Graftac Capsules

[PRODUCT NAME] belongs to a group of medicines known as immunosuppressants. Following your organ transplant (e.g. liver, kidney, heart) your body’s immune system will try to reject the new organ. [PRODUCT NAME] is used to control your body’s immune response enabling your body to accept the transplanted organ. [PRODUCT NAME] is often used in combination with other medicines that also suppress the immune system. You may also be given [PRODUCT NAME] for an ongoing rejection of your transplanted liver, kidney, heart or other organ or if any previous treatment you were taking was unable to control this immune response after your transplantation.

Do not take [PRODUCT NAME]

• 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 macrolide antibiotics (e.g erythromycin, clarithromycin, josamycin).
• If you are pregnant and breastfeeding your baby.
• [PRODUCT NAME] may alter the metabolism of oral contraceptives; other forms of contraception should be used.
• With live attenuated vaccines.
• With ciclosporin.
• With grapefruit juice.

Warnings and precautions

Talk to your doctor or pharmacist before taking [PRODUCT NAME]:

• You will need to take [PRODUCT NAME] every day as long as you need immunosuppression to prevent rejection of your transplanted organ. You should keep in regular contact with your doctor.
• Whilst you are taking [PRODUCT NAME], your doctor may want to carry out a number of tests (including blood, urine, heart function, visual and neurological tests) from time to time.

This is normal and will help your doctor to decide on the most appropriate dose of [PRODUCT NAME] for you.

• Please avoid taking any herbal remedies, e.g., St. John’s wort (Hypericum perforatum) or any other herbal products as this may affect the effectiveness and the dose of [PRODUCT NAME] that you need to receive. If in doubt, please consult your doctor prior to taking any herbal products or remedies.
• If you have liver problems or have had a disease, which may have affected your liver, please tell your doctor as this may affect the dose of [PRODUCT NAME] that you receive.
• If you feel strong abdominal pain accompanied or not with other symptoms, such as chills, fever, nausea or vomiting.
• If you have diarrhoea for more than one day, please tell your doctor, because it might be necessary to adapt the dose of [PRODUCT NAME] that you receive.
• If you have an alteration of the electrical activity of your heart called “QT prolongation”.
• Limit your exposure to sunlight and UV light whilst taking [PRODUCT NAME] by wearing appropriate protective clothing and using a sunscreen with a high sun protection factor. This is because of the potential risk of malignant skin changes with immunosuppressive therapy.
• If you need to have any vaccinations, please inform your doctor beforehand. Your doctor will advise you on the best course of action.
• Patients treated with [PRODUCT NAME] have been reported to have an increased risk of developing lymphoproliferative disorders (see section 4). Ask your doctor for specific advice on these disorders.

Tell your doctor immediately if during treatment you suffer from problems with your vision such as blurred vision, changes in colour vision, difficulty in seeing detail or if your field of vision becomes restricted.

Other medicines and [PRODUCT NAME]

Always tell your healthcare professional if you are taking any other medicines. (This includes all complementary or traditional medicines.) [PRODUCT NAME] must not be taken simultaneously with ciclosporin. [PRODUCT NAME] blood levels can be affected by other medicines you take, and blood levels of other medicines can be affected by taking [PRODUCT NAME], which may require interruption, an increase or a decrease in [PRODUCT NAME] dose.

Tell your doctor if you are taking or have recently taken any of the following medicines:

• Antifungal medicines and antibiotics (particularly so-called macrolide antibiotics) used to treat infections e.g., ketoconazole, fluconazole, itraconazole, voriconazole, clotrimazole, and isavuconazole, erythromycin, clarithromycin, josamycin, and rifampicin.
• Letermovir, used to prevent illness caused by CMV (human cytomegalovirus).
• HIV protease inhibitors (e.g ritonavir, nelfinavir, saquinavir), the booster medicine cobicistat and combination tablets, used to treat HIV infection.
• HCV protease inhibitors (e.g., telaprevir, boceprevir and the combination ombitasvir/paritaprevir/ritonavir with or without dasabuvir), used to treat hepatitis C infection.

Do not share medicines prescribed for you with any other person. Always take [PRODUCT NAME] exactly as your doctor has instructed you. You should check with your doctor or pharmacist if you are unsure. Make sure that you receive the same tacrolimus medicine every time you collect your prescription, unless your transplant specialist has agreed to change to a different tacrolimus medicine.

[PRODUCT NAME] should be taken twice a day. If the appearance of this medicine is not the same as usual, or if dosage instructions have changed, speak to your doctor or pharmacist as soon as possible to make sure that you have the right medicine.

