0.5 mg, 1 mg, 3 mg, 5 mg hard prolonged
-release capsules tacrolimus
What Tacforius is and what it is used for
Tacforius contains the active substance tacrolimus. It is an immunosuppressive drug. After an organ transplant (liver, kidney), the body’s immune system tries to reject the new organ. Tacforius is used to control your body’s immune system so that it accepts the transplanted organ.
You may also be given Tacforius for an ongoing rejection reaction against your transplanted liver, kidney, heart, or another organ when other treatment you received failed to control the immune system after your transplant.
What you need to know before you take Tacforius
Do not take Tacforius
- if you are allergic to tacrolimus or any of the other ingredients of this medicine (listed in section 6)
- if you are allergic to sirolimus or any macrolide antibiotic (eg erythromycin, clarithromycin, josamycin).
Warnings and precautions
Tacrolimus immediate-release capsules (eg Tacni) and Tacforius prolonged-release capsules both contain the active substance tacrolimus. However, Tacforius prolonged-release capsules are taken once daily, while tacrolimus immediate-release capsules are taken twice daily. This is because Tacforius prolonged-release capsules have a delayed release (slower release over a longer period) of tacrolimus. Tacforius prolonged-release capsules and tacrolimus immediate-release capsules are not interchangeable.
Tell your doctor if any of the following apply to you:
- if you are taking any medicines mentioned below under the heading “Other medicines and Tacforius”.
- if you have or have had liver problems
- if you have diarrhea that lasts more than a day
- if you experience severe abdominal pain, possibly accompanied by other symptoms, such as chills, fever, nausea, or vomiting
- if you have a change in the heart rhythm, so-called “QT prolongation”.
Avoid taking herbal medicines, e.g. St. John’s wort ( Hypericum perforatum ) or other herbal products as this may affect the effectiveness of Tacforius and the dose you need to take. If in doubt, consult your doctor before taking any herbal medicines or products.
Your doctor may need to adjust the dose of Tacforius.
You should have regular contact with your doctor, who may occasionally need to perform blood, urine, heart function, and eye tests to determine the correct dose of Tacforius.
You should limit exposure to sunlight and UV light (ultraviolet light) while taking Tacforius. This is because immunosuppressive drugs can increase the risk of getting skin cancer. Use suitable protective clothing and sunscreen with a high sun protection factor.
Handling Precautions:
Direct contact with any part of the body, for example, skin or eyes, or inhalation of the powder in the capsules should be avoided. In case of such contact, skin and eyes must be rinsed.
Children and young people
Tacforius is not recommended for children and adolescents under the age of 18.
Other medicines and Tacforius
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Concomitant treatment with Tacforius and ciclosporin (another medicine used to prevent rejection of transplanted organs) is not recommended.
If you need to see a doctor other than your transplant specialist, tell the doctor you are taking tacrolimus. The doctor may need to consult with your transplant specialist if you are going to use another medicine that can increase or decrease the concentration of tacrolimus in the blood.
Blood concentrations of Tacforius may be affected by other medicines you are taking and blood levels of other medicines may be affected by your taking Tacforius, which means that the dosage of Tacforius may need to be stopped, increased, or decreased.
In some patients, tacrolimus blood concentrations have increased when they took other medicines at the same time. This can lead to serious side effects, such as problems with the kidneys and nervous system and heart rhythm disturbances (see section 4).
The influence on the concentrations of Tacforius in the blood can occur very quickly after another medicine has started to be used. Therefore, continuous repeated monitoring of the concentration of Tacforius in the blood may be necessary for the first days after you start taking another medicine and at frequent intervals as long as the treatment with the other medicine is ongoing. Some other medicines can reduce the concentration of tacrolimus in the blood, which can increase the risk of transplant rejection.
