Prograf

Patient Information Leaflet: Important Information

Prograf, 0.5 mg, hard capsules
Prograf, 1 mg, hard capsules
Prograf, 5 mg, hard capsules
Tacrolimus

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Contents of the Leaflet:

• 1. What is Prograf and what is it used for
• 2. Important information 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 is Prograf and what is it used for

Prograf belongs to a group of medicines called immunosuppressants. After an organ transplant (e.g. liver, kidney, or heart), the patient's immune system will try to reject the new organ.
Prograf is used to control the body's immune response and allow the transplanted organ to be accepted.
Prograf is often used in combination with other medicines that also suppress the immune system.
Prograf may also be used in cases of rejection of a transplanted liver, kidney, heart, or other organ, or if previous treatment did not control the immune response after organ transplantation.

2. Important information before taking Prograf

When not to take Prograf

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

Warnings and precautions

Before starting treatment with Prograf, discuss it with your doctor or pharmacist.

• Prograf should be taken every day, as long as immunosuppression is required to prevent rejection of the transplanted organ. You should remain under constant medical supervision.
• If you are taking Prograf, your doctor may order regular tests (blood tests, urine tests, heart function tests, vision tests, and neurological tests). These are routine tests that will help determine the correct dose of Prograf.
• You should avoid taking herbal preparations containing St. John's Wort (Hypericum perforatum) and other herbal preparations, as they may affect the efficacy and dose of Prograf that you need to take. If in doubt, consult your doctor before taking any herbal preparations.
• If you have liver function disorders or have had them in the past, inform your doctor, as these conditions may affect the dose of Prograf.
• If you experience severe abdominal pain with or without other symptoms such as chills, fever, nausea, or vomiting.
• If you experience diarrhea lasting more than one day, inform your doctor, as it may be necessary to adjust the dose of Prograf you are taking.
• If you experience a change in heart rhythm called "QT interval prolongation".
• You should limit exposure to sunlight and ultraviolet radiation, wearing protective clothing and using sunscreens with a high protection factor. This is due to the risk of developing malignant skin changes during immunosuppressive treatment.
• If you are to receive a vaccine, inform your doctor in advance. Your doctor will advise on the best course of action.
• In patients treated with Prograf, an increased risk of lymphoproliferative disorders has been observed (see section 4). Ask your doctor for specific advice on these disorders.
• If you have or have had damage to the smallest blood vessels, known as microangiopathy, inform your doctor if you experience: fever, bruising under the skin (which may look like red dots), unexplained fatigue, confusion, yellowing of the skin or eyes, decreased urine output, loss of vision, and seizures (see section 4). If you are taking tacrolimus with sirolimus or everolimus, the risk of these symptoms may increase.

Prograf and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take, including those obtained without a prescription and herbal preparations.
Do not take Prograf with cyclosporin.

If you need to visit a doctor other than a transplant specialist, tell the doctor that you are taking tacrolimus. The doctor may want to consult with a transplant specialist to determine if you should take a different medicine that may increase or decrease the level of tacrolimus in your blood.

The level of Prograf in your blood may change when taking other medicines, and the level of other medicines in your blood may change when taking Prograf.
Taking these medicines may require stopping treatment, increasing, or decreasing the dose of Prograf. In some patients, an increase in tacrolimus levels in the blood has been observed when taking other medicines. This may lead to serious side effects, such as kidney dysfunction, nervous system disorders, and heart rhythm disorders (see section 4).
The effect on Prograf levels in the blood may occur very quickly after starting to take another medicine, so it may be necessary to frequently monitor Prograf levels in the blood during the first few days after starting to take another medicine and often during continued treatment with another medicine. Some other medicines may cause a decrease in tacrolimus levels in the blood, which may increase the risk of rejection of the transplanted organ. In particular, you should tell your doctor about any medicines you are currently taking or have recently taken, including those containing the following active substances:

