Tacrolimus Cinfa 0.5 mg hard capsules EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

tacrolimus cinfa 0.5 mg hard capsules EFG

tacrolimus

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you must not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

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

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

tacrolimus cinfa 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.

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

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

You may also be given tacrolimus cinfa 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 taking 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 macrolide subgroup of antibiotics (e.g. erythromycin, clarithromycin, josamycin).

Warnings and precautions

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

• You will need to take tacrolimus every day for as long as immunosuppression is required to prevent rejection of your transplanted organ. You must maintain regular contact with your doctor.
• While taking tacrolimus, your doctor may periodically perform a series of tests (including blood and urine tests, heart function tests, and visual and neurological assessments). This is completely normal and will help your doctor determine the most appropriate dose of tacrolimus for you.
• Please avoid taking any herbal preparations, for example St. John’s wort (Hypericum perforatum), or any other herbal products, as these may affect the efficacy and required dose of tacrolimus. If you have any doubts, please consult your doctor before taking any herbal product or preparation.
• 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, 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 tacrolimus dose.
• If you have a disturbance in the heart's electrical activity called "QT interval prolongation".
• Limit your exposure to sunlight and UV light while taking tacrolimus by wearing appropriate protective clothing and using sunscreen with a high sun protection factor. This is due to the potential risk of malignant skin changes associated with immunosuppressive therapy.
• If you need to be vaccinated, please inform your doctor beforehand. Your doctor will advise you on the best course of action.
• Cases of increased risk of developing lymphoproliferative disorders have been reported in some patients treated with tacrolimus (see section 4). Ask your doctor for more information about these disorders.

Handling precautions:

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

Other medicines and tacrolimus cinfa

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.

Tacrolimus must not be taken 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 your transplant specialist if you are to take another medicine that could increase or decrease your blood levels of tacrolimus.

Blood levels of tacrolimus may be altered by other medicines you are taking, and blood levels of other medicines may be altered by tacrolimus, which may require interruption, increase, or decrease in the dose of tacrolimus.

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

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

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

• antifungals and antibiotics, especially those known as 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 drug cobicistat, and combined HIV tablets or non-nucleoside reverse transcriptase inhibitors (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 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 with ethinylestradiol (e.g. the oral contraceptive "pill") or danazol
• drugs 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 preparations containing St. John’s wort (Hypericum perforatum) or extracts of Schisandra sphenanthera.
• Cannabidiol (its use includes, among others, treatment of epileptic seizures).

Inform your doctor if you are receiving treatment for hepatitis C. Pharmacological treatment for hepatitis C may alter your liver function and may affect tacrolimus blood levels. Tacrolimus blood levels may 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 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. 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 may increase potassium levels in your blood, certain painkillers (so-called NSAIDs, e.g. ibuprofen), anticoagulants, or oral diabetic medication, while taking tacrolimus.

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

tacrolimus cinfa with food, drinks, and alcohol

You should generally take tacrolimus on an empty stomach or at least 1 hour before a meal or 2–3 hours after a meal. Grapefruit or grapefruit juice should be avoided while taking tacrolimus.

Pregnancy, breastfeeding, and fertility

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.

Tacrolimus passes into breast milk. Therefore, you must not breastfeed while receiving tacrolimus.

Driving and using machines

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

tacrolimus cinfa contains lactose

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

3. How to take tacrolimus cinfa

Follow exactly the dosing instructions for tacrolimus given by your doctor. If you have any doubts, ask your doctor or pharmacist.

Make sure you receive the same tacrolimus medicine each time you collect your prescription, unless your transplant specialist has agreed to switch to a different tacrolimus medicine. This medicine should be taken twice daily. If the appearance of your medicine is different than usual, or if the dosing instructions have changed, consult your doctor or pharmacist as soon as possible to ensure you have the correct medicine.

The initial dose to prevent rejection of your transplanted organ will be determined by your doctor based on your body weight. Initial doses just after transplantation are generally within the range of 0.075–0.30 mg per kg of body weight per day, depending on your transplanted organ.

Your dose depends on your general condition and on any other immunosuppressive medications you may be taking. Your doctor will need to perform regular blood tests to determine the correct dose and to adjust it from time to time. Your doctor will usually reduce your tacrolimus dose 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 at night. Tacrolimus should generally be taken on an empty stomach, or at least one hour before, or 2 to 3 hours after, a meal. 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 pouch.

If you take more tacrolimus cinfa than you should

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at 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 time for your next dose and then continue as before.

