TACROLIMUS CINFA 5 mg HARD CAPSULES

Introduction

Package Leaflet: Information for the User

tacrolimus cinfa 5 mg hard capsules EFG

tacrolimus

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is tacrolimus cinfa and what is it used for

tacrolimus cinfa belongs to a group of medicines called immunosuppressants. After your organ transplant (e.g. liver, kidney, heart), your body's immune system will try to reject the new organ.

tacrolimus cinfa is used to control your body's immune response, allowing it to accept the transplanted organ.

tacrolimus cinfa is often used in combination with other medicines that also suppress the immune system.

You may also receive tacrolimus cinfa to treat rejection that is occurring in your liver, kidney, heart, or other transplanted organ, or if any previous treatment you were following did not control this immune response after your transplant.

2. What you need to know before you take tacrolimus cinfa

Do not take tacrolimus cinfa

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take tacrolimus cinfa.

• You will need to take tacrolimus every day, as long as you need immunosuppression to prevent rejection of your transplanted organ. You should remain in regular contact with your doctor.
• While taking tacrolimus, your doctor may want to perform tests from time to time (including blood and urine tests, heart function tests, visual and neurological tests). This is quite normal and will help your doctor to decide the most suitable dose of tacrolimus for you.
• Please avoid taking any herbal preparations, e.g. St. John's Wort (Hypericum perforatum) or any other herbal products, as this may affect the efficacy and dose of tacrolimus you need to receive. If in doubt, please consult your doctor before taking any herbal products or preparations.
• If you have liver problems or have had a disease that may have affected your liver, please inform your doctor, as this may affect the dose of tacrolimus you receive.
• If you experience severe abdominal pain accompanied by other symptoms such as chills, fever, nausea, or vomiting.
• If you have diarrhea for more than a day, please inform your doctor, as it may be necessary to adjust the dose of tacrolimus you receive.
• If you have an alteration in the electrical activity of the heart called "prolongation of the QT interval".
• Limit your exposure to sunlight and UV light while taking tacrolimus, using adequate protective clothing and sunscreen with a high sun protection factor. This is due to the potential risk of malignant skin changes with immunosuppressive therapy.
• If you need to be vaccinated, please inform your doctor beforehand. He will advise you on the best course of action.
• It has been reported that some patients treated with tacrolimus have an increased risk of developing lymphoproliferative disorders (see section 4). Ask your doctor for more information about these disorders.

Handling precautions:

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

Other medicines and tacrolimus cinfa

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

Tacrolimus should not be taken with cyclosporin.

If you need to visit a different doctor from your transplant specialist, tell the doctor that you are taking tacrolimus. Your doctor may need to consult your transplant specialist if you need to use another medicine that may increase or decrease your blood level of tacrolimus.

The blood levels of tacrolimus may be changed due to other medicines you are taking, and the blood levels of other medicines may be changed by the administration of tacrolimus, which may require interruption, increase, or decrease of the dose of tacrolimus.

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

The effect on blood levels of tacrolimus can occur very soon after starting to use another medicine, so it may be necessary to monitor the blood level of tacrolimus frequently and continuously during the first few days of use of another medicine and frequently while continuing its use. Some other medicines may cause the blood levels of tacrolimus to decrease, which may increase the risk of rejection of the transplanted organ.

In particular, you should inform your doctor if you are using or have recently used medicines with active ingredients such as:

• antifungals and antibiotics, especially macrolide antibiotics used to treat infections, e.g. ketoconazole, fluconazole, itraconazole, posaconazole, voriconazole, clotrimazole, isavuconazole, miconazole, 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 cobicistat, and combination tablets or non-nucleoside reverse transcriptase inhibitors for HIV (efavirenz, etravirine, nevirapine) used to treat HIV infections
• HCV protease inhibitors (e.g. telaprevir, boceprevir, and 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 as a prevention of transplant rejection
• medicines for stomach ulcers 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 with ethinylestradiol (e.g. the 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 products containing St. John's Wort (Hypericum perforatum) or extracts of Schisandra sphenanthera.
• Cannabidiol (its use includes, among others, the treatment of epileptic seizures).

Tell your doctor if you are receiving treatment for hepatitis C. The pharmacological treatment for hepatitis C may change your liver function and may affect the blood levels of tacrolimus. The blood levels of tacrolimus may decrease or increase depending on the medicines prescribed for hepatitis C. Your doctor may need to closely monitor the blood levels of tacrolimus and make necessary dose adjustments after starting treatment for hepatitis C.

Tell 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. aciclovir, ganciclovir, cidofovir, foscarnet). These medicines may worsen kidney or nervous system problems when taken together with tacrolimus.

