Skip to Content
How to talk to a doctor about advanced ovarian cancer >>

Regadenoson

Class: Cardiac Function
VA Class: CV900
Chemical Name: Adenosine, 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]-, monohydrate
Molecular Formula: C15H18N8O5 • H2O
CAS Number: 875148-45-1
Brands: Lexiscan

Introduction

Pharmacologic stress test agent; A2A adenosine receptor agonist.1 2 3 4 5 6 7 8

Uses for Regadenoson

Radionuclide Myocardial Perfusion Imaging

Adjunct to radionuclide myocardial perfusion imaging in patients unable to undergo adequate stress testing with exercise.1 2 3

Regadenoson Dosage and Administration

Administration

IV Administration

Administer by rapid (i.e., over approximately 10 seconds) IV injection into a peripheral vein.1 Use 22-gauge or larger catheter or needle.1

After injection, immediately flush with 5 mL of 0.9% sodium chloride injection.1

Administer radionuclide myocardial perfusion imaging agent 10–20 seconds after flush; may inject radionuclide directly into same catheter as regadenoson.1 3 9

Some clinicians suggest BP monitoring every minute during infusion and 3–5 minutes into recovery.3 ECG monitoring also recommended.3

Rate of Administration

Administer over approximately 10 seconds.1

Dosage

Adults

Radionuclide Myocardial Perfusion Imaging
IV

0.4 mg (5 mL).1 3 9 (See Administration under Dosage and Administration.)

Special Populations

Hepatic Impairment

Dosage adjustment not necessary.1 6 9

Renal Impairment

Dosage adjustment not necessary.1 6 9

Geriatric Patients

Dosage adjustment not necessary.1 6 9

Cautions for Regadenoson

Contraindications

  • Second- or third-degree AV block (except in patients with a functioning artificial pacemaker).1 3

  • Sinus node dysfunction (except in patients with a functioning artificial pacemaker).1 3

  • Known hypersensitivity to regadenoson or any ingredient in the formulation.3 9

Warnings/Precautions

Cardiovascular and Cerebrovascular Effects

Serious cardiovascular and cerebrovascular events, including myocardial ischemic events, rhythm and conduction abnormalities, hypotension, hypertension, and stroke, reported rarely.1 32 Ensure availability of cardiac resuscitation equipment and trained staff prior to administration.1

Myocardial Ischemic Events

Risk of rare but serious adverse cardiovascular events, including MI and death, in patients receiving regadenoson as a cardiac stress testing agent during myocardial perfusion imaging; similar risk also observed with adenosine, another pharmacologic stress test agent.1 32 33 34 37 38

Avoid use in patients with signs and symptoms of acute myocardial ischemia (e.g., unstable angina, cardiovascular instability).1 32

If serious adverse reactions occur, may consider use of aminophylline, an adenosine antagonist, to shorten duration of increased coronary blood flow.1 However, do not use aminophylline in patients with regadenoson-associated seizures.1 (See Seizures under Cautions.)

Rhythm and Conduction Abnormalities

New-onset or recurrent supraventricular tachyarrhythmias, including atrial fibrillation with rapid ventricular response and atrial flutter, reported.1

Risk of first-, second-, or third-degree AV block, or sinus bradycardia requiring intervention.1 (See Contraindications under Cautions.)

Profound sinus bradycardia (heart rate <40 beats/minute) considered a relative contraindication to regadenoson stress testing by some clinicians.3

Hemodynamic and Associated Effects

Possible hypotension due to the vasodilating effects of the drug.1 3

Risk of serious hypotension may be increased 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.1 3

Clinically important increases in BP also possible; generally transient, resolving within 10–15 minutes.1

Cerebrovascular events (e.g., syncope, TIA, hemorrhagic or ischemic stroke, seizures) possibly related to hemodynamic effects of regadenoson reported.1

Respiratory Effects

Risk of dyspnea, bronchoconstriction, and respiratory compromise.1

Ensure availability of appropriate bronchodilator therapy and resuscitative measures prior to administration in patients with known or suspected bronchoconstrictive disease, COPD, or asthma.1

Some clinicians consider bronchospasm a contraindication to regadenoson stress testing.3

Seizures

Risk of new-onset or recurrent seizures, including tonic-clonic seizures.1 10 In some cases, seizure activity may be prolonged and require emergency management.1 10

Concomitant use of aminophylline may increase risk of seizures.1 (See Specific Drugs under Interactions.)

Sensitivity Reactions

Hypersensitivity

Risk of hypersensitivity reactions, possibly requiring resuscitative measures; manifestations have included anaphylaxis, angioedema, cardiac/respiratory arrest, decreased oxygen saturation, hypotension, throat tightness, urticaria, and rash.1 (See Contraindications under Cautions.)