• antifungal medicines and antibiotics, especially macrolide antibiotics, used to treat infections, such as ketoconazole, fluconazole, itraconazole, posaconazole, voriconazole, clotrimazole, isavuconazole, miconazole, caspofungin, telithromycin, erythromycin, clarithromycin, josamycin, azithromycin, rifampicin, rifabutin, isoniazid, and flucloxacillin
• letermovir, used to prevent cytomegalovirus (CMV) disease
• HIV protease inhibitors (e.g. ritonavir, nelfinavir, saquinavir), a medicine to increase the pharmacokinetics of cobicistat, and tablets or non-nucleoside reverse transcriptase inhibitors (efavirenz, etravirine, nevirapine) used to treat HIV infection
• HCV protease inhibitors (e.g. telaprevir, boceprevir, ombitasvir/paritaprevir/ritonavir with or without dasabuvir, elbasvir/grazoprevir, and glecaprevir/pibrentasvir) used to treat hepatitis C
• nilotinib and imatinib, idelalisib, ceritinib, crizotinib, apalutamide, enzalutamide, or mitotane (used to treat certain cancers)
• mycophenolic acid, used to suppress the immune system to prevent transplant rejection
• medicines used to treat stomach ulcers and acid reflux (e.g. omeprazole, lansoprazole, or cimetidine)
• anti-emetic medicines used to treat nausea and vomiting (e.g. metoclopramide)
• medicines containing aluminum or magnesium hydroxide (which neutralize stomach acid), used to treat heartburn
• hormonal medicines containing ethinyl estradiol (e.g. oral contraceptives) or danazol
• medicines used to treat high blood pressure or heart disease, such as nifedipine, nicardipine, diltiazem, and verapamil
• anti-arrhythmic medicines (amiodarone) used to control heart rhythm disorders (irregular heartbeat)
• medicines known as "statins" used to treat high cholesterol and triglycerides
• anti-epileptic medicines, such as carbamazepine, phenytoin, or phenobarbital
• metamizole, used to treat pain and fever
• corticosteroids prednisolone and methylprednisolone
• antidepressant nefazodone
• herbal products containing St. John's Wort (Hypericum perforatum) or Schisandra sphenanthera extract
• cannabidiol (used, among other things, to treat epileptic seizures). If you are being treated for hepatitis C, tell your doctor. Treatment of hepatitis C may change liver function and may affect tacrolimus levels in the blood. Tacrolimus levels in the blood may decrease or increase, depending on the medicines prescribed for hepatitis C. Your doctor may want to closely monitor tacrolimus levels in the blood and make necessary dose adjustments after starting hepatitis C treatment. If you are taking or plan to take ibuprofen, amphotericin B, antibiotics (co-trimoxazole, vancomycin, or aminoglycoside antibiotics such as gentamicin), or antiviral medicines (e.g. acyclovir, ganciclovir, cidofovir, or foscarnet), tell your doctor. These medicines taken with Prograf may increase the risk of kidney dysfunction and nervous system disorders. Tell your doctor if you are taking sirolimus or everolimus. If you are taking tacrolimus with sirolimus or everolimus, the risk of developing thrombotic microangiopathy, thrombocytopenic purpura, and hemolytic-uremic syndrome may increase (see section 4).

Tell your doctor if you are taking potassium supplements or potassium-sparing diuretics (e.g. amiloride, triamterene, or spironolactone), or antibiotics trimethoprim or co-trimoxazole, which may increase potassium levels in the blood, certain painkillers (non-steroidal anti-inflammatory drugs, e.g. ibuprofen), anticoagulants, or oral antidiabetic medicines.
If you are to receive a vaccine, inform your doctor in advance.

Taking Prograf with food and drink

Prograf should be taken on an empty stomach or at least 1 hour before a meal or 2 to 3 hours after a meal. You should avoid eating grapefruits and drinking grapefruit juice while taking Prograf.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. In one study, the course of pregnancy was evaluated in women treated with tacrolimus and in women treated with other immunosuppressive medicines. In this study, insufficient data were obtained to draw conclusions, but a higher frequency of miscarriages was observed in patients who had a liver or kidney transplant and were treated with tacrolimus, as well as a higher frequency of persistent hypertension and proteinuria in patients who had a kidney transplant. No increased risk of serious birth defects has been observed with Prograf.
Prograf passes into breast milk. Therefore, do not breastfeed while taking Prograf.

Driving and using machines

Do not drive or operate machinery if you experience dizziness or sleepiness after taking Prograf, or if you have vision disturbances. These symptoms are more common if you drink alcohol during treatment with Prograf.

Prograf contains lactose, sodium, and soy lecithin

Prograf contains lactose. If you have been diagnosed with intolerance to some sugars, consult your doctor before taking this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per capsule, which is essentially sodium-free.
The ink used to print on the capsules of Prograf 0.5 mg and 1 mg contains soy lecithin. If you are allergic to peanuts or soy, tell your doctor, who will decide whether you can take this medicine.

