ADOPORT 0.5 mg HARD CAPSULES

Introduction

Patient Information Leaflet

Adoport 0.5 mg hard capsules EFG

Adoport 1 mg hard capsules EFG

Adoport 2 mg hard capsules

Adoport 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.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack and other information

1. What is Adoport and what is it used for
2. What you need to know before you take Adoport
3. How to take Adoport
4. Possible side effects
5. Storage of Adoport

1. Contents of the pack and other information

1. What is Adoport and what is it used for

Adoport 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.

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

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

You may also receive Adoport 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 Adoport

Do not take Adoport:

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

Warnings and precautions

Consult your doctor or pharmacist before starting Adoport.

• You will need to take Adoport every day, as long as you need immunosuppression to prevent rejection of your transplanted organ. You should keep in regular contact with your doctor,
• while taking Adoport, your doctor may want to carry out regular tests (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 Adoport for you,
• 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 Adoport you need to receive. If in doubt, consult your doctor before taking any herbal products,
• 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 malignant skin changes with immunosuppressive therapy,
• 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 the solutions for injection, powder, or granules contained in tacrolimus products. If such contact occurs, wash the skin and eyes.

Other medicines and Adoport

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 medicines.

Adoport should not be taken with ciclosporin.

If you need to visit a different doctor 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 use another medicine that may increase or decrease your blood levels of tacrolimus.

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

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 may occur 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 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 taking or have recently taken medicines with active substances 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),
• HIV protease inhibitors (e.g. ritonavir, nelfinavir, saquinavir), the pharmacokinetic enhancer cobicistat, and non-nucleoside reverse transcriptase inhibitors for HIV (efavirenz, etravirine, nevirapine), used to treat HIV infections,
• HCV protease inhibitors (e.g. telaprevir, boceprevir, the combination ombitasvir/paritaprevir/ritonavir, with or without dasabuvir, elbasvir/grazoprevir, and glecaprevir/pibrentasvir), used in the treatment of 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 the treatment of stomach ulcers and acid reflux (e.g. omeprazole, lansoprazole, or cimetidine),
• antiemetics, used to treat nausea and vomiting (e.g. metoclopramide),
• magnesium or 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, a medicine 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, 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 your 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 your blood levels of tacrolimus and make necessary adjustments to the dose of tacrolimus after starting treatment for hepatitis C.

Tell your doctor if you are taking or need to take ibuprofen (used to treat fever, inflammation, and pain), antibiotics (cotrimoxazole, vancomycin, or aminoglycoside antibiotics such as gentamicin), amphotericin B (used to treat fungal infections), or antivirals (used to treat viral infections, e.g. aciclovir, ganciclovir, cidofovir, foscarnet). These medicines may worsen kidney or nervous system problems when taken with tacrolimus.

Tell your doctor if you are taking sirolimus or everolimus. When tacrolimus is taken with sirolimus or everolimus, the risk of thrombotic microangiopathy, 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 diuretics used for heart failure, high blood pressure, and nephropathy, (e.g. amiloride, triamterene, or spironolactone), or the antibiotics trimethoprim and cotrimoxazole, which may increase the levels of potassium in your blood, non-steroidal anti-inflammatory drugs (NSAIDs, e.g. ibuprofen) used for fever, inflammation, and pain, anticoagulants (which prevent blood clotting), or oral medicines for the treatment of diabetes, while taking tacrolimus.

If you need to be vaccinated, consult your doctor.

Adoport with food, drinks, and alcohol

Adoport should generally be taken on an empty stomach or at least 1 hour before a meal or 2 to 3 hours after a meal. You should avoid grapefruit or grapefruit juice while taking Adoport.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. A study evaluated the outcomes of pregnancy in women treated with tacrolimus and with other immunosuppressants. Although this study did not provide sufficient evidence to draw conclusions, higher rates of spontaneous abortion were reported among liver and kidney transplant patients treated with tacrolimus, as well as higher rates of persistent hypertension, associated with protein loss in the urine, among kidney transplant patients that developed during pregnancy or the postpartum period (a condition called preeclampsia). No increased risk of serious congenital anomalies was associated with the use of tacrolimus.

Adoport passes into breast milk. Therefore, you should not breastfeed while receiving Adoport.

Driving and using machines

Do not drive or use tools or machines if you feel dizzy or drowsy, or have problems seeing clearly after taking Adoport. These effects are more common when Adoport is taken with alcohol.

