1199505 LBN Posology Method of administration - As known from the use of iodinated contrast media, Interaction with other medicaments and other Adults hypersensitivity reactions can be aggravated in forms of interaction The product is indicated for intravenous 1199505 patients on beta-blockers, and particularly in the No interactions with other medicinal products have MRI of brain and spine administration only. presence of bronchial asthma. These patients been observed. Formal drug interaction studies have Infusion rate: 3-5 mL/min (higher infusion rates The recommended dose is 0.1 mmol/kg BW, i.e. may be refractory to standard treatment of not been carried out. up to 120 mL/min, i.e. 2 mL/sec, may be used for 0.2 mL/kg BW. In patients with brain tumors, an hypersensitivity reactions with beta-agonists. angiographic procedures). Beta-blockers, vasoactive substances, angiotensin- TM additional dose of 0.2 mmol/kg BW, i.e. 0.4 mL/kg - Befor e any contrast medium is injected, the patient converting enzyme inhibitors, angiotensin receptor Intravascular administration of contrast media BW, may improve tumor characterisation and should be questioned for a history of allergy antagonists: These medicinal products induce should, if possible, be done with the patient lying facilitate therapeutic decision making. (e.g. fish and seafood allergy, hay fever, hives), decreased efficacy of cardiovascular compensation down. After the administration, the patient should 0.5 mmol/mL Whole body MRI (including lesions of the liver, sensitivity to contrast media and bronchial asthma mechanisms of blood pressure changes. The be kept under observation for at least half an kidneys, pancreas, pelvis, lungs, heart, breast, as the reported incidence of adverse reactions application of contrast media may increase the Solution for injection hour, since experience shows that the majority of and musculoskeletal system) to contrast media is higher in patients with these incidence of hypersensitivity reactions in patients Glass vial undesirable effects occur within this time. gadoteric acid The recommended dose is 0.1 mmol/kg BW, conditions and premedication with antihistamines taking beta-blockers (see Special warnings and i.e. 0.2 mL/kg BW to provide diagnostically adequate For single patient use only, any unused solution and/or glucocorticoids may be considered. precautions for use). contrast. should be discarded. - During the examination, supervision by a Fertility, pregnancy and lactation Name of the proprietary medicinal product For angiography: The recommended dose for Paediatric population (0-18 years). Depending on physician is necessary. If hypersensitivity intravenous injection is 0.1 mmol/kg BW, i.e. the amount of Clariscan to be given to the child, it reactions occur, administration of the contrast Pregnancy Clariscan 0.5 mmol/ mL solution for injection 0.2 mL/kg BW to provide diagnostically adequate is preferable to use Clariscan vials with a single use medium must be discontinued immediately and, There are no data from the use of gadoteric acid in Clariscan 0.5 mmol/ mL solution for injection in contrast. syringe of a volume adapted to this amount in order if necessary, specific therapy instituted. A venous pregnant women. Animal studies do not indicate pre-filled syringe In exceptional circumstances (e.g. failure to gain to have a better precision of the injected volume. access should thus be kept during the entire direct or indirect harmful effects with respect to In neonates and infants the required dose should be reproductive toxicity (see Preclinical safety data). Qualitative and quantitative composition satisfactory images of an extensive vascular territory) examination. To permit immediate emergency administration of a second consecutive injection administered by hand. countermeasures, appropriate drugs (e.g. Clariscan should not be used during pregnancy 1 mL solution for injection contains 279.3 mg of 0.1 mmol/kg BW, i.e. 0.2 mL/kg BW may be Image acquisition adrenaline and antihistamines), an endotracheal unless the clinical condition of the woman requires gadoteric acid*(as gadoterate meglumine) justified. However, if the use of 2 consecutive doses Contrast enhanced MRI may be initiated immediately tube and a respirator should be ready at hand. use of gadoteric acid. equivalent to 0.5 mmol of Clariscan are anticipated prior to commencing after administration of the agent. Optimal imaging: Impaired renal function Breastfeeding angiography, the use of 0.05 mmol/kg BW Gadolinium containing contrast agents are Active ingredient Content per mL within 45 minutes after injection. Optimal image Prior to administration of Clariscan