Gravtell 0,5 mg/1 mg/5 mg Capsules

Each hard gelatin capsule contains the active ingredient tacrolimus. Tacrolimus is an immunosuppressive medicine. GRAVTELL is used to control your body’s immune response enabling your body to accept the transplanted organ. GRAVTELL is often used in combination with other medicines that also suppress the immune system.

Do not take GRAVTELL:

• if you are hypersensitive (allergic) to tacrolimus or any other macrolide antibiotic (erythromycin, clarithromycin).
• if you are hypersensitive (allergic) to any of the other ingredients of GRAVTELL (listed in section 6).
• If you are pregnant or breastfeeding.
• if you are taking oral contraceptives GRAVTELL 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

Special care should be taken with GRAVTELL:

• You will need to take GRAVTELL 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 GRAVTELL 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 quite normal and will help your doctor to decide on the most appropriate dose of GRAVTELL 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 GRAVTELL 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 GRAVTELL 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 GRAVTELL 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 GRAVTELL 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. See also Do not take GRAVTELL.
• Patients treated with GRAVTELL 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.

Do not share medicines prescribed for you with any other person. Always take GRAVTELL exactly as your doctor or pharmacist has instructed you. Check with your doctor or pharmacist if you are not sure.

Method of administration

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. It is recommended that the oral daily dose be taken in two divided doses. 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.

Dose

Your doctor will determine your dose depending on your type of transplant and your weight. GRAVTELL is taken orally twice daily, usually in the morning and evening. You should generally take GRAVTELL on an empty stomach or at least 1 hour before or 2 to 3 hours after the meal. The hard gelatin capsules should be swallowed whole with a glass of water. Do not drink grapefruit juice while taking GRAVTELL (see also Do not take GRAVTELL). Do not swallow the desiccant contained in the foil wrapper.

Duration of administration

Your doctor will tell you how long your treatment with GRAVTELL will last. If you have the impression that the effect of GRAVTELL is too strong or too weak, tell your doctor or pharmacist.

If you take more GRAVTELL than you should

You would have the symptoms including tremor, headache, nausea and vomiting, infections, urticaria, lethargy, increased blood urea nitrogen and elevated serum creatinine concentrations, and increase in alanine aminotransferase levels. In the event of overdosage, consult your doctor or pharmacist. If neither is available, contact the nearest hospital or poison centre.

If you forget to take GRAVTELL

Do not take a double dose to make up for forgotten individual doses.

Effects when treatment with GRAVTELL is stopped:

Stopping your treatment with GRAVTELL may increase the risk of rejection of your transplanted organ. Do not stop your treatment unless your doctor tells you to do so. If you have any further questions on the use of GRAVTELL, ask your doctor or pharmacist.

GRAVTELL can have side effects. Not all side effects reported for GRAVTELL are included in this leaflet. Should your general health worsen or if you experience any untoward effects while taking GRAVTELL, please consult your health care provider for advice.

If any of the following happens, stop taking GRAVTELL and tell your doctor immediately or go to the casualty department at your nearest hospital. These are very serious side effects. If you have them, you may have had a serious reaction to GRAVTELL. You may need urgent medical attention or hospitalisation. These are all serious side effects. You may need urgent medical attention.

Tell your doctor if you notice any of the following:

