Rapiscan

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ANNEX 1 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 

Rapiscan 400 microgram solution for injection 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 

Each 5 ml vial contains 400 micrograms regadenoson (80 micrograms/ml).  

 

For the full list of excipients, see section 6.1. 

 

3. PHARMACEUTICAL FORM 
 

Solution for injection  

Clear, colourless solution. 

 

4. CLINICAL PARTICULARS 
 

4.1 Therapeutic indications 
 

This medicinal product is for diagnostic use only. 

 

Rapiscan is a selective coronary vasodilator for use in adults as a pharmacological stress agent for: 

 

• radionuclide 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). 

 

4.2 Posology and method of administration 
 

Treatment with Rapiscan is restricted to use in a medical facility where cardiac monitoring and 

resuscitation equipment are available. 

 

Posology 

The recommended dose is a single injection of 400 micrograms regadenoson (5 ml) into a peripheral 

vein, with no dose adjustment necessary for body weight. 

 

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 

(see section 4.5). 

 

When possible, dipyridamole should be withheld for at least two days prior to Rapiscan administration 

(see section 4.5). 

 

Aminophylline may be used 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 Rapiscan (see section 

4.4). 

 

Regadenoson causes a rapid increase in heart rate (see sections 4.4 and 5.1). Patients should remain 

sitting or lying down and be monitored at frequent intervals after the injection until the ECG 

parameters, heart rate and blood pressure have returned to pre-dose levels. 

 

 



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Repeated use 

For use in radionuclide MPI: This product is to be administered only once within a 24 hour period. 

Safety and tolerability of repeated use of this product within 24 hours has not been characterised. 

 

 

For use in FFR: This product is to be administered no more than twice, no less than10 minutes apart, 

during any 24 hour period. When administered twice 10 minutes apart in a 24-hour period, full safety 

data for the second injection of Rapiscan are not available. 

 

Paediatric population 

 

The safety and efficacy of regadenoson in children below the age of 18 years have not yet been 

established. 

 

No data are available. 

 

Elderly 

No dose adjustment is necessary (see section 5.2). 

 

Hepatic impairment 

No dose adjustment is necessary (see section 5.2). 

 

Renal impairment 

No dose adjustment is necessary (see section 5.2). 

 

Method of administration  

 

For intravenous use. 

Radionuclide myocardial perfusion imaging (MPI):  

 

• Rapiscan should be administered as a rapid, 10-second injection into a peripheral vein using a 
22-gauge or larger catheter or needle. 

• 5 ml of sodium chloride 9 mg/ml (0.9%) solution for injection should be administered 
immediately after the injection of Rapiscan. 

• The radiopharmaceutical for the myocardial perfusion imaging agent should be administered 
10-20 seconds after the sodium chloride 9 mg/ml (0.9%) solution for injection. The 

radiopharmaceutical may be injected directly into the same catheter as Rapiscan. 

 

Fractional flow reserve (FFR): 

 

• Rapiscan should be administered as a rapid 10-second injection into a peripheral vein, using a 
22-gauge or larger catheter or needle 

• 10 ml of sodium chloride 9 mg/ml (0.9%) solution for injection should be administered 
immediately after the injection of Rapiscan.  

• FFR should be measured as the lowest value of Pd/Pa achieved during steady state hyperemia. 
 

4.3 Contraindications 
 

• 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. 
 

 



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4.4 Special warnings and precautions for use 
 

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.  

Radionuclide 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 including 

hypotension, hypertension, syncope and cardiac arrest. Patients who have had any symptoms or signs 

suggestive of acute myocardial ischaemia during exercise or recovery are likely to be at especially high 

risk of serious adverse reactions. 

 

Transient ischaemic attacks and cerebrovascular accident 

Regadenoson can cause transient ischaemic attack (see section 4.8). In post-marketing experience 

there have also been reports of cerebrovascular accident (CVA).  

 

Risk of seizure  

Caution should be used when administering regadenoson to patients with a history of seizures or other 

risk factors for seizures, including the concomitant administration of medicinal products that lower 

seizure threshold (e.g. antipsychotics, antidepressants, theophyllines, tramadol, systemic steroids and 

quinolones). 

 

 

 

 

 



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Aminophylline should be used with caution in patients with a history of seizures or who have other 

risk factors for seizures as it 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 regadenoson is not recommended. 

 

Atrial fibrillation or flutter 

Regadenoson 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 regadenoson. 

 

Bronchoconstriction 

Regadenoson may cause bronchoconstriction and respiratory arrest (see section 4.8) , 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 regadenoson administration. 

 

Long QT syndrome 

Regadenoson stimulates sympathetic output and may increase the risk of ventricular tachyarrhythmias 

in patients with a long QT syndrome. 

 

Warnings related to excipients 

This medicinal product contains less than1 mmol sodium (23 mg) per dose. However, the injection of 

sodium chloride 9 mg/ml (0.9%) solution given after regadenoson contains 45 mg of sodium. To be 

taken into consideration by patients on a controlled sodium diet. 

 

4.5 Interaction with other medicinal products and other forms of interaction  
 

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.  

 



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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. 

 

4.6 Fertility, pregnancy and lactation 
 

Pregnancy 

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). 

 

4.7 Effects on ability to drive and use machines 
 

Regadenoson administration may result in adverse reactions such as dizziness, headache, and dyspnoea 

(see section 4.8) soon after administration. However, most adverse reactions are mild and transient, 

resolving within 30 minutes after receiving regadenoson. Therefore, regadenoson would be expected to 

have no or negligible influence on the ability to drive or use machines once treatment has been 

completed and these reactions have resolved. 

 



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4.8 Undesirable effects 
 

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. 



