Adoport

Package leaflet: Information for the patient

ADOPORT 0.5 mg hard capsules (equivalent medicine), 0.75 mg hard capsules, 1 mg hard capsules (equivalent medicine), 2 mg hard capsules, 5 mg hard capsules (equivalent medicine)

Tacrolimus
Please read this leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What ADOPORT is and what it is used for

ADOPORT belongs to a group of medicines called immunosuppressants.
After an organ transplant (for example, liver, kidney, or heart), your immune system will attempt 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 for ongoing rejection of a transplanted liver, kidney, heart, or other organ, or
if one of the treatments you were taking was unable to control the immune response after transplantation.

2. What you need to know before taking ADOPORT

Do not take ADOPORT

• If you are allergic to tacrolimus or to any of the other ingredients of this medicine (listed in section 6).
• If you are allergic (hypersensitive) 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 taking ADOPORT.

• You will need to take ADOPORT every day for as long as you require immunosuppression to prevent rejection of your transplanted organ. You should maintain regular contact with your doctor.
• While you are taking ADOPORT, your doctor may decide to periodically prescribe a series of tests (including blood and urine tests, heart function tests, and eye and neurological examinations). This is standard practice, which allows your doctor to determine the most appropriate dose of ADOPORT for your condition.
• Avoid taking any herbal products, for example St. John’s wort (Hypericum perforatum) or any other herbal remedies, as these may reduce the effectiveness of ADOPORT and affect its dosage. If in doubt, consult your doctor before taking any herbal product or remedy.
• Inform your doctor if you have liver problems or have previously suffered from a disease that may have damaged your liver, as this may affect the dose of ADOPORT you need to take.
• If you experience severe abdominal pain, with or without other symptoms such as chills, fever, nausea, and vomiting.
• If you have diarrhoea for more than one day, inform your doctor, as it may be necessary to adjust your ADOPORT dose.
• If you have a disturbance in the electrical activity of the heart known as “prolongation of the QT interval”.
• Limit your exposure to sunlight and UV rays while taking ADOPORT by wearing protective clothing and using a high-protection sunscreen. This is due to the potential risk of malignant skin disorders associated with immunosuppressive therapy.
• If you need any vaccination, inform your doctor first, who will advise you accordingly.
• Patients treated with ADOPORT have been reported to have an increased risk of developing lymphoproliferative disorders (see section 4). Ask your doctor for specific information about these disorders.

Other medicines and ADOPORT
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription and herbal remedies.
ADOPORT must not be taken together with ciclosporin.
The blood levels of ADOPORT may be affected by other medicines, and the blood levels of other medicines may in turn be affected by ADOPORT: in such cases, it may be necessary to stop, increase, or decrease the dose of ADOPORT.
In particular, you must inform your doctor if you are taking or have recently taken medicines containing active substances such as:

• antifungal and antibiotic medicines, particularly so-called macrolide antibiotics used to treat infections, e.g. ketoconazole, fluconazole, itraconazole, voriconazole, clotrimazole, erythromycin, clarithromycin, josamycin, and rifampicin
• HIV protease inhibitors (e.g. ritonavir, nelfinavir, saquinavir), used to treat HIV infections
• HCV protease inhibitors (e.g. telaprevir, boceprevir), used to treat hepatitis C infections
• medicines for gastric ulcer or acid reflux (e.g. omeprazole, lansoprazole, or cimetidine)
• antiemetic medicines used to treat nausea and vomiting (e.g. metoclopramide)
• magnesium-aluminium hydroxide (antacid), used to treat heartburn
• hormonal treatments containing ethinylestradiol (e.g. the 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 triglyceride levels
• the antiepileptic medicines phenytoin or phenobarbital
• the corticosteroids prednisolone and methylprednisolone
• the antidepressant medicine nefazodone
• herbal preparations containing St. John’s wort (Hypericum perforatum) or extracts of Schisandra sphenanthera.