You should especially tell your doctor if you are taking or have recently taken medicines such as:
- drugs against fungal infections and antibiotics, especially so-called macrolide antibiotics that are used to treat infections, e.g. ketoconazole, fluconazole, itraconazole, posaconazole, voriconazole, clotrimazole, isavuconazole, miconazole, telithromycin, erythromycin, clarithromycin, josamycin, azithromycin, rifampicin, rifabutin, isoniazid and flucloxacillin
- letermovir is used to prevent diseases caused by CMV ( human cytomegalovirus )
- HIV – protease inhibitors (eg ritonavir, nelfinavir, saquinavir), the booster drug cobicistat and combination tablets, or HIV non-nucleoside reverse transcriptase inhibitors ( efavirenz, etravirine, nevirapine) used to treat HIV – infection
- HCV protease inhibitors (eg, telaprevir, boceprevir, the combination ombitasvir/paritaprevir/ritonavir with or without dasabuvir, elbasvir/grazoprevir and glecaprevir/pibrentasvir), used to treat hepatitis C infection
- nilotinib and imatinib, idelalisib, ceritinib, crizotinib, apalutamide, enzalutamide or mitotane (used to treat certain cancers)
- mycophenolic acid, which is used to suppress the immune system to prevent rejection of the transplanted organ
- medicines for stomach ulcers and acid reflux (eg omeprazole, lansoprazole, or cimetidine)
- medicines for nausea and vomiting (eg metoclopramide)
- cisapride or magnesium aluminum hydroxide used to treat heartburn
- Birth control pills or other hormone treatments containing ethinylestradiol, hormone treatments with danazol
- medicines for high blood pressure or heart problems (eg nifedipine, nicardipine, diltiazem, and verapamil)
- antiarrhythmics ( amiodarone ), medicines used to treat arrhythmias (irregular heartbeats)
- medicines called ‘statins’ used to treat high cholesterol and triglycerides (blood fats)
- carbamazepine, phenytoin, and phenobarbital used to treat epilepsy
- cannabidiol (used, among other things, for the treatment of epileptic seizures)metamizole, which is used to treat pain and fever
- the corticosteroids prednisolone and methylprednisolone, are used to treat inflammation and suppress the immune system (e.g. in case of rejection of the transplanted organ)
- nefazodone used to treat depression
- (Traditional) herbal medicines containing St. John’s wort ( Hypericum perforatum ) or extracts of Schisandra sphenanthera.
Tell your doctor if you are receiving treatment for hepatitis C. Drug treatment for hepatitis C can affect liver function and thus the tacrolimus concentration in the blood. The concentration of tacrolimus in the blood may decrease or increase depending on the medicines prescribed for hepatitis C. The doctor may need to monitor tacrolimus concentrations in the blood closely and adjust the Tacforius dose once you start treatment for hepatitis C.
Tell your doctor if you are taking or need to take ibuprofen (medicine for fever, inflammation, and pain), antibiotics (trimethoprim/sulfamethoxazole co-trimoxazole, vancomycin, or aminoglycoside antibiotics such as gentamicin), amphotericin B (medicine for fungal infections) or medicines for viral infections (e.g. . aciclovir, ganciclovir, cidofovir, foscarnet). These may worsen kidney or nervous system problems when taken with Tacforius.
Your doctor also needs to know if you are taking potassium supplements or certain diuretics, used in heart failure, high blood pressure, and kidney disease (eg amiloride, triamterene, or spironolactone ), or trimethoprim or trimethoprim/sulfamethoxazole antibiotics which can increase potassium levels in your blood, certain medicines used for fever, inflammation, and pain (so-called NSAIDs, eg ibuprofen ), blood thinners or oral medication to treat diabetes while you are taking Tacforius.
If you need to be vaccinated, you must tell your doctor about this in advance.
Tacforius with food and drink
Avoid grapefruit (even as grapefruit juice) when being treated with Tacforius, as it may affect blood levels of the drug.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine.
Tacrolimus is excreted in breast milk. Therefore, you should not breastfeed while taking Tacforius.
Driving ability and use of machinery
Do not drive or use tools or machines if you feel dizzy or sleepy, or have trouble seeing clearly after taking Tacforius. These effects are more common if you also drink alcohol.
Tacforius contains
Tacforius contains lactose
If you have an intolerance to some sugars, you should consult your doctor before taking this medicine.
Tacforius 5 mg capsules contain nycoccine
This can cause allergic reactions.
How to take Tacforius
Always take this medicine as directed by your doctor. Ask your doctor or pharmacist if you are unsure.
This medicine should only be prescribed to you by doctors experienced in the treatment of transplant patients.
Make sure you get the same tacrolimus medicine each time you pick up your prescription unless your transplant doctor has decided that you should switch to a different tacrolimus medicine. This medicine should be taken once daily. If the appearance of the medicine is not the same as usual, or if the dosage instructions have changed, talk to your doctor or pharmacist as soon as possible to make sure you have received the correct medicine.
