Prograf 5 mg hard capsules

Patient Information Leaflet

Introduction

Patient Information Leaflet

Prograf 0.5mg hard capsules

Prograf 1mg hard capsules

Prograf 5mg hard capsules

tacrolimus

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.

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

• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.

• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet Contents

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

1. What Prograf is and what it is used for

Prograf belongs to a group of medicines known as immunosuppressants. After 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, allowing it 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 to treat rejection of your liver, kidney, heart, or other transplanted organ that is already occurring, or if any previous treatment you were receiving has not been able to control this immune response after your transplant.

2. What you need to know before taking Prograf

Do not take Prograf

• If you are allergic (hypersensitive) to tacrolimus or to any of the other ingredients of Prograf (listed in section 6).
• If you are allergic (hypersensitive) to any antibiotic belonging to the macrolide antibiotic subgroup (e.g., erythromycin, clarithromycin, josamycin).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Prograf

• You will need to take Prograf every day for as long as immunosuppression is required to prevent rejection of your transplanted organ. You should maintain regular contact with your doctor.
• While taking Prograf, your doctor may periodically request a series of tests (including blood and urine analyses, cardiac function tests, and visual and neurological assessments). This is completely normal and will help your doctor determine the most appropriate dose of Prograf for you.
• Please avoid taking any herbal preparations, e.g., St. John’s wort (Hypericum perforatum), or any other herbal products, as these may affect the effectiveness and required dose of Prograf. If you have any doubts, please consult your doctor before taking any herbal products or preparations.
• If you have liver problems or have previously had a disease that may have affected your liver, please inform your doctor, as this may affect the dose of Prograf you receive.
• If you experience severe abdominal pain, with or without other symptoms such as chills, fever, nausea, or vomiting.
• If you have diarrhea for more than one day, please inform your doctor, as it may be necessary to adjust your Prograf dose.
• If you have a disturbance in the heart's electrical activity known as "QT interval prolongation."
• Limit your exposure to sunlight and UV light while taking Prograf by wearing appropriate protective clothing and using sunscreen with a high sun protection factor. This is due to the potential risk of malignant skin changes associated with immunosuppressive therapy.
• If you need to be vaccinated, please inform your doctor beforehand. Your doctor will advise you on the best course of action.
• It has been reported that some patients treated with Prograf have an increased risk of developing lymphoproliferative disorders (see section 4). Ask your doctor for more information about these disorders.
• If you have or have had damage to small blood vessels, known as thrombotic microangiopathy/thrombotic thrombocytopenic purpura/hemolytic uremic syndrome. Inform your doctor if you develop fever, bruising under the skin (which may appear as red spots), unexplained fatigue, confusion, yellowing of the skin or eyes, reduced urine output, vision loss, or seizures (see section 4). The risk of developing these symptoms may increase when tacrolimus is taken concomitantly with sirolimus or everolimus.

Handling precautions:

During preparation, avoid contact of any part of the body, such as skin or eyes, with the injectable solutions, powder, or granules contained in tacrolimus products, as well as inhalation near these substances. If such contact occurs, wash the skin and eyes thoroughly.

Other medicines and Prograf

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

Prograf must not be taken with cyclosporine.

If you need to visit a physician other than your transplant specialist, tell the doctor that you are taking tacrolimus. Your doctor may need to consult your transplant specialist before prescribing any additional medication that could increase or decrease your blood levels of tacrolimus.

Blood levels of Prograf may be altered by other medicines you are taking, and the blood levels of other medicines may also be affected by taking Prograf. This may require discontinuation, or adjustment (increase or decrease) of the dose of Prograf.

Some patients have experienced increased blood levels of tacrolimus while taking other medicines. This could lead to serious adverse effects such as kidney problems, nervous system disorders, and heart rhythm disturbances (see section 4).

The effect on Prograf blood levels may occur soon after starting another medicine, so it may be necessary to monitor Prograf blood levels frequently and continuously during the first days of starting a new medicine and regularly while continuing its use. Some other medicines may cause blood levels of tacrolimus to decrease, which could increase the risk of rejection of the transplanted organ. In particular, you must inform your doctor if you are taking or have recently taken medicines containing active substances such as:

