Prospect: Information for the User

Tacrólimus Stada 0.5 mg Hard Capsules EFG

Tacrólimus Stada 1 mg Hard Capsules EFG

Read this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, and you should not give it to other people, even if they have the same symptoms as you, as it may harm them.

• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this prospect. See section 4.

Tacrólimus Stada belongs to a group of medications known as immunosuppressants. After an organ transplant (e.g., liver, kidney, heart), the immune system of your body will attempt to reject the new organ.

Tacrólimus is used to control the immune response of your body, allowing you to accept the transplanted organ.

Tacrólimus is often used in combination with other medications that also suppress the immune system.

You may also receive tacrólimus to treat a rejection that is occurring in your liver, kidney, heart, or other transplanted organ when any previous treatment you were following fails to control this immune response after your transplant.

Do not take Tacrólimus Stada

• If you are allergic to tacrolimus or any of the other components of this medication (listed in section 6).
• If you are allergic to sirolimus or any macrolide antibiotic (e.g., erythromycin, clarithromycin, josamycin).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Tacrólimus Stada.

• You will need to take tacrolimus every day, as long as you require immunosuppression to prevent rejection of your transplanted organ. You should maintain regular contact with your doctor.
• While taking tacrolimus, your doctor may wish to perform occasional tests (including blood and urine analyses, cardiac function tests, visual and neurological examinations). This is completely normal and will help your doctor to 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 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 accompanied or not by 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 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 protective clothing and sunscreen with a high sun protection factor. This is due to the potential risk of skin malignancies 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). Please ask your doctor for more information about these disorders.
• If you have or have had small blood vessel lesions, known as microangiopathy, thrombotic thrombocytopenic purpura, or hemolytic uremic syndrome. Inform your doctor if you develop fever, skin hemorrhages (which may appear as red spots), unexplained fatigue, confusion, yellow discoloration of the skin or eyes, decreased urine output, vision loss, and convulsions (see section 4). When tacrolimus is taken with sirolimus or everolimus, the risk of these symptoms may increase.

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 medications and Tacrólimus Stada

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

Tacrolimus should 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 with your transplant specialist if you need to take another medication that may increase or decrease your tacrolimus blood levels.

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

Some patients have experienced increases in tacrolimus blood levels while taking other medications. 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 medication, so it may be necessary to monitor tacrolimus blood levels frequently and continuously during the first few days of use of another medication and frequently while continuing its use. Some other medications may cause tacrolimus blood levels to decrease, which may increase the risk of organ transplant rejection.In particular, you should inform your doctor if you are using or have used recently medications 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, caspofungin, telithromycin,erythromycin, clarithromycin, josamycin,azithromycin, rifampicin, rifabutin, isoniazid, and flucloxacillin
• letermovir, used to prevent diseases caused by CMV (human cytomegalovirus)

• protease inhibitors for HIV (e.g., ritonavir, nelfinavir, saquinavir), the potentiator cobicistat, and combined tablets,or non-nucleoside reverse transcriptase inhibitors for HIV (efavirenz, etravirine, nevirapine),used to treat HIV infection.
• protease inhibitors for HCV (e.g., telaprevir, boceprevir, and the combination ombitasvir/paritaprevir/ritonavir with or without dasabuvir,elbasvir/grazoprevir, and glecaprevir/pibrentasvir), used to treat HCV 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
• medications for stomach ulcers and acid reflux (e.g., omeprazole, lansoprazole, or cimetidine)
• antiemetics, used to treat nausea and vomiting (e.g., metoclopramide)

• magnesium hydroxide-aluminum(antacid),used to treat acidity
• hormonal treatments with ethinylestradiol(e.g., oral contraceptive pills)or with danazol
• medicationsused to treat hypertension or heart problems (such as nifedipine, nicardipine, diltiazem, and verapamil)
• antiarrhythmic medications (amiodarone) used to control arrhythmia (irregular heartbeat)
• statins used to treat high cholesterol and triglycerides
• antiepileptic medications carbamazepine,phenytoin, or phenobarbital
• metamizole, a medication used to treat pain and fever.
• prednisone and methylprednisolone corticosteroids,
• the antidepressant nefazodone

• herbal preparations containing St. John's Wort (Hypericum perforatum)or extracts ofSchisandra sphenanthera.
• cannabidiol (uses include the treatment of seizures).

Inform your doctor if you are receiving treatment for hepatitis C. The pharmacological treatment for hepatitis C may change your liver function and affect tacrolimus blood levels. Tacrolimus blood levels may decrease or increase depending on the medications prescribed for hepatitis C. Your doctor may need to closely monitor tacrolimus blood levels and make the necessary adjustments to the tacrolimus dose 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 may worsen kidney or nervous system problems when administered simultaneously with tacrolimus.