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Immune system disorders: 

Uncommon Hypersensitivity reactions including: Rash, urticaria, angioedema, anaphylaxis 

Psychiatric disorders: 

Uncommon Anxiety, insomnia 

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 disorders: 

Uncommon Vision blurred, eye pain 

Ear and labyrinth disorders: 

Uncommon Tinnitus 

Cardiac disorders: 

Very common Electrocardiogram ST segment changes 

Common Angina pectoris, atrioventricular block, tachycardia, palpitations, other 

ECG abnormalities including electrocardiogram QT corrected interval prolonged 

Uncommon Cardiac arrest, myocardial infarction, complete AV block, bradycardia, atrial flutter, 

new-onset, worsening or recurrence of atrial fibrillation 

Vascular disorders: 

Very common Flushing 

Common Hypotension 

Uncommon Hypertension, pallor, peripheral coldness 

Respiratory, thoracic and mediastinal disorders: 

Very common Dyspnoea 

Common Throat tightness, throat irritation, cough 

Uncommon Tachypnoea, wheezing 

Not known Bronchospasm, Respiratory arrest 

Gastrointestinal disorders: 

Very common Gastrointestinal discomfort 

Common Vomiting, nausea, oral discomfort 

Uncommon Abdominal distension, diarrhoea, faecal incontinence 

Skin and subcutaneous tissue disorders: 

Common Hyperhidrosis 

Uncommon Erythema 

Musculoskeletal and connective tissue disorders: 

Common Back, neck or jaw pain, pain in extremity, musculoskeletal discomfort 

Uncommon Arthralgia 

General disorders and administration site conditions: 

Very common Chest pain 

Common Malaise, asthenia 

Uncommon Pain at injection site, general body pain 

 

Description of selected adverse reactions 

Fatal cardiac arrest, life-threatening ventricular arrhythmias and myocardial infarction may result from 

the ischaemia induced by pharmacologic stress agents. Cardiac resuscitation equipment and trained 

staff should be available before administering regadenoson (see section 4.4). 

 

Sinoatrial and atrioventricular nodal block 

Regadenoson, can depress the SA and AV nodes and may cause first, second or third degree AV block, 

or sinus bradycardia requiring intervention. In clinical trials first degree AV block (PR prolongation 

> 220 msec) developed in 3% of patients within 2 hours of regadenoson administration; transient 

second degree AV block with one dropped beat was observed in one patient receiving regadenoson. In 



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postmarketing experience, third degree heart block and asystole have been reported within minutes of 

regadenoson administration. 

 

Hypotension 

Adenosine receptor agonists, including regadenoson induce arterial vasodilation and hypotension. In 

clinical trials, decreased systolic blood pressure (> 35 mm Hg) was observed in 7% of patients and 

decreased diastolic blood pressure (> 25 mm Hg) was observed in 4% of patients within 45 minutes of 

regadenoson administration. 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. In postmarketing experience, syncope and transient ischaemic attacks have been 

reported. 

 

Elevated blood pressure 

In clinical trials, increased systolic blood pressure (≥ 50 mm Hg) was observed in 0.7% of patients and 

increased diastolic blood pressure (≥ 30 mm Hg) in 0.5% of patients. Most increases resolved within 

10 to 15 minutes, but in some cases, increases were observed at 45 minutes following administration. 

 

Long QT syndrome 

Regadenoson increases sympathetic tone, which causes an increase in heart rate and a shortening of the 

QT interval. In a patient with a long QT syndrome, sympathetic stimulation can result in less 

shortening of the QT interval than is normal and may even cause a paradoxical increase in the QT 

interval. In these patients, the phenomenon of R-on-T syndrome can occur, wherein an extra beat 

interrupts the T wave of the previous beat, and this increases the risk of a ventricular tachyarrhythmia. 

 

Headache 

Headache was reported by 27% of subjects who received regadenoson in clinical trials. The headache 

was considered severe in 3% of subjects. 

 

Elderly population 

Older patients (≥ 75 years of age; n = 321) had a similar adverse reaction profile compared to younger 

patients (< 65 years of age; n = 1,016), but had a higher incidence of hypotension (2% versus < 1%). 

 

Reporting of suspected adverse reactions  

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 
 

In a study of healthy volunteers, symptoms of flushing, dizziness and increased heart rate were 

assessed as intolerable at regadenoson doses greater than 0.02 mg/kg. 

 

Treatment 

 

Aminophylline may be used to attenuate severe or persistent adverse reactions to regadenoson. 

Administration of aminophylline, solely for the purpose of terminating a regadenoson-induced seizure 

is not recommended (see section 4.4). 

 

 

 

 

 

 

 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


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5. PHARMACOLOGICAL PROPERTIES 
 

5.1 Pharmacodynamic properties 
 

Pharmacotherapeutic group: Cardiac therapy, other cardiac preparations, ATC code: C01EB21 

 

Mechanism of action 

 

Regadenoson is a low affinity agonist (Ki ≈ 1.3 µM) for the A2A adenosine receptor, with at least 10-

fold lower affinity for the A1 adenosine receptor (Ki > 16.5 µM), and very low, if any, affinity for the 

A2B and A3 adenosine receptors. Activation of the A2A adenosine receptor produces coronary 

vasodilation and increases coronary blood flow (CBF). Despite low affinity for the A2A adenosine 

receptor, regadenoson has high potency for increasing coronary conductance in rat and guinea pig 

isolated hearts, with EC50 values of 6.4 nM and 6.7-18.6 nM, respectively. Regadenoson shows 

selectivity (≥ 215-fold) for increasing coronary conductance (A2A-mediated response) relative to 

slowing of cardiac AV nodal conduction (A1-mediated response) as measured by AV conduction time 

(rat heart) or the S-H interval (guinea pig heart). Regadenoson preferentially increases blood flow in 

coronary relative to peripheral (forelimb, brain, pulmonary) arterial vascular beds in the anaesthetised 

dog. 

