MAGNEVIST 0.5 mmol/ml BAYER MIDDLE EAST

Transcription

1 08-15 MAGNEVIST 0.5 mmol/ml BAYER MIDDLE EAST Solution for injection Dimeglumine gadopentetate, for use in infants, children and adults 1. WHAT MAGNEVIST IS AND WHAT IT IS USED FOR Magnevist is a contrast medium for magnetic resonance imaging. It is a diagnostic agent. Intravenous injection of Magnevist provides more conclusive diagnostic information compared with a scan obtained without contrast medium (plain scan). With Magnevist, high-contrast images can be obtained of areas of the brain in which the bloodbrain barrier is impaired or absent or of body regions with an altered blood supply (perfusion) or altered extracellular spaces. Magnevist is used in: magnetic resonance imaging of the head and the spinal canal (cranial and spinal magnetic resonance imaging [MRI]) It is used in particular for detection of tumours as well as for further differential diagnostic evaluation if there is suspicion of a tumour of the protective membranes around the brain and the spinal cord (meningioma), a tumour of a nerve (e.g. of the acoustic nerve; [acoustic] neurinoma), tumours or metastases invading (infiltrating) the tissues (e.g. glioma). To detect small tumours and/or tumours not distinguishable from healthy tissue (isointense), if there is suspicion of recurrence of a tumour after surgery or radiation therapy, for obtaining differentiated images of rare growths such as haemangioblastomas, ependymomas and small pituitary adenomas, for improved determination of the extent of a tumour in the case of tumours not arising in the brain. Additionally, in the case of MRI of the spinal cord: to distinguish between tumours located within (intramedullary) and outside (extramedullary) the spinal cord; to identify non-fluid-filled (solid) parts of an already diagnosed spinal cord cyst (syrinx); to determine the extent of a tumour in the spinal cord (intramedullary tumour). Whole body MRI Use of Magnevist is recommended in tumour diagnostics particularly for better distinction between malignant and benign tumours of the female breast, to distinguish between tumour and scar tissue after treatment of tumours of the female breast, to distinguish between tumour and scar tissue of the active and passive musculoskeletal system, to distinguish between different components of bone tumours (tumour tissue, necrotic tissue and inflammatory tissue), to distinguish between different types of liver tumours, to distinguish between tumours located within and outside the kidneys, to determine the extent and distinguish between different components of tumours of the female reproductive organs (uterine appendages). Use of Magnevist is also recommend for the following specific purposes: for accurate tissue sampling (biopsy) of bone tumours, to distinguish between a new slipped disk and scar tissue, for visualisation of acutely damaged heart muscle tissue. 2. WHAT YOU NEED TO KNOW BEFORE YOU ARE GIVEN MAGNEVIST You must not be given Magnevist if you are hypersensitive (allergic) to dimeglumine gadopentetate or any other ingredient of Magnevist. BAYER-MAGNEVIST 0.5 mmol/ml - p.1/7

2 BAYER-MAGNEVIST 0.5 mmol/ml - p.2/7 Use of Magnevist is contraindicated in patients with severely impaired kidney function (GFR <30 ml/ min/1.73 m²). When should Magnevist be used with particular care? Magnevist must not be injected directly into the spinal canal (intrathecally). Hypersensitivity All contrast agents for intravenous administration, thus also Magnevist, can cause allergy-like or other hypersensitivity reactions (known as idiosyncratic reactions). Such reactions can occur in the skin, the respiratory system or the cardiovascular system, including shock (see also section 4. Possible sideeffects ). Most of these reactions occur within half an hour after administration of the contrast medium. As with other contrast media of this class, delayed reactions can occur in rare cases (after hours or days). As is also the case with other diagnostic investigations with contrast media, patient monitoring is recommended subsequent to the investigation procedure. The risk of hypersensitivity reactions is increased in the following cases: - in patients with an allergic predisposition, - in patients with bronchial asthma; in these patients the risk of muscular spasms of the bronchial musculature (bronchospasms), in particular, is increased, - in patients with previous reactions to contrast media. Before injection of a contrast medium the patient should therefore be asked about any history of allergies (e.g. allergy to seafood, hay fever, hives (urticaria)), hypersensitivity to contrast media or bronchial asthma, and administration of antihistamines and/ or glucocorticoids before the examination should be considered. - in patients taking beta blockers Patients taking beta blockers may fail to respond to treatment with beta-agonists in the event of a hypersensitivity reaction. - in patients with diseases of the cardiovascular system In this patient group hypersensitivity reactions can be particularly serious. Deaths have also been reported. In patients with serious heart disease (e.g. severe congestive heart failure or coronary heart disease) in particular, circulatory reactions may be more severe. If hypersensitivity reactions occur (see also Possible side effects? ) administration of the contrast