Inform your doctor if you are taking sirolimus or everolimus.When tacrolimus is taken with sirolimus or everolimus, the risk of microangiopathy, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome may increase (see section 4).

Your doctor also needs to know if you are taking potassium supplements or certain diureticspotassium-sparingdiuretics used for heart failure, hypertension, and nephropathy, (e.g., amiloride, triamterene, or spironolactone),or the antibiotics trimethoprim or cotrimoxazole that may increase potassium levels in the blood, certain analgesics (the so-calledAINEs, e.g., ibuprofen) used to treat fever, inflammation, and pain, anticoagulants (blood thinners), or oral medications for diabetes treatment while taking tacrolimus.

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

Taking Tacrólimus Stada with food and drinks

Take tacrolimus on an empty stomach or 2 to 3 hours after a meal. Wait at least one hour before the next meal. Avoid grapefruit (also in juice) while taking tacrolimus, as it may affect your levels.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

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 difficulty seeing clearly after taking this medication. These effects are more common if you also take alcohol.

Tacrolimus Stada contains lactose and sodium

This medication contains lactose. If your doctor has told you that you have a certain sugar intolerance, consult with him before taking this medication.

This medication contains less than 23 mg of sodium (1 mmol) per capsule; it is essentially "sodium-free."

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Make sure you receive the same medication with tacrolimus every time you pick up your prescription, unless your transplant specialist has agreed to switch to another medication different from tacrolimus.

This medication should 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 depends 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 the tacrolimus capsuleswith 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 capsules. Do not ingest the desiccant included in the aluminum bag.

If you take more Tacrolimus Stada than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately, or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested. It is recommended to bring the packaging and the medication leaflet to the healthcare professional.

If you forget to take Tacrolimus Stada

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

If you forget to take your capsules, wait until the next dose time and then continue as usual.

If you interrupt treatment with Tacrolimus Stada

Stopping treatment 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 questions 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 own defense mechanism to stop rejecting the 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 to infections, for example, skin, mouth, stomach, and intestinal, lung, and urinary tract infections.

Some infections can be severe or life-threatening and may include bacterial, viral, fungal, parasitic, or other infections. Inform your doctor immediately if you present signs of an infection, including:

• fever, cough, sore throat, feeling weak or generally unwell
• loss of memory, difficulty thinking, difficulty walking, or loss of vision: these may be due to a very rare and severe brain infection that can be life-threatening (multifocal progressive leukoencephalopathy or MPA)

Severe side effects may appear, including those listed below.

Inform your doctor immediately if you suspect you are experiencing any of the following severe side effects:

Frequent 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
• insufficient function of your transplanted organ
• blurred vision

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

• microangiopathic thrombosis (lesions in smaller blood vessels) including thesickle cell disease, a condition with the following symptoms: low or no urine production (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):

• thrombotic thrombocytopenic purpura (or TTP), a condition that includes lesions in smaller blood vessels and is characterized by fever and hemorrhages under the skin that may appear as red spots, with or without unexplained extreme fatigue, confusion, yellowing of the skin or eyes (jaundice), with symptoms of acute kidney failure (low or no urine production),loss of vision, and seizures.
• toxic epidermal necrolysis: erosion and blisters on the skin or mucous membranes, red and swollen skin that may peel off in large areas of the body
• blindness

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

• Stevens-Johnson syndrome:unexplained generalized skin pain, facial swelling, severe illness with blisters on the skin, mouth, eyes, and genitals, urticaria, swelling of the tongue, red or purple rash that spreads,skin peeling

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

Severe side 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
• cases of pure red cell aplasia (a very severe reduction in red blood cell count), 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).No exact frequency is known for these side effects. 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.
• cases of agranulocytosis (a significant 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
• posterior reversible encephalopathy syndrome (PRES): headache, confusion, mood changes, seizures, and visual disturbances. These may be signs of a condition known as posterior reversible encephalopathy 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 seeingdetailsor reduced visual field

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

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

• increased blood sugar, diabetes mellitus, increased potassium in the blood
• difficulty sleeping
• shaking, headache
• increased blood pressure
• abnormal liver function test results
• diarrhea, nausea
• kidney problems

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

• decreased blood cell count (platelets, red blood cells, or white blood cells), increased white blood cell count, changes in red blood cell count (see blood test results)

• 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) in hands and feet, dizziness, decreased ability to write, nervous system alterations.

• increased sensitivity to light, eye changes.