If you stop taking tacrolimus cinfa

Stopping 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 about 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 everyone will experience them.

Tacrolimus reduces your body's defense mechanisms that would otherwise allow you to reject your transplanted organ. Consequently, your body will not function as effectively as usual in fighting infections. Therefore, if you are taking tacrolimus, 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 experience symptoms of infection, including:

• Fever, cough, sore throat, weakness, or general malaise.
• Memory loss, difficulty thinking, difficulty walking, or vision loss – these symptoms may be due to a rare and serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).

Serious adverse effects have been reported, 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.
• Insufficient function of your transplanted organ.
• Blurred vision.

Uncommon serious 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, along with signs of infection.

Rare serious 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 signs 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 spread over 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, rashes, tongue swelling, red or purple rash that spreads, skin peeling.
• Torsades de Pointes: changes 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 tumors have been reported following 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 severe reduction in red blood cell count) and hemolytic anemia (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 infections, 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 severe 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 skin 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 color vision, difficulty seeing details, or reduced visual field.

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

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

• Increased blood sugar, diabetes mellitus, increased potassium in blood
• Difficulty sleeping
• Tremor, headache
• Increased blood pressure
• Abnormal liver function tests
• Diarrhea, 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)
• Decreased 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 electrolytes
• Anxiety symptoms, confusion and disorientation, depression, mood changes, nightmares, hallucinations, psychiatric disorders
• Seizures, disturbances in consciousness, tingling and numbness (sometimes painful) in hands and feet, dizziness, writing difficulties, nervous system disturbances
• Increased light sensitivity, eye disorders
• Ringing in the ears
• Reduced blood flow in heart vessels, faster heartbeat
• Bleeding, partial or complete blockage of blood vessels, decreased blood pressure
• Breathing difficulties, changes in lung tissue, fluid accumulation around the lungs, sore throat inflammation, cold, flu-like symptoms
• Inflammations or ulcers causing abdominal pain or diarrhea, stomach bleeding, mouth ulcers or inflammation, fluid accumulation in the abdomen, vomiting, abdominal pain, indigestion, constipation, flatulence, 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
• Insufficient kidney function, reduced urine output, difficulty or pain when urinating
• General weakness, fever, fluid retention, pain and discomfort, increased blood alkaline phosphatase enzyme, weight gain, sensation of altered temperature

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

• Changes in blood clotting, decreased count of all blood cells
• Dehydration
• Decreased proteins or blood sugar, increased phosphate in blood
• Coma, brain hemorrhage, stroke, paralysis, brain disorder, speech and language disturbances, memory problems
• Lens opacity
• Hearing difficulties
• Irregular heartbeat, cardiac arrest, decreased heart function, heart muscle disorder, increased heart muscle, stronger heartbeat, abnormal electrocardiogram, abnormal heart rate and pulse
• Blood clots in a vein of a limb, shock
• Breathing difficulties, 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 under sunlight
• Joint disorders
• Difficulty urinating, painful menstruation, abnormal menstrual bleeding
• Organ failure, flu-like illness, increased sensitivity to heat and cold, chest pressure sensation, nervousness or strange feeling, increased blood lactate dehydrogenase enzyme, weight loss

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

• Small skin hemorrhages due to blood clots
• Increased muscle rigidity
• Deafness
• Fluid accumulation around the heart
• Acute breathing difficulty
• Cyst formation in the pancreas
• Problems with blood flow in the liver
• Increased hair growth
• Thirst, ulceration, 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
• Painful urination with blood in urine
• Increased 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 may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide 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. Keep in the original packaging to protect from light and moisture.

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

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

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

Medicines must not be disposed of via wastewater or household waste. Dispose of containers and unused medicines at the SIGRE point in your pharmacy. If you have any doubts, ask your pharmacist how to dispose of containers and unused medicines. This will help protect the environment.

6. Contents of the pack and other information

Composition of tacrolimus cinfa

The active substance is tacrolimus. Each hard capsule contains 0.5 mg of tacrolimus (as tacrolimus monohydrate).

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

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

Appearance of the product and pack sizes

Ivory-colored capsules containing white powder.

tacrolimus cinfa 0.5 mg hard capsules EFG are available in single-dose PVC/PVDC/ALU blister packs contained within a protective aluminum pouch, which includes a desiccant to protect the capsules from moisture. The desiccant must not be swallowed.

Available pack sizes: 20, 30, 50, 60 or 100 (hospital pack) hard capsules.

Only certain 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 most recent revision of this leaflet: March 2025

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