 

Pharmacodynamic effects 

 

Coronary blood flow 

Regadenoson causes a rapid increase in CBF which is sustained for a short duration. In patients 

undergoing coronary catheterisation, pulsed-wave Doppler ultrasonography was used to measure the 

average peak velocity (APV) of CBF before and up to 30 minutes after administration of regadenoson  

(400 micrograms, intravenously). Mean APV increased to greater than twice baseline by 30 seconds 

and decreased to less than half of the maximal effect within 10 minutes (see section 5.2). 

 

Myocardial uptake of the radiopharmaceutical is proportional to CBF. Because regadenoson increases 

blood flow in normal coronary arteries with little or no increase in stenotic arteries, regadenoson causes 

relatively less uptake of the radiopharmaceutical in vascular territories supplied by stenotic arteries. 

Myocardial radiopharmaceutical uptake after regadenoson  administration is therefore greater in areas 

perfused by normal relative to stenosed arteries. The same applies to the FFR measurement where the 

maximal myocardial blood flow is decreased in presence of severe coronary artery stenosis.  

 

Radionuclide myocardial perfusion imaging (MPI) 

 

Haemodynamic effects 

The majority of patients experience a rapid increase in heart rate. The greatest mean change from 

baseline (21 bpm) occurs approximately 1 minute after administration of regadenoson. Heart rate 

returns to baseline within 10 minutes. Systolic blood pressure and diastolic blood pressure changes 

were variable, with the greatest mean change in systolic pressure of −3 mm Hg and in diastolic 

pressure of −4 mm Hg approximately 1 minute after regadenoson  administration. An increase in blood 

pressure has been observed in some patients (maximum systolic blood pressure of 240 mm Hg and 

maximum diastolic blood pressure of 138 mm Hg). 

 

Respiratory effects 

The A2B and A3 adenosine receptors have been implicated in the pathophysiology of 

bronchoconstriction in susceptible individuals (i.e., asthmatics). In in vitro studies, regadenoson has 

been shown to have little binding affinity for the A2B and A3 adenosine receptors. The incidence of a 

FEV1 reduction > 15% from baseline after regadenoson  administration was assessed in three 

randomised, controlled clinical studies. In the first study in 49 patients with moderate to severe COPD, 

the rate of FEV1 reduction > 15% from baseline was 12% and 6% following regadenoson  and 

placebo dosing, respectively (p=0.31). In the second study in 48 patients with mild to moderate asthma 



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who had previously been shown to have bronchoconstrictive reactions to adenosine monophosphate, 

the rate of FEV1 reduction > 15% from baseline was the same (4%) following both regadenoson  and 

placebo dosing. In the third study in 1009 patients with mild or moderate asthma (n=537) and 

moderate or severe COPD (n=472) the incidence of FEV1 reduction >15% from baseline was 1.1% 

and 2.9% in patients with asthma (p=0.15) and 4.2% and 5.4% in patients with COPD (p=0.58) 

following regadenoson  and placebo dosing, respectively. In the first and second studies, dyspnoea was 

reported as an adverse reaction following regadenoson  dosing (61% for patients with COPD; 34% for 

patients with asthma) while no subjects experienced dyspnoea following placebo dosing. In the third 

study dyspnoea was reported more frequently following regadenoson  (18% for patients with COPD; 

11% for patients with asthma) than placebo, but at a lower rate than reported during clinical 

development (see Section 4.8). A relationship between increased severity of disease and the increased 

incidence of dyspnoea was apparent in patients with asthma, but not in patients with COPD. The use 

of bronchodilator therapy for symptoms was not different between regadenoson  and placebo. 

Dyspnoea did not correlate with a decrease in FEV1. 

 

Fractional Flow Reserve (FFR) 

Haemodynamic Effects 

In the measurement of FFR, the time to peak maximum hyperaemia was 30±13 seconds. The mean 

duration of hyperaemic plateau was 163 (±169) seconds and maximum hyperaemia lasted at least 

19 seconds in 90% of patients, however, in the individual patient the duration of hyperaemia varied 

between 10 seconds to more than 10 minutes. Hyperaemia may fluctuate between sub-maximum and 

maximum until it slowly vanishes. The 10-second window of steady state hyperaemia can be too short 

for performing extensive pressure pullback recordings to assess complex or diffuse coronary artery 

disease. Repeat dosing within 10 minutes – except in patients where the duration of hyperaemia lasted 

for more than 10 minutes – caused a similar effect on peak and duration of maximum hyperaemia.  

 

Clinical efficacy and safety 

 

Clinical studies have demonstrated the efficacy and safety of regadenoson  in patients indicated for 

pharmacologic stress radionuclide MPI and for the measurement of FFR. 

 

Pharmacologic stress radionuclide MPI 

The efficacy and safety of regadenoson for pharmacologic stress radionuclide MPI were determined 

relative to adenosine in two randomised, double- blind studies (ADVANCE MPI 1 and ADVANCE 

MPI 2) in 2,015 patients with known or suspected coronary artery disease who were referred for a 

clinically-indicated pharmacologic stress MPI. A total of 1,871 of these patients had images considered 

valid for the primary efficacy evaluation, including 1,294 (69%) men and 577 (31%) women with a 

median age of 66 years (range 26-93 years of age). Each patient received an initial stress scan using 

adenosine (6-minute infusion using a dose of 0.14 mg/kg/min, without exercise) with a radionuclide 

gated SPECT (single photon emission computed tomography) imaging protocol. After the initial scan, 

patients were randomised to either regadenoson  or adenosine, and received a second stress scan with 

the same radionuclide imaging protocol as that used for the initial scan. The median time between 

scans was 7 days (range of 1-104 days). 

 

The most common cardiovascular histories included hypertension (81%), coronary artery bypass graft 

(CABG), percutaneous transluminal coronary angioplasty (PTCA) or stenting (51%), angina (63%), 

and history of myocardial infarction (41%) or arrhythmia (33%); other medical history included 

diabetes (32%) and COPD (5%). Patients with a recent history of serious uncontrolled ventricular 

arrhythmia, myocardial infarction, or unstable angina, a history of greater than first degree AV block, 

or with symptomatic bradycardia, sick sinus syndrome, or a heart transplant were excluded. A number 

of patients took cardioactive medicinal products on the day of the scan, including β-blockers (18%), 

calcium channel blockers (9%), and nitrates (6%). 