• Frequent side effects:
• opportunistic infections Viral, Bacterial, Fungal, Protozoal Infection. Generalised and localised infections can occur
• benign as well as malignant tumours have been reported
• anaemia, Leukopenia, Thrombocytopenia, Leukocytosis, Red blood cell analyses abnormal
• allergic and anaphylactoid reactions have been observed in patients receiving tacrolimus
• hyperglycaemic conditions, Diabetes mellitus, Hyperkalaemia Hypomagnesaemia, Hypophosphataemia, Hypokalaemia, Hypocalcaemia, Hyponatraemia, Fluid overload, Hyperuricaemia, Appetite decreased, Metabolic acidoses, Hyperlipidaemia, Hypercholesterolaemia, Hypertriglyceridaemia, Other electrolyte abnormalities
• Insomnia, Anxiety symptoms, Confusion and Disorientation, Depression, Depressed mood, Mood disorders and Disturbances, nightmare, hallucination, mental disorders
• Tremor, Headache, Seizures, Disturbances in consciousness, Paraesthesias and Dysaesthesias, Peripheral neuropathies, Dizziness, Writing impaired, nervous system disorders
• Blurred Vision, Photophobia, Eye disorders
• Tinnitus
• Ischaemic coronary artery disorders, Tachycardia
• Hypertension, Haemorrhage, Thrombembolic and ischaemic events, Peripheral vascular disorders, Vascular hypotensive disorders
• Dyspnoea, Parenchymal lung disorders, Pleural effusion, Pharyngitis, Cough, Nasal congestion and Inflammations
• Diarrhoea, Nausea, Gastrointestinal inflammatory conditions, Gastrointestinal ulceration and Perforation, Gastrointestinal Haemorrhages, Stomatitis and Ulceration, Ascites, Vomiting, Gastrointestinal and abdominal pains, Dyspeptic signs and Symptoms, Constipation, Flatulence, Bloating and Distension, Loose stools, Gastrointestinal signs and symptoms
• Cholestasis and Jaundice, Hepatocellular damage and Hepatitis, Cholangitis
• Pruritus, Rash, Alopecias, Acne, Sweating increased
• Arthralgia, Muscle spasms, Pain in extremity, Back pain
• Renal failure, Renal failure acute, Oliguria, Renal tubular necrosis, Nephropathy toxic, Urinary abnormalities, Bladder and urethral symptoms
• Asthenic conditions, Febrile disorders, Oedema, Pain and Discomfort, Body temperature perception disturbed

Less frequent side effects:

• Coagulopathies, Abnormal Coagulation and Bleeding analyses, Pancytopenia, Neutropenia Thrombotic Thrombocytopenic Purpura, Hypoprothrombinaemia, Thrombotic microangiopathy
• Hirsutism
• Ventricular arrhythmias and Cardiac arrest, Heart failures, Cardiomyopathies, Ventricular hypertrophy, Supraventricular arrhythmias, Palpitations
• Dehydration, Hypoproteinaemia, Hyperphosphataemia, Hypoglycaemia
• Psychotic disorder
• Coma, Central nervous system haemorrhages and Cerebrovascular accidents, Paralysis and Paresis, Encephalopathy, Speech and language abnormalities, Amnesia, Hypertonia, Myasthenia
• Cataract, Blindness
• Hypoacusis, Deafness neurosensory, Hearing impaired
• Pericardial effusion, Torsades de Pointes
• Infarction, Venous thrombosis deep limb, Shock
• Respiratory failures, Respiratory tract disorders, Asthma, Acute respiratory distress syndrome
• Ileus paralytic, Acute and Chronic pancreatitis, Gastrooesophageal reflux disease, Impaired gastric emptying, Subileus, Pancreatic pseudocyst
• Hepatitic artery thrombosis, Venoocclusive liver disease, hepatic failure, Bile duct stenosis
• Dermatitis, Photosensitivity, Toxic epidermal necrolysis (Lyell's syndrome), Stevens Johnson syndrome
• Joint disorders, Mobility decreased
• Anuria, Haemolytic uraemic syndrome, Nephropathy, Cystitis haemorrhagic Dysmenorrhoea and Uterine bleeding
• Multi-organ failure, Influenza like illness, Temperature intolerance, Chest pressure sensation, Feeling jittery, Feeling abnormal, Thirst, Fall, Chest tightness, Ulcer, Fat tissue increased
• Amylase increased, ECG investigations abnormal, Heart rate and Pulse investigations abnormal, Weight decreased, Blood lactate Dehydrogenase increased, Echocardiogram abnormal, Electrocardiogram QT prolonged

Side effects with frequency unknown:

• Pure red cell aplasia, Agranulocytosis, Haemolytic anaemia
• Optic neuropathy

If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Reporting of side effects

If you get side effects, talk to your doctor or pharmacist or nurse. You can also report side effects to SAHPRA via the “6.04 Adverse Drug Reaction Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8. By reporting side effects, you can help provide more information on the safety of GRAVTELL.

Store all medicines out of reach of children. Store at or below 25 °C. Do not remove blisters from carton until required for use. Store in original packaging. There are no special storage instructions for GRAVTELL. Do not use after the expiry date stated on the carton. Return all unused medicine to your pharmacist.