The starting dose to prevent the rejection of your transplanted organ will be determined by your doctor calculated according to your body weight. Initial doses just after transplantation will generally be in the range of 0,075 to 0,30 mg per kg body weight per day depending on the transplanted organ. Your dose depends on your general condition and on which other immunosuppressive medication you are taking. Regular blood tests by your doctor will be required to define the correct dose and to adjust the dose from time to time. Your doctor will usually reduce your [PRODUCT NAME] dose once your condition has stabilised. Your doctor will tell you exactly how many capsules to take and how often.

If you have the impression that the effect of [PRODUCT NAME] is too strong or too weak, tell your doctor of pharmacist.

• [PRODUCT NAME] is taken orally twice daily, usually in the morning and evening. You should generally take [PRODUCT NAME] on an empty stomach or at least 1 hour before or 2 to 3 hours after a meal.
• The capsules should be swallowed whole with a glass of water.
• Take the hard capsules immediately following removal from the blister.
• Avoid grapefruit and grapefruit juice while taking [PRODUCT NAME].
• Do not swallow the desiccant contained in the foil wrapper.

If you take more [PRODUCT NAME] than you should

In the event of over dosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison centre. There is no specific antidote to overdosage and treatment must be symptomatic and supportive.

If you forget to take [PRODUCT NAME]

Do not take a double dose to make up for a forgotten individual doses. If you forget to take your capsule, take it as soon as you remember. If it is nearly time for the next dose, take it at the usual time.

If you stop taking [PRODUCT NAME]

Stopping your treatment with [PRODUCT NAME] may increase the risk of rejection of your transplanted organ. Do not stop taking your capsules even if you are feeling well, unless your doctor tells you. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

[PRODUCT NAME] can have side effects. Not all side effects reported for [PRODUCT NAME] are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking [PRODUCT NAME], please consult your doctor, pharmacist or other healthcare professional for advice.

[PRODUCT NAME] reduces your body’s own defence mechanism to stop you rejecting your transplanted organ. Consequently, your body will not be as good as usual at fighting infections. So if you are taking [PRODUCT NAME] you may therefore catch more infections than usual such as infections of the skin, mouth, stomach and intestines, lungs and urinary tract. Severe side effects may occur, including the ones listed below. Tell your doctor immediately if you have or suspect 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 result of immunosuppression.
• Thrombotic Thrombocytopenic Purpura (or TTP), a condition characterised by fever and bruising under the skin that may appear as red pinpoint dots, with or without unexplained extreme tiredness, confusion, yellowing of the skin or eyes (jaundice), with symptoms of acute renal failure (low or no urine output).
• Cases of pure red cell aplasia (a very severe reduction in red blood cell counts) and haemolytic anaemia (decreased number of red blood cells due to abnormal breakdown accompanied with tiredness) have been reported. You may have no symptoms or depending on the severity of the condition, you may feel: fatigue, apathy, abnormal paleness of the skin (pallor), shortness of breath, dizziness, headache, chest pain and coldness in hands and feet.
• Cases of agranulocytosis (a severely lowered number of white blood cells accompanied with ulcers in the mouth, fever and infection(s)). You may have no symptoms or you may feel sudden fever, rigors and sore throat.
• Allergic and anaphylactic reactions with the following symptoms: a sudden itchy rash (hives), swelling of hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing) and you may feel you are going to faint.
• Posterior Reversible Encephalopathy Syndrome (PRES): headache, altered mental status, seizures, and visual disturbances.
• Torsades de Pointes: change in the heart frequency that can be accompanied or not by symptoms, such as chest pain (angina), faint, vertigo or nausea, palpitations (feeling the heartbeat) and difficulty breathing.
• Gastrointestinal perforation: strong abdominal pain accompanied or not with other symptoms, such as chills, fever, nausea or vomiting.
• Stevens-Johnson syndrome: unexplained widespread skin pain, facial swelling, serious illness with blistering of skin, mouth, eyes and genitals, hives, tongue swelling, red or purple skin rash that spreads, skin shedding.
• Toxic epidermal necrolysis: erosion and blistering of skin or mucous membranes, red swollen skin that can detach in large parts of the body.
• Haemolytic uraemic syndrome, a condition with the following symptoms: low or no urine output (acute renal failure), extreme tiredness, yellowing of the skin or eyes (jaundice) and abnormal bruising or bleeding and signs of infection.

• Store at or below 30 °C in the original package.
• Keep the blister in the outer carton.
• Use all the capsules within 12 months of opening the aluminium wrapping surrounding the blister.
• In-use blister pack should be stored at or below 25 °C.
• Take the capsule immediately after removing from the blister.
• STORE ALL MEDICINES OUT OF REACH OF CHILDREN.
• Do not use [PRODUCT NAME] after the expiry date stated printed on the label or carton.
• Return all unused medicine to your pharmacist.
• Do not dispose of unused medicine in drains or sewerage systems (e.g., toilets).