 

Comparison of the images obtained with regadenoson  to those obtained with adenosine was performed 

as follows. Using the 17-segment model, the number of segments showing a reversible perfusion defect 

was calculated for the initial adenosine study and for the randomised study obtained using regadenoson  



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or adenosine. In the pooled study population, 68% of patients had 0-1 segments showing reversible 

defects on the initial scan, 24% had 2-4 segments, and 9% had ≥ 5 segments. The agreement rate for 

the image obtained with regadenoson  or adenosine relative to the initial adenosine image was 

calculated by determining how frequently the patients assigned to each initial adenosine category (0-1, 

2-4, 5-17 reversible segments) were placed in the same category with the randomised scan. The 

agreement rates for regadenoson  and adenosine were calculated as the average of the agreement rates 

across the three categories determined by the initial scan. The ADVANCE MPI 1 and ADVANCE MPI 

2 studies, individually and combined, demonstrated that regadenoson  is similar to adenosine in 

assessing the extent of reversible perfusion abnormalities: 

 

 ADVANCE 

 

ADVANCE Combined 
 MPI 1 MPI 2 Studies 
 (n = 1,113) (n = 758) (n = 1,871) 
Adenosine – Adenosine Agreement Rate (± SE) 61 ± 3% 64 ± 4% 62 ± 3% 
Number of Patients (n) 372 259 631 
Adenosine – regadenoson  Agreement Rate (± SE) 62 ± 2% 63 ± 3% 63 ± 2% 
Number of Patients (n) 741 499 1,240 
Rate Difference (regadenoson  – Adenosine) (± 

SE) 

1 ± 4% -1 ± 5% 0 ± 3% 
95% Confidence Interval -7.5, 9.2% -11.2, 8.7% -6.2, 6.8% 

 

In ADVANCE MPI 1 and ADVANCE MPI 2, the Cicchetti-Allison and Fleiss-Cohen weighted kappas 

of the median score of three blinded readers with respect to ischaemia size category (not counting 

segments with normal rest uptake and mild/equivocal reduction in stress uptake as ischaemic) for the 

combined studies of regadenoson with the adenosine scan were moderate, 0.53 and 0.61, respectively; 

as were the weighted kappas of two consecutive adenosine scans, 0.50 and 0.55, respectively. 

 

 

Suboptimal Exercise Stress Test 

 

In the EXERRT trial the efficacy and safety of regadenoson was evaluated in patients with suboptimal 

Exercise Stress in an open-label randomized, multi-center, non-inferiority study when regadenoson 

administered either at 3 minutes during recovery (exercise with regadenoson) or at rest 1 hour later 

(regadenoson only). 

 

All 1404 patients initially had a baseline MPI scan at rest in accordance with ASNC 2009 guidelines. 

 

Patients initiated exercise using a standard or modified Bruce protocol. Patients who did not achieve ≥ 

85% maximum predicted heart rate (MPHR) and/or ≥ 5 METS (metabolic equivalents), transitioned 

into a 3-5 minutes walking recovery where during the first 3 minutes of recovery, patients were 

randomized 1:1. 

 

Therefore, 1147 patients were randomized in two groups: 578 patients from the exercise with 

regadenoson group and 569 from the regadenoson only group to either 3 minutes recovery (for the 

exercise with regadenoson group) or at rest 1 hour later (for the regadenoson only group). 

  

Patients from both groups (exercise with regadenoson and regadenoson only) underwent a SPECT 

Myocardial Perfusion Imaging (MPI) at 60-90 minutes post-regadenoson administration.  

 

The baseline MPI scan at rest, and the MPI scans for the exercise with regadenoson and regadenoson 

only groups constituted the MPI 1 phase. 

  

Subsequentially, patients from both groups, returned 1-14 days later, to undergo a second stress MPI 

regadenoson study without exercise.  

The baseline MPI scans at rest and those without exercise at 1-14 days later from both groups, 

constituted the MPI 2 phase. 
 

The images from MPI 1 and MPI 2 were compared for presence or absence of perfusion defects.  

The level of agreement between the MPI 1 (exercise with regadenoson) and the MPI 2 reads was 



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similar to the level of agreement between MPI 1 (regadenoson only) and MPI 2 reads.  

 

For two patients from the exercise with regadenoson group, a serious cardiac adverse reaction was 

reported. Upon case review, both patients, experienced ischemic symptoms and ECG changes during 

exercise or recovery prior to regadenoson administration.  

No serious cardiac adverse reactions occurred in patients receiving regadenoson 1 hour following 

inadequate exercise stress.  

 

Measurement of FFR 

For the measurement of FFR, five independent studies have been conducted. A total of 249 patients, 

who were clinically indicated to undergo coronary angiography with invasive measurement of FFR, 

received regadenoson, with 88 of those patients receiving regadenoson twice.  

FFR was measured after IV infusion of adenosine and IV injection of regadenoson (400 μg). 

Adenosine was administered first, followed by regadenoson as its hyperaemia may last unpredictably 

and the measured FFR values were compared. 

 

The most common cardiovascular conditions were patients with a medical history of hypertension, 

dyslipidemia / hypercholesterolemia, diabetes mellitus, smoking, prior PCI and prior MI.  

 

For FFR measurement, a diagnosis of inducible ischemia was made according to the measurement of 

FFR of 0.8 (>0.8 represents the absence of inducible ischemia vs ≤ 0.8 representing the presence of 

inducible ischemia). Adenosine was treated as a gold standard to estimate sensitivity, specificity, and 

the proportion of accuracy. 