3. How to take Prograf

Always take Prograf exactly as your doctor has told you. If you are unsure, ask your doctor or pharmacist.
When collecting your prescription, make sure you receive the same tacrolimus-containing medicine each time, unless your transplant specialist has advised you to switch to a different tacrolimus-containing medicine. The medicine should be taken twice a day. If the medicine looks different from usual or there are different instructions for its use, consult your doctor or pharmacist as soon as possible to ensure you have received the correct medicine.
Your doctor will determine the initial dose to prevent rejection of the transplanted organ based on your body weight. The usual initial dose given immediately after transplantation depends on the type of transplanted organ and is usually between 0.075 mg/kg body weight/day and 0.30 mg/kg body weight/day.
The dose also depends on your overall health and other immunosuppressive medicines you are taking. To determine the correct dose and adjust it during treatment, your doctor will order regular blood tests. If your condition is stable, your doctor will reduce the dose of Prograf. Your doctor will tell you exactly how many capsules to take and how often. Prograf should be taken orally, twice a day, usually in the morning and evening. Prograf should be taken on an empty stomach or at least 1 hour before a meal or 2 to 3 hours after a meal. The capsules should be swallowed whole, with a glass of water. You should avoid eating grapefruits and drinking grapefruit juice while taking Prograf. Do not swallow the desiccant found in the packaging.

If you take more Prograf than you should

If you accidentally take a higher dose of Prograf than prescribed, contact your doctor or go to the nearest hospital immediately.

If you forget to take Prograf

Do not take a double dose to make up for a forgotten dose.
If you forget to take your Prograf capsules, wait until the next time you are supposed to take them, and then take the capsules as scheduled.

If you stop taking Prograf

Stopping Prograf may increase the risk of rejection of the transplanted organ.
Do not stop treatment unless your doctor tells you to.
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 suppresses the body's immune system to prevent rejection of the transplanted organ.
As a result, the body's ability to fight infections is reduced. Therefore, while taking Prograf, you are more prone to infections than usual, such as skin, mouth, stomach, and intestinal infections, lung and urinary tract infections. Some infections can be severe or life-threatening and may include bacterial, viral, fungal, parasitic, or other infections.
Tell your doctor immediately if you experience symptoms of infection, including:

• fever, cough, sore throat, weakness, or general feeling of being unwell
• memory loss, difficulty thinking, difficulty walking, or loss of vision - these may be caused by a very rare, serious brain infection that can be life-threatening (progressive multifocal leukoencephalopathy, PML). Severe side effects may occur, including those listed below.

If you experience or suspect you have any of the following severe side effects, tell your doctor immediately:

Severe side effects that occur frequently (may occur in less than 1 in 10 people):

• perforation of the gastrointestinal tract: severe abdominal pain, with or without other symptoms, such as chills, fever, nausea, or vomiting
• organ dysfunction
• blurred vision Severe side effects that occur infrequently (may occur in less than 1 in 100 people):
• microangiopathic hemolytic anemia (damage to the smallest blood vessels), including hemolytic-uremic syndrome, with symptoms such as: little or no urine output, extreme fatigue, yellowing of the skin or eyes (jaundice), and unexplained bruising or bleeding
• thrombotic thrombocytopenic purpura: a condition characterized by damage to the smallest blood vessels and symptoms such as fever, bruising under the skin (which may look like red dots), unexplained fatigue, confusion, yellowing of the skin or eyes (jaundice), and decreased urine output
• toxic epidermal necrolysis: peeling or blistering of the skin and mucous membranes; red, swollen skin may peel off over large areas of the body
• blindness Severe side effects that occur rarely (may occur in less than 1 in 1000 people):
• Stevens-Johnson syndrome: an unexplained, widespread skin pain, facial swelling, severe illness, with blisters on the skin, mouth, eyes, and genitals, hives, tongue swelling, and a spreading red or purple rash
• Torsades de pointes: a change in heart rhythm, which may be accompanied by symptoms such as chest pain (angina), fainting, dizziness, or nausea, and palpitations (feeling of heartbeat) and difficulty breathing Severe side effects with unknown frequency (frequency cannot be estimated from available data):
• opportunistic infections (bacterial, fungal, viral, and parasitic): prolonged diarrhea, fever, and sore throat
• benign and malignant tumors, including skin cancer and a rare type of cancer called Kaposi's sarcoma. Symptoms include skin changes, such as new or changed skin discolorations, spots, or lumps.
• pure red cell aplasia (a significant decrease in red blood cells), hemolytic anemia (a decrease in red blood cells due to abnormal breakdown, accompanied by fatigue) and febrile neutropenia (a decrease in white blood cells that fight infection, with fever). The exact frequency of these side effects is unknown. You may not have any symptoms or, depending on the severity of the condition, you may experience fatigue, apathy, unusual paleness (pallor), shortness of breath, dizziness, headache, chest pain, and coldness in hands and feet.
• agranulocytosis (a significant decrease in white blood cells, with mouth ulcers, fever, and infection/infections). You may not have any symptoms or you may experience sudden high temperature, chills, and sore throat.
• allergic and anaphylactic reactions with symptoms such as sudden itchy rash (hives), swelling of hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing) and a feeling of impending faint
• posterior reversible encephalopathy syndrome (PRES): headache, confusion, mood changes, seizures, and blurred vision. These may be symptoms of a condition known as posterior reversible encephalopathy syndrome, which has been reported in some patients treated with tacrolimus.
• optic neuropathy (abnormalities of the optic nerve): vision problems, such as blurred vision, changes in color vision, difficulty seeing details, or restricted field of vision