• ringing in the ears.
• decreased blood flow in cardiac vessels, 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, pharyngeal inflammation, cough, symptoms similar to the flu.
• inflammations or ulcers that cause abdominal pain or diarrhea, stomach bleeding, mouth or esophageal inflammation, fluid accumulation in the abdomen, vomiting, abdominal pain, indigestion, constipation, flatulence, swelling, loose stools, gastrointestinal problems.
• liver function and enzyme changes, yellowing of the skin 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 insufficiency, decreased urine production, difficulty or pain while urinating.
• general weakness, fever, fluid retention, pain, and discomfort, increased alkaline phosphatase enzyme in the blood, weight gain, feeling of altered temperature.

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

• changes in blood clotting, decreased count of all blood cells.
• dehydration, decreased blood protein or sugar, increased phosphate in the blood.
• coma, cerebral hemorrhage, stroke, paralysis, cerebral disorder, speech and language disorders, memory problems.
• cloudy cornea.
• hearing difficulties.

• irregular heartbeat, cardiac arrest, decreased heart function, altered heart muscle, increased heart muscle, faster heart rate, abnormal electrocardiogram, abnormal heart rate and pulse.

• blood clots in a vein of an extremity, shock.

• respiratory difficulties, alterations in the respiratory tract, asthma.
• intestinal obstructions, increased blood levels of the amylase enzyme, reflux of stomach contents into the throat, delayed stomach emptying.
• dermatitis, sunburn sensation.
• joint disorders.

• difficulty urinating, painful menstruation, and abnormal menstrual bleeding.
• failure of some organs, illness similar to the flu, increased sensitivity to heat and cold, feeling of pressure in the chest, nervousness or strange sensation, increased lactate dehydrogenase enzyme in the blood, weight loss.

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

• small hemorrhages in your skin due to blood clots.
• increased muscle stiffness.

• blindness.
• hearing loss.
• fluid accumulation around the heart.

• acute respiratory difficulty.
• pancreatic cyst formation.

• problems with blood flow in the liver.

• severe illness with blisters on the skin, mouth, eyes, and genitals, increased hair growth.
• thirst, dizziness, feeling of chest pressure, decreased mobility, ulcer.

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

• muscle weakness.

• abnormal echocardiogram.
• liver insufficiency, bile duct narrowing.

• painful urination with blood in the urine.
• increased body fat.

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

• alteration of the optic nerve (optic neuropathy)

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 prospectus. You can also report them 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 below 30°C.

Store in the original packaging (inside the aluminum bag) to protect it from moisture and light.

Do not use this medication 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. Once the aluminum bag is opened, the medication must be used within one year.

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

Composition of Tacrólimus Stada

Tacrólimus Stada 0.5 mg hard capsules EFG

The active ingredient is tacrólimus.

Each capsule contains 0.5 mg of tacrólimus.

The other components are:

• Capule content: Povidone K-30, sodium croscarmellose (E-468), lactose, magnesium stearate.
• Capule coating: titanium dioxide (E-171), yellow iron oxide (E-172), gelatin.

Tacrólimus Stada 1 mg hard capsules EFG

The active ingredient is tacrólimus.

Each capsule contains 1 mg of tacrólimus.

The other components are:

• Capule content: Povidone K-30, sodium croscarmellose (E-468), lactose, magnesium stearate.

• Capule coating: titanium dioxide (E-171), red iron oxide (E-172), gelatin.

Appearance of the product and packaging size

Tacrólimus Stada 0.5 mg hard capsules EFG

Hard capsules with a white body and a white cap, containing white powder.

Tacrólimus Stada 1 mg hard capsules EFG

Hard capsules with a white body and a white cap, containing white powder.

Tacrólimus Stada is presented as a blister pack containing10 capsules inside a protective aluminum bag that includes a desiccant that protects the capsules from moisture. The desiccant should not be swallowed.

Tacrólimus Stada is available in blister packs containing 10 capsules each. Packs of 30, 50, 60, 100, and 150 capsules.

Only some of the packaging sizes may be marketed.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder

STADA Laboratorios, S.L.

Frederic Mompou 5

08960 Sant Just Desvern (Barcelona)

Spain

[email protected]

Responsible manufacturer

Laboratorios Cinfa, S.A.

Olaz-Chipi, 10.

Industrial Park Areta (Huarte-Pamplona (Navarra)) - 31620

Spain

or

STADA Arzneimittel AG

Stadastrasse 2- 18

D-61118 (Bad Vilbel)

Germany

or

Eurogenerics, N.V.

Heizel Esplanade, b22 (Brussels) - 1020

Belgium

This medicinal product is authorized in the Member States of the EEA with the following names:

GermanyTacro-cell 0.5 mg/1 mg hard capsules

SpainTacrólimus Stada 0.5 mg/1 mg hard capsules EFG

Last review date of this leaflet:April 2023

More detailed information about this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/