• antifungal agents and antibiotics, especially macrolide antibiotics used to treat infections, e.g., ketoconazole, fluconazole, itraconazole, posaconazole, voriconazole, clotrimazole, isavuconazole, miconazole, caspofungin, telithromycin, erythromycin, clarithromycin, josamycin, azithromycin, rifampicin, rifabutin, isoniazid, and flucloxacillin
• letermovir, used to prevent diseases caused by CMV (human cytomegalovirus)
• HIV protease inhibitors (e.g., ritonavir, nelfinavir, saquinavir), the pharmacokinetic enhancer cobicistat, and combined tablets or non-nucleoside reverse transcriptase inhibitors for HIV (efavirenz, etravirine, nevirapine) used to treat HIV infection
• HCV protease inhibitors (e.g., telaprevir, boceprevir, the combination ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, elbasvir/grazoprevir, and glecaprevir/pibrentasvir), used to treat hepatitis C infection
• nilotinib and imatinib, idelalisib, ceritinib, crizotinib, apalutamide, enzalutamide, or mitotane (used to treat certain types of cancer)
• mycophenolic acid, used to suppress the immune system to prevent transplant rejection
• medicines for stomach ulcer and acid reflux (e.g., omeprazole, lansoprazole, or cimetidine)
• antiemetics, used to treat nausea and vomiting (e.g., metoclopramide)
• magnesium-aluminum hydroxide (antacid), used to treat acidity
• hormonal treatments containing ethinylestradiol (e.g., the oral “pill” contraceptive) or danazol
• medicines used to treat high blood pressure or heart problems, such as nifedipine, nicardipine, diltiazem, and verapamil
• antiarrhythmic medicines (amiodarone) used to control arrhythmia (irregular heartbeat)
• medicines known as “statins” used to treat high cholesterol and triglycerides
• antiepileptic medicines carbamazepine, phenytoin, or phenobarbital
• metamizole, used to treat pain and fever
• corticosteroids prednisone and methylprednisolone
• the antidepressant nefazodone
• herbal medicines containing St. John’s wort (Hypericum perforatum) or extracts of Schisandra sphenanthera
• cannabidiol (used, among others, for the treatment of epileptic seizures)

Inform your doctor if you are receiving treatment for hepatitis C. Pharmacological treatment for hepatitis C may alter your liver function and may affect tacrolimus blood levels. Tacrolimus blood levels may either decrease or increase depending on the medicines prescribed for hepatitis C. Your doctor may need to closely monitor your tacrolimus blood levels and make necessary dose adjustments of Prograf after starting hepatitis C treatment.

Inform your doctor if you are taking ibuprofen, amphotericin B, antibiotics (cotrimoxazole, vancomycin, or aminoglycoside antibiotics such as gentamicin), or antivirals (e.g., aciclovir, ganciclovir, cidofovir, or foscarnet). These medicines may worsen kidney or nervous system problems when taken together with Prograf.

Inform your doctor if you are taking sirolimus or everolimus. When tacrolimus is taken together with sirolimus or everolimus, the risk of developing thrombotic microangiopathy, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome may increase (see section 4).

Your doctor also needs to know if you are taking potassium supplements or potassium-sparing diuretics (e.g., amiloride, triamterene, or spironolactone), or the antibiotics trimethoprim and cotrimoxazole, which may increase potassium levels in your blood, certain painkillers (so-called NSAIDs, e.g., ibuprofen), anticoagulants, or oral antidiabetic medications, while taking Prograf.

If you need to be vaccinated, please inform your doctor beforehand.

Taking Prograf with food and drinks

You should generally take Prograf on an empty stomach, or at least 1 hour before a meal or 2–3 hours after eating. You must avoid grapefruit or grapefruit juice while taking Prograf.

Pregnancy and lactation

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. One study evaluated pregnancy outcomes in women treated with tacrolimus and other immunosuppressants. Although this study did not provide sufficient evidence to draw definitive conclusions, higher rates of spontaneous abortion were reported among liver and kidney transplant patients treated with tacrolimus, as well as higher rates of persistent hypertension associated with protein loss in the urine occurring during pregnancy or the postpartum period (a condition called preeclampsia) in kidney transplant patients. No increased risk of major congenital defects was found to be associated with the use of Prograf.

Prograf passes into breast milk. Therefore, you should not breastfeed while receiving Prograf.

Driving and using machines

Do not drive and do not operate tools or machinery if you feel dizzy or drowsy, or if you have difficulty seeing clearly after taking Prograf. These effects are more frequent if Prograf is taken together with alcohol.

Prograf contains lactose, sodium, and lecithin (soy)

This medicine contains lactose. If your doctor has informed you of an intolerance to certain sugars, please consult with him before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per capsule; i.e., it is essentially "sodium-free".

The printing ink used on Prograf 0.5 mg and 1 mg capsules contains soy lecithin. If you are allergic to peanuts or soy, consult your doctor to determine whether you should use this medicine.