The following side effects may also occur after taking Prograf, which may be severe:

• very common (may occur in more than 1 in 10 people):
• increased blood sugar levels, diabetes, increased potassium levels in the blood
• insomnia
• muscle tremors, headache
• increased blood pressure
• abnormal liver function tests
• diarrhea, nausea
• kidney dysfunction
• common (may occur in less than 1 in 10 people):
• decreased blood cell count (platelets, red blood cells, or white blood cells), increased white blood cell count, changes in red blood cell count (visible in blood tests)
• decreased magnesium, phosphorus, potassium, calcium, or sodium levels in the blood, fluid retention, increased uric acid or fat levels in the blood, decreased appetite, increased blood acidity, other electrolyte disturbances
• anxiety symptoms, confusion and disorientation, depression, mood changes, nightmares, hallucinations, and psychiatric disorders
• seizures, impaired consciousness, tingling and numbness (sometimes painful) of hands and feet, dizziness, impaired writing ability, and nervous system disorders
• increased sensitivity to light, eye disorders
• tinnitus
• decreased blood flow to the heart, rapid heartbeat
• bleeding, partial or complete blockage of blood vessels, decreased blood pressure
• shortness of breath, changes in lung tissue, fluid accumulation in the pleura, inflammation of the throat, cough, and flu-like symptoms
• inflammatory or ulcerative conditions causing abdominal pain or diarrhea, gastrointestinal bleeding, inflammation and ulceration of the mouth, fluid accumulation in the abdomen, vomiting, abdominal pain, indigestion, constipation, bloating and gas, loose stools, gastrointestinal symptoms
• abnormal liver enzyme tests and liver dysfunction, yellowing of the skin due to liver disorders, liver cell damage, and liver inflammation
• itching, rash, hair loss, acne, excessive sweating
• joint pain, limb pain, back pain, and foot pain, muscle cramps
• kidney failure, decreased urine output, difficult or painful urination
• general weakness, fever, fluid retention, pain and discomfort, increased alkaline phosphatase activity in the blood, weight gain, and temperature regulation disorders
• uncommon (may occur in less than 1 in 100 people):
• changes in blood clotting and bleeding parameters, decreased blood cell count
• dehydration
• decreased protein or sugar levels in the blood, increased phosphate levels in the blood
• coma, brain bleeding, stroke, paralysis, and paresis, cerebral disorders, speech disorders, and language disorders
• cataract
• hearing disorders
• irregular heartbeat, cardiac arrest, heart failure, heart muscle disorders, heart enlargement, increased heart rate, abnormal ECG results, abnormal heart rhythm and heart rate
• blood clots in the veins of the limbs, shock
• breathing difficulties, respiratory system disorders, asthma
• intestinal obstruction, increased amylase activity in the blood, gastroesophageal reflux, delayed gastric emptying, fluid accumulation in the abdomen, vomiting, abdominal pain, indigestion, constipation, bloating and gas, loose stools, gastrointestinal symptoms
• skin inflammation, increased sensitivity to sunlight
• joint disorders
• inability to urinate, painful menstruation, and abnormal menstrual bleeding
• organ failure, flu-like symptoms, increased sensitivity to heat and cold, feeling of pressure in the chest, irritability, or malaise, increased lactate dehydrogenase activity in the blood, weight loss
• rare (may occur in less than 1 in 1000 people):
• small, bloody spots on the skin due to blood clots
• increased muscle tone
• deafness
• fluid accumulation around the heart
• severe shortness of breath
• pancreatic cyst
• impaired blood flow through the liver
• excessive hair growth
• thirst, fall, feeling of pressure in the chest, decreased mobility, ulcers
• very rare (may occur in less than 1 in 10,000 people):
• muscle weakness
• abnormal echocardiogram
• liver failure, narrowing of the bile ducts
• painful urination with blood
• increased fat tissue

