Prograf 5 mg/ml concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Prograf 5 mg/ml concentrate for solution for infusion

tacrolimus

Read the entire leaflet carefully before you start using 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, pharmacist or nurse.

• 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, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Prograf is and what it is used for

2. What you need to know before using Prograf

3. How to use 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 attempt 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 occurring in your liver, kidney, heart, or other transplanted organ, or if any previous treatment you were receiving has not succeeded in controlling this immune response after your transplant.

2. What you need to know before you start using Prograf

Do not use Prograf

• If you are allergic (hypersensitive) to tacrolimus or to any antibiotic belonging to the macrolide antibiotic subgroup (e.g., erythromycin, clarithromycin, josamycin).
• If you are allergic (hypersensitive) to any of the other components of Prograf (listed in section 6), especially to hydrogenated and polyoxylated castor oil or to similar substances.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting treatment with Prograf.

• While receiving Prograf, your doctor may wish to carry out periodic tests (including blood and urine tests, 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 product or preparation.
• If you have liver problems or have had any illness 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 electrical activity of the heart 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 vaccination, 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 further 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 volume, vision loss, or seizures (see section 4). The risk of these symptoms may increase when tacrolimus is taken together with sirolimus or everolimus.

Handling precautions:

During preparation, avoid contact of the skin or eyes with, and inhalation of, the injection solutions, powder, or granules contained in tacrolimus products. 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 used with cyclosporine.

If you need to visit a doctor other than your transplant specialist, tell the doctor that you are taking tacrolimus. Your doctor may need to consult with your transplant specialist if you are prescribed another medicine 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 be altered by taking Prograf, which may require interruption, increase, or decrease in the dose of Prograf. Some patients have experienced increases in blood levels of tacrolimus while taking other medicines. This could lead to serious adverse effects such as kidney problems, nervous system problems, and heart rhythm disorders (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 taking another medicine and regularly while continuing its use. Some other medicines may cause blood levels of tacrolimus to decrease, which may increase the risk of transplanted organ rejection. In particular, inform your doctor if you are taking or have recently taken medicines containing the following active substances:

• antifungal and antibiotic agents, 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 booster drug cobicistat, and HIV combination tablets or non-nucleoside reverse transcriptase inhibitors (efavirenz, etravirine, nevirapine) used to treat HIV infections
• 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., oral contraceptive "pill") 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 other things, to treat 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 decrease or increase depending on the medicines prescribed for hepatitis C. Your doctor may need to closely monitor tacrolimus blood levels and make necessary dose adjustments of Prograf after starting hepatitis C treatment.

Inform your doctor if you are taking or need to take ibuprofen, amphotericin B, antibiotics (cotrimoxazole, vancomycin, or aminoglycoside antibiotics such as gentamicin), or antivirals (e.g., acyclovir, 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 diabetic medication while receiving Prograf.

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

Use of Prograf with food and beverages

Grapefruit or grapefruit juice should be avoided while taking Prograf.

Pregnancy and lactation

If you are pregnant or breastfeeding, think you may be pregnant, or plan 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 in this study there was insufficient 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 malformations associated with the use of Prograf was found.

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

Prograf contains hydrogenated and polyoxylated castor oil and ethanol

• Prograf contains hydrogenated and polyoxylated castor oil, which may, in a small number of patients, cause a severe allergic reaction. If you have previously experienced this problem, please inform your doctor.
• This medicine contains 81% ethanol (alcohol), corresponding to an amount of 638 mg per dose, equivalent to 16 ml of beer or 7 ml of wine. The small amount of alcohol contained in this medicine does not produce any perceptible effect.

3. How to use Prograf

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

0.01–0.10 mg per kg of body weight per day

depending on your transplanted organ.

Prograf is for intravenous infusion only after dilution. The product must be prepared by healthcare professionals. Additional instructions for healthcare professionals are provided at the end of this leaflet. You will receive Prograf as a continuous infusion over 24 hours, and never as a rapid injection.

Prograf may cause moderate irritation if not administered directly into a vein.

Treatment with Prograf should not last longer than 7 days. After this, your doctor will prescribe Prograf capsules instead.

Your dose depends on your general condition and on any other immunosuppressive medication 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.

If you use more Prograf than you should

If you have received too much Prograf, your doctor will adjust the next dose accordingly.