medium must be stopped immediately and - if necessary - specific treatment initiated via an intravenous access. It is advisable to use a flexible intravenous cannula or catheter (for rapid intravenous access) throughout the X-ray examination. In order to be able to respond immediately in an emergency appropriate drugs and instruments for emergency treatment (including endotracheal tube and ventilator) should be held ready. Impaired kidney function Magnevist is dialyzable. All patients, particularly patients over 65 years of age, should be checked for impaired kidney function by asking them about their previous medical history and/or performing appropriate laboratory tests. Use of Magnevist and other contrast media containing gadolinium in patients with severely impaired kidney function (GFR <30 ml/min/1.73 m²) has been associated with occurrence of cases of nephrogenic systemic fibrosis (NSF). Magnevist should therefore not be used in these patients (see section 2. You must not be given Magnevist ). The risk of development of NSF in patients with moderately impaired kidney function is not known. Magnevist should therefore be used with caution in these patients (GFR ml/min/1.73 m²). Newborns and small children In newborns and small children up to the age of 1 year Magnevist should only be used after careful consideration on account of the immaturity of the kidneys. Infants and small children In infants and small children an automatic administration system must not be used so as to avoid accidental overdose. In this patient group the required dose should be administered by hand. Cerebral seizures

3 BAYER-MAGNEVIST 0.5 mmol/ml - p.3/7 In patients with epilepsy or brain lesions there may be an increased risk of seizures during the examination such as has been observed rarely in association with administration of Magnevist. In these patients appropriate precautions should be taken (e.g. careful observation) and the necessary equipment and drugs should be held ready for use in the event of a seizure occurring. Use of Magnevist together with other medicines: It is known from the use of contrast media that hypersensitivity reactions occurring in patients taking beta blockers can be more severe (see also Section When should Magnevist be used with particular care? ). Influence on diagnostic tests Because of the pentameglumine pentetate contained in the contrast medium solution, serum iron values determined using complexometric methods (e.g. bathophenanthroline) may be too low for up to 24 hours after administration of Magnevist. Please tell your doctor if you are taking/using or have recently taken/used other medicines, even if these were non-prescription medicines. Using Magnevist together with food and drink You should not eat anything for two hours before the examination so as to avoid nausea and vomiting during the examination. Pregnancy and breast-feeding The safety of using Magnevist during pregnancy has not yet been conclusively demonstrated. The benefit of this examination should therefore be carefully weighed up against the potential risk. Very small amounts of Magnevist (not more than 0.04% of the administered dose) enter the breast milk. Experience to date has shown no evidence of a risk to the breast-fed infant. Driving and using machines No effects on the ability to drive and operate machines are known. If you have any further questions about using this medicine please ask your doctor or pharmacist. 3. HOW MAGNEVIST IS GIVEN Magnevist is for intravenous administration only. General: The usual precautions for magnetic resonance imaging (MRI), e.g. exclusion of cardiac pacemakers and ferromagnetic implants, must be observed. Between 0.14 Tesla and 1.5 Tesla the recommended doses are independent of the field strength of the magnet. The required dose of Magnevist is to be administered by intravenous injection only; it can also be given as bolus injection. Contrast-enhanced MRI can start immediately after administration. The contrast medium should be administered with the patient lying down, if possible, and the patient should be kept under supervision after the administration as the majority of adverse reactions occur within 30 minutes. Infants and small children (up to 2 years) In order to avoid accidental overdose, in this patient group the required dose should be administered by hand (see also section When should Magnevist be used with particular care? ). Anxiety Marked agitation, restlessness and pain can increase the risk of adverse reactions or intensify contrast-medium induced reactions. These patients may be given a sedative. What dosages of Magnevist are used? Cranial and spinal MRI The following dosage recommendations apply to adults, adolescents and children (including infants and small children): The administration of 0.2 ml Magnevist per kg body weight is usually sufficient to provide good contrast enhancement and to answer the relevant clinical questions. If strong clinical suspicion of pathology persists despite a normal scan a further injection of 0.2 ml Magnevist/kg, in adults even of 0.4 ml Magnevist/kg body weight, within 30 minutes with subsequent MRI may increase the informative value of the examination. To exclude metastases or in the case of tumour recurrences in adults the administration of 0.6 ml Magnevist/kg body weight often increases the diagnostic certainty.