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, please inform your doctor. You can also report side effects directly to the Department of Drug Monitoring, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, PL-02 222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. You can also report side effects to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Prograf

Keep Prograf out of the sight and reach of children.
Take the hard capsules immediately after removal from the blister pack.
Do not use Prograf after the expiry date stated on the carton and blister pack after {EXP.}. The expiry date refers to the last day of the month.
Use all capsules within 1 year of opening the aluminum pouch.
There are no special storage instructions for the medicinal product.
Store in the original packaging to protect from moisture.

6. Contents of the pack and other information

What Prograf contains

Prograf, 0.5 mg, hard capsules

• The active substance is tacrolimus. Each capsule contains 0.5 mg of tacrolimus as tacrolimus monohydrate.
• The other ingredients are: capsule content: hypromellose 6 mPas, croscarmellose sodium, lactose monohydrate, magnesium stearate. capsule shell: titanium dioxide (E171), yellow iron oxide (E172), gelatin. Ink on capsule shell: shellac, soy lecithin, hydroxypropylcellulose, simethicone, red iron oxide (E172). Prograf, 1 mg, hard capsules
• The active substance is tacrolimus. Each capsule contains 1 mg of tacrolimus as tacrolimus monohydrate.
• The other ingredients are: capsule content: hypromellose 6 mPas, croscarmellose sodium, lactose monohydrate, magnesium stearate. capsule shell: titanium dioxide (E171), gelatin. Ink on capsule shell: shellac, soy lecithin, hydroxypropylcellulose, simethicone, red iron oxide (E172). Prograf, 5 mg, hard capsules
• The active substance is tacrolimus. Each capsule contains 5 mg of tacrolimus as tacrolimus monohydrate.
• The other ingredients are: capsule content: hypromellose 6 mPas, croscarmellose sodium, lactose monohydrate, magnesium stearate. capsule shell: titanium dioxide (E171), red iron oxide (E172), gelatin. Ink on capsule shell: shellac, titanium dioxide (E171), and propylene glycol.

What Prograf looks like and contents of the pack

Prograf, 0.5 mg, hard capsules
Opaque, light yellow capsules with "0.5 mg" and "[f] 607" printed in red, containing a white powder.
Prograf, 0.5 mg, hard capsules are available in blisters or perforated unit dose blisters, each containing 10 capsules, in a package with a desiccant. Do not swallow the desiccant. Available in packs of 20, 30, 50, 60, or 100 hard capsules in blisters and packs of 20x1, 30x1, 50x1, 60x1, or 100x1 hard capsules in perforated unit dose blisters.
Prograf, 1 mg, hard capsules
Opaque, white capsules with "1 mg" and "[f] 617" printed in red, containing a white powder.
Prograf, 1 mg, hard capsules are available in blisters or perforated unit dose blisters, each containing 10 capsules, in a package with a desiccant. Do not swallow the desiccant. Available in packs of 20, 30, 50, 60, 90, or 100 hard capsules in blisters and packs of 20x1, 30x1, 50x1, 60x1, 90x1, or 100x1 hard capsules in perforated unit dose blisters.
Prograf, 5 mg, hard capsules
Opaque, reddish-gray capsules with "5 mg" and "[f] 657" printed in white, containing a white powder.
Prograf, 5 mg, hard capsules are available in blisters or perforated unit dose blisters, each containing 10 capsules, in a package with a desiccant. Do not swallow the desiccant. Available in packs of 30, 50, 60, or 100 hard capsules in blisters and packs of 30x1, 50x1, 60x1, or 100x1 hard capsules in perforated unit dose blisters.
Not all pack sizes may be marketed.
In Poland, packs of 30 capsules are available.

Marketing authorization holder and manufacturer

Marketing authorization holder:
Astellas Pharma Sp. z o.o.
ul. Żwirki i Wigury 16C
02-092 Warsaw
Tel.: (22) 545 11 11
Manufacturer:
Astellas Ireland Co., Ltd.
Killorglin, County Kerry V93FC86
Ireland

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Prograf:
Austria, Cyprus, Czech Republic, Denmark, Germany, Greece, Spain, Finland, France, Hungary, Iceland, Ireland, Italy, Malta, Norway, Poland, Portugal, Slovakia, Slovenia, Sweden
Prograft:
Belgium, Luxembourg, Netherlands
Date of last revision of the leaflet: 02/2025