The starting dose to prevent rejection of your transplanted organ is determined by your doctor and calculated according to your body weight. The starting doses immediately after the transplant are normally within the range
0.10-0.30 mg per kg of body weight per day
depending on which organ was transplanted. In the treatment of rejection, the same dosage can be used.
The dose depends on your general condition and which other immunosuppressive medicine(s) you are receiving.
After you have started treatment with Tacforius, your doctor will take blood samples often to arrive at the right dose. Then, regular blood tests are required that your doctor takes to determine the correct dose and to adjust the dose from time to time. The dose of Tacforius is usually reduced by the doctor when your condition has stabilized. Your doctor will tell you exactly how many capsules to take.
You will need to take Tacforius every day for as long as you need immunosuppression to prevent rejection of your transplanted organ. You should be in regular contact with your doctor.
Tacforius is taken orally once daily in the morning. Take Tacforius on an empty stomach or 2 to 3 hours after a meal. Wait at least 1 hour for the next meal. Take the capsules immediately after removing them from the blister. The capsules should be swallowed whole with a glass of water. Do not swallow the desiccant contained in the aluminum bag.
If you have taken too much Tacforius
If you have accidentally taken too many capsules, contact your doctor or nearest emergency department immediately
If you forget to take Tacforius
If you forget to take your Tacforius capsules in the morning, take them as soon as possible on the same day. Do not take a double dose the next morning.
If you stop taking Tacforius
Stopping treatment with Tacforius may increase the risk of rejection of your transplanted organ. Do not stop your treatment until your doctor tells you to.
If you have any further questions about this medicine, ask your doctor or pharmacist.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tacforius weakens the body’s defense mechanisms (the immune system), which makes the body’s ability to fight infection worse. When you take Tacforius, you may therefore get more infections than usual.
Some infections can be serious or life-threatening and can include infections caused by bacteria, viruses, fungi, parasites, or other infections.
Contact a doctor immediately if you develop signs of infection, such as:
- Fever, cough, sore throat, feeling weak or generally unwell
- Memory loss, trouble thinking, difficulty walking, or vision loss – may be due to a very rare, serious infection of the brain, which can be life-threatening ( progressive multifocal leukoencephalopathy, or PML)
Serious side effects have been reported, including allergic and anaphylactic reactions. Benign and malignant tumors have been reported during treatment with Tacforius.
Contact your doctor immediately if you have or suspect you have any of the following serious side effects:
Serious common side effects ( may affect up to 1 in 10 users):
- Gastrointestinal perforation: severe abdominal pain possibly accompanied by other symptoms, such as chills, fever, nausea, or vomiting.
- Inadequate function of the transplanted organ.
- Blurred vision.
Serious uncommon side effects ( may affect up to 1 in 100 users):
- The hemolytic uremic syndrome is 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 bruising or bleeding and signs of infection.
Serious rare side effects ( may affect up to 1 in 1,000 users):
- Thrombotic thrombocytopenic purpura (or TTP): a condition characterized by fever and bruising under the skin that may look like red pin-sized dots, 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).
- Toxic epidermal necrolysis: lesions and blisters on the skin or mucous membranes, red swollen skin that can detach from large parts of the body.
- Blindness.
Serious very rare side effects ( may affect up to 1 in 10,000 users):
- Stevens-Johnson syndrome: unexplained widespread skin pain, facial swelling, severe illness with blistering of the skin, mouth, eyes, and genitals, hives, swollen tongue, the red or purple rash that spreads, flaky skin.
- Torsades de Pointes: change in heart rate that may, but may not, be accompanied by symptoms such as chest pain (angina), weakness, dizziness or nausea, palpitations, and difficulty breathing.
Serious side effects – frequency not known (frequency cannot be estimated from available data):
- Opportunistic infections (caused by bacteria, fungi, viruses, and protozoa ): prolonged diarrhea, fever, and sore throat.
- Benign and malignant tumors have been reported after treatment as a result of immunosuppression.
- Cases of pure erythrocyte aplasia (a very severe decrease in the number of red blood cells ), hemolytic anemia (decreased number of red blood cells due to increased breakdown, accompanied by fatigue) and febrile neutropenia (a decrease in the number of white blood cells that fight infection, accompanied by fever) have been reported. It is not known exactly how often these side effects occur. You may be asymptomatic or experience symptoms such as fatigue, apathy, abnormal pallor, shortness of breath, dizziness, headache, chest pain, and cold hands and feet, depending on the severity of the condition.