4 BAYER-MAGNEVIST 0.5 mmol/ml - p.4/7 Maximum dose: 0.6 ml (adults) or 0.4 ml (children) Magnevist/kg body weight. Whole body MRI The following dosage recommendations apply to adults, adolescents and children: The administration of 0.2 ml Magnevist per kg body weight is usually sufficient to provide good contrast enhancement and to answer the relevant clinical questions. There is limited experience of use for whole body MRI in children under 2 years. In special cases, e.g. in the case of lesions with a poor blood supply and/or a small extracellular space, 0.4 ml Magnevist per kg body weight may be necessary for sufficient contrast, particularly when relatively weakly T1 weighted scanning sequences are used. To exclude lesions or renewed tumour development in adults administration of 0.6 ml Magnevist/kg body weight can increase the diagnostic yield. For visualisation of blood vessels in adults the maximum dose may be necessary, depending on the examination technique and the region to be examined. Maximum dose: 0.6 ml (adults) or 0.4 ml (children) Magnevist/kg body weight. Dosage recommendations / maximum dosages Normal dose in adults and 0.2 ml Magnevist/kg body weight children For difficult questions 0.4 ml Magnevist/kg body weight Maximum dose in children 0.6 ml Magnevist/kg body weight Maximum dose in adults If you have been given more than the permitted amount of Magnevist (more than 0.3 mmol/kg) No signs of poisoning after an overdose have so far been observed or reported during clinical use. In the case of accidental intravascular overdose the following symptoms are conceivable on account of the increased salt content (hyperosmolality) of the solution: Systemic: increased pressure in the pulmonary arteries, increased blood volume (hypervolaemia), increased urine volume (osmotic diuresis), fluid loss (dehydration). Local: vascular pain. In patients with poor kidney function monitoring of kidney function should be performed. In the case of accidental overdose Magnevist can be removed from the body by using an artificial kidney machine (haemodialysis). Poisoning due to accidental oral intake of the contrast medium is extremely unlikely in view of Magnevist s extremely low gastrointestinal absorption rate (<1%). If you have any further questions about using this medicine please ask your doctor or pharmacist. 4. POSSIBLE SIDE-EFFECTS Like all medicines, Magnevist can have side-effects but these need not necessarily occur in every patient. The following criteria were used as the basis for the frequency specifications concerning side effects (check refs on this one): Very common: occurring in more than 1 treated patients in 10 Common: 1 to 10 patients treated out of 100 Uncommon 1 to 10 patients treated out of 1000 Rare: 1 to 10 patients treated out of 10,000 Very rare: less than 1 treated patient in 10,000 Significant side-effects or signs you should look out for: Side effects occurring in association with the use of Magnevist are usually of mild to moderate severity and of short duration. However, serious and life-threatening reactions, including deaths, have also been observed. Anaphylactic reactions, which can occur independently of the administered dose and the route of administration, can be first signs of beginning shock. The most commonly observed reactions are nausea, vomiting, headache, dizziness, and various types of reactions at the injection site (e.g. pain, sensation of cold, sensation of heat). Delayed reactions are rare (see also section When should Magnevist be used with particular care? ). The estimations of frequency are based both on data obtained from clinical studies before marketing authorisation was granted as well as on data from spontaneous reports received afterwards.

