Prograf

Leaflet attached to the packaging: patient 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.
• In case of any doubts, consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including those not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of 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. Package contents and other information

1. What is Prograf and what is it used for

Prograf belongs to a group of medicines called immunosuppressants. After organ transplantation (e.g. liver, kidney, or heart), the patient's immune system will try to reject the new organ.
Prograf is used to control the immune system's 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 system's response after organ transplantation.

2. Important information before taking Prograf

When not to take Prograf

• If the patient is allergic (hypersensitive) to tacrolimus or any of the other ingredients of Prograf (listed in section 6).
• If the patient is 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. The patient should remain under constant medical supervision.
• If Prograf is used, the 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.
• Herbal preparations containing St. John's Wort (Hypericum perforatum) and other herbal preparations should be avoided, as they may affect the efficacy and dose of Prograf that needs to be taken. In case of doubts, consult a doctor before taking any herbal preparations.
• If the patient has liver function disorders or has had them in the past, they should inform their doctor, as these conditions may affect the dose of Prograf.
• If the patient experiences severe abdominal pain with or without other symptoms such as chills, fever, nausea, or vomiting.
• If diarrhea persists for more than one day, the patient should inform their doctor, as it may be necessary to adjust the dose of Prograf.
• If there is a change in the electrical activity of the heart called "QT interval prolongation".
• Exposure to sunlight and ultraviolet radiation should be limited, 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 the patient is to receive a vaccine, they should inform their doctor in advance. The 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). The patient should ask their doctor for specific advice on these disorders.
• If there is or has been damage to the smallest blood vessels, known as microangiopathy/thrombotic microangiopathy/hemolytic-uremic syndrome. The patient should inform their doctor if they experience: fever, bruising under the skin (which may look like red dots), unexplained fatigue, confusion, yellowing of the skin or eyes, decreased urine output, vision loss, and seizures (see section 4). If tacrolimus is taken with sirolimus or everolimus, the risk of these symptoms may increase.

Prograf and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take, including over-the-counter medicines and herbal preparations.
Prograf should not be taken at the same time as cyclosporin.

If a visit to a doctor other than a transplant specialist is necessary, the patient should inform the doctor about taking tacrolimus. The doctor may want to consult with a transplant specialist to determine if the patient should take a different medicine that may increase or decrease the level of tacrolimus in the blood.

The level of Prograf in the blood may change due to the use of other medicines, and the level of other medicines in the blood may change due to the use of Prograf.
The use of these medicines may require stopping treatment, increasing or decreasing the dose of Prograf. In some patients, an increase in the level of tacrolimus in the blood has been observed during the use of other medicines. This may lead to serious side effects, such as kidney function disorders, nervous system disorders, and heart rhythm disorders (see section 4).
The effect on the level of Prograf in the blood may occur very quickly after starting to take another medicine, so it may be necessary to frequently monitor the level of Prograf 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 the level of tacrolimus in the blood, which may increase the risk of rejection of the transplanted organ. In particular, the patient should tell their doctor about currently or recently used medicines containing active substances such as:

• antifungal and antibiotic medicines, 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 cytomegalovirus (CMV) diseases
• HIV protease inhibitors (e.g. ritonavir, nelfinavir, saquinavir), a drug that increases the pharmacokinetics of cobicistat, and tablets or non-nucleoside reverse transcriptase inhibitors of HIV (efavirenz, etravirine, nevirapine) used to treat HIV infection
• HCV protease inhibitors (e.g. telaprevir, boceprevir, ombitasvir/paritaprevir/ritonavir in combination with dasabuvir or without it, 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)
• antiemetic 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
• antiarrhythmic medicines (amiodarone) used to control heart rhythm disorders (irregular heartbeat)
• medicines known as "statins" used to treat high cholesterol and triglycerides
• antiepileptic medicines, e.g. 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). The patient should tell their doctor if they are being treated for hepatitis C. 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. The doctor may want to closely monitor tacrolimus levels in the blood and make necessary dose changes after starting hepatitis C treatment. The patient should tell their doctor if they are taking or plan to take ibuprofen, amphotericin B, antibiotics (cotrimoxazole, vancomycin, or aminoglycoside antibiotics such as gentamicin), or antiviral medicines (e.g. acyclovir, ganciclovir, cidofovir, or foscarnet). These medicines taken with Prograf may increase the risk of kidney function disorders and nervous system disorders. The patient should inform their doctor about taking sirolimus or everolimus. If tacrolimus is taken with sirolimus or everolimus, the risk of developing thrombotic microangiopathy, thrombocytopenic purpura, and hemolytic-uremic syndrome may increase (see section 4).