3. How to take Prograf

Follow exactly the administration instructions for Prograf given by your doctor. If in doubt, consult your doctor or pharmacist again.

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

This medicine must be taken twice daily. If this medicine looks different than usual, or if the dosage instructions have changed, consult your doctor or pharmacist as soon as possible to ensure you have the correct medicine.

The initial dose to prevent rejection of your transplanted organ will be determined by your doctor based on your body weight. Initial doses just after transplantation will generally be within the range of

0.075 – 0.30 mg per kg of body weight per day

depending on your transplanted organ.

Your dose depends on your general condition and other immunosuppressive medications you may be taking. Your doctor will need to perform regular blood tests to determine the correct dose and to adjust it from time to time. Your doctor will usually reduce your dose of Prograf once your condition has stabilized. 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 at night. Prograf should generally be taken on an empty stomach, or at least one hour before, or 2 to 3 hours after meals. The capsules must be swallowed whole with a glass of water. Avoid grapefruit and grapefruit juice while taking Prograf. Do not ingest the desiccant included in the aluminum pouch.

If you take more Prograf than you should

If you accidentally take more Prograf than you should, contact your doctor or go to the nearest hospital emergency department, or call the Toxicology Information Service at: 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Prograf

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

If you forget to take a Prograf capsule, wait until the time for your 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 treatment unless your doctor tells you to.

If you have any further questions about 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.

Prograf reduces your body's own defence mechanism that would normally allow it to reject your transplanted organ. As a result, your body will not work as effectively as usual in fighting infections. Therefore, if you are taking Prograf, you are more likely than normal to develop infections, for example, infections of the skin, mouth, stomach and intestines, lungs, and urinary tract.

Some infections may be serious or fatal and may include those caused by bacteria, viruses, fungi, parasites, or other infections.

Inform your doctor immediately if you have symptoms of an infection, including:

• Fever, cough, sore throat, feeling weak or generally unwell
• Memory loss, difficulty thinking, trouble walking, or loss of vision – these symptoms may be due to a very rare but serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML)

Serious side effects may occur, including those listed below.

Inform your doctor immediately if you suspect you are experiencing any of the following serious side effects:

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

• Gastrointestinal perforation: severe abdominal pain with or without other symptoms such as chills, fever, nausea, or vomiting.
• Inadequate function of your transplanted organ.
• Blurred vision.

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

• Thrombotic microangiopathy (damage to the smallest blood vessels), including haemolytic uraemic syndrome with the following symptoms: low or no urine output (acute kidney failure), extreme tiredness, yellowing of the skin or eyes (jaundice), and bruising or abnormal bleeding, and signs of infection.

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

• Thrombotic thrombocytopenic purpura: includes damage to the smallest blood vessels and is characterised by fever and bruising under the skin that may appear as red spots, with or without unexplained extreme fatigue, confusion, yellowing of the skin or eyes (jaundice), symptoms of acute kidney failure (low or no urine output), loss of vision, and seizures.
• Toxic epidermal necrolysis: erosion and blistering of the skin or mucous membranes, red and swollen skin that may peel off in large areas of the body.
• Blindness.

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

• Stevens-Johnson syndrome: unexplained widespread skin pain, facial swelling, a serious illness with blistering of the skin, mouth, eyes, and genitals, rashes, swelling of the tongue, red or purple rash that spreads, and skin peeling.
• Torsades de pointes: change in heart rate that may or may not be accompanied by symptoms such as chest pain (angina), fainting, dizziness or nausea, palpitations (awareness of heartbeats), and difficulty breathing.

Serious side effects of unknown frequency (frequency cannot be estimated from available data):

• Opportunistic infections (bacterial, fungal, viral, and protozoal): prolonged diarrhoea, fever, and sore throat.
• Benign and malignant tumours have been reported after treatment as a result of immunosuppression, including malignant skin cancers and a rare type of cancer that may include skin lesions known as Kaposi's sarcoma. Symptoms include skin changes such as new discolourations or changes in existing moles, lesions, or lumps.
• Cases of pure red cell aplasia (a marked reduction in red blood cell count), haemolytic anaemia (reduction in red blood cells due to abnormal breakdown accompanied by fatigue), and febrile neutropenia (a decrease in the type of white blood cells that fight infections, accompanied by fever) have been reported. The exact frequency of these side effects is unknown. You may have no symptoms, or depending on the severity, you may experience: fatigue, apathy, unusual paleness of the skin (pallor), difficulty breathing, dizziness, headache, chest pain, and feeling cold in hands and feet.
• Cases of agranulocytosis (a marked decrease in white blood cells accompanied by mouth ulcers, fever, and infection(s)). You may have no symptoms or may suddenly experience fever, chills, and sore throat.
• Allergic and anaphylactic reactions with the following symptoms: sudden itchy rash (hives), swelling of hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing), and feeling faint.
• Posterior reversible encephalopathy syndrome (PRES): headache, confusion, mood changes, seizures, and visual disturbances. These could be signs of a disorder known as posterior reversible encephalopathy syndrome, which has been reported in some patients treated with tacrolimus.
• Optic neuropathy (damage to the optic nerve): vision problems such as blurred vision, changes in colour vision, difficulty seeing details, or reduced visual field.