 

Study Sensitivity Specificity 
Classification agreement 

Cohen’s kappa 

Stolker et al. 2015 (n=149) 98% 97% 0.94 

van Nunen et al. 2015 (n=98) 98% 95% 0.94 

 

Aminophylline 

 

Aminophylline (100 mg, administered by slow intravenous injection over 60 seconds) injected 1 minute 

after 400 micrograms regadenoson in subjects undergoing cardiac catheterisation, was shown to 

shorten the duration of the coronary blood flow response to regadenoson as measured by pulsed- wave 

Doppler ultrasonography. Aminophylline has been used to attenuate adverse reactions to regadenoson 

(see section 4.4). 

 

Effect of caffeine 

In a study of adult patients undergoing pharmacological stress radionuclide MPI with regadenoson , 

randomized to placebo (n=66) or caffeine (200 mg, n=70 or 400 mg, n=71) administered 90 minutes 

before the test, caffeine compromised the diagnostic accuracy of detecting reversible perfusion defects 

(p<0.001). There was no statistical difference between 200 mg and 400 mg caffeine with regadenoson . 

Also, there was no apparent effect of 200 mg or 400 mg of caffeine on regadenoson plasma 

concentrations. 

 

Safety and tolerability testing 

In ADVANCE MPI 1 and ADVANCE MPI 2, the following pre-specified safety and tolerability 

endpoints comparing regadenoson  to adenosine achieved statistical significance: (1) a summed score 

of both the presence and severity of the symptom groups of flushing, chest pain, and dyspnoea was 

lower with regadenoson  (0.9 ± 0.03) than with adenosine (1.3 ± 0.05); and (2) the symptom groups of 

flushing (21% vs 32%), chest pain (28% vs 40%), and ‘throat, neck or jaw pain’ (7% vs 13%) were less 

frequent with regadenoson ; the incidence of headache (25% vs 16%) was more frequent with 

regadenoson . 

 

Paediatric population 

The European Medicines Agency has deferred the obligation to submit the results of studies with 



14 

regadenoson  in one or more subsets of the paediatric population with myocardial perfusion 

disturbances (see section 4.2 for information on paediatric use). 

 

5.2 Pharmacokinetic properties 
 

Absorption 

Regadenoson  is administered by intravenous injection for pharmacologic stress radionuclide MPI. The 

regadenoson plasma concentration-time profile in healthy volunteers is multi-exponential in nature and 

best characterised by 3-compartment model. The maximal plasma concentration of regadenoson is 

achieved within 1 to 4 minutes after injection of regadenoson  and parallels the onset of the 

pharmacodynamic response (see section 5.1). The half-life of this initial phase is approximately 2 to 4 

minutes. An intermediate phase follows, with a half-life on average of 30 minutes coinciding with loss 

of the pharmacodynamic effect. The terminal phase consists of a decline in plasma concentration with a 

half-life of approximately 2 hours. Within the dose range of 0.003-0.02 mg/kg (or approximately 

0.18-1.2 mg) in healthy subjects, clearance, terminal half-life or volume of distribution do not appear 

dependent upon the dose. 

 

Distribution 

Regadenoson is moderately bound to human plasma proteins (25-30%). 

 

Biotransformation 

The metabolism of regadenoson is unknown in humans. Incubation with rat, dog, and human liver 

microsomes as well as human hepatocytes produced no detectable metabolites of regadenoson. 

Following intravenous administration of 
14

C-radiolabeled regadenoson to rats and dogs, most 

radioactivity (85-96%) was excreted in the form of unchanged regadenoson. These findings indicate 

that metabolism of regadenoson does not play a major role in the elimination of regadenoson. 

 

Elimination 

In healthy volunteers, 57% of the regadenoson dose is excreted unchanged in the urine (range 19-77%), 

with an average plasma renal clearance around 450 ml/min, i.e., in excess of the glomerular filtration 

rate. This indicates that renal tubular secretion plays a role in regadenoson elimination. 

 

Multiple injections 

Up to three consecutive injections of regadenoson (100 and 200 μg) have been tested in healthy 

volunteers, and two consecutive doses of 400 μg in healthy volunteers, as well as in patients assessed 

for FFR. Transient dose dependent increases in heart rate occurred following administration of each 

dose of regadenoson, whereas no consistent dose-related effect on systolic blood pressure was 

observed. Mean plasma concentrations increased in a dose-related manner and by successive doses as 

observed in healthy volunteers. 

Special populations 

A population pharmacokinetic analysis including data from subjects and patients demonstrated that 

regadenoson clearance decreases in parallel with a reduction in creatinine clearance (CLcr) and 

increases with increased body weight. Age, gender, and race have minimal effects on the 

pharmacokinetics of regadenoson. 

 

Renal impairment 

The disposition of regadenoson was studied in 18 subjects with various degrees of renal function and in 

6 healthy subjects. With increasing renal impairment, from mild (CLcr 50 to < 80 ml/min) to moderate 

(CLcr 30 to < 50 ml/min) to severe renal impairment (CLcr < 30 ml/min), the fraction of regadenoson 

excreted unchanged in urine and the renal clearance decreased, resulting in increased elimination half-

lives and AUC values compared to healthy subjects (CLcr ml/min). However, the maximum observed 

plasma concentrations as well as volumes of distribution estimates were similar across the groups. The 

plasma concentration-time profiles were not significantly altered in the early stages after dosing when 

most pharmacologic effects are observed. No dose adjustment is needed in patients with renal 

impairment.  

 



15 

The pharmacokinetics of regadenoson in patients on dialysis has not been assessed.  

 

Hepatic impairment 

Greater than 55% of the regadenoson dose is excreted unchanged in the urine and factors that decrease 

clearance do not affect the plasma concentration in the early stages after dosing when clinically 

meaningful pharmacologic effects are observed. The pharmacokinetic parameters of regadenoson have 

not been specifically evaluated in those with varying degrees of hepatic impairment. However, post-hoc 

analysis of data from the two Phase 3 clinical trials showed that the pharmacokinetics of regadenoson 

were not affected in a small subset of patients with laboratory values suggestive of impaired hepatic 

function (2.5-fold transaminase elevation or 1.5-fold elevation of serum bilirubin or prothrombin time). 