it is (i.e. 0.1 mL/kg BW) for each dose may be of benefit, sequence: T1-weighted recommended that all patients are screened for excreted into breast milk in very small amounts Tetraxetan (DOTA) 202.46 mg depending on the imaging equipment available. renal dysfunction by obtaining laboratory tests. (see Preclinical safety data). At clinical doses, no Contraindications effects on the infant are anticipated due to the small Gadolinium oxide 90.62 mg Special populations There have been reports of nephrogenic systemic Hypersensitivity to gadoteric acid, to meglumine or amount excreted in milk and poor absorption from * Gadoteric acid: gadolinium complex with1,4,7,10 fibrosis (NSF) associated with use of some Impaired renal function to any medicinal products containing gadolinium. the gut. tetraazacyclododecane N,N’,N”,N’’’ tetraacetic acid gadolinium-containing contrast agents in patients Clariscan should only be used in patients with severe Special warnings and precautions for use Continuing or discontinuing breast feeding for a (tetraxetan (DOTA)) renal impairment (GFR < 30 mL /min/1.73m2) and in with acute or chronic severe renal impairment period of 24 hours after administration of Clariscan, Clariscan is administered strictly by intravenous 2 For the full list of excipients, see Pharmaceutical (GFR < 30 mL/min/1.73m ). Patients undergoing liver patients in the perioperative liver transplantation injection only. In the event of extravasation should be at the discretion of the doctor and particulars period after careful risk/benefit assessment and transplantation are at particular high risk since the lactating mother. local intolerance reactions may be observed, incidence of acute renal failure is high in this group. if the diagnostic information is essential and not necessitating short term local treatment. Fertility Pharmaceutical form available with non-contrast enhanced MRI As there is a possibility that NSF may occur with Clariscan must not be administered by subarachnoid Clariscan, it should therefore only be used in patients There are no clinical data available with regard to Solution for injection. (see Special warnings and precautions for use). If it effects on fertility. Solution for injection in pre-filled syringe. is necessary to use Clariscan the dose should not (or epidural) injections. with severe renal impairment and in patients in Clear, colourless to slightly yellow solution. exceed 0.1 mmol/kg body weight. Appropriate facilities should be readily available for the perioperative liver transplantation period after Effects on ability to drive and use machines careful risk/benefit assessment and if the diagnostic More than one dose should not be used during a coping with any complication of the procedure, as No studies on the effects on the ability to drive and Contrast medium 279.3 mg/mL scan. Because of the lack of information on repeated well as for emergency treatment of severe reaction information is essential and not available with concentration equivalent to 0.5 mmol/mL non-contrast enhanced MRI. use machines have been performed. Ambulant administration, Clariscan injections should not be to the contrast agent itself (e.g. hypersensitivity, patients while driving vehicles or operating Osmolality at 37 °C 1350 mOsm.kg-1 repeated unless the interval between injections is at seizures). Haemodialysis shortly after Clariscan administration machinery should take into account that nausea Viscosity at 20 °C 3.0 mPa.s least 7 days. The usual precaution for MRI examination should may be useful at removing Clariscan from the body. may incidentally occur. Viscosity at 37 °C 2.1 mPa.s Elderly (aged 65 years and above) be taken, such as exclusion of patients with There is no evidence to support the initiation of Undesirable effects pH value 6.5 – 8.0 No dosage adjustment is considered necessary. pacemakers, vascular clips, infusion pumps, nerve haemodialysis for prevention or treatment of NSF in Caution should be exercised in elderly patients patients not already undergoing haemodialysis. Side effects in association with the use of gadoteric Clinical particulars stimulators, cochlear implants, or suspected (see Special warnings and precautions for use). intracorporeal metallic foreign bodies, particularly Elderly acid are usually mild to moderate in intensity and Indications Impaired hepatic function in the eye. As the renal clearance of gadoteric acid may be impaired transient in nature. A sensation of heat, cold and/or in the elderly, it is particularly important to screen pain at the injection site is the most frequently This medicinal product is for diagnostic use only. The adult dose applies to these