If you interrupt treatment with Prograf

Interrupting your treatment with Prograf may increase the risk of rejection of your transplanted organ. Do not interrupt treatment unless instructed by your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Prograf reduces your body's own defence mechanism that allows rejection of your transplanted organ. Consequently, your body will not function as effectively as usual in fighting infections. Therefore, if you are taking Prograf, you will be more susceptible than usual to 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, difficulty walking, or loss of vision – these symptoms may be due to a very rare and serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML)

Serious adverse effects may occur, including those listed below.

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

Frequent serious adverse 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 adverse 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 fatigue, yellowing of the skin or eyes (jaundice), and abnormal bruising or bleeding and signs of infection.

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

• Thrombotic thrombocytopenic purpura: includes damage to the smallest blood vessels and is characterized 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), vision loss, 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 adverse effects (may affect up to 1 in 10,000 people):

• Stevens-Johnson syndrome: unexplained widespread skin pain, facial swelling, severe illness with blistering of the skin, mouth, eyes, and genitals, hives, tongue swelling, red or purple rash that spreads, 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 heartbeat), and difficulty breathing.

Serious adverse effects with unknown frequency (frequency cannot be estimated from available data):

• Opportunistic infections (bacterial, fungal, viral, and protozoal): prolonged diarrhea, 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 discolorations or changes in existing ones, lesions, or lumps.
• Cases of pure red cell aplasia (a very marked reduction in red blood cell count), haemolytic anaemia (decrease 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 infection, accompanied by fever) have been reported. The exact frequency of these adverse effects is unknown. You may have no symptoms, or depending on the severity, you may experience: fatigue, apathy, abnormal paleness of the skin (pallor), difficulty breathing, dizziness, headache, chest pain, and cold sensation in hands and feet.
• Cases of agranulocytosis (a marked decrease in white blood cell count 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 adverse effects may also occur after receiving Prograf and may be serious:

Very common adverse 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 adverse 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 of magnesium, phosphate, potassium, calcium, or sodium in blood, fluid overload, increased uric acid or lipids in 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 consciousness level, tingling and numbness (sometimes painful) in hands and feet, dizziness, decreased 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 bloating, 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.
• Kidney insufficiency, reduced urine output, limitation or pain when urinating.
• General weakness, fever, fluid accumulation in the body, pain and discomfort, increased alkaline phosphatase enzyme in blood, weight gain, sensation of altered temperature.

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

• Changes in blood coagulation, reduction in all types of blood cells.
• Dehydration.
• Reduction of proteins or sugar in blood, increased phosphate in blood.
• Coma, brain haemorrhage, stroke, paralysis, brain disorders, speech and language abnormalities, memory problems.
• Lens opacity.
• Hearing deterioration.
• Irregular heartbeat, cardiac arrest, reduced heart performance, disorders of the heart muscle, increased heart muscle size, 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 to sunlight.
• Joint disorders.
• Inability to urinate, painful menstruation, abnormal menstrual bleeding.
• Failure of some organs, flu-like illness, increased sensitivity to heat and cold, chest tightness, restlessness or abnormal sensation, increased blood lactate dehydrogenase enzyme, weight loss.

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

• Small skin bleedings due to blood clots.
• Increased muscle stiffness.
• 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 adverse effects (may affect up to 1 in 10,000 people):

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

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse 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 adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Prograf

Keep out of sight and reach of children.

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

Store the ampoule in the original packaging to protect it from light.

Do not store above 25°C.

6. Contents of the container and additional information

Composition of Prograf

• The active substance is tacrolimus. 1 ml of concentrate for solution for infusion contains 5 mg.
• The other components are polyoxyl 35 hydrogenated castor oil and anhydrous ethanol.

Appearance of the product and contents of the container

The concentrate is a clear, colourless solution presented in transparent glass ampoules. Each ampoule contains 1 ml of concentrate for solution for infusion, which must be diluted before use.

Each carton contains 10 ampoules.

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, 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/

This information is intended for healthcare professionals only:

Prograf 5 mg/ml concentrate for solution for infusion must not be injected undiluted. When diluting, this medicinal product must not be mixed with other medicinal products.

Prograf 5 mg/ml concentrate for solution for infusion must be diluted in 5% glucose solution (w/v) or in physiological saline solution, in polyethylene, polypropylene or glass containers, but not in PVC containers. Only clear, colourless solutions should be used.

The concentration of the infusion solution must be between 0.004 and 0.100 mg/ml. The total volume of infusion over a 24-hour period should be 20–500 ml.

The diluted solution must not be administered as an intravenous bolus.

The infusion solution must be used within 24 hours.

Any unused concentrate remaining in an opened vial or any unused reconstituted solution must be immediately discarded to avoid contamination.