Inform your doctor if you are taking or need to take ibuprofen, amphotericin B, antiviral medicines (e.g. aciclovir). These may worsen kidney or nervous system problems when taken together with ADOPORT.
Your doctor will also need to know if you are taking potassium supplements or potassium-sparing diuretics (e.g. amiloride, triamterene, or spironolactone), certain painkillers (so-called NSAIDs, e.g. ibuprofen), anticoagulants, or oral medicines for diabetes while being treated with ADOPORT.
If you are due to receive vaccinations, please inform your doctor beforehand.
ADOPORT with food and drink
ADOPORT should generally be taken on an empty stomach, or at least 1 hour before or 2–3 hours after a meal. During treatment with ADOPORT, you must avoid consuming grapefruit and grapefruit juice.
Pregnancy and breastfeeding

• If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
• ADOPORT is excreted in breast milk; therefore, you must not breastfeed while being treated with ADOPORT.

Driving and using machines
If you feel dizzy or drowsy after taking ADOPORT, or if you have problems with clear vision, you should not drive or operate tools or machinery. These effects are more likely to occur when ADOPORT is taken together with alcoholic beverages.
ADOPORT contains lactose
ADOPORT contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.

3. How to take ADOPORT

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Make sure you receive the same tacrolimus-containing medicine each time you present your prescription at the pharmacy, unless your transplant specialist has decided to switch you to a different tacrolimus-containing medicine.
This medicine must be taken twice daily. If this medicine looks different than usual, or if the dosage instructions have changed, consult your doctor or pharmacist as soon as possible to ensure you have the correct medicine.
The initial dose to prevent organ rejection will be determined by your doctor and will be calculated based on your body weight. Generally, initial doses immediately after transplantation range between 0.075 and 0.30 mg per kg of body weight per day, depending on the transplanted organ.
Your dose depends on your general condition and on which other immunosuppressive medicines you are taking. Your doctor will regularly prescribe blood tests to determine the most appropriate dose and adjust it periodically. Generally, your doctor will reduce the dose of ADOPORT once your condition has stabilized. Your doctor will tell you exactly how many capsules to take and how often.

• ADOPORT must be taken orally twice daily, usually in the morning and evening. ADOPORT should generally be taken on an empty stomach or at least 1 hour before or 2–3 hours after a meal.
• Swallow the capsules whole with a glass of water.
• Take the hard capsules immediately after removing them from the blister.
• While being treated with ADOPORT, avoid consuming grapefruit and grapefruit juice.
• Do not ingest the desiccant contained in the packaging.

If you take more ADOPORT than you should
If you have taken too much ADOPORT by mistake, contact your doctor immediately or go to the nearest hospital emergency department.
If you forget to take ADOPORT
Do not take a double dose to make up for a missed dose.
If you have forgotten to take your ADOPORT capsules, wait until it is time for your next dose and then continue as before.
If you stop taking ADOPORT
Stopping treatment with ADOPORT may increase the risk of rejection of the transplanted organ. Do not stop treatment unless specifically instructed by your doctor.
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
ADOPORT reduces the body's defence mechanisms and prevents them from rejecting the transplanted organ.
As a result, your body will not be as effective as usual in fighting infections. Therefore, during treatment with ADOPORT, you may be more prone than usual to infections, such as those affecting the skin, mouth, stomach and intestine, lungs, and urinary tract.

Serious side effects may occur, including those listed below. Immediately consult your doctor if you have or think you may have any of the following serious side effects:

