Rapiscan · 4.8 Undesirable effects · 1

HOS-095586 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile Adverse reactions in most patients receiving regadenoson in clinical trials were mild, transient (usually resolving within 30 minutes after receiving regadenoson) and required no medical intervention. Adverse reactions occurred in approximately 80% of patients. The most common adverse reactions reported during clinical development in a total of 1,651 patients/subjects were: dyspnoea (29%), headache (27%), flushing (23%), chest pain (19%), electrocardiogram ST segment changes (18%), gastrointestinal discomfort (15%) and dizziness (11%). Regadenoson 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 (see section 4.4). 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 regadenoson but should not be used solely for the purpose of terminating a seizure induced by regadenoson (see section 4.4). Tabulated list of adverse reactions Assessment of adverse reactions for regadenoson is based on safety data from clinical studies and post-marketing experience. All adverse reactions are presented in the table below and are listed by system organ class and frequency. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10) uncommon (≥ 1/1,000 to < 1/100) and rare (≥ 1/10,000 to < 1/1,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Immune system disorders: Uncommon Hypersensitivity reactions including: Rash, urticaria, angioedema, anaphylaxis and/or throat tightness. Psychiatric disorders: Uncommon Anxiety, insomnia 6  Nervous system disorders: Very common Headache, dizziness Common Paraesthesia, hypoaesthesia, dysgeusia Uncommon Convulsions, syncope, transient ischaemic attack, unresponsiveness to stimuli, depressed level of consciousness, tremor, somnolence Rare Cerebrovascular accident Eye di

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HOS-095582 · has-contraindication-information · PDF-Seite 3

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Second or third degree atrioventricular (AV) block or sinus node dysfunction, unless these patients have a functioning artificial pacemaker. • Unstable angina that has not been stabilised with medical therapy. • Severe hypotension. • Decompensated states of heart failure. 3

HOS-095581 · has-indication-information · PDF-Seite 2

This medicinal product is for diagnostic use only. Rapiscan is a selective coronary vasodilator for use in adults as a pharmacological stress agent for: • myocardial perfusion imaging (MPI) in patients unable to undergo adequate exercise stress. • the measurement of fractional flow reserve (FFR) of a single coronary artery stenosis during invasive coronary angiography, when repeated FFR measurements are not anticipated (see sections 4.2 and 5.1).

HOS-095584 · has-interaction-information · PDF-Seite 5

Methylxanthines Methylxanthines (e.g., caffeine and theophylline) are non-specific adenosine receptor antagonists and may interfere with the vasodilation activity of regadenoson (see section 5.1). Patients should avoid consumption of any medicinal products containing methylxanthines as well as any medicinal products containing theophylline for at least 12 hours before regadenoson administration (see section 4.2). Dipyridamole Dipyridamole increases blood adenosine levels and the response to regadenoson may be altered when blood adenosine levels are increased. When possible, dipyridamole should be withheld for at least two days prior to regadenoson administration (see section 4.2). Cardioactive medicinal products In clinical studies, regadenoson was administered to patients taking other cardioactive medicinal products (i.e., β-blockers, calcium channel blockers, ACE inhibitors, nitrates, cardiac glycosides, and angiotensin receptor blockers) without apparent effects on the safety or efficacy profile of regadenoson. Other interactions Regadenoson does not inhibit the metabolism of substrates for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 in human liver microsomes, indicating that it is unlikely to alter the pharmacokinetics of medicinal products metabolised by these cytochrome P450 enzymes. Regadenoson does not significantly inhibit the transporters OAT1, OAT3, OCT1, OATP1B1, OATP1B3, MATE1, MATE2-K, BCRP, P-gp, BSEP, ENT 1 or ENT2 at 1 µM. The data are insufficient to conclude about the risk of interactions at the level of these transporters given that a single concentration was evaluated in most instances. Regadenoson may have a modest inhibitory effect on the active renal transporter, OCT2, and has been found to be likely substrate for BCRP, ENT1 or ENT2 mediated transport. However, given the proposed duration of use, the effects of the drug transporters are unlikely to be clinically relevant.

HOS-095585 · has-pregnancy-information · PDF-Seite 5

Pregnancy 5 There are no adequate data from the use of regadenoson in pregnant women. Animal studies on pre- and post-natal development have not been conducted. Fetotoxicity, but not teratogenicity, was noted in embryo-fetal development studies (see section 5.3). The potential risk for humans is unknown. Regadenoson should not be used during pregnancy unless clearly necessary. Breast-feeding It is unknown whether regadenoson is excreted in human breast milk. The excretion of regadenoson in milk has not been studied in animals. A decision should be made whether to discontinue breast- feeding or to abstain from regadenoson administration taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. If regadenoson is administered, the woman should not breast-feed for at least 10 hours (that is, at least 5 times the plasma elimination half-life) following regadenoson administration. Fertility Fertility studies with regadenoson have not been performed (see section 5.3).

HOS-095583 · has-warning-information · PDF-Seite 4

Regadenoson has the potential to cause serious and life-threatening reactions, including those listed below (see also section 4.8). Continuous ECG monitoring should be performed and vital signs should be monitored at frequent intervals until the ECG parameters, heart rate and blood pressure have returned to pre-dose levels. Regadenoson should be used with caution and should only be administered in a medical facility with cardiac monitoring and resuscitation equipment. Aminophylline may be administered in doses ranging from 50 mg to 250 mg by slow intravenous injection (50 mg to 100 mg over 30-60 seconds) to attenuate severe and/or persistent adverse reactions to regadenoson but should not be used solely for the purpose of terminating a seizure induced by regadenoson. Myocardial ischaemia Fatal cardiac arrest, life-threatening ventricular arrhythmias, and myocardial infarction may result from the ischaemia induced by pharmacologic stress agents like regadenoson. Regadenoson should be used with caution in patients with recent myocardial infarction. Single Photon Emission Computed Tomography (SPECT) MPI clinical trials conducted with regadenoson excluded patients with recent (within 3 months) myocardial infarction. Clinical trials for the measurement of FFR excluded patients with an acute myocardial infarction, or within 5 days of an acute myocardial infarction. Sinoatrial and atrioventricular nodal block 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. Hypotension 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. Elevated blood pressure Regadenoson 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 regadenoson administration until blood pressure is well controlled Combination with exercise Use of regadenoson involving exercise has been associated with serious adverse reactions inclu

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