Leaflet: information for the user

tacrolimus cinfa 0.5 mg hard capsules EFG

tacrolimus

Read this 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, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

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

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

3.How to take tacrolimus cinfa

4.Possible side effects

5.Storage of tacrolimus cinfa

6.Contents of the pack and additional information

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

tacrolimus cinfa is used to control the immune response of your body, 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 receive tacrolimus cinfa to treat a rejection that is occurring in your liver, kidney, heart or other transplanted organ, or if any previous treatment you were following, fails to control this immune response after your transplant.

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 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 stay in regular contact with your doctor.
• While taking tacrolimus, your doctor may wish to carry out occasional tests (including blood and urine tests, cardiac function tests, visual and neurological examinations). This is completely normal and will help your doctor decide on the most suitable dose of tacrolimus for you.
• Please avoid taking any herbal preparations, for example St. John's Wort (Hypericum perforatum) or any other herbal product, 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 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 accompanied or not by other symptoms, such as chills, fever, nausea or vomiting.
• If you have diarrhoea for more than one day, please inform your doctor as it may be necessary to adjust the dose of tacrolimus you receive.
• If you have a heart rhythm disorder called "prolongation of the QT interval".
• Limit your exposure to sunlight and UV light while taking tacrolimus using suitable protective clothing and using a high-factor sun cream. 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 on the best course of action.
• It has been reported that some patients treated with tacrolimus have increased the risk of developing lymphoproliferative disorders (see section 4). Ask your doctor for more information about these disorders.

Precautions for handling:

During preparation, avoid contact with any part of the body such as the skin or eyes, as well as breathing 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

Inform your doctor or pharmacist if you are taking, have taken recently or may need to take any other medicine, including those obtained without a prescription and herbal preparations.

Tacrolimus should not be taken with ciclosporin.

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 need to take another medicine that may increase or decrease your tacrolimus blood level.

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

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

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

You should inform your doctor if you are using or have used recently medicines with active principles such as:

• antifungals and antibiotics, especially macrolide antibiotics used for the treatment of 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 human cytomegalovirus (CMV)
• HIV protease inhibitors, e.g. ritonavir, nelfinavir, saquinavir, the cobicistat potentiator and combined 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
• 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)
• aluminium-magnesium hydroxide (antacid), used to treat acidity
• hormonal treatments with ethinylestradiol (e.g. the oral contraceptive pill) or danazol
• medicines used to treat hypertension or heart problems, such as nifedipine, nicardipine, diltiazem and verapamil
• antiarrhythmic medicines (amiodarone) used to control arrhythmia (irregular heartbeat)
• 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 Schisandra sphenanthera extracts.
• Cannabidiol (its use includes, among others, the treatment of epilepsy).

Inform your doctor if you are receiving treatment for hepatitis C. The pharmacological treatment for hepatitis C may change 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 the 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 medicinesmay worsen kidney or nervous system problems when taken togetherwith tacrolimus.

Your doctor also needs to know if you are taking potassium supplements or diuretics that save potassium (e.g. amiloride, triamterene or spironolactone), or the antibiotics trimethoprim and cotrimoxazole that may increase potassium levels in your blood, some analgesics (the so-called NSAIDs, e.g. ibuprofen), anticoagulants, or oral diabetes medication, 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 meals or 2-3 hours after them. You should avoid grapefruit or grapefruit juice while taking tacrolimus.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medicine.

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

Driving and operating machinery

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

tacrolimus cinfa contains lactose.

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

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

Make sure you receive the same medication with tacrolimus every time you pick up your prescription, unless your transplant specialist has agreed to change to another medication different from tacrolimus. This medication must be taken twice a day. If the appearance of this medication is not the same as always, or if the dosing instructions have changed, consult your doctor or pharmacist as soon as possible to ensure you have the correct medication.

The initial dose to prevent rejection of your transplanted organ will be set by your doctor, calculated according to your body weight. Initial doses shortly after the transplant will generally be within the range of 0.075-0.30 mg per kg of body weight and per day, depending on the transplanted organ.

Your dose will depend on your general condition, and any other immunosuppressive medication you may be taking. Your doctor will need to perform regular blood tests to determine the correct dose, and to adjust the dose 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 you should take, and how often.

Tacrolimus is taken orally twice a day, usually in the morning and at night. In general, you should take tacrolimus on an empty stomach or at least one hour before, or 2 to 3 hours after eating. 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 bag.

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, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take tacrolimus cinfa

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

If you forget to take this medication, wait until the next scheduled dose and then continue as usual.

If you interrupt treatment with tacrolimus cinfawith 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 other doubts about the use of this medication, ask your doctor or pharmacist.

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

Tacrolimus reduces your body's defense mechanism that allows it to reject your transplanted organ. Consequently, your body will not function as well as usual in fighting off infections. Therefore, if you are taking tacrolimus, you will be more prone than usual to suffering from infections, for example, skin, mouth, stomach, and intestinal, 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 weak or generally unwell.

-Memory loss, problems thinking, difficulty walking, or loss of vision – these symptoms may be due to a very rare and severe brain infection that can be fatal (multifocal progressive leukoencephalopathy or MEL).

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

Common severe side 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.

-Organ transplant failure.

-Blurred vision.

Less common severe side effects (may affect up to 1 in 100 people):

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

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

-Purpura thrombocytopenic thrombosis (PTT), characterized by fever and hemorrhages under the skin that may appear as red spots, with or without 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 appear in large areas of the body.

-Blindness

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

-Stevens-Johnson syndrome: inexplicable generalized skin pain, facial swelling, severe disease with blistering of the skin, mouth, eyes, and genitals, rashes, swelling of the tongue, red or purple rash that spreads, skin peeling.