Ensure immediate availability of appropriate personnel and resuscitative equipment.1

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether regadenoson is distributed into milk.1 Interrupt nursing or discontinue drug.1 Based on pharmacokinetics of regadenoson, may consider interrupting nursing for 10 hours after drug administration.1

Pediatric Use

Safety and efficacy not established in pediatric patients ≤18 years of age.1

Geriatric Use

Similar adverse effect profile in patients ≥75 years of age and younger adults (i.e., patients <65 years of age); however, higher incidence of hypotension observed in older patients.1

Population pharmacokinetic analysis indicate that age has minimal influence on pharmacokinetics of regadenoson;1 however, decreased renal clearance may occur with increasing age.7 9

Hepatic Impairment

Effect of hepatic impairment on pharmacokinetics of regadenoson not established.1

Renal Impairment

Reduced clearance is possible with increasing renal impairment.1 6 8 9 (See Special Populations under Pharmacokinetics.) However, serious adverse effects related to renal impairment generally have not been reported.1

Pharmacokinetics of regadenoson not established in patients undergoing dialysis.1 8 Prolonged chest discomfort and nausea have been reported in at least one dialysis-dependent patient who received the drug.8

Common Adverse Effects

Dyspnea,1 2 3 headache,1 2 3 flushing,1 2 3 chest discomfort,1 2 3 angina pectoris or ST-segment depression,1 2 3 dizziness,1 2 3 chest pain,1 2 3 nausea,1 2 3 abdominal discomfort,1 2 3 dysgeusia,1 3 warm feeling.1 3

Interactions for Regadenoson

Drugs Metabolized by Hepatic Microsomal Enzymes

Does not inhibit CYP1A2, 2C8, 2C9, 2C19, 2D6, or 3A4 in human liver microsomes; unlikely to alter pharmacokinetics of drugs metabolized by these CYP isoenzymes.1

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Have been administered concurrently with no apparent differences in safety and efficacy1

β-Adrenergic blocking agents

Have been administered concurrently with no apparent differences in safety and efficacy1

Some clinicians state that anti-ischemic cardiac drugs such as β-adrenergic blocking agents should be discontinued for ≥48 hours prior to performing diagnostic imaging3

Angiotensin II receptor antagonists

Have been administered concurrently with no apparent differences in safety and efficacy1

Calcium channel-blocking agents

Have been administered concurrently with no apparent differences in safety and efficacy1

Some clinicians state that anti-ischemic cardiac drugs such as calcium channel-blocking agents should be discontinued for ≥48 hours prior to performing diagnostic imaging3

Cardiac glycosides

Have been administered concurrently with no apparent differences in safety and efficacy1

Dipyridamole

Potential increased activity of regadenoson1

If possible, withhold dipyridamole for ≥2 days prior to regadenoson administration1 3

Methylxanthines (aminophylline, caffeine, theophylline)

Inhibits vasodilating effects of regadenoson1

Aminophylline: May be used to terminate persistent adverse effects of regadenoson; however, may increase risk of seizures associated with regadenoson1

Avoid methylxanthines (theophylline, aminophylline, caffeinated beverages) for ≥12 hours prior to regadenoson administration1 3

Some clinicians suggest that aminophylline be avoided for 24 hours before regadenoson administration;3 use clinical judgment9

Avoid methylxanthines in patients who experience regadenoson-associated seizures1

Nitrates

Have been administered concurrently with no apparent differences in safety and efficacy1

Some clinicians state that anti-ischemic cardiac drugs such as nitrates should be discontinued for ≥48 hours prior to performing diagnostic imaging3

Regadenoson Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations achieved within 1–4 minutes following IV injection.1 3 8

Elimination

Metabolism

Not fully elucidated; does not appear to be metabolized by CYP isoenzymes.9 No detectable metabolites have been identified.1

Elimination Route

In healthy adults, approximately 57% of regadenoson is eliminated unchanged in urine (range: 19–77%);1 6 7 renal tubular secretion also involved.1 7

Half-life

Initial phase: 2–4 minutes (onset of pharmacodynamic response).1

Intermediate phase: Approximately 30 minutes (loss of pharmacodynamic effect).1

Terminal phase: Approximately 2 hours (decrease in plasma concentrations).1

Special Populations

Decreased clearance and increased half-life and AUC observed with increasing renal impairment.1 6 8 9 However, plasma concentration-time profile not substantially altered in early stages after dosing when most pharmacologic effects observed.1 6 (See Renal Impairment under Dosage and Administration.)

Increased clearance observed with increased body weight.1

Minimal effects of age, gender, and race on regadenoson pharmacokinetics.1

Stability

Storage

Parenteral

Injection

25°C (15–30°C permitted).1

Actions

  • Low affinity A2A adenosine receptor agonist.1 3 4 5 7 Activation of the A2A adenosine receptor induces coronary vasodilation and increases coronary blood flow.1 3

  • Increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, resulting in a greater difference in radiopharmaceutical uptake in myocardium supplied by normal versus stenotic coronary arteries.1

  • Hemodynamic effects include reductions in BP and increases in heart rate.1

  • Binds to the A1 adenosine receptor with at least tenfold lower affinity; no appreciable binding affinity for A2B and A3 receptors.1 3 4 5 7 A2B and A3 adenosine receptors have been implicated in the pathophysiology of bronchoconstriction in susceptible individuals (i.e., asthmatics).1 (See Respiratory Effects under Cautions.)