- Cases of agranulocytosis (severe reduction in the number of white blood cells along with mouth sores, fever, and infection (s)). You may be symptom-free or experience symptoms such as sudden fever, stiffness, and sore throat.
- Allergic and anaphylactic reactions with the following symptoms: sudden itchy rash ( hives ), swelling of the hands, feet, ankles, face, lips, mouth, or throat (which may cause difficulty in swallowing or breathing) and you may feel that you are about to faint.
- Posterior reversible encephalopathy syndrome (PRES): headache, confusion, mood swings, seizures, and visual disturbances. This may be a sign of a condition called posterior reversible encephalopathy syndrome, which has been reported in some patients treated with tacrolimus.
- Optic neuropathy (optic nerve involvement): problems with your vision such as blurred vision, changes in color vision, difficulty seeing details, or your field of vision becoming restricted.
The side effects listed below may also occur after receiving Tacforius and may be serious:
Very common side effects ( may affect more than 1 in 10 users):
- Increased blood sugar, diabetes mellitus, increased potassium in the blood
- Difficulty sleeping
- Tremors, headache
- Increased blood pressure
- Abnormal liver function tests
- Diarrhea, nausea
- Kidney problems
Common side effects ( may affect up to 1 in 10 users):
- Decreased number of blood cells ( platelets, red or white blood cells ), increased number of white blood cells, changed the number of red blood cells (seen in blood samples)
- Decreased magnesium, phosphate, potassium, calcium, or sodium in the blood, increased amount of fluid in the body, increased amount of uric acid or fats in the blood, decreased appetite, increased acidity in the blood, and other changes in blood salts (seen in blood tests)
- Anxiety, confusion, disorientation, depression, mood changes, nightmares, hallucinations, mental illness
- Convulsions, disturbances of consciousness, tingling or numbness (sometimes painful) in the hands and feet, dizziness, reduced ability to write, nervous system disorders
- Increased photosensitivity, eye diseases
- Earrings
- Reduced blood flow in the vessels of the heart, faster heartbeat
- Bleeding, partial or complete blockage of blood vessels decreased blood pressure
- Shortness of breath, changes in the lungs, fluid accumulation around the lung, inflammation of the throat, cough, flu-like symptoms
- Inflammation or ulcers causing abdominal pain or diarrhea, bleeding in the stomach, inflammation or ulcers in the mouth, fluid retention in the abdomen, vomiting, abdominal pain, indigestion, constipation, gas, bloating, loose stools, stomach problems
- Bile duct problems, yellowing of the skin due to liver problems, damage to liver tissue, and inflammation of the liver
- Itching, rash, hair loss, acne, increased sweating
- Pain in joints, limbs, back and feet, muscle twitching
- Insufficient functioning of the kidneys reduced urine production, impaired or painful urination
- General weakness, fever, fluid accumulation in the body, pain and discomfort, increase in alkaline phosphatases in the blood, weight gain, the sensation of disturbed temperature perception
Uncommon side effects ( may affect up to 1 in 100 users):
- Changes in the clotting ability of the blood, reduced numbers of all types of blood cells (seen in blood samples)
- Dehydration
- Decreased protein or sugar in the blood, increased phosphate in the blood
- Coma, cerebral hemorrhage, stroke, paralysis, brain disease, speech and language difficulties, memory problems
- Clouding in the lens of the eye
- Impaired hearing
- Irregular heartbeats, cardiac arrest, decreased force of the heart, disease of the heart muscle, enlargement of the heart muscle, stronger heartbeat, abnormal EKG, abnormal heart rate and pulse
- Blood clot in a vein in the leg or arm, shock
- Difficulty breathing, respiratory disease, asthma
- Obstructions in the intestinal passage, increased blood level of enzyme et amylase, regurgitation of contents from the stomach to the throat, prolonged emptying of the stomach
- Skin inflammation, burning sensation in the sun
- Joint diseases
- Inability to urinate, painful periods, and abnormal menstrual bleeding
- Impaired function in several organs, flu-like symptoms, increased sensitivity to heat and cold, pressure on the chest, nervousness or abnormal feeling, increase in the enzyme lactate dehydrogenase in the blood, weight loss
Rare side effects ( may affect up to 1 in 1,000 users)
- Small skin bleeding due to blood clots
- Increased muscle stiffness
- Deafness
- Accumulation of fluid around the heart
- Acute breathing difficulties
- Cyst formation in the pancreas
- Problems with blood flow in the liver
- Severe disease with blistering of the skin, mouth, eyes, and genitals, increased hairiness
- Thirst falls, feeling of pressure on the chest, reduced mobility, wounds
Very rare side effects ( may affect up to 1 in 10,000 users):
- Muscle weakness
- Abnormal echocardiogram ( ECG )
- Liver failure
- Painful urination with blood in the urine
- The increased amount of adipose tissue
How to store Tacforius
Keep this medicine out of the sight and reach of children.
Use before the expiry date which is stated on the carton and blister after “EXP”.
The expiration date is the last day of the specified month.
Store in the original packaging. Light sensitive. Moisture sensitive. No special temperature instructions.
Use all prolonged-release capsules within one year of opening the aluminum foil.
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
The active substance is tacrolimus
One capsule of Tacforius 0.5 mg contains 0.5 mg tacrolimus (as a monohydrate).
One capsule of Tacforius 1 mg contains 1 mg of tacrolimus (as a monohydrate).
One capsule of Tacforius 3 mg contains 3 mg tacrolimus (as a monohydrate).
One capsule of Tacforius 5 mg contains 5 mg tacrolimus (as a monohydrate).
Other ingredients are:
Capsule contents
Hypromellose 2910, ethyl cellulose, lactose, magnesium stearate.
Capsule shell
Tacforius 0.5 mg/1 mg/3 mg prolonged-release hard capsules: red iron oxide (E 172), yellow iron oxide (E 172) , titanium dioxide (E 171), gelatin
Tacforius 5 mg prolonged-release hard capsules: red iron oxide (E 172), yellow iron oxide (E 172), titanium dioxide (E 171), black iron oxide (E 172), nycoccin (E 124), gelatin
Ink
Shellac, propylene glycol, black iron oxide (E 172), potassium hydroxide
Appearance and package sizes of the medicine
Tacforius 0.5 mg hard prolonged-release capsules
Hard gelatin capsules are marked with “TR” on the light yellow capsule cap and “0.5 mg” on the light orange body of the capsule.
Tacforius 1 mg hard prolonged-release capsules
Hard gelatin capsules are marked with “TR” on the white capsule cap and “1 mg” on the light orange body of the capsule.
Tacforius 3 mg hard prolonged-release capsules
Hard gelatin capsules marked with “TR” on the light orange capsule cap and “3 mg” on the light orange capsule body.
Tacforius 5 mg hard prolonged-release capsules
Hard gelatin capsules marked with “TR” on the gray capsule cap and “5 mg” on the light orange capsule body.
Tacforius 0.5 mg/3 mg/5 mg prolonged-release hard capsules
Supplied in blisters or perforated unit-dose blisters with 10 capsules in a protective aluminum pouch, containing desiccant. Packs of 30, 50, and 100 prolonged-release capsules are available in blisters, and packs of 30×1, 50×1, and 100×1 prolonged-release capsules are available in perforated single-dose blisters.
Tacforius 1 mg hard prolonged-release capsules
Supplied in blisters or perforated unit-dose blisters with 10 capsules in a protective aluminum pouch, containing desiccant. Packs of 30, 50, 60 and 100 hard prolonged-release capsules are available in blisters, and packs of 30×1, 50×1, 60×1, and 100×1 hard prolonged-release capsules are available in perforated single-dose blisters.
Marketing Authorisation Holder
Teva BV
Swensveg 5
2031 GA Haarlem
Netherlands
Manufacturer
Merkle GmbH
Ludwig-Merckle-Straße 3
89143 Blaubeuren
Germany
PLIVA Hrvatska doo
Prilaz baruna Filipovića 25
10000 Zagreb
Croatia
Teva Czech Industries s.r.o
Ostravská 29, cp 305
Opava-Komárov
74770
Czech Republic
Teva Operations Poland Sp. Zoo
ul. Mogilska 80
31-546 Cracow
Poland
Teva Pharma SLU
C/C, n. 4, Poligono Industrial Malpica
ES-50016 Zaragoza
Spain
Teva Pharmaceutical Works Private Limited Company
Pallagi út 13
4042 Debrecen
Hungary
Contact the representative of the Marketing Authorization Holder if you would like to know more about this medicine:
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