Adoport contains lactose and sodium

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

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

3. How to take Adoport

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

Make sure you receive the same tacrolimus medicine each time you collect your prescription, unless your transplant specialist has agreed to change to a different tacrolimus medicine.

This medicine should be taken twice a day. If the appearance of this medicine is not the same as 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. The initial doses immediately after transplantation are usually within the range of

0.075 mg to 0.30 mg per kg of body weight and per day,

depending on the transplanted organ.

Your dose depends on your overall 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 dose of Adoport once your condition has stabilized.

Your doctor will tell you exactly how many capsules to take and how often.

• Adoport is taken orally twice a day, usually in the morning and at night. It should generally be taken on an empty stomach or at least 1 hour before a meal or 2 to 3 hours after a meal,
• the capsules should be swallowed whole with a glass of water,
• avoid grapefruit and grapefruit juice while taking Adoport,
• take the hard capsules immediately after removal from the blister,
• do not ingest the desiccant included in the aluminum bag.

If you take more Adoport than you should

If you have accidentally taken more Adoport than you should, consult your doctor immediately or go to the emergency department of the nearest hospital.

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 Adoport

Do not take a double dose to make up for forgotten doses. If you have forgotten to take your capsules, wait until the next dose and then continue as before.

If you stop taking Adoport

Stopping your treatment with Adoport may increase the risk of rejection of the 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.

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

Some infections can be serious 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, problems thinking, difficulty walking, or loss of vision - these symptoms may be due to a rare and serious brain infection that can be fatal (progressive multifocal leukoencephalopathy or PML).

Severe adverse effects may occur, including those described below.

Inform your doctor immediately if you suspect or have suffered 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.

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

• Thrombotic microangiopathy (lesions in the smallest blood vessels) including 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 abnormal bruising or bleeding and signs of infection.

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

• Thrombocytopenic purpura: includes lesions in the smallest blood vessels and is characterized by fever and bruising under the skin that can 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 output), loss of vision, and seizures,
• toxic epidermal necrolysis: erosion and blistering of the skin or mucous membranes, reddened and swollen skin that can peel off in 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 can include skin lesions known as Kaposi's sarcoma. Symptoms include skin changes such as new colors or changes in existing ones, lesions or lumps,
• cases of pure red cell aplasia (a significant reduction in red blood cell count), hemolytic anemia (reduction in the number of red blood cells due to abnormal breakdown of them 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 not known. 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 significant decrease in the number of white blood cells accompanied by sores in the mouth, 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 can 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 (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 Adoport 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)

• Reduction in the number of blood cells (platelets, red blood cells, or white blood cells), increased white blood cell count, changes in red blood cell counts (see blood tests),

changes in the counts of red blood cells (see blood tests),

• decreased magnesium, phosphate, potassium, calcium, or sodium in the blood, fluid overload, increased uric acid or lipids in the blood, decreased appetite, increased 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, alterations of the nervous system,
• 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,
• shortness of breath, changes in lung tissue, fluid accumulation around the lung, inflammation of the pharynx, cough, flu-like symptoms,
• inflammations or ulcers that cause abdominal pain or diarrhea, stomach bleeding, mouth ulcers, fluid retention in the abdomen, vomiting, abdominal pain, indigestion, constipation, flatulence, bloating, loose stools, stomach problems,
• changes in liver enzymes and liver function, yellowing of the skin due to liver problems, liver tissue damage, and liver inflammation,
• itching, rash, hair loss, acne, increased sweating,
• joint pain, limb pain, back pain, and foot pain, muscle spasms,
• insufficient kidney function, decreased urine production, difficulty or pain when urinating
• general weakness, fever, fluid retention, pain, and discomfort, increased alkaline phosphatase in the blood, weight gain, altered temperature sensation.

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

• Changes in blood coagulation, decrease in all blood cell counts,
• dehydration, decreased protein or sugar in the blood, increased phosphate in the blood,
• coma, cerebral hemorrhage, stroke, paralysis, cerebral disorder, speech and language disorders, memory problems,
• lens opacity,
• difficulty hearing,
• 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, respiratory tract disorders, asthma,
• intestinal obstruction, increased blood amylase level, reflux of stomach contents into the throat, delayed stomach emptying,
• dermatitis, burning sensation 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 sensation, increased lactate dehydrogenase 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,
• breathing difficulties,
• pancreatic cyst formation,
• problems with blood flow in the liver,
• increased hair growth,
• thirst, falls, feeling of pressure in the chest, decreased mobility, ulcer.

