Timely, innovative solutions for your Stroke program

VISIPAQUE Prescribing Information UKJB6704 – Revised December 2015PRESCRIBING INFORMATION VISIPAQUE™ Injection (iodixanol)Please refer to full national Summary of Product Characteristics (SPC) before prescribing. Indications and approvals may vary in different countries. Further information available on request. PRESENTATION An isotonic, aqueous solution containing iodixanol, a non-ionic, dimeric contrast medium, available in two strengths containing either 270 mg or 320 mg iodine per ml. INDICATIONS For diagnostic use only X-ray contrast medium for use in adults in cardioangiography, cerebral angiography (conventional), peripheral arteriography (conventional), abdominal angiography (i.a. DSA), urography, venography, CT enhancement, studies of the upper gastrointestinal tract, arthrography and hysterosalpingography (HSG) Lumbar, thoracic and cervical myelography in adults. In children for cardioangiography, urography, CT enhancement and studies of the upper gastrointestinal tract. DOSAGE AND ADMINISTRATION Adults and children: Dosage varies depending on the type of examination, age, weight, cardiac output, general condition of patient and the technique used (see SPC and package leaflet). The product is for intravenous, intra-arterial and intrathecal use, and for use in body cavities. CONTRAINDICATIONS Manifest thyrotoxicosis. Hypersensitivity to the active substance or to any of the excipients. WARNINGS AND PRECAUTION Hypersensitivity: A positive history of allergy, asthma, or reaction to iodinated contrast media indicates need for special caution. Premedication with corticosteroids or H1 and H2 antagonists might be considered in these cases. Although the risk of serious reactions with VISIPAQUE is regarded as remote, iodinated contrast media may provoke serious life-threatening hypersensitivity reactions, including fatal anaphylactic/anaphylactoid reactions. Therefore the necessary drugs and equipment must be available for immediate treatment. Patients should be observed closely for at least 30 minutes following administration of contrast medium, however delayed reactions may occur. Use of beta blockers may be a risk factor for anaphylactoid reactions and patients may present with atypical symptoms of hypersensitivity which may be misinterpreted as a vagal reaction. Coagulopathy: Non-ionic iodinated contrast media inhibit blood coagulation in vitro, less than ionic contrast media. When performing vascular catheterisation procedures one should pay meticulous attention to the angiographic technique and flush the catheter frequently (e.g. with heparinised saline) so as to minimize the risk of procedure-related thrombosis and embolism. Serious, rarely fatal, thromboembolic events causing myocardial infarction and stroke have been reported during angio-cardiographic procedures with both ionic and non-ionic contrast media. Advanced life support facilities should be readily available. There is a risk of thromboembolism in patients with homocystinuria. Hydration: Ensure adequate hydration before and after examination especially in patients with multiple myeloma, renal dysfunction, diabetes mellitus, paraproteinemias, the elderly, children and infants. Cardio-circulatory reactions: Care should be taken in patients with serious cardiac disease and pulmonary hypertension as they may develop hemodynamic changes or arrhythmias. Rarely severe life-threatening reactions and fatalities of cardiovascular origin such as cardiac-, cardio-respiratory arrest and myocardial infarction have occurred. CNS: In intravascular application, care should be taken in patients with acute stroke, or acute intracranial bleeding, in patients with altered blood brain barrier, cerebral oedema or acute demyelinisation. Renal and Hepatic: Particular care is required in patients with severe disturbance of both renal and hepatic function as they may have significantly delayed contrast medium clearance. Major risk factor for contrast medium-induced nephropathy is underlying renal dysfunction. Diabetes mellitus and the volume of iodinated

contrast medium administered are contributing factors in the presence of renal dysfunction. Additional concerns are dehydration, advanced arteriosclerosis, poor renal perfusion and the presence of other factors that may be nephrotoxic, such as certain medications or major surgery. For haemodialysis patients, correlation of time of contrast media injection with the haemodialysis session is unnecessary. DM and Metformin: To prevent lactic acidosis in diabetic patients treated with metformin, administration of metformin should be discontinued at the time of administration of contrast medium and withheld for 48 hours and reinstituted only after renal function has been re-evaluated and found to be normal. (Refer to SPC). Special care should also be taken in patients with hyperthyroidism, serious cardiac disease, pulmonary hypertension, arteriosclerosis, patients predisposed to seizures (acute cerebral pathology, tumours, epilepsy, alcoholics and drug addicts), and patients with myasthenia gravis or phaeochromocytoma. One should also be aware of the possibility of inducing transient hypothyroidism in premature infants receiving contrast media. After intrathecal use the patient should rest with head and thorax elevated for one hour and outpatients should not be alone for 24 hours. All iodinated contrast media may interfere with laboratory tests for thyroid function, bilirubin, proteins, or inorganic substances (e.g. iron, copper, calcium, and phosphate). An increased risk of delayed reactions (flu-like or skin reactions) has been associated with patients treated with interleukin-2 up to two weeks previously. PREGNANCY AND LACTATION The safety of VISIPAQUE in pregnancy has not been established. The product should not be used in pregnancy unless benefit outweighs risk and it is considered essential by the physician. Thyroid function should be checked in neonates during the first week of life, following administration of iodinated contrast agents to the mother during pregnancy and repeat testing of thyroid function is recommended at 2 to 6 weeks of age, particularly in low birth weight newborn or premature newborn. Contrast media are poorly excreted in breast milk and minimal amounts are absorbed by the intestine. Breast feeding may be continued normally. ABILITY TO DRIVE AND USE MACHINES It is not advisable to drive or use machines for one hour after injection or for 24 hours after intrathecal procedure. UNDESIRABLE EFFECTS Undesirable effects are usually mild to moderate, and transient in nature. Serious reactions and fatalities are only seen on very rare occasions, these may include acute-on-chronic renal failure, acute renal failure, anaphylactic or anaphylactoid shock, hypersensitivity reaction followed by cardiac reactions (Kounis’ syndrome), cardiac or cardio-respiratory arrest and myocardial infarction. Hypersensitivity may present as respiratory or cutaneous symptoms like dyspnoea, rash, erythema, urticaria, pruritus, skin reactions, angioneurotic oedema, hypotension, fever, laryngeal oedema, bronchospasm or pulmonary oedema. In patients with autoimmune diseases cases of vasculitis and SJS-like syndrome were observed. They may occur immediately after injection or up to a few days later, irrespective of dose, and mild symptoms may be the first signs of serious anaphylactoid reaction/shock. Intravascular use: Uncommon: hypersensitivity, headache, flushing, nausea, vomiting, rash, pruritus, urticaria, feeling hot, chest pain. Rare: dizziness, arrhythmia (including bradycardia, tachycardia), myocardial infarction, hypotension, cough, pain, discomfort, shivering (chills), pyrexia, administration site reactions including extravasation. Very rare: agitation, anxiety, cerebrovascular accident, sensory abnormalities including taste, amnesia, paraesthesia, syncope, cardiac arrest, transient cortical blindness, visual impairment, hypertension, ischaemia, dyspnoea, abdominal pain/discomfort, angioedema, erythema, back pain, muscle spasm, impairment of renal function including acute renal failure, feeling cold, asthenic conditions (e.g. malaise, fatigue). Frequency unknown: thrombocytopenia, anaphylactoid reaction, anaphylactoid shock, confusional state, coma,

motor dysfunction, disturbances in consciousness, convulsion, transient contrast-induced encephalopathy (including hallucination), tremor, cardiac failure, ventricular hypokinesia, myocardial ischaemia, cardio-respiratory arrest, conduction abnormalities, coronary artery thrombosis, angina pectoris, spasm of coronary arteries, arterial spasm, thrombosis, thrombophlebitis, shock, pulmonary oedema, respiratory arrest, respiratory failure, acute or aggravated pancreatitis, salivary gland enlargement, bullous dermatitis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, drug rash with eosinophilia and systemic symptoms, drug eruption, dermatitis allergic, skin exfoliation, arthralgia, iodism. Intrathecal use: Uncommon: headache (may be severe and lasting), vomiting. Frequency unknown: hypersensitivity including anaphylactic/anaphylactoid reactions, dizziness, transient contrast induced encephalopathy including amnesia, hallucination, confusion, nausea, muscle spasm, shivering, pain at injection site. Hysterosalpingography: Very common: abdominal pain, vaginal haemorrhage. Common: headache, nausea, pyrexia. Frequency unknown: hypersensitivity, vomiting, shivering, injection site reaction. Arthrography: Common: injection site pain. Frequency unknown: hypersensitivity including anaphylactic anaphylactoid reactions, shivering. GI tract: Common: diarrhoea, abdominal pain, nausea. Uncommon: vomiting. Frequency unknown: hypersensitivity including anaphylactic/anaphylactoid reactions, shivering. OVERDOSE In the event of accidental overdosing, the water and electrolyte losses must be compensated by infusion. Renal function should be monitored for at least the next 3 days. If needed, haemodialysis may be used to remove iodixanol from the patient’s system. Treatment of overdose is symptomatic. PHARMACODYNAMIC PROPERTIES ATC code: V08A B09. In 64 diabetic patients with serum creatinine levels of 115 - 308 µmol/L, VISIPAQUE use resulted in 3% of patients experiencing a rise in creatinine of ≥ 44.2 µmol/L and 0% of the patients with a rise of ≥ 88.4 µmol/L. The release of enzymes (alkaline phosphatase and N-acetyl-β-glucosaminidase) from the proximal tubular cells is less than after injections of non-ionic monomeric contrast media and the same trend is seen compared to ionic dimeric contrast media. VISIPAQUE is also well tolerated by the kidney. INSTRUCTIONS FOR USE AND HANDLING Do not mix with other medicinal products. Like all parenteral products, VISIPAQUE should be inspected visually for particulate matter, discolouration and the integrity of the container prior to use. The product should be drawn into the syringe immediately before use. Containers are intended for single use only; any unused portions must be discarded. VISIPAQUE may be warmed to body temperature (37°C) before administration. MARKETING AUTHORISATION HOLDER GE Healthcare AS, Nycoveien 1-2, Postboks 4220 Nydalen, N-0401 Oslo, Norway. CLASSIFICATION FOR SUPPLY Subject to medical prescription (POM). MARKETING AUTHORISATION NUMBERS PL 0637/0018-19 (Glass vials/bottles and polypropylene bottles with stopper and screw cap). DATE OF REVISION OF TEXT December 2015 PRICE: 320mgI/ml, 10x50ml: £208.22

Clariscan UK prescribing informationJB7195 - March 2017PRESCRIBING INFORMATION CLARISCAN™ – gadoteric acid Please refer to full national Summary of Product Characteristics (SmPC) before prescribing. Further information available on request. PRESENTATION Clariscan 0.5 mmol/mL solution for injection. Solution for injection containing 279.3 mg/ml gadoteric acid (as gadoterate meglumine) equivalent to 0.5 mmol/mL. INDICATIONS For diagnostic use only. Contrast agent for contrast enhancement in MRI for a better visualisation/delineation. Adult and paediatric population (0-18 years): lesions of the brain, spine, and surrounding tissues. Adults and children over 6 months Whole body MRI. Non-coronary angiography in adults only. DOSAGE AND METHOD OF ADMINISTRATION This medicinal product should only be administered by trained healthcare professionals with technical expertise in performing and interpreting gadolinium enhanced MRI. MRI of brain and spine: Adults: The recommended dose is 0.1 mmol/kg BW, i.e. 0.2 mL/kg BW. In patients with brain tumours, an additional dose of 0.2 mmol/kg BW, i.e. 0.4 mL/kg BW, may improve tumor characterisation and facilitate therapeutic decision making. Children (0-18 years): The recommended and maximum dose of Clariscan is 0.1 mmol/kg body weight. Do not use more than one dose during a scan. Careful consideration in neonates up to 4 weeks and infants up to 1 year of age. Lack of information on repeated administration, Clariscan injections should not be repeated before 7 days. Whole body MRI (including lesions of the liver, kidneys, pancreas, pelvis, lungs, heart, breast, and musculoskeletal system): Adults and children over 6 months: The recommended dose is 0.1 mmol/kg BW, i.e. 0.2 mL/kg BW. Angiography: Adults only: The recommended dose, IV injection is 0.1 mmol/kg BW, i.e. 0.2 mL/kg BW. Impaired renal function: Clariscan should only be used in patients with severe renal impairment (GFR < 30 mL/min/1.73 m2) and in patients in the perioperative liver transplantation period after careful risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast enhanced MRI If it is necessary to use Clariscan the dose should not exceed 0.1 mmol/kg body weight. Clariscan injections should not be repeated before 7 days. Impaired hepatic function: The adult dose applies. Caution recommended, especially in perioperative liver transplantation period. Elderly (aged 65 years and above): No dosage adjustment, but exercise caution. CONTRAINDICATIONS Hypersensitivity to gadoteric acid, to meglumine or to any medicinal products containing gadolinium. WARNINGS AND PRECAUTIONS Appropriate facilities should be readily available for any complication, as well as for emergency treatment of severe reaction to the contrast agent (e.g. hypersensitivity, seizures). The usual precaution for MRI examination should be taken. Regarding any metallic object such as exclusion of patients with pacemakers, vascular clips, infusion pumps, nerve stimulators, cochlear implants, or suspected intracorporeal metallic foreign bodies, particularly in the eye. Not for intrathecal use: For intravenous injection only. Clariscan must not be administered by subarachnoid (or epidural) injections. Extravasation: In the event of extravasation local intolerance reactions may be observed, necessitating short term local treatment. Hypersensitivity reactions: Hypersensitivity reactions can occur, including life-threatening, and may be either allergic or non-allergic. They can be either immediate (less than 60

minutes), or delayed (up to 7 days). Anaphylactic reactions can occur immediately and can be fatal. Symptoms of an existing asthma may be aggravated. Hypersensitivity reactions can be aggravated in patients on beta-blockers, particularly those with bronchial asthma. These patients may be refractory to standard treatment of hypersensitivity reactions with beta-agonists. Caution in patients with a history of allergy (e.g. fish and seafood allergy, hay fever, hives), sensitivity to contrast media and bronchial asthma and premedication with antihistamines and/or glucocorticoids may be considered. Appropriate support measures should be available. Nephrogenic Systemic Fibrosis (NSF): Reports of NSF associated with use of some gadolinium-containing contrast agents in patients with acute or chronic severe renal impairment (GFR < 30 mL/min/1.73 m2). Incidence of acute renal failure is high in patients undergoing liver transplantation. Clariscan should only be used in patients with severe renal impairment and in patients in the perioperative liver transplantation period after careful risk/benefit assessment and if the diagnostic information is essential and not available with non-contrast enhanced MRI. Prior to administration of Clariscan, it is recommended that all patients are screened for renal dysfunction. CNS disorders: Special precaution is necessary in patients with a low threshold for seizures. Cardiovascular disease: Clariscan should only be administered after careful benefit assessment. Patient preparation: Nausea and vomiting are known possible undesirable effects when using MRI contrast agents. The patient should therefore refrain from eating for 2 hours prior to the investigation. UNDESIRABLE EFFECTS NSF [see Warnings and Precautions]. Clinical Studies Experience: Immune system disorders: Uncommon: Hypersensitivity, anaphylactic reaction, anaphylactoid reaction. Psychiatric disorders: Very rare: Agitation, anxiety. Eye disorders: Rare: Conjunctivitis, ocular hyperaemia, vision blurred, lacrimation increased, eyelid oedema. Nervous system disorders: Very common: Paraesthesia, headache. Rare: Dysgeusia. Very rare: Coma, convulsion, syncope, presyncope, dizziness, parosmia, tremor. Cardiac disorders: Very rare: Cardiac arrest, bradycardia, tachycardia, arrhythmia, palpitations. Respiratory, thoracic and mediastinal disorders: Very rare: Respiratory arrest, Rare: Pulmonary oedema, bronchospasm, laryngospasm, pharyngeal oedema, dyspnoea, nasal congestion, sneezing, cough, dry throat. Gastrointestinal disorders: Common: Nausea, vomiting. Very rare: Diarrhoea, abdominal pain, salivary hypersecretion. Skin and subcutaneous system disorders: Common: Pruritus, erythema, rash. Rare: Urticaria, hyperhidrosis. Very rare: Eczema, angioedema. Isolated cases of NSF have been reported with gadoteric acid, most of which were in patients co-administered other gadolinium-containing contrast agents. Vascular disorders: Very rare: Hypotension, hypertension, vasodilatation, pallor. Musculoskeletal and connective tissue disorders: Very rare: Muscle contracture, muscular weakness, back pain. General disorders and administration site conditions: Common: Feeling hot, feeling cold, injection site. Very rare: Chest discomfort, fever, chills, face oedema, asthenia, injection site discomfort, back pain, malaise, thoracic pain, superficial phlebitis, decreased oxygen saturation. Injection site reaction, injection site oedema, injection site extravasation, injection site inflammation (in case of extravasation), injection site necrosis (in case of extravasation). See full SmPC for adverse reactions reported with other intravenous MRI contrast agents. Postmarketing experience: The most

commonly reported adverse reactions following administration are nausea, vomiting, pruritus and hypersensitivity reactions. The most frequently observed hypersensitivity reactions are localised, extended or generalised skin reactions which most often occur immediately (during the injection or within one hour after the start of injection) or sometimes delayed (one hour to several days after injection). Immediate reactions include one or more effects, which appear simultaneously or sequentially, which are most often cutaneous, respiratory and/or cardiovascular reactions. Each sign may be a warning sign of a starting shock and go very rarely to death. DRUG INTERACTIONS No formal studies. No interactions with other medicinal products have been observed. Beta-blockers, vasoactive substances, angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists: These medicinal products induce decreased efficacy of cardiovascular compensation mechanisms of blood pressure. Contrast media may increase the incidence of hypersensitivity reactions in patients taking beta-blockers. PREGNANCY AND LACTATION No data in pregnant women. Clariscan should not be used during pregnancy unless the clinical condition of the woman requires use of gadoteric acid. Nursing Mothers: At clinical doses, no effects on the infant are anticipated due to the small amount excreted in milk and poor absorption from the gut. Continuing or discontinuing breast feeding for a period of 24 hours after administration, should be at the discretion of the doctor and lactating mother. Fertility: no clinical data. SPECIAL POPULATIONS Neonates and infants: Clariscan should only be used in neonates up to 4 weeks of age and infants up to 1 year age after careful consideration. Elderly (aged 65 years and above): Patients should be screened due to age related decline in renal function. OVERDOSE Clariscan can be removed by haemodialysis. However, there is no evidence that haemodialysis is suitable for prevention of NSF. EFFECTS ON THE ABILITY TO DRIVE AND USE MACHINES No studies. Ambulant patients while driving vehicles or operating machinery should take into account that nausea may incidentally occur. INSTRUCTIONS FOR USE AND HANDLING For single use. The solution for injection should be inspected visually prior to use. Only clear solutions free of visible particles should be used. In neonates and infants the required dose should be administered by hand. The peel-off tracking label on the syringes/vials/bottles should be stuck onto the patient record. The dose used should also be recorded. See SmPC for full instructions. MARKETING AUTHORISATION HOLDER GE Healthcare AS, P.O. Box 4220 Nydalen, NO-0401 OSLO, NORWAY MARKETING AUTHORISATION HOLDER PL 00637/0065 and PL 00637/0066 CLASSIFICATION FOR SUPPLY Subject to medical prescription DATE OF REVISION OF THE TEXT March 2017 Cost: 10x20ml: £759

Stroke represents a significant socioeconomic burden to health economies globally. In the EU, the financial burden of stroke is about €62bn (US$70bn) per year and accounts for around for 2-3% of the entire healthcare expenditure in the region. In the US, the total cost of stroke in 2010 was estimated at US$73.7bn.1 Significant progress in treatment and prevention has been made but access to these interventions remains variable in particular in low and middle income countries.

The latest key figures for Stroke are:

1. The Economist Intelligence Unit Limited (2016). Addressing the global stroke burden

million Stroke and TIA survivors

leading cause of death globally

stroke patients have access to

acute treatment

of strokes occur in low and middle countries and has

doubled in the past 4 decades

of Stroke survivors have long term residual

disability

million deaths due to stroke

million strokes annually

The burden of stroke

50

2nd

<5%70%

50%

515

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Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard.

Adverse events should also be reported to GE Healthcare Limited.

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported GE Healthcare Ltd,

email: UKpharmacovigilance@ge.com.

LOGIQ  S7

LOGIQ  E9

LOGIQ  S8LOGIQ  P9/7

Using lean methodology and a kaizen approach to optimise care design and delivery

Rapid transport

Right and rapid diagnosis

Right and rapid treatment

Follow-up and secondary detection

Early Detection

REVOLUTIONTM CT Uncompromised image quality

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FASTSTROKE CT APPLICATION Simplifies and organizes CT images for fast

evaluation of Stroke patients

CARESCAPETM MONITORS Monitoring stroke patients throughout diagnosis and treatment

PRE-HOSPITAL DIAGNOSIS Researching new technologies for pre-hospital diagnosis2

2. Technology in development that represents ongoing research and development efforts. These technologies are not products and may never become products. Not for sale.

SEERTM 1000 HOLTER MONITOR Specifically developed for A-fib detection

LOGIQTM ULTRASOUND Designed for Rapid assessment

VISIPAQUETM Prepared to Protect

SIGNATM PREMIER MR WITH EDWI Ultra High Performance MR system delivering speed with uncompromised quality

ALGORITHM SERVER + ECG RECORDERS Specifically developed for Afib detection

VSCANTM ULTRASOUND Pocket-sized ultrasound enabling sound

diagnosis and fast referral

MR & CT CONTRAST AGENTS

MR FAST BRAIN PROTOCOL & 48 CHANNEL HEAD COIL Faster scan times with improved image resolution

A new software solution for High Acuity Patients. Designed for you to connect intelligence with care.

IGSTM 630 INTERVENTIONAL X-RAY Accurate planning, rapid lesion access,

precise assessment

CLARISCANTM

Gadoteric Acid + GE Healthcare expertise

GE Healthcare is committed to enabling the delivery of a new standard of stroke care by providing products and services across the complete pathway of care that have been specifically developed to enable the delivery of clinical, financial and operational outcomes. Our portfolio encompasses the whole stroke pathway with technologies that enable prevention, diagnosis, treatment, follow-up and rehabilitation of stroke and TIA. Our mission is to work closely with our institutional partners to identify and understand the key challenges in managing stroke patients and delivering better outcomes and focusing our research and engineering efforts to develop solutions that address the emerging challenges.

GE Healthcare PartnersCentricity High Acuity Critical Care

GE Healthcare’s vision for stroke