The patient should tell their doctor if they are taking potassium or using potassium-sparing diuretics (e.g. amiloride, triamterene, or spironolactone), or antibiotics trimethoprim or cotrimoxazole, which may increase potassium levels in the blood, certain painkillers (non-steroidal anti-inflammatory drugs, e.g. ibuprofen), anticoagulant or oral antidiabetic medicines.
If the patient is to receive a vaccine, they should inform their doctor in advance.

Using 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. The patient should avoid eating grapefruits and drinking grapefruit juice while taking Prograf.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist 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. The study did not provide sufficient data 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 associated with proteinuria, which develops during pregnancy or postpartum (pre-eclampsia). No increased risk of serious congenital anomalies has been demonstrated with the use of Prograf.
Prograf passes into breast milk. Therefore, breastfeeding should be avoided during treatment with Prograf.

Driving and using machines

The patient should not drive vehicles or operate any machinery or tools if they experience dizziness or drowsiness, or vision disturbances after taking Prograf. These symptoms occur more frequently if the patient consumes alcohol during treatment with Prograf.

Prograf contains lactose, sodium, and soybean lecithin

Prograf contains lactose. If the patient has been diagnosed with intolerance to some sugars, they should contact their doctor before taking the medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per capsule, which means it is considered "sodium-free".
The ink used to print on the capsules of Prograf 0.5 mg and 1 mg contains soybean lecithin. If the patient is allergic to peanuts or soy, they should tell their doctor, who will decide whether to take this medicine.

3. How to take Prograf

Prograf should always be taken as directed by the doctor. In case of doubts, the patient should consult their doctor or pharmacist.
When picking up the prescription, the patient should make sure to receive the same medicine containing tacrolimus each time, unless the transplant specialist has recommended switching to a different tacrolimus-containing medicine. The medicine should be taken twice a day. If the medicine looks different than usual or there are other instructions regarding its dosage, the patient should consult their doctor or pharmacist as soon as possible to ensure they have received the correct medicine.
The doctor will determine the initial dose to prevent rejection of the transplanted organ based on the patient's body weight. The usual initial dose of Prograf 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 the patient's overall health and other immunosuppressive medicines being taken. To determine the correct dose and modify it during treatment, the doctor will order regular blood tests. If the patient's condition is stable, the doctor will reduce the dose of Prograf. The doctor will tell the patient 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. The patient should avoid eating grapefruits and drinking grapefruit juice while taking Prograf. The desiccant in the packaging should not be swallowed.

Taking a higher dose of Prograf than recommended

If the patient accidentally takes a higher dose of Prograf than recommended, they should contact their doctor or go to the nearest hospital immediately.

Missing a dose of Prograf

The patient should not take a double dose to make up for a missed dose.
If the patient forgets to take a dose of Prograf, they should wait until the next scheduled dose and then take the medicine as directed.