The following side effects may also occur after receiving Prograf and may be serious:

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

• Increased blood sugar, diabetes mellitus, increased potassium in the blood.
• Difficulty sleeping.
• Tremors, headache.
• Increased blood pressure.
• Abnormalities in liver function tests.
• Diarrhoea, nausea.
• Kidney problems.

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

• Reduction in blood cells (platelets, red blood cells, or white blood cells), increased white blood cell count, changes in red blood cell counts (see blood tests).
• Reduction in magnesium, phosphate, potassium, calcium, or sodium in the blood, fluid overload, increased uric acid or lipids in the blood, decreased appetite, increased blood acidity, other changes in blood salts.
• Anxiety symptoms, confusion and disorientation, depression, mood changes, nightmares, hallucinations, mental disorders.
• Seizures, disturbances in level of consciousness, tingling and numbness (sometimes painful) in hands and feet, dizziness, reduced ability to write, nervous system disorders.
• Increased sensitivity to light, eye disorders.
• Ringing in the ears.
• Reduced blood flow in heart vessels, faster heartbeat.
• Bleeding, partial or complete blockage of blood vessels, reduced blood pressure.
• Difficulty breathing, changes in lung tissue, fluid accumulation around the lungs, inflammation of the pharynx, cough, flu-like symptoms.
• Inflammations or ulcers causing abdominal pain or diarrhoea, stomach bleeding, mouth ulcers or inflammation, fluid accumulation in the abdomen, vomiting, abdominal pain, indigestion, constipation, flatulence, abdominal swelling, loose stools, stomach problems.
• Changes in liver function and liver enzymes, jaundice of the skin due to liver problems, liver tissue damage, and liver inflammation.
• Itching, rash, hair loss, acne, increased sweating.
• Joint, limb, back, and foot pain, muscle spasms.
• Insufficient kidney function, reduced urine production, difficulty or pain when urinating.
• General weakness, fever, fluid accumulation in the body, pain and discomfort, increased blood alkaline phosphatase enzyme, weight gain, sensation of altered temperature.

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

• Changes in blood clotting, reduction in all types of blood cells.
• Dehydration.
• Reduction in blood proteins or sugar, increased blood phosphate.
• Coma, brain haemorrhage, stroke, paralysis, brain disorders, speech and language abnormalities, memory problems.
• Clouding of the lens.
• Hearing impairment.
• Irregular heartbeat, cardiac arrest, reduced heart performance, heart muscle disorders, enlarged heart muscle, stronger heartbeat, abnormal ECG, abnormal heart rate and pulse.
• Blood clot in a vein of a limb, shock.
• Difficulty breathing, respiratory tract disorders, asthma.
• Intestinal obstruction, increased blood level of amylase enzyme, reflux of stomach contents into the throat, delayed stomach emptying.
• Dermatitis, burning sensation in sunlight.
• Joint disorders.
• Inability to urinate, painful menstruation, abnormal menstrual bleeding.
• Organ failure, flu-like illness, increased sensitivity to heat and cold, chest tightness, restlessness or abnormal sensation, increased blood lactate dehydrogenase enzyme, weight loss.

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

• Small skin bleeds due to blood clots.
• Increased muscle rigidity.
• Deafness.
• Fluid accumulation around the heart.
• Acute breathing difficulty.
• Cyst formation in the pancreas.
• Problems with blood flow in the liver.
• Increased hair growth.
• Thirst, falls, chest tightness, decreased mobility, ulcer.

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

• Muscle weakness.
• Abnormal echocardiogram.
• Liver failure, narrowing of the bile vessel.
• Pain when urinating, blood in the urine.
• Increase in fatty tissue.