5 BAYER-MAGNEVIST 0.5 mmol/ml - p.5/7 None of the individual undesirable effects resulted in a frequency greater than Occasional. On the basis of experiences gathered in connection with administration to more than 11,000 patients in clinical studies, the undesirable effects listed in the following table have been judged to be drug-related. Uncommon ( 1/1000, <1/100) Organ system Immune system Rare (<1/1000) anaphylactoid reactions/allergic reactions/ anaphylactoid shock, mild swelling of the skin (Quincke's oedema), pink eye (conjunctivitis)*, cough*, itching (pruritus)*, runny nose (rhinitis), sneezing*, hives (urticaria)*, bronchial muscle cramps (bronchospasm) and cramps of the muscles around the voice box (laryngospasm), swelling of the voice box or of the throat (laryngeal or pharyngeal oedema), low blood pressure (hypotension), shock Blood temporary changes in serum iron and serum bilirubin levels Nervous system dizziness*, headaches*, disturbances of sensation (paraes- disorientation*, confusion, restlessness (agitation), thesia)* disturbances of vision, hearing, speech or smell, seizures (convulsions)*, trembling (tremor)*, ear pain, unusual weakness (asthenia)*, coma, sleepiness (somnolence), burning sensation Eyes watering eyes, eye pain Cardiovascular system clinically relevant temporary disturbances of heart rate (increase in heart rate (tachycardia*, reflex tachycardia), drop in heart rate (bradycardia)) and hypotention, hypertension, disturbances of cardiac rhythm (arrhythmia)* and disturbances of cardiac function as well as cardiac arrest Uncommon ( 1/1000, <1/100) Vascular system Respiratory system Gastrointestinal tract queasiness*, vomiting*, disorders of the sense of taste (dysgeusia)* Rare (<1/1000) circulatory reactions possibly accompanied by widening of the small blood vessels (peripheral vasodilatation)*, a subsequent fall in blood pressure (hypotension) and fainting (syncope), increase in heart rate (reflex tachycardia), shortness of breath*, restlessness (agitation), confusion and a decrease in the oxygen content of the blood (cyanosis) and sometimes leading to loss of consciousness, inflammation of the vein - in some cases following a blood clot (thrombophlebitis)* temporary changes in respiratory rate (increase or drop in respiratory rate), shortness of breath*, difficulty breathing*, cough*, respiratory arrest, (pulmonary oedema, throat irritations/feeling of constriction in the throat* pharyngolaryngeal pain/ complaints in the pharynx*, sneezing* stomach-ache*, diarrhoea*, dry mouth*, saliva flow, toothache*, soft tissue pain and unfamiliar unexplained sensations (paraesthesia) in the mouth* Hepatobiliary system temporary changes (increase) in liver enzyme values, elevated blood bilirubin Skin and subcutaneous tissue mild skin swelling (Quincke s oedema), erubescences* and reddening (flush)* with widening of the blood vessels (vasodilatation)*, hives (urticaria)*, itching (pruritus)* and skin rash (exanthemas)* Muscular and skeletal system pain in the limbs (extremities)*

6 BAYER-MAGNEVIST 0.5 mmol/ml - p.6/7 Uncommon ( 1/1000, <1/100) Kidneys and urinary tract General symptoms sensation of heat*, sensation of cold*, pain* Rare (<1/1000) urinary incontinence, an urgent need to pass urine, elevated serum creatinine values and acute kidney failure in patients who already have poor kidney function back pain, joint pain, pain in the thoracic cavity (chest pain)*, discomfort*, chills, sweating, vasovagal reactions, changes (increase or drop) in body temperature, fever*, swollen face*, peripheral swellings (oedemas)*, fatigue*, thirst* and local reactions in the area of the injection site Leaking into the tissue (extravasation) with local pain*, sensation of cold*, mild sensation of heat *and swelling (oedemas*), inflammation, tissue destruction (tissue necrosis), inflammation of lthe vein (phlebitis), phlebitis in some cases after a blood clot (thrombophlebitis), disturbances of sensation (paraesthesia)*, swelling*, irritation*, discharge of blood from the