• Opportunistic infections (bacterial, fungal, viral, and protozoal): prolonged diarrhoea, fever, and sore throat.
• Benign and malignant tumours have been reported following treatment, as a consequence of immunosuppression.
• Thrombotic thrombocytopenic purpura (TTP), a condition characterised by fever and subcutaneous bruising appearing as red spots, with or without unexplained extreme fatigue, confusion, yellowing of the skin or eyes (jaundice), and symptoms of acute renal failure (reduced or absent urine output).
• Cases of pure red cell aplasia (a severe reduction in red blood cell count) and haemolytic anaemia (reduced red blood cell count due to abnormal destruction, accompanied by fatigue) have been reported. You may have no symptoms, or depending on the severity of the condition, you may experience: fatigue, apathy, abnormal paleness of the skin, shortness of breath, dizziness, headache, chest pain, and cold hands and feet.
• Cases of agranulocytosis (a severely reduced white blood cell count accompanied by mouth ulcers, fever, and infections) have been reported. You may have no symptoms or may experience sudden fever, stiffness or sore throat.
• Allergic or anaphylactic reactions with the following symptoms: sudden itching (urticaria), swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty swallowing and breathing), and you may feel weak.
• Reversible posterior encephalopathy syndrome (PRES): headache, altered mental status, seizures, and visual disturbances.
• Torsades de pointes: changes in heart rate, which may or may not be accompanied by symptoms such as chest pain (angina), weakness, dizziness or nausea, palpitations (strong awareness of heartbeat), and difficulty breathing.
• Gastrointestinal perforation: severe abdominal pain, with or without other symptoms such as chills, fever, nausea, and vomiting.
• Stevens-Johnson syndrome: unexplained widespread skin pain, facial swelling, a serious illness with blistering of the skin, mouth, eyes, and genitals, urticaria, tongue swelling, red or purplish skin rash that spreads, skin peeling.
• Toxic epidermal necrolysis: erosion and blistering of the skin or mucous membranes, red and swollen skin that may peel off large areas of the body.
• Haemolytic uremic syndrome, a condition with the following symptoms: reduced or no urine output (acute renal failure), extreme fatigue, yellowing of the skin or eyes (jaundice), abnormal itching or bleeding, and signs of infection.
• Insufficient function of the transplanted organ.

The following side effects may also occur after taking ADOPORT:
Very common side effects (may affect more than 1 in 10 people):

• Increased blood sugar levels, type 2 diabetes, increased blood potassium levels
• Difficulty sleeping
• Tremor, headache (cephalalgia)
• Increased blood pressure
• Diarrhoea, nausea
• Kidney problems

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

• Reduced levels of magnesium, phosphate, potassium, calcium, or sodium in the blood, fluid overload, increased blood levels of uric acid or lipids, decreased appetite, increased blood acidity, other changes in blood electrolyte balance
• Anxiety, confusion and disorientation, depression, mood changes, nightmares, hallucinations, psychiatric disorders
• Seizures, altered consciousness, tingling and numbness (sometimes painful) in the hands and feet, dizziness, impaired writing ability, nervous system disorders
• Blurred vision, increased sensitivity to light, eye disorders
• Ringing in the ears
• Reduced blood flow in the heart vessels, rapid heartbeat
• Bleeding, complete or partial blockage of blood vessels, reduced blood pressure
• Shortness of breath, changes in lung tissue, fluid accumulation around the lungs, pharyngitis, cough, flu-like symptoms
• Inflammations or ulcers causing abdominal pain or diarrhoea, bleeding in the stomach, mouth ulcers, fluid accumulation in the abdomen, vomiting, abdominal pain, indigestion, constipation, excess intestinal gas (flatulence), bloating, loose stools, stomach discomfort
• 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, limb, or back pain, muscle spasms
• Insufficient kidney function, reduced urine production, impaired or painful urination
• General weakness, fever, fluid accumulation in the body, pain and discomfort, increased blood alkaline phosphatase enzyme, weight gain, altered temperature sensation.