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 can increase potassium levels in your blood, some painkillers (so-called NSAIDs, e.g. ibuprofen), anticoagulants, or oral medication for diabetic treatment, while taking tacrolimus.

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

tacrolimus cinfa with food, drinks, and alcohol

Generally, you should take tacrolimus on an empty stomach or at least 1 hour before a meal or 2-3 hours after it. You should avoid grapefruit or grapefruit juice while taking tacrolimus.

Pregnancy, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Tacrolimus passes into breast milk. Therefore, you should not breast-feed while receiving tacrolimus.

Driving and using machines

Do not drive and do not use tools or machines if you feel dizzy or drowsy, or have problems seeing clearly after taking tacrolimus. These effects are more frequently observed if tacrolimus is taken with alcohol.

tacrolimus cinfa contains lactose.

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take tacrolimus cinfa

Follow exactly the instructions for administration of tacrolimus given by your doctor. If you are in doubt, ask your doctor or pharmacist.

Make sure you receive the same medicine with tacrolimus each time you collect your prescription, unless your transplant specialist has agreed to change to a different medicine with tacrolimus. This medicine should be taken twice a day. If the appearance of this medicine is not the same as 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. The initial doses just after transplantation will generally be within the range of 0.075-0.30 mg per kg body weight per day, depending on your transplanted organ.

Your dose depends on your general condition and any other immunosuppressive medication you may be taking. Your doctor will need to perform blood tests regularly to determine the correct dose and to adjust the dose from time to time. Your doctor will usually reduce your dose of tacrolimus once your condition has stabilized. Your doctor will tell you exactly how many capsules to take and how often.

Tacrolimus is taken orally, twice a day, usually in the morning and evening. In general, you should take tacrolimus on an empty stomach or at least 1 hour before a meal or 2-3 hours after it. The capsules should be swallowed whole with a glass of water. Avoid grapefruit and grapefruit juice while taking tacrolimus. Do not ingest the desiccant included in the aluminum blister.

If you take more tacrolimus cinfa than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take tacrolimus cinfa

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

If you forget to take this medicine, wait until the next dose and then continue as before.

If you stop taking tacrolimus cinfa

Stopping your treatment with tacrolimus 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 on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Tacrolimus reduces the body's defense mechanism that allows it to reject the transplanted organ. Consequently, the body will not function as well as usual in fighting infections. Therefore, if you are taking tacrolimus, you will be more prone than usual to suffer from infections, such as skin, mouth, stomach, and intestinal infections, lung and urinary tract infections.

Some infections can be severe or fatal and may include infections 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 of weakness or general malaise.
• Memory loss, thinking problems, difficulty walking, or vision loss – these symptoms may be due to a rare and severe brain infection (progressive multifocal leukoencephalopathy or PML).

Severe adverse effects have been reported, including those listed below. Inform your doctor immediately if you suspect you are suffering from any of the following severe adverse effects:

Frequent severe adverse effects (may affect up to 1 in 10 people):

• Gastrointestinal perforation: severe abdominal pain accompanied or not by other symptoms such as chills, fever, nausea, or vomiting.
• Insufficient function of the transplanted organ.
• Blurred vision.

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

• Hemolytic uremic syndrome with the following symptoms: low or no urine output (acute kidney failure), extreme fatigue, yellowing of the skin or eyes (jaundice), and bruising or abnormal bleeding and signs of infection.

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

• Thrombotic thrombocytopenic purpura (TTP), 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), and symptoms of acute kidney failure (low or no urine output).
• Toxic epidermal necrolysis: erosion and blistering of the skin or mucous membranes, red and swollen skin that may affect large areas of the body.
• Blindness

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

• Stevens-Johnson syndrome: unexplained generalized skin pain, facial swelling, severe disease with blistering of the skin, mouth, eyes, and genitals, rash, swelling of the tongue, red or purple skin 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 (feeling heartbeats) and difficulty breathing.

Severe adverse effects of 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 tumors 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 colors or changes in existing ones, lesions, or bumps.
• Cases of pure red cell aplasia (a very severe reduction in red blood cell count) and hemolytic anemia (decrease in red blood cell count due to abnormal breakdown of red blood cells, accompanied by fatigue) and febrile neutropenia (a decrease in the type of white blood cells that fight infections, accompanied by fever). The exact frequency of these adverse effects is unknown. You may not have symptoms or, depending on the severity of the condition, you may feel: fatigue, apathy, abnormal paleness of the skin (pallor), difficulty breathing, dizziness, headache, chest pain, and feeling cold in hands and feet.
• Cases of agranulocytosis (a severe decrease in the number of white blood cells, accompanied by mouth sores, fever, and infection(s)). You may not have symptoms or you may feel sudden fever, chills, and sore throat.
• Allergic and anaphylactic reactions with the following symptoms: sudden itchy skin rash (hives), swelling of hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing or breathing) and you may feel like you are going to faint.
• Posterior reversible encephalopathy syndrome (PRES): headache, confusion, mood changes, seizures, and vision changes. 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 (optic nerve damage): vision problems such as blurred vision, changes in color vision, difficulty seeing details, or reduced visual field.