vessels into the surrounding tissue (haemorrhagia)* reddening of the skin (erythema)*, complaints* * Undesirable effects from clinical studies Delayed and transient inflammation-like reactions such as fever, chills and an increase in C-reactive protein were frequently observed among patients with renal insufficiency requiring dialysis who received Magnevist. These patients had undergone MRI investigation with Magnevist on the day before haemodialysis. Cases of nephrogenic systemic fibrosis (NSF) have been reported in association with use of Magnevist. Please inform your doctor or pharmacist if any of the listed side-effects becomes particularly troublesome or if you experience side-effects which are not mentioned in this leaflet. 5- HOW MAGNEVIST SHOULD BE STORED Keep medicines out of the reach of children. Do not use after the expiry date printed on the container/pack after Use before. Storage conditions Store below 30 C Vials, bottles and pre-filled syringes should be stored in their cartons in order to protect the contents from light. Note on stability after opening Once the container has been opened Magnevist remains stable for a duration of 24 hours. This period is based on the possibility of microbiological contamination and not on the physico-chemical stability. From the microbiological point of view the preparation should be used at once unless the container is opened in such a way that a risk of microbial contamination can be ruled out. If the preparation is not used at once the user is responsible for the duration and conditions of storage before use. Date of revision of the text: February FURTHER INFORMATION What Magnevist contains The active ingredient is dimeglumine gadopentetate. The inactive ingredients are: pentameglumine pentetate, meglumine and water for injections. Appearance of Magnevist and contents of the pack: Magnevist is a clear, particle-free solution for injection. Magnevist is supplied in the following packs: Vials of 10 ml, 15 ml or 20 ml. 5 pre-filled syringes containing 10, 15 or 20 ml. 10 vials of 5, 10, 15, 20 or 30 ml. 10 bottles of 100 ml. Manufacturer Bayer Schering Pharma AG D Berlin Magnevist is a contrast medium which is excreted by the kidneys and was developed specially for magnetic resonance imaging. Magnevist is eliminated from the body practically completely within 24 hours.

7 BAYER-MAGNEVIST 0.5 mmol/ml - p.7/7 Detailed information on this medicine which is required by the doctor is available in special publications. The following information is only for doctors and medical personnel: 1 ml aqueous solution for injection contains 469 mg dimeglumine gadopentetate (equivalent to mg gadolinium). If the preparation is to be given with an automatic administration system the suitability of the system for the intended use must be documented by the medical device manufacturer. The instructions for use of the medical devices must always be observed. In infants and small children use of an automatic administration system is not allowed. Concentration of dimeglumine gadopentetate (mg/ml) (mmol/ml) Content of dimeglumine gadopentetate in (g) 5-ml vial ml vial/pre-filled syringe ml vial/pre-filled syringe ml vial/pre-filled syringe ml vial ml bottle 46.9 Physicochemical / physical properties ph Viscosity (mpa.s or cp) at 20 C at 37 C Osmolality (mosm/kg H 2 O) 1960 Specific gravity (g/ml) at 20 C at 37 C Notes on use Notes regarding use of the vials Magnevist should not be taken up into the syringe until immediately prior to the examination. The rubber plug may not be pierced through more than once. Any contrast medium solution not used in one examination must be discarded. The following instructions apply to use of the prefilled syringe: The ready-to-use syringe should not be taken from the pack and prepared for the injection until immediately prior to the examination. The sealing cap should not be removed until immediately before the ready-to-use syringe is used. Any contrast medium solution not used during an examination procedure must be discarded.