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

• Blood clotting disorders, reduced count of all blood cells
• Dehydration
• Reduced levels of proteins or sugar in the blood, increased blood phosphate levels
• Coma, brain haemorrhage, stroke, paralysis, brain disorders, speech and language abnormalities, memory problems
• Blurred vision due to a lens abnormality in the eye
• Hearing impairment
• Irregular heartbeat or cardiac arrest, reduced heart performance, heart muscle disorders, thickening of the heart muscle, stronger heartbeat, ECG abnormalities, abnormalities in heart rate and rhythm
• Blood clots (thrombi) in a limb vein, shock
• Breathing difficulties, respiratory tract disorders, asthma
• Intestinal obstruction, increased blood levels of amylase enzyme, reflux of stomach contents into the throat (gastroesophageal reflux), delayed stomach emptying
• Dermatitis, burning sensation when exposed to sunlight
• Joint disorders
• Inability to urinate, painful menstruation, abnormal menstrual bleeding
• Organ failure, flu-like illness, increased sensitivity to heat and cold, chest tightness, extreme nervousness or discomfort, increased blood lactate dehydrogenase enzyme, weight loss.

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

• Small skin haemorrhages due to blood clots
• Increased muscle stiffness
• Blindness
• Deafness
• Fluid accumulation around the heart
• Acute breathlessness
• Cyst formation in the pancreas
• Problems with blood flow in the liver
• Increased hair growth (hirsutism)
• Thirst, fainting, chest tightness, reduced mobility, ulcer.

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

• Muscle weakness
• Abnormalities in echocardiogram
• Liver failure, narrowing of the bile duct
• Painful urination with blood in the urine
• Increased fatty tissue.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website: http://www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Adoport

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label after "EXP". The expiry date refers to the last day of that month.
Use all capsules within 12 months after opening the aluminium wrapper surrounding the blister. Once the aluminium wrapper has been opened, do not store at temperatures above 25°C.
Take the capsules immediately after removing them from the blister.
Do not store at temperatures above 30°C. Store in the original packaging to protect the medicine from moisture.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What ADOPORT Contains

• The active substance is tacrolimus. Each capsule contains 0.5 mg, 0.75 mg, 1 mg, 2 mg, or 5 mg of tacrolimus (as monohydrate).
• The other components are:
  Capsule contents: lactose monohydrate, hypromellose (E464), sodium croscarmellose (E468), and magnesium stearate (E572).
  Hard gelatin capsule shell:
  • ADOPORT 0.5 mg: gelatin, titanium dioxide (E171), sodium lauryl sulfate, sorbitan laurate, and yellow iron oxide (E172)
  • ADOPORT 0.75 mg: gelatin, titanium dioxide (E171), yellow iron oxide (E172), FD&C Blue No. 1 (E133), shellac (E904), propylene glycol (E1520), potassium hydroxide (E525), and black iron oxide (E172)
  • ADOPORT 1 mg: gelatin, titanium dioxide (E171), sodium lauryl sulfate, sorbitan laurate, yellow iron oxide (E172), red iron oxide (E172), and black iron oxide (E172)
  • ADOPORT 2 mg: gelatin, titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172), FD&C Blue No. 1 (E133), shellac (E904), propylene glycol (E1520), potassium hydroxide (E525), and black iron oxide (E172)
  • ADOPORT 5 mg: gelatin, titanium dioxide (E171), sodium lauryl sulfate, sorbitan laurate, and red iron oxide (E172)

Description of the Appearance of ADOPORT and Contents of the Package
ADOPORT 0.5 mg is presented as hard capsules with an opaque white body and an ivory cap, containing a white to off-white powder (length: 14.5 mm).
ADOPORT 0.75 mg is presented as hard capsules with an opaque light green body, with "0.75 mg" printed in black on the cap, containing a white to off-white powder (length: 14.5 mm).
ADOPORT 1 mg is presented as hard capsules with an opaque white body and a light brown cap, containing a white to off-white powder (length: 14.5 mm).
ADOPORT 2 mg is presented as hard capsules with an opaque dark green body, with "2 mg" printed in black on the cap, containing a white to off-white powder (length: 14.5 mm).
ADOPORT 5 mg is presented as hard gelatin capsules with an opaque white body and an orange cap, containing a white to off-white powder (length: 15.8 mm).