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

• Muscle weakness,
• altered echocardiogram,
• liver failure, bile duct narrowing,
• pain when urinating 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 does not appear 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 Adoport

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

Do not use this medicine after the expiration date that appears on the packaging and on the aluminum bag after CAD/EXP. The expiration date is the last day of the month indicated.

After the first opening of the aluminum bag containing the blister pack, the capsules should be used within the next 12 months. Do not store above 25°C after opening the aluminum bag.

Take the capsules as soon as you remove them from the blister pack.

Do not store above 30°C. Store in the original packaging to protect it from moisture.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE collection point in the 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 Adoport 0.5 mg hard capsules

• The active ingredient is tacrolimus. Each capsule contains 0.5 mg of tacrolimus (as monohydrate).
• The other ingredients are:
• Capsule content: lactose monohydrate, hypromellose (E 464), sodium croscarmellose (E 468), and magnesium stearate (E 572).
• Hard gelatin capsule: gelatin, titanium dioxide (E 171), sodium lauryl sulfate, sorbitan laurate, and yellow iron oxide (E 172).

Composition of Adoport 1 mg hard capsules

• The active ingredient is tacrolimus. Each capsule contains 1 mg of tacrolimus (as monohydrate).
• The other ingredients are:
• Capsule content: lactose monohydrate, hypromellose (E 464), sodium croscarmellose (E 468), and magnesium stearate (E 572).
• Hard gelatin capsule: gelatin, titanium dioxide (E 171), sodium lauryl sulfate, sorbitan laurate, yellow iron oxide (E 172), red iron oxide (E 172), and black iron oxide (E 172).

Composition of Adoport 2 mg hard capsules

• The active ingredient is tacrolimus. Each capsule contains 2 mg of tacrolimus (as monohydrate).
• The other ingredients are:

• Capsule content: lactose monohydrate, hypromellose (E 464), sodium croscarmellose (E 468), and magnesium stearate (E 572).
• Hard gelatin capsule: gelatin, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), brilliant blue FCF (E 133), shellac (E 904), propylene glycol (E 1520), potassium hydroxide (E 525), and black iron oxide (E 172).

Composition of Adoport 5 mg hard capsules

• The active ingredient is tacrolimus. Each capsule contains 5 mg of tacrolimus (as monohydrate).
• The other ingredients are:

• Capsule content: lactose monohydrate, hypromellose (E 464), sodium croscarmellose (E 468), and magnesium stearate (E 572).
• Hard gelatin capsule: gelatin, titanium dioxide (E 171), sodium lauryl sulfate, sorbitan laurate, and red iron oxide (E 172).

Appearance of the Product and Package Contents

Adoport 0.5 mg are hard gelatin capsules with a white opaque body and an ivory cap, containing white to almost white powder (length: 14.5 mm).

Adoport 1 mg are hard gelatin capsules with a white opaque body and a light brown cap, containing white to almost white powder (length: 14.5 mm).

Adoport 2 mg are hard capsules of dark green opaque color, printed in black with 2 mg on the cap, containing white to almost white powder (length: 14.5 mm).

Adoport 5 mg are hard gelatin capsules with a white opaque body and an orange cap, containing white to almost white powder (length: 15.8 mm).

Adoport is packaged in PVC/PE/PVdC/Aluminum blisters, in an aluminum bag with a desiccant to protect from moisture. The desiccant should not be swallowed.

Packages of 7, 10, 14, 20, 28, 30, 50, 60, 90, and 100 hard capsules.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Sandoz Farmacéutica, S.A.

Centro Empresarial Parque Norte

Edificio Roble

C/ Serrano Galvache, 56

28033 Madrid

Spain

Manufacturer

Lek Pharmaceuticals d.d.,

Verovskova 57,

1526 Ljubljana,

Slovenia

or

Lek Pharmaceuticals d.d.,

Trimlini 2D,

9220 Lendava,

Slovenia

or

LEK S.A.,

Ul. Domaniewska 50C,

02-672 Warszawa,

Poland

or

Salutas Pharma GmbH,

Otto-von-Guericke-Allee 1,

D-39179 Barleben,

Germany

or

S.C. Sandoz S.R.L.,

Str. Livenzeni nr. 7A,

RO-540472 Targu Mures,

Romania

Date of the Last Revision of this Prospectus:May 2025.

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