Advice to Patients

  • Importance of informing patients about serious adverse effects associated with regadenoson, such as MI, arrhythmias, cardiac arrest, heart block, substantial changes in BP, bronchoconstriction, hypersensitivity reactions, seizures, and stroke.1

  • Importance of instructing patients to avoid consumption of any products containing methylxanthines (e.g., caffeinated coffee, tea, other caffeinated beverages, caffeine-containing drug products, aminophylline, theophylline) for at least 12 hours before scheduled radionuclide myocardial perfusion imaging.1 3

  • Importance of informing patients, prior to regadenoson administration, of the most common adverse effects that have been reported in association with use of regadenoson during myocardial perfusion imaging (e.g., shortness of breath, headache, flushing).1 3

  • Importance of informing patients with COPD or asthma to discuss their respiratory history and administration of pre- and post-study bronchodilator therapy with their clinician before scheduling a myocardial perfusion imaging study with regadenoson.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., aminophylline, theophylline), as well as any concomitant illnesses (e.g., COPD, asthma, seizure disorder).1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Regadenoson (Monohydrate)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV Use

0.08 mg/mL (of anhydrous regadenoson)

Lexiscan (available as 5-mL, single-use prefilled syringes)

Astellas

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.

References

1. Astellas Pharma US, Inc. Lexiscan (regadenoson) injection prescribing information. Northbrook, IL; 2014 July.

2. Iskandrian AE, Bateman TM, Belardinelli L et al. Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial. J Nucl Cardiol. 2007 Sep-Oct; 14:645-58.

3. Henzlova MJ, Cerqueira MD, Hansen CL et al. ASNC imaging guidelines for nuclear cardiology procedures: stress protocols and tracers. J Nucl Cardiol. 2009. Available from website. Accessed 2009 Feb 27.

4. Thomas GS, Tammelin BR, Schiffman GL et al. Safety of regadenoson, a selective adenosine A2A agonist, in patients with chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled trial (RegCOPD trial). J Nucl Cardiol. 2008; 15:319-28. [PubMed 18513638]

5. Leaker BR, O’Connor B, Hansel TT et al. Safety of regadenoson, an adenosine A2A receptor agonist for myocardial perfusion imaging, in mild asthma and moderate asthma patients: a randomized, double-blind, placebo-controlled trial. J Nucl Cardiol. 2008; 15:329-36. [PubMed 18513639]

6. Gordi T, Blackburn B, Lieu H. Regadenoson pharmacokinetics and tolerability in subjects with impaired renal function. J Clin Pharmacol. 2007; 47:825-33. [PubMed 17585115]

7. Gordi T, Frohna P, Sun HL et al. A population pharmacokinetic/pharmacodynamic analysis of regadenoson, an adenosine A2A-receptor agonist, in healthy male volunteers. Clin Pharmacokinet. 2006; 45:1201-12. [PubMed 17112296]

8. Laighold S, Druz R. Initial clinical experience with a selective A2A receptor agonist, regadenoson, in a patient with end-stage renal disease on hemodialysis. J Nucl Cardiol. 2009. Published online 22 Jan 2009.

9. Astellas Pharma US Inc, Deerfield, IL: Personal communication.

10. Page RL, Spurck P, Bainbridge JL et al. Seizures associated with regadenoson: a case series. J Nucl Cardiol. 2012; 19:389-91. [PubMed 22002651]

32. US Food and Drug Administration. FDA drug safety communications: FDA warns of rare but serious risk of heart attack and death with cardiac nuclear stress test drugs Lexiscan (regadenoson) and Adenoscan (adenosine). 2013 Nov 20. From the FDA website.

33. Shah S, Parra D, Rosenstein RS. Acute myocardial infarction during regadenoson myocardial perfusion imaging. Pharmacotherapy. 2013; 33:e90-5. [PubMed 23471769]

34. Hsi DH, Marreddy R, Moshiyakhov M et al. Regadenoson induced acute ST-segment elevation myocardial infarction and multivessel coronary thrombosis. J Nucl Cardiol. 2013; 20:481-4. [PubMed 23460076]

35. Iskandrian AE, Bateman TM, Belardinelli L et al. Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial. J Nucl Cardiol. 2007 Sep-Oct; 14:645-58. [PubMed 17826318]

36. Cavalcante JL, Barboza J, Ananthasubramaniam K. Regadenoson is a safe and well-tolerated pharmacological stress agent for myocardial perfusion imaging in post-heart transplant patients. J Nucl Cardiol. 2011; 18:628-33. [PubMed 21626090]

37. Polad JE, Wilson LM. Myocardial infarction during adenosine stress test. Heart. 2002; 87:E2. [PubMed 11796565]

38. Raza JA, Khan NU, Mustafa JS et al. ST segment elevation during adenosine pharmacological stress testing in a patient with coronary artery disease. Am Heart Hosp J. 2009; 7:E122-4. [PubMed 20354958]

Hide