Reporting of side effects

If you experience any side effect, talk to your doctor or pharmacist, even if it is a possible side effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Prograf

Keep Prograf out of the sight and reach of children.

Take the hard capsules immediately after removing them from the blister pack.

Do not use this medicine after the expiry date stated on the packaging and blister pack after EXP. The expiry date refers to the last day of the month indicated.

Use all capsules within 1 year after opening the aluminium bag.

This medicine does not require any special storage conditions.

Store in the original packaging to protect from moisture.

Medicines should not be disposed of via wastewater or household waste. Dispose of unused medicines and their containers at a SIGRE point in your pharmacy. If you are unsure, ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the container and additional information

Composition of Prograf

Prograf 0.5 mg hard capsules

• The active substance is tacrolimus. Each capsule contains 0.5 mg of tacrolimus as tacrolimus monohydrate.
• The other components are:

Capsule contents: hypromellose, sodium croscarmellose, lactose monohydrate, magnesium stearate.

Capsule shell: titanium dioxide (E 171), yellow iron oxide (E 172), gelatin.

Printing ink for the capsule shell: shellac glaze, lecithin (from soy), hydroxypropyl cellulose, simethicone, red iron oxide (E 172).

Prograf 1 mg hard capsules

• The active substance is tacrolimus. Each capsule contains 1 mg of tacrolimus as tacrolimus monohydrate.
• The other components are:

Capsule contents: hypromellose, sodium croscarmellose, lactose monohydrate, magnesium stearate.

Capsule shell: titanium dioxide (E 171), gelatin.

Printing ink for the capsule shell: shellac glaze, lecithin (from soy), hydroxypropyl cellulose, simethicone, red iron oxide (E 172).

Prograf 5 mg hard capsules

• The active substance is tacrolimus. Each capsule contains 5 mg of tacrolimus as tacrolimus monohydrate.
• The other components are:

Capsule contents: hypromellose, sodium croscarmellose, lactose monohydrate, magnesium stearate.

Capsule shell: titanium dioxide (E 171), red iron oxide (E 172), gelatin.

Printing ink for the capsule shell: shellac glaze, titanium dioxide (E 171), and propylene glycol.

Appearance of the Product and Contents of the Package

Prograf 0.5 mg hard capsules

Opaque light yellow hard capsules printed in red with “0.5 mg” and “[f] 607”, containing white powder.

Prograf 0.5 mg hard capsules are available in blisters or in pre-cut single-dose blisters, with 10 capsules inside a protective aluminum pouch containing a desiccant to protect the capsules from moisture. The desiccant must not be swallowed. Packaging sizes available: 20, 30, 50, 60, and 100 hard capsules in blisters, and 20, 30, 50, 60, and 100 hard capsules in single-dose blisters.

Prograf 1 mg hard capsules

Opaque white hard capsules printed in red with “1 mg” and “[f] 617”, containing white powder.

Prograf 1 mg hard capsules are available in blisters or in pre-cut single-dose blisters, with 10 capsules inside a protective aluminum pouch containing a desiccant to protect the capsules from moisture. The desiccant must not be swallowed. Packaging sizes available: 20, 30, 50, 60, 90, and 100 hard capsules in blisters, and 20, 30, 50, 60, 90, and 100 hard capsules in single-dose blisters.

Prograf 5 mg hard capsules

Opaque grayish-red hard capsules printed in white with “5 mg” and “[f] 657”, containing white powder.

Prograf 5 mg hard capsules are available in blisters or in pre-cut single-dose blisters, with 10 capsules inside a protective aluminum pouch containing a desiccant to protect the capsules from moisture. The desiccant must not be swallowed. Packaging sizes available: 30, 50, 60, and 100 hard capsules in blisters, and 30, 50, 60, and 100 hard capsules in single-dose blisters.

Only certain package sizes may be marketed.

Marketing Authorization Holder and Manufacturing Responsible Party

Marketing Authorization Holder:

Astellas Pharma, S.A.

Paseo de la Castellana, 259 D - 31st Floor

28046 Madrid (Spain)

Manufacturing Responsible Party:

Astellas Ireland Co. Limited

Killorglin

County Kerry, V93FC86

Ireland

This medicinal product is authorised in the European Economic Area member states under the following names:

Prograf:

Austria, Cyprus, Czech Republic, Denmark, Germany, Greece, Spain, Finland, France, Hungary, Ireland, Italy, Malta, Norway, Poland, Portugal, Slovakia, Slovenia, Sweden.

Prograft:

Belgium, Luxembourg, Netherlands.

Date of the most recent review of this leaflet: March 2026

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/