patients. Caution is Hypersensitivity recommended, especially in the case of perioperative patients aged 65 years and older for renal dysfunction. observed reactions. Clariscan is a contrast agent indicated for liver transplantation period (see above impaired - Hypersensitivity reactions can occur, including Paediatric population During clinical trials, headache and paresthesia enhancement of the contrast in Magnetic Resonance renal function). life-threatening (see Undesirable effects) Neonates and infants were very commonly observed (>1/10), and nausea, Imaging for a better visualization/delineation. Hypersensitivity reactions may be either allergic Paediatric population (aged 0-18 years) Due to immature renal function in neonates up vomiting and skin reactions such as erythematous Adult population and paediatric population (described as anaphylactic reactions when to 4 weeks of age and infants up to 1 year of age, rash and pruritus were commonly observed Encephalic and Spinal MRI, Whole body MRI: serious) or non-allergic. They can be either (0-18 years): The recommended and maximum dose of Clariscan Clariscan should only be used in these patients after (>1/100 to <1/10). - lesions of the brain, spine, and surrounding immediate (less than 60 minutes), or delayed careful consideration. is 0.1 mmol/kg body weight. More than one dose (up to 7 days).Anaphylactic reactions can occur Since post-marketing, the most commonly reported tissues should not be used during a scan. In neonates and infants the required dose should be adverse reactions following administration of - whole body MRI (see Posology and method of immediately and can be fatal. Hypersensitivity administered by hand. Due to immature renal function in neonates up reactions may be independent of the dose, may gadoteric acid are nausea, vomiting, pruritus and administration) CNS disorders to 4 weeks of age and infants up to 1 year of age, occur after even the first dose of the product, and hypersensitivity reactions. Use for whole body is not recommended in children Like with other gadolinium containing contrast less than 6 months Clariscan should only be used in these patients after are often unpredictable. In hypersensitivity reactions, the reactions most careful consideration, at a dose not exceeding agents special precaution is necessary in patients frequently observed are skin reactions, which can be In adults only: - There is always a risk of hypersensitivity with a low threshold for seizures. 0.1 mmol/kg body weight. More than one dose regardless of the dose injected. localized, extended or generalized. - lesions or stenoses of the non-coronary arteries should not be used during a scan. Because of the Precautionary measures should be taken, e.g. close These reactions occur most often immediately (MR Angiography). lack of information on repeated administration, - Patients who have already experienced a reaction monitoring. All equipment and drugs necessary to (during the injection or within one hour after the during previous administration of a gadolinium- counter any convulsions, which may occur, must be Posology and method of administration Clariscan injections should not be repeated unless start of injection) or sometimes delayed (one hour the interval between injections is at least 7 days. containing MRI contrast agent present an made ready for use beforehand. to several days after injection), presenting as skin This medicinal product should only be administered Use for whole body MRI is not recommended in increased risk of experiencing another reaction Cardiovascular disease reactions in this case. by trained healthcare professionals with technical on subsequent administration of the same children less than 6 months of age. In patients with severe cardiovascular disease Immediate reactions include one or more effects, expertise in performing and interpreting gadolinium product, or possibly other products, and are Clariscan should only be administered after careful enhanced MRI. Angiography: Clariscan is not recommended for therefore considered to be at high risk. which appear simultaneously or sequentially, angiography in children under 18 years of age due benefit assessment because only limited data are which are most often cutaneous, respiratory to insufficient data on its efficacy and safety in this - The injection of gadoteric acid may aggravate available so far. and/or cardiovascular reactions. Each sign may be a indication (see Special warnings and precautions for symptoms of an existing asthma. In patients Patient preparation warning sign of a starting shock and go very rarely use). with asthma unbalanced by the treatment, the Nausea and vomiting are known possible to death. decision to use gadoteric acid must be made undesirable effects when using MRI contrast agents. after careful evaluation of the risk/benefit ratio. The patient should therefore refrain from eating for 2 hours prior to the investigation. Isolated cases of nephrogenic systemic fibrosis The following adverse reactions were reported with Biotransformation Polypropylene bottles of 50 mL (filled to 50 mL) and (NSF) have been reported with gadoteric acid, other intravenous contrast agents for MRI. No metabolites were detected. 