Stopping treatment with Prograf

Stopping treatment with Prograf may increase the risk of rejection of the transplanted organ.
The patient should not stop treatment unless their doctor decides to do so.
If the patient has any further doubts about taking this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Prograf can cause side effects, although not everybody gets them.
Prograf weakens the body's defense mechanism to prevent rejection of the transplanted organ.
As a result, the body's ability to fight infections is reduced. Therefore, during treatment with Prograf, the patient is more susceptible 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.
The patient should tell their doctor immediately if they experience symptoms of infection, including:

• fever, cough, sore throat, weakness, or general feeling of being unwell
• memory loss, difficulty thinking, difficulty walking, or vision loss - 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 any of the following severe side effects occur or are suspected, the patient should tell their doctor immediately:

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

• perforation of the digestive tract: severe abdominal pain, which may be accompanied by other symptoms such as chills, fever, nausea, or vomiting
• disorders of the transplanted organ
• blurred vision

Severe side effects that occur infrequently (may occur in less than 1 in 100 patients):

• microangiopathic hemolytic anemia (damage to the smallest blood vessels), including hemolytic-uremic syndrome, with symptoms such as: small amount of urine or no urine output (acute kidney failure), extreme fatigue, yellowing of the skin or eyes (jaundice), and unexplained bruising or bleeding
• thrombocytopenic purpura: a condition characterized by damage to the smallest blood vessels and symptoms such as fever and bruising under the skin (which may look like red dots) with or without unexplained fatigue, confusion, yellowing of the skin or eyes (jaundice), acute kidney failure (small amount of urine or no urine output), vision loss, and seizures
• 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 1,000 patients):

• Stevens-Johnson syndrome: unexplained, widespread skin pain, facial swelling, severe illness, with blisters on the skin, mouth, eyes, and genitals, hives, swelling of the tongue, and a spreading red or purple rash
• Torsades de pointes: a change in heart rate, which may be accompanied by symptoms such as chest pain (angina), fainting, dizziness, or nausea, palpitations (feeling of heartbeat), and difficulty breathing

Severe side effects that occur very rarely (may occur in less than 1 in 10,000 patients):

• opportunistic infections (bacterial, fungal, viral, and protozoal): prolonged diarrhea, fever, and sore throat
• benign and malignant tumors that occur during treatment due to immunosuppression, including skin cancers and a rare type of cancer that may appear as skin lesions, called Kaposi's sarcoma. Symptoms include skin lesions, such as new or changed pigmentation, spots, or lumps.
• pure red cell aplasia (a significant decrease in the number of red blood cells), hemolytic anemia (a decrease in the number of red blood cells due to abnormal breakdown, accompanied by fatigue), and febrile neutropenia (a decrease in the number of white blood cells that fight infection, with fever). The exact frequency of these side effects is unknown. The patient may not have any symptoms or, depending on the severity of the disease, may experience fatigue, apathy, unnatural paleness (pallor), shortness of breath, dizziness, headache, chest pain, and coldness in the hands and feet.
• agranulocytosis (a significant decrease in the number of white blood cells, with mouth ulcers, fever, and infection/infections). The patient may not have any symptoms or may experience a sudden increase in body temperature, chills, and sore throat.
• allergic and anaphylactic reactions with symptoms such as: sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing), and a feeling of impending fainting
• 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 limited field of vision

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

• increased blood sugar levels, diabetes, increased potassium levels in the blood
• insomnia
• muscle tremors, headache
• increased blood pressure
• abnormal liver function test results
• diarrhea, nausea
• kidney function disorders

Side effects that occur frequently (may occur in less than 1 in 10 patients):

• decreased number of blood cells (platelets, red blood cells, or white blood cells), increased number of white blood cells, 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 disorders
• anxiety symptoms, confusion, and disorientation, depression, mood changes, nightmares, hallucinations, and psychiatric disorders
• seizures, impaired consciousness, tingling and numbness (sometimes painful) of the hands and feet, dizziness, impaired writing ability, and nervous system disorders
• increased sensitivity to light, eye disorders
• ringing in the ears
• decreased blood flow in the heart vessels, 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, flu-like symptoms
• inflammatory or ulcerative conditions causing abdominal pain or diarrhea, gastrointestinal bleeding, inflammation and ulceration of the mouth, fluid accumulation in the abdominal cavity, vomiting, abdominal pain, indigestion, constipation, bloating and gas, loose stools, gastrointestinal symptoms
• abnormal liver enzyme test results and liver function disorders, 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, temperature regulation disorders