ADOPORT is packaged in PVC/PE/PVdC/aluminum blisters, placed in an aluminum pouch containing a desiccant to protect the medicine from moisture. The desiccant must not be ingested.
Pack sizes: 7, 10, 14, 20, 28, 30, 50, 60, 90, and 100 hard capsules.
Not all pack sizes may be marketed.

Marketing Authorization Holder:
Sandoz S.p.A.
Largo U. Boccioni 1
21040 Origgio (VA)
Italy

Manufacturers:
Salutas Pharma GmbH, Otto-von-Guericke-Allee 1, D-39179 Barleben, Germany
Salutas Pharma GmbH, Dieselstrasse 5, D-70839 Gerlingen, Germany (only for 0.5 mg, 1 mg, and 5 mg hard capsules)
Lek Pharmaceuticals d.d., Verovskova 57, 1526 Ljubljana, Slovenia
S.C. Sandoz S.R.L., Str. Livenzeni nr. 7A, RO-540472 Târgu Mureș, Romania
LEK S.A., Ul. Domaniewska 50C, 02-672 Warsaw, Poland
Lek Pharmaceuticals d.d., Trimlini 2D, 9220 Lendava, Slovenia

This medicinal product is authorized in the European Economic Area (EEA) Member States under the following names:

| Country | Product Name | |----------------|--------------| | Austria | Adport 0.5 mg - Hartkapseln
Adport 1 mg - Hartkapseln
Adport 5 mg - Hartkapseln
Adport 2 mg - Hartkapseln | | Belgium | Adoport 0.5 mg harde capsules
Adoport 1 mg harde capsules
Adoport 5 mg harde capsules
Adoport 2 mg harde capsules
Adoport 0.75 mg harde capsules | | Czech Republic | Tacrolimus Sandoz 0.5 mg
Tacrolimus Sandoz 1 mg
Tacrolimus Sandoz 5 mg
Tacrolimus Sandoz 2 mg
Tacrolimus Sandoz 0.75 mg | | Denmark | Adport | | Finland | Adport 2 mg kapseli, kova
Adport 0.75 mg kapseli, kova | | France | ADOPORT 0.5 mg, gélule
ADOPORT 1 mg, gélule
ADOPORT 5 mg, gélule
ADOPORT 2 mg, gélule | | Germany | Crilomus 0.5 mg Hartkapseln
Crilomus 1 mg Hartkapseln
Crilomus 5 mg Hartkapseln
Crilomus 2 mg Hartkapseln
Crilomus 0.75 mg Hartkapseln | | Hungary | Adport 0.5 mg kemény kapszula
Adport 1 mg kemény kapszula
Adport 5 mg kemény kapszula | | Italy | ADOPORT | | Netherlands | Adport 0.5 mg, capsules, hard
Adport 1 mg, capsules, hard
Adport 5 mg, capsules, hard
Adport 2 mg, capsules, hard
Adport 0.75 mg, capsules, hard | | Poland | CIDIMUS | | Romania | TACROLIMUS SANDOZ 0.5 mg capsule
TACROLIMUS SANDOZ 1 mg capsule
TACROLIMUS SANDOZ 5 mg capsule | | Slovenia | Adoport 0.5 mg trde kapsule
Adoport 1 mg trde kapsule
Adoport 5 mg trde kapsule
Adoport 2 mg trde kapsule
Adoport 0.75 mg trde kapsule | | Spain | Adoport 0.5 mg cápsulas duras EFG
Adoport 1 mg cápsulas duras EFG
Adoport 5 mg cápsulas duras EFG
Adoport 2 mg cápsulas duras EFG | | Sweden | Adport, 2 mg kapsel, hård
Adport, 0.75 mg kapsel, hård | | United Kingdom | Adoport 0.5 mg Capsules, hard
Adoport 1 mg Capsules, hard
Adoport 5 mg Capsules, hard
Adoport 2 mg Capsules, hard
Adoport 0.75 mg Capsules, hard |