100 mL (filled to 100 mL), closed with halobutyl most of which were in patients co-administered It is therefore possible that they also occur during Elimination rubber stopper held in place by a plastic screw cap other gadolinium-containing contrast agents examination with Clariscan Gadoteric acid is eliminated rapidly (89% after with pull-off ring and tamper proof ring. Packed in (see Special warnings and precautions for use). outer box of 1 and 10 units. System Organ Adverse reaction 6 h, 95% after 24 h) in unchanged form through the The adverse reactions are listed in the table below by Class kidneys by glomerular filtration. Excretion via the Not all pack sizes may be marketed. SOC (System Organ Class) and by frequency with the feces is negligible. The elimination half-life amounts Blood and Haemolysis Instructions for use/handling following guidelines: very common (≥1/10), common to about 1.6 hours in patients with a normal renal lymphatic system (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), function. For single use. disorders rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), Special characteristics in patients with renal The solution for injection should be inspected visually not known (cannot be estimated from the available Psychiatric Confusion prior to use. Only clear solutions free of visible disorders impairment data). The data presented are from clinical trials In renally impaired patients, the elimination half- particles should be used. Vials and bottles: - Prepare Eye disorders Blindness transient, eye pain when available, or from an observational study life was increased to approximately 5 hours for a a syringe with a needle. For vials, remove the plastic involving 82,103 patients. Ear and labyrinth Tinnitus, ear pain creatinine clearance between 30 and 60 mL/min and disk. For polypropylene bottles remove the plastic disorders approximately 14 hours for a creatinine clearance screw cap or top plastic lid by pulling the top ring. System Organ Frequency : adverse reaction Respiratory, Asthma between 10 and 30 mL/min. After cleaning the stopper with a pad soaked in Class thoracic and alcohol, puncture the stopper with the needle. Immune system Uncommon: hypersensitivity, mediastinal Preclinical safety data Withdraw the quantity of product required for the disorders anaphylactic reaction, disorders Non-clinical data reveal no special hazard for examination and inject it intravenously. anaphylactoid reaction Gastrointestinal Dry mouth humans based on conventional studies of safety Pre-filled syringes: Inject intravenously the quantity disorders Psychiatric Very rare: agitation, anxiety pharmacology, repeated dose toxicity, genotoxicity of product required for the examination. disorders Skin and Dermatitis bullous or toxicity to reproduction. The remaining contrast medium in the vial/bottle, subcutaneous Animal studies have shown negligible secretion the connecting lines and all disposable components Nervous system Very common: paraesthesia, tissue disorders (less than 1% of the dose) of gadoteric acid in in the injector system must be discarded after the disorders headache Renal and urinary Urinary incontinence, renal maternal milk. examination Rare: dysgeusia disorders tubular necrosis, renal failure Pharmaceutical Particulars The peel-off tracking label on the syringes/vials/ Very rare: coma, convulsion, acute syncope, presyncope, dizziness, bottles should be stuck onto the patient record Investigations Electrocardiogram PR List of Excipients parosmia, tremor to enable accurate recording of the gadolinium prolongation, blood iron Meglumine contrast agent used. The dose used should also be Eye disorders Very rare: conjunctivitis, ocular increased, blood bilirubin Tetraxetan (DOTA) recorded. If electronic patient records are used, the hyperaemia, vision blurred, increased, serum ferritin Water for injections name of the product, the batch number and the dose lacrimation increased, eyelid increased, liver function test should be entered into the patient record. oedema abnormal Incompatibilities Any unused medicinal product or waste material