RPS EU July See Prescribing Information at the end of this presentation

Transcription

1 RPS EU July 2015 See Prescribing Information at the end of this presentation

2 The first and only selective A2A adenosine receptor agonist licensed for radionuclide myocardial perfusion imaging in adult patients1 Fast and efficient protocol May be used in patients with asthma or COPD2 1 2 Rapiscan (regadenoson) Summary of Product Characteristics, RPS EU Ltd Adenosine receptor agonists may cause bronchoconstriction and respiratory compromise. For patients with known or suspected bronchoconstrictive disease, chronic obstructive pulmonary disease (COPD) or asthma, appropriate bronchodilator therapy and resuscitative measures should be available prior to Rapiscan administration. RPS EU July

3 Adenosine Dipyridamole Dobutamine Mechanism of Action Direct vasodilator Indirect vasodilator Inotrope May cause heart block / arrhythmias Yes Yes Yes Patient groups No asthma/copd No asthma/copd Asthma/COPD only Administration Infusion Infusion Stepped infusion Weight- based dosing Yes Yes Yes Timing of radiopharmaceutical 3 mins 3-5 mins post- infusion variable Adenoscan (adenosine) Summary of Product Characteristics, Sanofi Aventis Persantin (dypyridamole) Summary Product Characteristics, Boeringer Ingelheim Dobutamine, Summary of Product Characteristics, various suppliers RPS EU July

4 Attribute Rapid onset of action Fast off- set of action A 2A Agonist direct vasodilator Avoid A 1 Avoid A 2B and A 3 Simplified dosing Rapid administration Non- weight based No drug/drug interactions No dose adjustment for liver or kidney function Criteria 1-4 Potent Low affinity & fast elimination Receptor binding and functional selectivity for coronary vasodilation Causes heart block Causes asthma (bronchoconstriction) Selective coronary vasodilation Clearance not closely associated with weight Not metabolised, cleared unchanged Reversible Effect attenuated by aminophylline 5 1 Rapiscan (regadenoson) Summary of Product Characteristics, RPS EU Ltd 2 Jacobson MA. Molecular biology of adenosine receptors. In: Belardinelli L, Pelleg A, eds. Adenosine and Adenine Nucleotides: From Molecular Biology to Integrative Physiology. Norwell, MA:Kluwer Academic Publishers; 1995: Belardinelli L, Shryock JC, Snowdy S, et al. The A2A adenosine receptor mediates coronary vasodilation. J Pharmacol Exp Ther 1998;284: Palosa Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease Eur Respir J 2002; 20: Patients should avoid consumption of any products containing methylxanthines as well as any medicinal products containing theophylline for at least 12 hours before Rapiscan administration RPS EU July

5 Low-affinity / High potency selective A 2A adenosine receptor agonist High selectivity At least 10-fold lower affinity for the A 1 receptor regadenoson Weak, if any, affinity for the A 2B and A 3 receptors A 2A adenosine receptor activation produces coronary vasodilation and increases coronary blood flow (CBF) adenosine 1 Rapiscan (regadenoson) Summary Product Characteristics, RPS EU, London. 2 Gao Z, Li Z, Baker SP, et al. Novel short-acting A 2A adenosine receptor agonists for coronary vasodilation: inverse relationship between affinity and duration of action of A 2A agonists. J Pharmacol Exp Ther 2001;298: RPS EU July

6 Regadenoson-induced coronary hyperemia Intracoronary APV Ratio Time (min) Lieu HD, Shryock JC, von Mering GO, et al. Rapiscan, a selective A 2A adenosine receptor agonist, causes dose-dependent increases in coronary blood flow velocity in humans. J Nucl Cardiol 2007;14: RPS EU July

7 Single standard dose (400 mcg in 5 ml) for all patients No dose adjustments for age, weight, gender hepatic or renal function Full 10 second IV injection No need for infusion pump 10 second saline flush (5ml) Rapiscan (400 mcg regadenoson / 5ml) Saline Flush (5ml) Inject Radiopharmaceutical Seconds seconds after flush inject radiopharmaceutical Administration protocol completed within 1 minute Rapiscan (regadenoson) Summary of Product Characteristics, RPS EU RPS EU July

8 Adenoscan (adenosine) 140 mcg/kg/min iv infusion Total drug burden (80kg person) 6 min 67,200 mcg Persantin (dipyridamole) 142 mcg/kg/min iv infusion 4 min within 3-5 min 45,440 mcg Rapiscan (regadenoson) 400 mcg/5ml iv injection 1 min Inject radiopharmaceutical 400 mcg Adenoscan (adenosine) Summary of Product Characteristics, Sanofi Aventis Persantin (dypyridamole) Summary Product Characteristics, Boeringer Ingelheim Rapiscan (regadenoson) Summary of Product Characteristics, RPS EU RPS EU July