No dose adjustment is needed in patients with hepatic impairment. 

 

Elderly patients 

Based on a population pharmacokinetic analysis, age has a minor influence on the pharmacokinetics of 

regadenoson. No dose adjustment is needed in elderly patients. 

 

Paediatric population 

The pharmacokinetic parameters of regadenoson have not yet been studied in the paediatric population 

(< 18 years). 

 

5.3 Preclinical safety data 
 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, single and repeated dose toxicity, genotoxicity, or embryo-fetal development. Signs of 

maternal and fetal toxicity were seen in rats and rabbits (reduced fetal weights, delays in ossification 

[rats], reduced litter size and number of live fetuses [rabbits]), but not teratogenicity. Fetal toxicity was 

noted following repeated daily administration of regadenoson, but at doses sufficiently in excess of the 

recommended human dose. Fertility and pre- and post-natal studies have not been conducted. 

 

 

6. PHARMACEUTICAL PARTICULARS 
 

6.1 List of excipients 
 

Disodium phosphate dihydrate 

Sodium dihydrogen phosphate monohydrate  

Propylene glycol 

Disodium edetate  

Water for injections 

 

6.2 Incompatibilities 
 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 

products. 

 

 

6.3 Shelf life 
 

4 years 

 

6.4 Special precautions for storage 
 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 
 

5 ml solution in a single use Type 1 glass vial with (butyl) rubber stopper and aluminium over-seal.  



16 

 

Pack size of 1. 

 

6.6 Special precautions for disposal and other handling 
 

This medicinal product should be inspected visually for particulate matter and discolouration prior to 

administration. 

 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 
 

GE Healthcare AS 

Nycoveien 1 

NO-0485 Oslo 

Norway 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 
 

EU/1/10/643/001 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 

Date of first authorisation: 06/09/2010 

Date of latest renewal: 24/04/2015 

 

 

10. DATE OF REVISION OF THE TEXT 
 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

http://www.ema.europa.eu./
http://www.ema.europa.eu./


17 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING 
SUPPLY AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 



18 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 

Name and address of the manufacturer responsible for batch release 

 

AndersonBrecon (UK) Ltd  

Wye Valley Business Park  

Hay-on-Wye, Hereford  

HR3 5PG, United Kingdom 

 

 

 

Millmount Healthcare Limited,  

Block 7, City North Business Campus,  

Stamullen, Co Meath, K32 YD60 

Ireland 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 

Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION 

 

• Periodic Safety Update Reports 

 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE 
USE OF THE MEDICINAL PRODUCT  

 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 

agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 

updates of the RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 
being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

 

If the dates for submission of a PSUR and the update of a RMP coincide, they can be submitted at the 

same time. 

 

 



19 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

 



20 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



21 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

OUTER CARTON 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Rapiscan 400 microgram solution for injection  

regadenoson 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each 5 ml vial contains 400 micrograms regadenoson (80 micrograms/ml). 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: Disodium phosphate dihydrate, sodium dihydrogen phosphate monohydrate, propylene 

glycol, disodium edetate, water for injections 

 

See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Solution for injection 

1 vial  

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use. 

For single use only. 

Read the package leaflet before use.  

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

Use product only in medical facilities with cardiac monitoring and resuscitation equipment. 

For diagnostic use only. 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 



22 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

 

GE Healthcare AS 

Nycoveien 1 

NO-0485 Oslo 

Norway 

 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/10/643/001 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC: {number}  

SN: {number} 

NN: {number}  

 



23 

 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

VIAL LABEL 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Rapiscan 400 microgram solution for injection  

Regadenoson 

Intravenous use 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

400 micrograms 

 

 

6. OTHER 

 



24 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 
 



25 

PACKAGE LEAFLET: INFORMATION FOR THE USER 

 

Rapiscan 400 microgram solution for injection 

Regadenoson 

 

Read all of this leaflet carefully before you are given this medicine because it contains important 

information for you. 

 

- Keep this leaflet. You may need to read it again. 
- If you have any further questions, ask your doctor or pharmacist. 
If you get any side effects, talk to your doctor, or pharmacist. This includes any possible side effects not 

listed in this leaflet. See section 4.  

 

What is in this leaflet: 

1. What Rapiscan is and what it is used for 
2. What you need to know before you are given Rapiscan 
3. How Rapiscan is given 
4. Possible side effects 
5. How to store Rapiscan 
6. Contents of the pack and other information 
 

 

1. What Rapiscan is and what it is used for 
 

Rapiscan contains the active substance regadenoson. This belongs to a group of medicines called 

‘coronary vasodilators’. It makes the heart arteries expand and heart rate increase. This makes more 

blood flow to the muscles of the heart. 

 

This medicine is for diagnostic use only. 

 

Rapiscan is used in a type of heart scan in adults called ‘myocardial perfusion imaging’. 

 

The scan uses a radioactive substance called a ‘radiopharmaceutical’ to create images. These images 

show how well blood flows to the muscles of the heart. Usually, exercise on a treadmill is used to put 

the heart under stress before a scan. During the exercise, a small amount of radiopharmaceutical is 

injected into the body, often into a vein in the hand. Images are then taken of the heart. The doctor can 

then see if the heart muscles are getting enough blood flow when it is under stress.  

If you are unable to exercise enough to reach sufficient stress to the heart, Rapiscan will be injected to 

provide a stress of similar amplitude to the heart to increase the blood flow.  

 

Rapiscan is also used during catheterisation and imaging arteries of the heart (invasive coronary 

angiography) to expand the arteries of the heart to measure the difference in pressure, caused by a 

narrowing within one or more arteries. During cardiac catheterisation, a long thin tube called a 

catheter is inserted either through your femoral or radial artery and threaded through your blood 

vessels to your heart. The doctor performing the catheterisation may also want to measure the 

difference in pressure (fractional flow reserve) due to a narrowing detected in one or more arteries of 

the heart. 