Cardiac disorders Very rare: cardiac arrest, Adverse reaction in children In the absence of compatibility studies, this should be disposed of in accordance with local bradycardia, tachycardia, Adverse events related to gadoteric acid are medicinal product must not be mixed with other requirements. medicinal products. arrhythmia, palpitations uncommon in children. The expectedness of these Marketing Authorization Holder and Vascular disorders Very rare: hypotension, events is identical to that of the events reported in Shelf life Manufactured by: hypertension, vasodilatation, adults. GE Healthcare AS 3 years pallor Reporting of suspected adverse reactions: Nycoveien 1 Reporting suspected adverse reactions after Bottles P.O. Box 4220 Nydalen Respiratory, Very rare: respiratory authorisation of the medicinal product is important. NO-0401 OSLO thoracic and arrest, pulmonary oedema, Chemical and physical in-use stability has been It allows continued monitoring of the benefit/risk NORWAY mediastinal bronchospasm, laryngospasm, demonstrated for 48 hours at room temperature. balance of the medicinal product. Healthcare disorders pharyngeal oedema, dyspnoea, From a microbiological point of view, the product Date of revision of the text professionals are asked to report any suspected nasal congestion, sneezing, should be used immediately. If not used immediately, adverse reactions via the national reporting system. January 2021 cough, dry throat in-use storage times and conditions prior to use are Overdose the responsibility of the user and would normally not Gastrointestinal Common: nausea, vomiting be longer than 24 hours at 2 to 8° C, unless opening Clariscan is a trademark of GE Healthcare. disorders Very rare: diarrhoea, abdominal Clariscan can be removed by haemodialysis. has taken place in controlled and validated aseptic GE and GE Monogram are trademarks of the pain, salivary hypersecretion However, there is no evidence that haemodialysis conditions. is suitable for prevention of nephrogenic systemic General Electric Company. Skin and Common: pruritus, erythema, fibrosis (NSF). Special precautions for storage subcutaneous rash tissue disorders Rare: urticaria, hyperhidrosis Pharmacological properties Vials/bottles: Store below 30°C Very rare: eczema, angioedema Pre-filled syringes: Do not freeze Not known: nephrogenic Pharmacodynamic Properties Nature and contents of container systemic fibrosis Pharmacotherapeutic group: paramagnetic contrast Clariscan is filled in the following containers: Musculoskeletal Very rare: muscle contracture, media for magnetic resonance imaging and connective muscular weakness, back pain ATC code: V08 CA 02 Vials tissue disorders This product has no specific pharmacodynamic Glass vials (type I, colourless) of 10 mL (filled to 5 or activity. 10 mL) and 20 mL (filled to 15 or 20 mL), closed General Common: feeling hot, feeling with halobutyl rubber stopper sealed with caps of disorders and cold, injection site pain Gadoteric acid is a paramagnetic agent for Magnetic aluminium with coloured plastic top. Packed in outer administration Very rare : malaise, thoracic Resonance Imaging (MRI). The contrast-enhancing box of 1 and 10 units. site conditions pain, chest discomfort, fever, effect is mediated by gadoteric acid which is an ionic chills, face oedema, asthenia, gadolinium complex composed out of Gadolinium Pre-filled syringes injection site discomfort, oxide and 1,4,7,10 tetraazacyclododecane- Polymer syringe: Poly-cycloolefin, Crystal Clear injection site reaction, injection N,N’,N’’,N’’’ tetraacetic acid (DOTA), and present as Polymer (CCP) syringe of 20 mL (filled to 10, 15, and site oedema, injection site meglumine salt. 20 mL), label graduated per mL with tip cap and extravasation, injection halobutyl plunger stopper attached to a plunger rod. Pharmacokinetic properties site inflammation (in case Packed in outer box of 1 and 10 units. of extravasation), injection Distribution Bottles site necrosis (in case of After intravenous injection, Clariscan is distributed in Glass bottles (type I, colourless) of 50 mL (filled extravasation), superficial the extracellular fluids of the body. The distribution to 50 mL) and 100 mL(filled to 100 mL), closed phlebitis volume was approx. 18 L which is approximately with halobutyl rubber stopper sealed with caps of equal to the volume of extra-cellular fluid. Gadoteric aluminium with coloured plastic top. Investigations Very rare: decreased oxygen acid does not bind to proteins like serum albumin. Packed in outer box of 1 and 10 units. saturation Gadoteric acid is poorly excreted in the milk and crosses slowly through the placenta barrier. 1199505 LBN