Side effects that occur infrequently (may occur in less than 1 in 100 patients):

• changes in blood clotting and bleeding parameters, decreased number of all types of blood cells
• dehydration
• decreased protein or sugar levels in the blood, increased phosphate levels in the blood
• coma, brain bleeding, stroke, paralysis, and paresis, brain 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 rate and rhythm
• 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, abdominal bloating and gas
• skin inflammation, increased sensitivity to sunlight
• joint disorders
• urination disorders, painful menstruation, and abnormal menstrual bleeding
• organ failure, flu-like symptoms, increased sensitivity to heat and cold, feeling of chest tightness, irritability, or malaise, increased lactate dehydrogenase activity in the blood, weight loss

Side effects that occur rarely (may occur in less than 1 in 1,000 patients):

• 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
• feeling of thirst, falling, feeling of chest tightness, decreased mobility, ulcers

Side effects that occur very rarely (may occur in less than 1 in 10,000 patients):

• muscle weakness
• abnormal echocardiogram
• liver failure, bile duct stenosis
• painful urination with blood
• increased fat tissue

Reporting side effects

If the patient experiences any side effects, including those not listed in this leaflet, they should tell their doctor. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Prograf

Prograf should be stored out of sight and reach of children.
The capsules should be taken 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. Package contents 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 contents: hypromellose 6 mPas, croscarmellose sodium, lactose monohydrate, magnesium stearate. capsule shell: titanium dioxide (E171), iron oxide yellow (E172), gelatin. Ink on the capsule shell: shellac, soybean lecithin, hydroxypropylcellulose, simethicone, iron oxide red (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 contents: hypromellose 6 mPas, croscarmellose sodium, lactose monohydrate, magnesium stearate. capsule shell: titanium dioxide (E171), gelatin. Ink on the capsule shell: shellac, soybean lecithin, hydroxypropylcellulose, simethicone, iron oxide red (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 contents: hypromellose 6 mPas, croscarmellose sodium, lactose monohydrate, magnesium stearate. capsule shell: titanium dioxide (E171), iron oxide red (E172), gelatin. Ink on the 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 the imprint "0.5 mg" and the imprint "[f] 607" in red, containing a white powder.
Prograf, 0.5 mg, hard capsules are available in blister packs or perforated unit dose blister packs containing 10 capsules, in a package with a desiccant. Do not swallow the desiccant. Packs of 20, 30, 50, 60, or 100 hard capsules in blister packs and packs of 20x1, 30x1, 50x1, 60x1, or 100x1 hard capsules in perforated unit dose blister packs are available.
Prograf, 1 mg, hard capsules
Opaque, white capsules with the imprint "1 mg" and the imprint "[f] 617" in red, containing a white powder.
Prograf, 1 mg, hard capsules are available in blister packs or perforated unit dose blister packs containing 10 capsules, in a package with a desiccant. Do not swallow the desiccant. Packs of 20, 30, 50, 60, 90, or 100 hard capsules in blister packs and packs of 20x1, 30x1, 50x1, 60x1, 90x1, or 100x1 hard capsules in perforated unit dose blister packs are available.
Prograf, 5 mg, hard capsules
Opaque, reddish-gray capsules with the imprint "5 mg" and the imprint "[f] 657" in white, containing a white powder.
Prograf, 5 mg, hard capsules are available in blister packs or perforated unit dose blister packs containing 10 capsules, in a package with a desiccant. Do not swallow the desiccant. Packs of 30, 50, 60, or 100 hard capsules in blister packs and packs of 30x1, 50x1, 60x1, or 100x1 hard capsules in perforated unit dose blister packs are available.
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
Phone: (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