Prograf capsules are usually taken twice a day, in the morning and evening.
• The number of capsules to take will vary from person to person. It is important to follow the instructions given by your doctor. These will be printed on the dispensing label that your pharmacist has put on the medicine.
• Prograf capsules should be taken on an empty stomach, at least one hour before or two to three hours after food.
• The capsules should be swallowed whole with a drink of water as soon as they are taken out of the blister.
• Do not swallow the desiccant contained in the foil wrapper.
• If you forget to take a dose just take your next dose at the usual time. Leave out the missed dose. Do not take a double dose to make up for a missed dose.
• Avoid eating grapefruit and drinking grapefruit juice while taking tacrolimus.
• Do not stop taking this medicine unless your doctor tells you to. Stopping treatment may increase the risk of your body rejecting the transplant.

Warning!

• This medicine may cause various side effects that could reduce your ability to drive or operate machinery safely. These effects may be enhanced by drinking alcohol. You should make sure you are aware of your reaction to this medicine before driving or operating machinary.
• Unless your doctor or pharmacist tells you otherwise, you should avoid eating grapefruit or drinking grapefruit juice while taking this medicine, as it may increase the level of this medicine in your blood and therefore increase the risk of side effects.
• This medicine can cause the amount of potassium in your bloodstream to increase. For this reason you should avoid consuming large amounts of foods that have a high potassium content, for example dried fruit, bananas, tomatoes and 'low sodium' salt, while you are taking the medicine. You should also avoid taking potassium supplements.
• This medicine increases your susceptibility to infections because the suppressed immune system is less able to fight them. For this reason, consult your doctor immediately if you develop a sore throat, fever, any other signs of infections, or begin to feel generally unwell.
• People receiving long-term or intensive immunosuppressive treatment are at increased risk of developing lymphomas and other cancers, particularly skin cancer. To reduce the risk of skin cancer, you should minimise your exposure to strong sunlight and UV light by wearing appropriate clothing to protect your skin and using a sunscreen with a high protection factor. Discuss this with your doctor.
• During treatment with this medicine your doctor will need to monitor various things to make sure the treatment is working properly and not causing side effects. Your blood pressure, nervous system and eyesight will be monitored, and your heart using an ECG. You will also need blood tests to monitor your kidney and liver function, blood sugar, blood clotting, blood cells, levels of salts (electrolytes, eg potassium), and amount of the medicine in your blood. Measuring the level of medicine in your blood helps your doctor to prescribe you the correct dose.
• If you have diarrhoea for more than one day while taking this medicine you should tell your doctor. Having diarrhoea can affect the amount of medicine in your blood and extra monitoring of your tacrolimus blood level is recommended.

Use with caution in

• Decreased kidney function.
• Decreased liver function.
• Heart disease.
• People with an abnormal heart rhythm present from birth and seen on a heart monitoring trace (ECG) as a 'prolonged QT interval'.
• High blood pressure (hypertension).
• Infections.
• People with fluid overload or swelling due to excess fluid retention (oedema).
• People being treated with corticosteroids.
• Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (Prograf capsules contain lactose).

Not to be used in

• People who are allergic to macrolide-type antibiotics, eg erythromycin, clarithromycin.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding

Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

• This medicine should only be used during pregnancy if there is no safer alternative and if the potential benefits outweigh the potential risk to the developing baby. If this medicine is used during pregnancy there is a risk of premature delivery and side effects of tacrolimus on the baby. The newborn baby should be carefully monitored for any side effects of the medicine, in particular on the kidneys.
• Women who could get pregnant should ideally use a non-hormonal method of contraception, eg condoms, to prevent pregnancy while taking this medicine. This is because tacrolimus could affect the metabolism of hormonal contraceptives. Seek further medical advice from your doctor.
• This medicine passes into breast milk. The manufacturer recommends that mothers who need to take this medicine should not breastfeed. However, limited data suggests that the levels of tacrolimus in breast milk are low and probably do not adversely affect a breastfeeding baby. You should get medical advice from your doctor if you want to breastfeed while taking this medicine. If you do decide to breastfeed the baby should be carefully monitored.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here, it does not mean that all people using this medicine will experience that or any side effect.

• Increased risk of infections (see warning section above).
• Headache.
• Shaking, usually of the hands (tremor).
• Disturbances of the gut such as diarrhoea, constipation, nausea, vomiting, wind, indigestion or abdominal pain.
• Difficulty sleeping (insomnia).
• High blood pressure (hypertension).
• Raised blood sugar level (hyperglycaemia).
• Disturbances in the normal levels of chemical components (electrolytes) in the blood, eg raised potassium, decreased sodium, magnesium, calcium.
• Raised cholesterol level (hypercholesterolaemia).
• Disturbances in the normal levels of blood cells in the blood.
• Kidney problems such as decreased kidney function or kidney failure.
• Skin reactions such as rash, itch, acne, sweating, hair loss.
• Blurred vision.
• Shortness of breath (dyspnoea)
• Appetite and weight changes.
• Pain in the muscles or joints.
• Visual disturbances.
• Anxiety and agitation.
• Confusion.
• Depression.
• Dizziness.
• Changes in sensation, such as pins and needles, tingling, numbness.
• Seizures.
• Heart problems such as chest pain, abnormal heartbeats, enlargement of the heart, heart failure.
• Liver problems such as jaundice, hepatitis, liver failure.
• Ulceration or bleeding in the gut.
• Bleeding.
• Abnormal blood clots in the blood vessels (thromboembolism).

The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to make sure that the combination is safe.

The immunosuppressant ciclosporin should not be used at the same time as this medicine.

The anticoagulant dabigatran should not be used at the same time as this medicine.

This medicine should not be used in combination with mifamurtide.

There may be an increased risk of side effects on the kidneys if this medicine is taken with other medicines that can affect the kidneys, such as the following:

• ACE inhibitors, eg captopril, enalapril
• aciclovir
• aminoglycoside antibiotics, eg gentamicin
• amphotericin
• co-trimoxazole
• ganciclovir
• non-steroidal anti-inflammatory painkillers (NSAIDs), eg ibuprofen, diclofenac, naproxen
• trimethoprim
• vancomycin.

There may be an increased risk of the level of potassium in your blood rising too high (hyperkalaemia) if any of the following are taken in combination with this medicine:

• ACE inhibitors, eg captopril, enalapril
• angiotensin II receptor antagonists, eg losartan, valsartan
• potassium salts, eg potassium citrate for cystitis
• potassium-sparing diuretics, eg amiloride, spironolactone, triamterene
• potassium supplements
• potassium-containing salt substitutes, eg Low-Salt.

The following medicines may increase the level of tacrolimus in the blood, which could increase the risk of side effects. If you are taking any of these with tacrolimus your doctor may need to reduce your dose of tacrolimus:

• the macrolide antibiotics clarithromycin, erythromycin, telithromycin
• the azole antifungals fluconazole, ketoconazole, itraconazole, posaconazole, voriconazole
• HIV protease inhibitors such as atazanavir, ritonavir, nelfinavir, saquinavir, fosamprenavir
• boceprevir
• chloramphenicol (by mouth or injection)
• crizotinib
• danazol
• diltiazem
• dronedarone
• felodipine
• lansoprazole
• nicardipine
• nifedipine
• omeprazole
• ranolazine
• verapamil.

Hormonal contraceptives such as the pill and the patch may also increase the blood level of tacrolimus. Tacrolimus may also affect the metabolism of these hormonal contraceptives. For this reason women who could get pregnant should ideally use a non-hormonal method of contraception, eg condoms, to prevent pregnancy while taking this medicine. Get further advice from your doctor or pharmacist.

The following medicines may decrease the level of tacrolimus in the blood, which may make it less effective and lead to transplant rejection. If you are taking any of these at the same time your doctor may need to increase your dose of tacrolimus:

• caspofungin
• efavirenz
• phenobarbital
• phenytoin (tacrolimus may also increase the blood level of phenytoin)
• rifabutin
• rifampicin
• sevelamer
• the herbal remedy St John's wort (Hypericum perforatum). You should not take this herbal remedy while you are taking tacrolimus.

Corticosteroids such as methylprednisolone may increase or decrease the blood level of tacrolimus. Your doctor will adjust your tacrolimus dose as required.

Vaccines may be less effective in people taking this medicine. This is because tacrolimus suppresses the action of the immune system and could prevent the body from forming adequate antibodies. Live vaccines should be avoided during treatment with this medicine because they may cause infection. Live vaccines include the following: oral polio; rubella; measles, mumps and rubella (MMR); BCG; yellow fever and oral typhoid vaccines.