 

2. What you need to know before you are given  Rapiscan 
 

Do not take Rapiscan: 

• if you have slow heart rate (high degree heart block or sinus node disease), and don’t have a 
pacemaker fitted. 

• if you have chest pain that occurs unpredictably (unstable angina) and that has not improved 
after treatment. 

• if you have low blood pressure (hypotension). 

• if you have heart failure. 



26 

• if you are allergic to regadenoson or any of the other ingredients of Rapiscan listed in section 6 
of this leaflet. 

 

Talk to your doctor or nurse before taking Rapiscan 

Your doctor needs to know before you are given Rapiscan: 

• if you have had a recent serious heart problem (for example a heart attack or abnormal heart 
rhythms). 

• if you have a heart rhythm where your heartbeat is very fast or uneven (atrial fibrillation or 
atrial flutter) 

• if you have high blood pressure that is not controlled, especially if this has been accompanied 
by recent episodes of nose bleed, headache or blurred or double vision. 

• if you have had episodes of mini strokes (called transient ischaemic attacks)  

• if you have a heart rhythm disorder called long QT syndrome. 

• if you have episodes of heart block (which can slow the heart down) or a very slow heart rate.  

• if you have any heart or blood vessel condition, particularly one that gets worse when your 
blood pressure decreases. These include low blood volume (caused, for example, by severe 

diarrhoea or dehydration or taking water pills), inflammation around the heart (pericarditis) and 

some forms of heart valve or artery disease (for example, aortic or mitral stenosis). 

• if you have a condition that causes fits (seizures), such as epilepsy, or if you have ever had fits. 

• if you have asthma or lung disease. 
If any of these apply to you, tell your doctor before you are given the injection. 

 

Children and adolescents  

Rapiscan should not be used in children and adolescents below the age of 18 years. 

 

Other medicines and Rapiscan 

Please tell your doctor if you are taking or have recently taken any other medicines including medicines 

obtained without prescription. 

 

Particular care should be taken with the following medicines: 

• theophylline, a medicine used to treat asthma and other lung diseases, must not be used for at 
least 12 hours before you are given Rapiscan because it can block the effect of Rapiscan. 

• dipyridamole, a medicine used to prevent blood clots, must not be used for at least two days 
before you are given Rapiscan because it can change the effect of Rapiscan. 

 

Rapiscan with food and drink 

Do not eat food or have drinks containing caffeine (for example, tea, coffee, cocoa, cola or chocolate) 

for at least 12 hours before you are given Rapiscan. This is because caffeine can interfere with the 

effect of Rapiscan. 

 

Pregnancy and breast-feeding  

Before you are given Rapiscan, tell your doctor: 

• if you are pregnant, think you are pregnant or planning to have a baby. There is no adequate 
information on the use of Rapiscan in pregnant women. Harmful effects have been seen in 

animal studies but it is not known if there is a risk to humans. Your doctor will only give you 

Rapiscan if it is clearly necessary. 

• if you are breast-feeding. It is not known whether Rapiscan can pass into breast milk and will 
only be given to you if your doctor thinks it is necessary. You should avoid breast-feeding for at 

least 10 hours after you are given Rapiscan. 

 

Ask your doctor for advice before using any medicine. 

 

Driving and using machines 

Rapiscan may make you feel dizzy. It may cause other symptoms (headache or shortness of breath) 

that could affect your ability to drive or use machinery. These effects usually do not last longer than 

30 minutes. Do not drive or operate machinery until these effects have improved. 



27 

 

Rapiscan contains sodium  

This medicine contains less than 1 mmol sodium (23 mg) per dose. After you have been given 

Rapiscan, you will be given an injection of sodium chloride 9 mg/ml (0.9%) solution which contains 

45 mg of sodium. To be taken into consideration if you are on a controlled sodium diet. 

 

3. How Rapiscan is given 
 

Rapiscan is injected by a healthcare professional (a doctor, nurse or medical technician) in a 

medical facility where your heart and blood pressure can be monitored. It is injected directly into a 

vein, as a single dose of 400 micrograms in a 5 ml solution – the injection will take about 10 seconds 

to complete. The dose injected does not depend on your weight. 

 

You will also be given an injection of sodium chloride 9 mg/ml (0.9%) solution (5 ml), and an 

injection of a small amount of a radioactive substance (radiopharmaceutical). 

When you are given Rapiscan, your heart rate will increase quickly. Your heart rate and blood 

pressure will be monitored. 

 

After the Rapiscan injection you will need to sit or lie down until your heart rate and blood pressure 

return to your normal levels. The doctor, nurse or medical technician will let you know when you can 

stand up. 

 

A scan of your heart will be made after enough time has passed to allow the radiopharmaceutical to 

reach the heart muscle.  

During catheterisation of the arteries of the heart, your doctor may measure the pressure difference 

(also known as fractional flow reserve – FFR) due to a narrowing in one or more arteries of the heart.  

 

If deemed necessary, a second dose of 400 micrograms can be injected at least 10 minutes after the first 

dose for such pressure difference measurement during the same catheterization procedure. Heart rate 

and blood pressure will be monitored during the entire procedure. 

 

 

If you are given more Rapiscan than you should 

Some people have had flushing, dizziness and increased heart rate when they have been given too 

much Rapiscan. If your doctor thinks that you are having severe side effects, or the effects of Rapiscan 

are lasting too long, they may give you an injection of a medicine called aminophylline that reduces 

these effects. 

 

4. Possible side effects 
 

Like all medicines, Rapiscan can cause side effects, although not everybody gets them. 

 

The side effects are usually mild. They normally start soon after the Rapiscan injection and are 

usually over within 30 minutes. They don’t usually need any treatment. 