9 Like adenosine and dipyridamole, Rapiscan SPC indicates 1-3 Patients should avoid consumption methylxanthine (caffeine) and theophylline containing products for at least 12 hours before Aminophylline (50 mg to 100 mg over seconds) may be used to attenuate severe and/or persistent adverse reactions. Aminophylline may prolong a seizure or cause multiple seizures because of its proconvulsant effect. Therefore administration of aminophylline solely for the purpose of terminating a seizure induced by Rapiscan is not recommended. Should not be used in patients with Hypersensitivity to the active substance Second or third degree atrioventricular (AV) block or sinus node dysfunction, unless have a functioning artificial pacemaker. Unstable angina that has not been stabilised with medical therapy. Severe hypotension. Decompensated states of heart failure Unlike adenosine or dipyridamole Rapiscan may be used in patients with asthma or COPD 4 1 Adenoscan (adenosine) Summary of Product Characteristics, Sanofi Aventis 2 Persantin (dypyridamole) Summary Product Characteristics, Boeringer Ingelheim 3 Rapiscan (regadenoson) Summary of Product Characteristics, RPS EU 4 Adenosine receptor agonists may cause bronchoconstriction and respiratory compromise. For patients with known or suspected bronchoconstrictive disease, chronic obstructive pulmonary disease (COPD) or asthma, appropriate bronchodilator therapy and resuscitative measures should be available prior to Rapiscan administration. RPS EU July

10 Study Design Adenosine (initial scan) double blinded & randomised Adenosine Regadenoson Overall Results adenosine vs regadenoson 0 ± 3% (-6.2, 6.8%) Individual patient results PDS = Perfusion Defect Size (%) Two randomised, double-blind studies N = 2,015 patients with known or suspected CAD Primary outcome Detection of reversible perfusion defects PDS Regadenoson Y=0.9602x R=0.97, p<0.001 PDS Initial Adenosine 1 Rapiscan (regadenoson) Summary of Product Characteristics, RPS EU Ltd 2 Mahmarian JJ, Cerqueira MD, Iskandrian AE, et al. Regadenoson induces comparable left ventricular perfusion defects as adenosine: a quantitative analysis from the ADVANCE MPI 2 trial. JACC Cardiovasc Imaging 2009;2(8): RPS EU July

11 SPECT perfusion images from the same patient collected on different days about a week apart after adenosine and Rapiscan stress and at rest. Reproduced with Permission Zoghbi G and Iskandrian A. Regadenoson Myocardial Perfusion Imaging. Imaging Med 2010; 2: RPS EU July

12 Q1: How did you feel? Q2: How does this test compare to the first adenosine test? 50% CMH test p< % CMH test p< % 40% 30% 30% 20% 20% 10% 10% 0% Comfortable A Little Uncomfortable Very Uncomfortable Extremely Uncomfortable 0% Much better Somewhat Better About the Same Somewhat Worse Much Worse Adenosine Rapiscan Cerqueira MD et al, on behalf of the ADVANCE MPI Trial Investigators. Effects of age, gender, obesity and diabetes on the efficacy and safety of the selective A 2 A agonist Rapiscan versus adenosine: integrated ADVANCE MPI trial results. J Am Coll Cardiol 2008;1: RPS EU July

13 Adverse reactions in most patients were mild, transient and required no medical intervention Most common adverse reactions headache, dizziness dyspnoea chest pain electrocardiogram ST segment changes flushing discomfort in the stomach Dyspnoea did not correlate with a decrease in FEV 1. Rapiscan (regadenoson) Summary of Product Characteristics, RPS EU Ltd RPS EU July

14 Selective A 2A adenosine receptor agonist Simplified dosing 10 second injection Single unit dosing No weight determination and dose preparation No need for an infusion pump No need for an extension line or iv fluids Reduces supplies and waste Improved tolerability over adenosine Alternative to dobutamine stress for patients susceptible to a bronchonconstrictive response RPS EU July

15 Indication: Pharmacological stress agent for radionuclide myocardial perfusion imaging in adult patients. Dosage and Administration: Each 5 ml vial contains 400 micrograms regadenoson, which is injected over 10 seconds into a peripheral vein followed by 5 ml saline (0.9% sodium chloride) solution flush. The radiopharmaceutical should be administered seconds after saline injection. The same catheter may be used for Rapiscan and the radiopharmaceutical. Patients should avoid consumption of any products containing methylxanthines (e.g. caffeine) as well as any medicinal products containing theophylline for at least 12 hours before Rapiscan administration. When possible, dipyridamole should be withheld for at least two days prior to Rapiscan administration. Contra-indications: Hypersensitivity to active substance or excipients; patients with second or third degree AV block or sinus node dysfunction who do not have a functioning artificial pacemaker; unstable angina that has not been stabilised with medical therapy; severe hypotension; decompensated heart failure. Precautions: Rapiscan has the potential to cause serious and life- threatening reactions. Continuous ECG monitoring should be performed and vital signs monitored at frequent intervals until ECG parameters, heart rate and blood pressure have returned to pre-dose levels. Fatal cardiac arrest, life-threatening ventricular arrhythmias, and myocardial infarction may result from the ischaemia induced by pharmacologic stress agents like regadenoson. Rapiscan should be used in caution in patients with recent myocardial infarction. Clinical trials conducted with regadenoson excluded patients with recent (within 3 months) myocardial infarction. Adenosine receptor agonists including regadenoson can depress the sinoatrial (SA) and AV nodes and may cause first, second or third degree AV block, or sinus bradycardia. Adenosine receptor agonists including regadenoson induce arterial vasodilation and hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, hypovolemia, left main coronary artery stenosis, stenotic valvular heart disease, pericarditis or pericardial effusions, or stenotic carotid artery disease with cerebrovascular insufficiency. Rapiscan may cause clinically significant increases in blood pressure, which in some patients can lead to hypertensive crisis (see section 4.8). The risk of significant increases in blood pressure may be higher in patients with uncontrolled hypertension. Consideration should be given to delaying Rapiscan administration until blood pressure is well controlled. Use of Rapiscan involving exercise has been associated with serious adverse reactions including hypotension, hypertension, syncope and cardiac arrest. Patients who have had any symptoms or signs suggestive of acute myocardial ischemia during exercise or recovery are likely to be at especially high risk of serious adverse reactions. Rapiscan can cause transient ischaemic attack. In post-marketing experience there have also been reports of cerebrovascular accident (CVA). Caution should be used when administrating Rapiscan to patients with a history of seizures or other risk factor for seizures, including the concomitant administration of medicinal products that lower seizure threshold (e.g. antipsychotics, antidipressants, theophyllines, tramadol, systemic steroids and quinolones). Aminophylline may prolong a seizure or cause multiple seizures because of its proconvulsant effect. Therefore administration of aminophylline solely for the purpose of terminating a seizure induced by Rapiscan is not recommended. Rapiscan should be used with caution in patients with a history of atrial fibrillation or flutter. In post- marketing experience there have been cases of worsening or recurrence of atrial fibrillation after administration of Rapiscan. Adenosine receptor agonists, including Rapiscan, may cause bronchoconstriction and respiratory compromise especially in patients with known or suspected bronchoconstrictive disease, chronic obstructive pulmonary disease (COPD) or asthma. Appropriate bronchodilator therapy and resuscitative measures should be available prior to Rapiscan administration. Regadenoson stimulates sympathetic output and may increase the risk of ventricular tachyarrhythmias in patients with a long QT syndrome. This medicinal product contains less than 1 mmol sodium (23 mg) per dose. However, the injection of sodium chloride 9 mg/ml (0.9%) solution given after Rapiscan contains 45 mg of sodium. To be taken into consideration by patients on a controlled sodium diet. Undesirable effects: Adverse reactions in most patients were mild, transient (usually resolving within 30 minutes) and required no medical intervention. Rapiscan may cause myocardial ischaemia (potentially associated with fatal cardiac arrest, life- threatening ventricular arrhythmias, and myocardial infarction), hypotension leading to syncope and transient ischaemic attacks, elevated blood pressure leading to hypertension and hypertensive crises, and SA/AV node block leading to first, second or third degree AV block, or sinus bradycardia requiring intervention. Signs of hypersensitivity (rash, urticaria, angioedema, anaphylaxis and/or throat tightness) may be immediate or delayed onset. Aminophylline may be used to attenuate severe or persistent adverse reactions to Rapiscan but should not be used solely for the purpose of terminating a seizure induced by Rapiscan. Very common adverse events reported were dyspnoea, headache, flushing, chest pain, electrocardiogram ST changes, gastrointestinal discomfort, and dizziness. Common adverse events reported were paraesthesia, hypoaesthesia, dysgeusia, angina pectoris, atrioventricular block, tachycardia, palpitations, other ECG abnormalities including electrocardiogram QT corrected interval prolonged, hypotension, throat tightness, throat irritation, cough, vomiting, nausea, oral discomfort, back, neck or jaw pain, pain in extremity, musculoskeletal discomfort, hyperhidrosis, malaise, and asthenia. See SPC for details of other undesirable effects. Presentation: One carton contains a single vial of Rapiscan (400 micrograms regadenoson in 5mL solution for injection). Price: Please see your local distributor. ATC code: C01EB21. Legal Classification: POM. Marketing authorization holder: Rapidscan Pharma Solutions EU Ltd, Regent s Place, 338 Euston Road, London, NW1 3BT, United Kingdom. Marketing authorization number: EU/1/10/643/001 Date of preparation: JUNE Adverse events should be reported to your local regulatory authority. Please contact your local distributor for reporting forms or safety@rapiscan-mpi.com. In the UK: Adverse events should be reported. Reporting forms and information can be found at Adverse events should also be reported by phone , fax , or safety@rapiscan-mpi.com. RPS EU July