-Torsades de Pointes: change in heart rate that may or may not be accompanied by symptoms such as chest pain (angina), fainting, dizziness, nausea, palpitations (feeling heartbeats), and difficulty breathing.

Severe side effects of unknown frequency (frequency cannot be estimated from available data):

• Oportunist infections (bacterial, fungal, viral, and protozoal): prolonged diarrhea, fever, and sore throat.
• Cancerous and non-cancerous 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 to existing ones, lesions, or lumps.
• Pure red cell aplasia (a very severe reduction in red blood cell count) and hemolytic anemia (a decrease in red blood cell count due to abnormal rupture 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 side effects is unknown. You may not have symptoms or, depending on the severity of your condition, you may feel: fatigue, apathy, abnormal paleness of the skin (pallor), difficulty breathing, dizziness, headache, chest pain, and a feeling of coldness in your hands and feet.
• Agranulocytosis (a severe decrease in white blood cell count accompanied by mouth sores, fever, and infection(s)). You may not have symptoms or you may feel fever, chills, and sudden sore throat.
• Allergic and anaphylactic reactions with the following symptoms: sudden itching 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.
• Reversible posterior leukoencephalopathy syndrome (RPLS): headache, confusion, mood changes, seizures, and visual disturbances. These may be signs of a condition known as reversible posterior leukoencephalopathy syndrome, which has been reported in some patients treated with tacrolimus.
• Optic neuropathy (alteration of the optic nerve): vision problems such as blurred vision, changes in color vision, difficulty seeing details, or reduced visual field.

The following side effects may also appear after receiving tacrolimus and may be severe:

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

-Increased blood sugar, diabetes mellitus, increased potassium in the blood

-Difficulty sleeping

-Tremor, headache

-Increased blood pressure

-Abnormal liver function tests

-Diarrhea, nausea

-Kidney problems

Common side effects (may affect up to 1 in 10 people)

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

-Decreased magnesium, phosphate, potassium, calcium, or sodium in the blood, fluid overload, increased uric acid or lipid levels in the blood, decreased appetite, increased blood acidity, other electrolyte changes

-Anxiety symptoms, confusion, and disorientation, depression, mood changes, nightmares, hallucinations, mental disorders

-Seizures, altered 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 your ears

-Decreased blood flow to the heart, faster heart rate

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

-Difficulty breathing, changes in lung tissue, fluid accumulation around the lung, pharyngitis, cold-like symptoms

-Inflammations or ulcers that cause abdominal pain or diarrhea, stomach bleeding, mouth or throat inflammation, fluid accumulation in the abdomen, vomiting, abdominal pain, indigestion, constipation, flatulence, bloating, loose stools, gastrointestinal problems

-Changes in liver function and enzymes, jaundice due to liver problems, liver tissue damage, and inflammation

-Itching, rash, hair loss, acne, increased sweating

-Joint pain, extremities, back, and foot pain, muscle spasms

-Kidney function failure, decreased urine production, difficulty or pain urinating

-General weakness, fever, fluid retention, pain and discomfort, increased alkaline phosphatase enzyme in the blood, weight gain, altered body temperature sensation

Less common side effects (may affect up to 1 in 100 people)

-Changes in blood clotting, decreased count of all blood cells

-Dehydration

-Decreased blood sugar or protein, increased phosphate in the blood

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

-Cloudy cornea

-Difficulty hearing

-Irregular heartbeat, heart stoppage, decreased heart function, altered heart muscle, increased heart muscle, stronger heartbeat, abnormal electrocardiogram, abnormal heart rate and pulse

-Blood clots in a vein of an extremity, shock

-Difficulty breathing, respiratory tract disorders, asthma

-Intestinal obstruction, increased amylase enzyme levels in the blood, gastroesophageal reflux, delayed stomach emptying

-Dermatitis, sunburn sensation

-Joint disorders

-Difficulty urinating, painful menstruation, and abnormal menstrual bleeding

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

Less common side effects (may affect up to 1 in 1,000 people)

-Small hemorrhages in your skin due to blood clots

-Increased muscle stiffness

-Deafness

-Fluid accumulation around the heart

-Acute difficulty breathing

-Pancreatic cyst formation

-Liver blood flow problems

-Increased hair growth

-Thirst, dizziness, chest pressure sensation, decreased mobility, ulcer

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

-Muscle weakness

-Abnormal echocardiogram

-Liver failure, bile duct narrowing

-Painful urination with blood in the urine

-Increased fatty tissue

Reporting side effects

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

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

Store below30°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 that appears on the packaging and on the blister pack after CAD. The expiration date is the last day of the month indicated.

Use all capsules within a 1-year period after opening the aluminum pouch.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and unused medicines at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medicines. By doing so, you will help protect the environment.

Tacrolimus cinfa composition

The active ingredient 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 coating: titanium dioxide (E-171), yellow iron oxide (E-172), and gelatin.

Product appearance and packaging size

Off-white capsules containing white powder.

tacrolimus cinfa 0.5 mg hard capsules EFG are presented in PVC/PVDC/ALU pre-cut single-dose blisters within a protective aluminum bag, which includes a desiccant that protects the capsules from moisture. The desiccant should not be swallowed.

They are available in packaging of 20, 30, 50, 60, or 100 (clinical packaging) hard capsules.

Only some packaging sizes may be commercially available.

Marketing authorization holder and responsible manufacturer

Cinfa Laboratories, S.A.

Carretera Olaz-Chipi, 10. Areta Industrial Estate.

31620 Huarte (Navarra) - Spain

Last review date of this leaflet: March 2025

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