The following adverse effects may also occur after receiving tacrolimus and may be severe:

Very frequent 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

-Diarrhea, nausea

-Kidney problems

Frequent adverse effects (may affect up to 1 in 10 people)

-Decrease in blood cell count (platelets, red blood cells, or white blood cells), increase in white blood cell count, changes in red blood cell count (see blood test)

-Decrease in magnesium, phosphate, potassium, calcium, or sodium in the blood, fluid overload, increase in uric acid or lipids in the blood, decrease in appetite, increase in blood acidity, other changes in blood salts

-Symptoms of anxiety, confusion, and disorientation, depression, mood changes, nightmares, hallucinations, mental disorders

-Seizures, alterations in consciousness, tingling and numbness (sometimes painful) of hands and feet, dizziness, difficulty writing, nervous system disorders

-Increased sensitivity to light, eye disorders

-Hearing sounds in the ears

-Decreased blood flow in the cardiac vessels, faster heart rate

-Bleeding, partial or complete blockage of blood vessels, decreased blood pressure

-Difficulty breathing, changes in the respiratory tract, asthma

-Intestinal obstruction, increased blood level of the amylase enzyme, reflux of stomach contents into the throat, delayed stomach emptying

-Dermatitis, sensation of burning under sunlight

-Joint disorders

-Difficulty urinating, painful and abnormal menstrual bleeding

-Failure of some organs, flu-like illness, increased sensitivity to heat and cold, feeling of pressure in the chest, nervousness or strange feeling, increase in lactate dehydrogenase enzyme in the blood, weight loss

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

-Changes in blood coagulation, decrease in all blood cell counts

-Dehydration

-Decrease in protein or sugar in the blood, increase in phosphate in the blood

-Coma, cerebral hemorrhage, stroke, paralysis, brain disorder, speech and language disorders, memory problems

-Cataract

-Hearing difficulty

-Irregular heartbeat, cardiac arrest, decreased cardiac function, alteration of the heart muscle, increased heart muscle, stronger heartbeat, abnormal electrocardiogram, abnormal heart rate and pulse

-Blood clots in a limb vein, shock

-Breathing difficulties, changes in the respiratory tract, asthma

-Intestinal obstruction, increased blood level of the amylase enzyme, reflux of stomach contents into the throat, delayed stomach emptying

-Dermatitis, sensation of burning under sunlight

-Joint disorders

-Difficulty urinating, painful and abnormal menstrual bleeding

-Failure of some organs, flu-like illness, increased sensitivity to heat and cold, feeling of pressure in the chest, nervousness or strange feeling, increase in lactate dehydrogenase enzyme in the blood, weight loss

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

-Small bleeding spots on the skin due to blood clots

-Increased muscle stiffness

-Deafness

-Fluid accumulation around the heart

-Acute difficulty breathing

-Cyst formation in the pancreas

-Problems with blood flow in the liver

-Increased hair growth

-Thirst, falls, feeling of pressure in the chest, decreased mobility, ulcers

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

-Muscle weakness

-Abnormal echocardiogram

-Liver failure, narrowing of the bile duct

-Painful urination with blood in the urine

-Increased fatty tissue

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Tacrolimus Cinfa

Keep this medicine out of the sight and reach of children.

Store below 30°C. Store in the original packaging to protect it from light and moisture.

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

Do not use after the expiration date shown on the packaging and on the blister pack after CAD. The expiration date is the last day of the month indicated.

Use all the capsules within 1 year of opening the aluminum bag.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE collection point in your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Tacrolimus Cinfa

The active ingredient is tacrolimus. Each hard capsule contains 5 mg of tacrolimus (as tacrolimus monohydrate).

The other ingredients are: povidone, sodium croscarmellose (E-468), anhydrous lactose, magnesium stearate.

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

Appearance and Packaging Size

Red capsules containing white powder.

Tacrolimus Cinfa 5 mg hard capsules EFG are presented in PVC/PVDC/ALU precut unit dose blisters within an aluminum protective bag, which includes a desiccant that protects the capsules from moisture. The desiccant should not be swallowed. They are available in packs of 30, 50, 60, or 100 (clinical pack) hard capsules.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Laboratorios Cinfa, S.A.

Carretera Olaz-Chipi, 10. Polígono Industrial Areta.

31620 Huarte (Navarra) - Spain

Date of the Last Revision of this Prospectus: March 2025

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.