 

More serious side effects include: 

• sudden stopping of the heart or damage to the heart, heart block (a disorder of the heart’s 
electrical signal, where the signal cannot pass from the upper to the lower chambers), rapid 

heart beat 

• low blood pressure which may result in fainting or mini strokes (including weakness of the face 
or an inability to speak). Rarely, Rapiscan can cause a stroke (also known as a cerebrovascular 

accident). 

• an allergic reaction which can cause rash, wheals/weals, swelling under the skin near the eyes or 
throat, throat tightness, and difficulty in breathing may occur immediately or have delayed onset 

after Rapiscan injection 

 

Tell your doctor straight away if you think you are having severe side effects. Your doctor may then 



28 

give you an injection of a medicine called aminophylline that reduces these effects. 

 

Very common side effects 

(affects more than 1 user in 10) 

• headache, dizziness 

• shortness of breath 

• chest pain 

• changes in heart tracing tests (electrocardiogram) 

• flushing 

• discomfort in the stomach 
 

Common side effects 

(affects 1 to 10 users in 100) 

• heart pain (angina), abnormal heart rhythms, rapid heart beat, feeling the heart skipping a beat, 
fluttering, or beating too hard or fast (palpitations) 

• low blood pressure 

• throat tightness, throat irritation, cough 

• being sick (vomiting), feeling sick (nausea) 

• feeling unwell or weak 

• excessive sweating 

• pain in the back, arms, legs, neck or jaw 

• discomfort in the bones and muscles 

• pins and needles, reduced sensation, taste changes 

• discomfort in the mouth 
 

Uncommon side effects 

(affects 1 to 10 users in 1,000) 

• sudden stopping of the heart or damage to the heart, heart block (a disorder of the heart’s 
electrical signal, where the signal cannot pass from the upper to the lower chambers), slow heart 

beat 

• fits, fainting, mini strokes (including weakness of the face or an inability to speak), reduced 
responsiveness (which may include a comatose state), trembling, sleepiness 

• an allergic reaction which can cause rash, wheals/weals, swelling under the skin near the eyes or 
throat, throat tightness, difficulty breathing 

• wheezing 

• rapid breathing 

• high blood pressure, paleness, cold extremities 

• blurred vision, eye pain 

• anxiety, difficulty sleeping 

• ringing in the ears 

• bloating, diarrhoea, involuntary loss of faeces 

• redness of the skin 

• pain in the joints 

• pain or discomfort around the area injected, body pain 
 

Not known 

(frequency cannot be estimated from the available data) 

• difficulty in breathing (bronchospasm) 

• respiratory arrest 
 

Reporting of side effects 

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects you can help provide more information on the safety of this 

medicine. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


29 

5. How to store Rapiscan 
 

Keep out of the reach and sight of children. 

 

Do not use Rapiscan after the expiry date which is stated on the vial and carton after EXP. This medicine 

does not require any special storage conditions. 

 

Rapiscan must not be used if the solution if it is discoloured or particulate matter is present. 

 

Medicines should not be disposed of via wastewater or household waste. These measures will help to protect 

the environment . The healthcare professionals will be responsible for the storage and disposal of this 

medicinal product.  

 

6. Contents of the pack and further information  
 

What Rapiscan contains 

The active substance in Rapiscan is regadenoson. Each 5 ml vial of Rapiscan contains 400 micrograms of 

regadenoson. 

 

The other ingredients are: disodium edetate, disodium phosphate dihydrate, sodium dihydrogen phosphate 

monohydrate, propylene glycol, water for injections. 

 

What Rapiscan looks like and contents of the pack 

Rapiscan solution for injection is a clear, colourless solution with no particles visible. Rapiscan is supplied in 

a carton containing a single use 5 ml glass vial with a rubber stopper and aluminium sealed cap. 

 

Marketing Authorisation Holder and Manufacturer 

 

Marketing Authorisation Holder:  

 

GE Healthcare AS 

Nycoveien 1 

NO-0485 Oslo 

Norway 

 

Manufacturer:  

 

AndersonBrecon (UK) Ltd  

Wye Valley Business Park  

Hay-on-Wye, Hereford  

HR3 5PG, United Kingdom 

 

 

Millmount Healthcare Limited  

Block 7, City North Business Campus,  

Stamullen, Co Meath, K32 YD60 Ireland 

 

 

 

 

 

 

 

 

 

 

 



30 

 

This leaflet was last revised in MM/YYYY 

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency website: 

http://www.ema.europa.eu 

 

This leaflet is available in all EU/EEA languages on the European Medicines Agency website. 

 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


31 

 

The following information is intended for healthcare professionals only: 

 

Rapiscan should be administered as a rapid, 10-second injection into a peripheral vein using a 22-gauge or 

larger catheter or needle. 

 

5 ml of sodium chloride 9 mg/ml (0.9%) solution for injection should be administered immediately after the 

injection of Rapiscan. 

 

The radiopharmaceutical for the myocardial perfusion imaging agent should be administered 10-20 seconds 

after the sodium chloride 9 mg/ml (0.9%) solution for injection. The radiopharmaceutical may be injected 

directly into the same catheter as Rapiscan. 

 

 

For the measurement of FFR, Rapiscan should be administered as a rapid, 10-second injection into a 

peripheral vein using a 22-gauge or larger catheter or needle. 10 mL of sodium chloride 9 mg/ml 

(0.9%) solution for injection should be administered immediately after the injection of Rapiscan. 

Standard catheterisation and FFR measurement techniques are to be followed, and FFR should be measured 

as the lowest value of Pd/Pa achieved during steady state maximum hyperemia. 

 

If deemed necessary, a second dose of 400 micrograms can be injected at least 10 minutes after the 

first dose for FFR measurement during the same catheterization procedure. 

 

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 

products. 

 

This medicinal product should be inspected visually for particulate matter and discolouration prior to 

administration. 

 

Any unused product or waste material should be disposed of in accordance with local requirements. 

 

For further information, please refer to the complete Summary of Product Characteristics.  


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET