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Adenosine

Pronunciation

Class: Class IV Antiarrhythmics
VA Class: CV300
Chemical Name: 6-Amino-9-β-dribofuranosyl-9H-purine
Molecular Formula: C10H13N5O4
CAS Number: 58-61-7
Brands: Adenocard, Adenoscan

Introduction

Antiarrhythmic and pharmacologic stress test agent; endogenous nucleoside.1 2 3 4 17 24 31

Uses for Adenosine

Do not confuse Adenosine (Adenocard, Adenoscan) with adenosine phosphate (used as adjunctive therapy in the treatment of complications of varicose veins; see Adenosine Phosphate 92:92.). No evidence to suggest that the drugs are therapeutic alternatives.

Treatment of Supraventricular Tachyarrhythmias

Termination of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (e.g., Wolff-Parkinson-White syndrome).1 14 24 26 31

Drug of choice for terminating stable, regular narrow-QRS-complex (narrow-complex) tachycardias, including supraventricular tachycardias (SVTs).7 26 31

Attempt appropriate vagal maneuvers (e.g., Valsalva maneuver, carotid sinus massage) when clinically indicated prior to adenosine use.1 24 31

Also has been recommended for treatment of stable, wide-complex tachycardias of supraventricular origin+ 28 31 or those with a previously defined reentry pathway.31

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May consider adenosine in patients with unstable narrow-complex reentry SVT while preparing for cardioversion; however, do not delay cardioversion to administer the drug or to establish IV access.31 (See Cardiovascular and Cerebrovascular Effects under Cautions.)

Not effective in terminating arrhythmias not due to reentry involving the AV or sinus node (e.g., atrial flutter, atrial fibrillation, ventricular tachycardia).1 4 14 24 31 Risk of serious arrhythmias and/or hypotension in patients with preexcited arrhythmias.18 19 26 27 29 (See Cardiovascular and Cerebrovascular Effects under Cautions.)

Some clinicians state that adenosine is contraindicated in patients with atrial fibrillation or flutter associated with Wolff-Parkinson-White syndrome; risk of dramatically accelerating ventricular rate.28 31

Considered drug of choice for SVT in infants and children when drug therapy indicated.31 May attempt appropriate vagal maneuvers first in those with probable SVT provided such intervention does not delay chemical or electrical cardioversion.31 If vascular access is immediately available, may administer adenosine by rapid IV injection.3 31 However, if patient unstable or vascular access not readily available, implement cardioversion immediately.3 31

May be used in pediatric patients with wide-complex tachycardias prior to synchronized cardioversion (to determine if the rhythm is SVT with aberrancy).31 Do not delay cardioversion to administer adenosine.31 (See Cardiovascular and Cerebrovascular Effects under Cautions.)

Thallium Stress Test

Adjunct to thallous (thallium) chloride TI 201 myocardial perfusion scintigraphy (thallium stress test) in patients unable to undergo adequate stress testing with exercise.2 10 17

Diagnosis of Supraventricular Tachycardias

Adjunct to vagal maneuvers and clinical assessment to establish a specific diagnosis in patients with undefined,31 stable, regular narrow-complex SVT.15 16 26 31

AHA discourages overuse for diagnostic purposes; use only in suspected arrhythmias of supraventricular origin.27 28 31 (See Cardiovascular and Cerebrovascular Effects under Cautions.)

Adenosine Dosage and Administration

Administration

Do not confuse adenosine with adenosine phosphate. (See Uses.)

Administer by peripheral IV injection 1 31 or IV infusion depending on use.2 17

Also has been administered via a central vein13 31 or by intraosseous injection in pediatric patients without reliable/immediate IV access.6 21 31

Safety and efficacy of intracoronary administration (as adjunct to thallium stress test) not established.2

For solution compatibility information, see Compatibility under Stability.

IV Injection

Supraventricular tachyarrhythmias (e.g., PSVT): Administer by rapid IV (“bolus”) injection into a peripheral vein.1 31

To ensure the drug reaches the systemic circulation, inject directly into a vein.1 If given through an IV line, inject as closely as possible to the patient’s venous access, then follow each dose with a rapid flush of 0.9% sodium chloride injection (e.g., flush with ≥5 mL for pediatric patients and 20 mL for adults).1 31

Rate of Administration

Supraventricular tachyarrhythmias (e.g., PSVT): Administer over 1–2 seconds.1 31

IV Infusion

Thallium Stress Test: Administer by continuous infusion into a peripheral vein.2 17

Rate of Administration

Administer over 6 minutes.2 17

Dosage

Pediatric Patients

Supraventricular Tachyarrhythmias
PSVT
IV

Children <50 kg: Initially, 0.05–0.1 mg/kg.1 If conversion of PSVT does not occur within 1–2 minutes, increase subsequent doses by 0.05–0.1 mg/kg until sinus rhythm is established or a maximum single dose of 0.3 mg/kg (not exceeding 12 mg) has been given.1

Children ≥50 kg: Initially, 6 mg.1 If conversion does not occur within 1–2 minutes, a 12-mg dose may be administered and repeated once, if necessary.1 Maximum single dose is 12 mg.1

Pediatric emergency cardiovascular care (ECC) guidelines recommend initial dose of 0.1 mg/kg (maximum single dose of 6 mg) in children.31 A second dose of 0.2 mg/kg (maximum single dose of 12 mg) may be given, if necessary.31

A lower initial dose (50% of the usual recommended initial dose for children)27 28 may be effective if given via a central vein, because the rhythm effects of adenosine are concentration dependent.4 8 28

Intraosseous

Pediatric ECC guidelines recommend initial dose of 0.1 mg/kg (maximum single dose of 6 mg) in children.31 A second dose of 0.2 mg/kg (maximum single dose of 12 mg) may be given, if necessary.31

Adults

Supraventricular Tachyarrhythmias
PSVT
IV

Initially, 6 mg.1 31 If conversion does not occur within 1–2 minutes, administer a 12-mg dose; may repeat 12-mg dose once, if necessary.1 31

If recurs after conversion (because of the drug’s short half-life), additional doses of adenosine or a longer-acting AV nodal blocking agent (e.g., diltiazem, β-adrenergic blocking agent) may be used.31 If adenosine fails to convert PSVT, rate control may be attempted with a nondihydropyridine calcium-channel blocking agent (e.g., diltiazem, verapamil) or a β-adrenergic blocking agent.31

A lower initial dose of adenosine (3 mg for adults)27 28 31 may be effective if given via a central vein because the rhythm effects of adenosine are concentration dependent.4 8 28

Thallium Stress Test
IV

0.14 mg/kg per minute for 6 minutes (total dose of 0.84 mg/kg).2 17

Administer required dose of thallous (thallium) chloride TI 201 at the midpoint (i.e., after the first 3 minutes) of the adenosine infusion2 17 and as close as possible to the venous access site to prevent an inadvertent increase in the dose of adenosine (the contents of the IV tubing) being administered.2

Prescribing Limits

Pediatric Patients

Supraventricular Tachyarrhythmias
PSVT
IV

Children <50 kg: Manufacturer recommends maximum single dose of 0.3 mg/kg (do not exceed 12 mg).1

Children ≥50 kg: Manufacturer recommends maximum single dose of 12 mg.1

Pediatric ECC guidelines recommend maximum single dose of 6 mg for initial injection and maximum single dose of 12 mg for second injection, if necessary.31

Intraosseous

Pediatric ECC guidelines recommend maximum single dose of 6 mg for initial injection and maximum single dose of 12 mg for second injection, if necessary.31

Adults

Supraventricular Tachyarrhythmias
PSVT
IV

Maximum recommended single dose is 12 mg.1

Special Populations

Cardiac Transplant Patients

Administer with caution and in reduced dosages (e.g., 3 mg in adults)31 because of risk of cardiac denervation-related hypersensitivity.3 28 (See Cardiovascular and Cerebrovascular Effects under Cautions.)

Cautions for Adenosine

Contraindications

  • Known hypersensitivity to adenosine.1 2

  • Second- or third-degree AV block (except in patients with a functioning artificial pacemaker).1 2

  • Sinus node disease (e.g., sick sinus syndrome, symptomatic bradycardia [except in those with a functioning artificial pacemaker]).1 2 14

  • Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma).2 22

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 2 32 37 Ensure availability of cardiac resuscitation equipment and trained staff prior to administration.1 2 32

Myocardial Ischemic Events

Risk of rare but serious adverse cardiovascular events, including MI and death, in patients receiving adenosine as a cardiac stress testing agent during myocardial perfusion imaging; similar risk also observed with regadenoson, another pharmacologic stress test agent.2 32 33 34 37 38 39

Avoid use in patients with signs or symptoms of acute myocardial ischemia (e.g., unstable angina, cardiovascular instability).2 32

Rhythm and Conduction Abnormalities

Risk of first-, second-, or third-degree heart block, sinus bradycardia, and, rarely, sinus pause due to the drug's direct depressant effects on SA and AV nodes.1 2 28 Avoid use in patients with sinus node dysfunction or high-grade AV block unless patient has a functioning artificial pacemaker (see Contraindications under Cautions); use caution in patients with preexisting first-degree AV block or bundle branch block.1 2 Discontinue therapy in patients who develop persistent or symptomatic high-level AV block.1 2

When used for termination of PSVT, new arrhythmias (VPCs, atrial premature complexes, atrial fibrillation, sinus bradycardia, sinus tachycardia, skipped beats, and varying degrees of AV nodal block) may occur at the time of conversion to normal sinus rhythm.1 2 7 8 12 28 29 Such arrhythmias generally transient and self-limiting,1 although episodes of asystole, sometimes fatal, have been reported.1 Ventricular fibrillation (both resuscitated and fatal events) also reported.1 29 In most cases, these adverse effects occurred in patients receiving concomitant therapy with digoxin or digoxin and verapamil; a causal relationship, however, not established.1 (See Specific Drugs under Interactions.)

Hemodynamic and Associated Effects

Marked hypotension possible due to potent peripheral vasodilating effects of the drug; risk may be increased in patients with autonomic dysfunction, stenotic valvular heart disease, pericarditis or pericardial effusion, stenotic carotid artery disease with cerebrovascular insufficiency, or hypovolemia.1 2 Discontinue in patients who develop persistent or symptomatic hypotension.2

Clinically important increases in BP also may occur; generally transient, but may persist for several hours.1 2

Cerebrovascular events, including hemorrhagic and ischemic stroke, possibly related to hemodynamic effects of the drug, also reported.2

Respiratory Effects

Risk of dyspnea, bronchoconstriction, bronchospasm, and respiratory compromise.1 2 3 12 14 22 23

May exacerbate symptoms (e.g., bronchoconstriction) in patients with asthma.1 2 3 12 22 23 (See Contraindications under Cautions.)

Use with caution in patients with obstructive lung disease not associated with bronchoconstriction (e.g., emphysema, bronchitis).1 2 22 23 Ensure availability of appropriate resuscitative measures.2 Discontinue drug in patients who develop severe respiratory difficulty.1 2

Seizures

Risk of new-onset or recurrent seizures.1 2 Seizure activity, including tonic-clonic (grand mal) seizures, reported; in some cases, prolonged and required emergency management.2

Concomitant use of aminophylline may increase risk of seizures.2 (See Specific Drugs under Interactions.)

Sensitivity Reactions

Hypersensitivity

Risk of hypersensitivity reactions, possibly requiring resuscitative measures; manifestations have included dyspnea, throat tightness, flushing, erythema, and chest discomfort.1 2 (See Contraindications under Cautions.)

Ensure availability of appropriate personnel and resuscitative equipment.2

Specific Populations

Pregnancy

Category C.1 2

Because of its rapid onset and brief duration of action, adenosine may have advantages over other antiarrhythmic agents (e.g., verapamil, digoxin) in the acute treatment of PSVT in pregnant women in whom vagal maneuvers have failed.24 25 26 28 Use with caution because hypotension may compromise placental (fetal) blood flow.28

Lactation

Not known whether adenosine is distributed into milk.7 30 Discontinue nursing or the drug.2 Some clinicians suggest that breast-feeding may be possible because of the drug’s short half-life.28 30

Pediatric Use

Safety and efficacy (as adjunct to thallium stress test) not established in children ≤18 years of age.2

Safety and efficacy (as antiarrhythmic for PSVT) not established in pediatric patients; however, IV adenosine has been used for the treatment of PSVT in neonates, infants, children, and adolescents1 24 31 and some clinicians consider it a drug of choice for SVT in pediatric patients.24 31

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1 2 Use with caution since increased sensitivity cannot be ruled out;2 some geriatric patients may have diminished cardiac or nodal dysfunction, concomitant disease, or drug therapy that may alter hemodynamic function and result in severe bradycardia or AV block.1

Hepatic Impairment

Hepatic function not required for therapeutic effect or inactivation; hepatic dysfunction not expected to alter efficacy or tolerability.1 2

Renal Impairment

Renal function not required for therapeutic effect or inactivation; renal dysfunction not expected to alter efficacy or tolerability.1 2

Common Adverse Effects

For termination of PSVT: Facial flushing,1 4 8 10 13 14 24 31 shortness of breath/dyspnea,1 4 10 13 14 24 31 chest pressure,1 4 8 24 nausea,1 headache,1 lightheadedness,1 dizziness,1 10 numbness,1 tingling in the arms.1

As an adjunct to thallium stress test: Facial flushing,2 9 17 chest discomfort,2 17 dyspnea or urge to breathe deeply,2 9 17 headache,2 9 17 throat/neck/jaw discomfort,2 9 GI discomfort,2 9 lightheadedness/dizziness,2 9 17 upper extremity discomfort,2 9 ST-segment depression,2 8 first- or second-degree AV block,2 9 paresthesia,2 9 hypotension,2 nervousness,2 9 arrhythmias.2

Interactions for Adenosine

Specific Drugs

Drug

Interaction

Comments

ACE inhibitors

Potential for additive/synergistic depressant effects on SA and AV nodes1

Use with caution1

β-Adrenergic blocking agents

Potential for additive/synergistic depressant effects on SA and AV nodes1 2

Use with caution1 2

Calcium channel-blocking agents

Potential for additive/synergistic depressant effects on SA and AV nodes1 2

Use with caution1 2

Carbamazepine

Possible increased degree of heart block1 27

Reduce initial adenosine dose to 3 mg in adults31

Digoxin or digoxin/verapamil

Potential for additive/synergistic depressant effects on SA and AV nodes; serious and/or life-threatening effects (asystole, ventricular fibrillation) reported rarely1 2

Use with caution and with appropriate resuscitative measures available1

Dipyridamole

Potentiation of adenosine vasoactive effects1 2 4 24

Some experts recommend reduction in initial adenosine dose to 3 mg in adults31

Safety and efficacy of adenosine in presence of dipyridamole not established; in general, withhold administration of drugs that inhibit or augment pharmacologic effects of adenosine for at least 5 half-lives prior to adenosine administration2

Methylxanthines (aminophylline, caffeine, theophylline)

Inhibition of adenosine vasoactive effects1 2 3 4 20 24 27

Aminophylline: Concomitant use may increase risk of seizures2

Increased doses of adenosine may be required1 7 20 24 31

Safety and efficacy of adenosine in presence of methylxanthines not established; in general, withhold administration of drugs that inhibit or augment pharmacologic effects of adenosine for at least 5 half-lives prior to adenosine administration2

Do not use methylxanthines in patients who experience adenosine-induced seizures2

Quinidine

Potential for additive/synergistic depressant effects on SA and AV nodes1

Use with caution1

Adenosine Pharmacokinetics

Elimination

Metabolism

Rapidly metabolized intracellularly to inactive metabolites.1 2

Elimination Route

Cleared by cellular uptake, primarily by erythrocytes and vascular endothelial cells.1 2

Half-life

<10 seconds.1 2

Stability

Storage

Parenteral

Injection

15–30°C.1 2 Do not refrigerate.1 2

If crystallization occurs, warm to room temperature.1 2

Contains no preservative; discard unused solution.1 2

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.9%

Y-Site Injection Compatibility

Compatible

Abciximab

Actions

  • Slows conduction time through the AV node; can interrupt reentrant pathways through the AV node and restore normal sinus rhythm in patients with PSVT, including that associated with Wolff-Parkinson-White syndrome.1 4

  • Increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, resulting in a greater difference in thallous (thallium) chloride TI 201 uptake in myocardium supplied by normal versus stenotic coronary arteries.2 28

  • Potent vasodilator in most vascular beds; however, vasoconstriction is produced in renal afferent arterioles and hepatic veins.1 2 4

  • Produces a net mild to moderate reduction in systolic, diastolic, and mean arterial blood pressure and a reflex increase in heart rate.2 12

  • May exert pharmacologic effects by activation of purine (cell-surface A1 and A2 adenosine) receptors; relaxation of vascular smooth muscle may be mediated by reduction in calcium uptake through inhibition of slow inward calcium current and activation of adenylate cyclase in smooth muscle cells.2 4

  • May reduce vascular tone by modulation of sympathetic neurotransmission.2

  • Respiratory stimulant, probably because of activation of carotid body chemoreceptors; IV administration produces an increase in minute ventilation and a reduction in arterial PCO2 resulting in respiratory alkalosis.1 2 12

Advice to Patients

  • Importance of informing patients about serious adverse effects associated with adenosine, such as MI, arrhythmias, cardiac arrest, heart block, substantial changes in BP, bronchoconstriction, hypersensitivity reactions, seizures, and stroke.1 2 24

  • Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., aminophylline, theophylline), caffeine-containing foods or beverages,27 as well as any concomitant illnesses (e.g., asthma, COPD).1 2

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2

  • Importance of informing patients of other important precautionary information.1 2 (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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Adenosine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for rapid IV injection only

3 mg/mL*

Adenocard

Astellas

Adenosine Injection

Injection, for IV infusion only

3 mg/mL

Adenoscan

Astellas

AHFS DI Essentials. © Copyright, 2004-2015, Selected Revisions June 29, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Astellas Pharma US, Inc. Adenocard IV (adenosine injection) prescribing information. Northbrook, IL; 2012 May.

2. Astellas Pharma US, Inc. Adenoscan IV (adenosine injection) prescribing information. Northbrook, IL; 2014 Aug.

3. The American Heart Association in Collaboration with the International Liaison Committee on Resuscitation. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2000; 102(Suppl I): I-114, I-158, I-161, I-162, I-315, I-317.

4. Pelleg A, Porter S. The pharmacology of adenosine. Pharmacotherapy. 1990; 10:157-74. [IDIS 387514] [PubMed 2196534]

5. Getschman SJ, Dietrich AM, Franklin WH et al. Intraosseous adenosine. Arch Pediatr Adolesc Med. 1994; 148:616-9. [PubMed 8193689]

6. Friedman FD. Intraosseous adenosine for the termination of supraventricular tachycardia in an infant. Ann Emerg Med. 1996; 28:356-8. [IDIS 372678] [PubMed 8780485]

7. Fujisawa, Deerfield, IL: Personal communication on adenosine FirstRelease.

8. DiMarco JP, Miles W, Akhtar M et al. Adenosine for paroxysmal supraventricular tachycardia: dose ranging and comparison with verapamil. Ann Intern Med. 1990; 113:104-10. [IDIS 268656] [PubMed 2193560]

9. Nishimura S, Mahmarian JJ, Boyce TM et al. Equivalence between adenosine and exercise thallium-201 myocardial tomography: a multicenter, prospective, crossover trial. J Am Coll Cardiol. 1992; 20:265-75. [PubMed 1634661]

10. Gupta NC, Esterbrooks DJ, Hilleman DE et al. Comparison of adenosine and exercise thallium-201 single-photon emission computed tomography (SPECT) myocardial perfusion imaging. J Am Coll Cardiol. 1992; 19:248-57. [PubMed 1732349]

11. Maxwell DL, Fuller RW, Conradson T-B et al. Contrasting effects of two xanthines, theophylline and enprofylline, on the cardio-respiratory stimulation of infused adenosine in man. Acta Physiol Scand. 1987; 131:459-65. [PubMed 3425350]

12. Biaggioni I, Olafsson B, Robertson RM et al. Cardiovascular and respiratory effects of adenosine in conscious man: evidence for chemoreceptor activation. Circulation Res. 1987; 61:779-86. [IDIS 237045] [PubMed 3677336]

13. McIntosh-Yellin NL, Drew BJ, Scheinman MM. Safety and efficacy of central intravenous bolus administration of adenosine for termination of supraventricular tachycardia. JACC 1993; 741-5.

14. DiMarco JP, Sellers TD, Lerman BB et al. Diagnostic and therapeutic use of adenosine in patients with supraventricular tachyarrhythmias. JACC. 1985; 6:417-25. [PubMed 4019929]

15. Labadet CD, Villamil AM, Pinski SL. Administration of adenosine in sinus rhythm for diagnostic of supraventricular tachycardia. Circulation. 1999; 99:724-5. [IDIS 423754] [PubMed 9950745]

16. Belhassen B, Fish R, Viskin S et al. Administration of adenosine in sinus rhythm for diagnostic of supraventricular tachycardia. Circulation. 1999; 99:725. [PubMed 9950746]

17. O’Keefe JH, Bateman TM, Silverstri R et al. Safety and diagnostic accuracy of adenosine thallium-201 scintigraphy in patients unable to exercise and those with left bundle branch block. Am Heart J. 1992; 124:614-21. [PubMed 1514488]

18. Brodsky MA, Hwang C, Hunter D et al. Life-threatening alterations in heart rate after the use of adenosine in atrial flutter. Am Heart J. 1995; 130:564-71. [IDIS 353694] [PubMed 7661076]

19. Brodsky MA Allen BJ, Grimes JA et al. Enhanced atrioventricular conduction during atrial flutter after intravenous adenosine. N Engl J Med. 1994; 330:288-9. [IDIS 324300] [PubMed 8272096]

20. Berul CI. Higher adenosine dosage required for supraventricular tachycardia in infants treated with theophylline. Clin Pediatr. 1993; 32:167-8.

21. Friedman FD. Intraosseous adenosine for the termination of supraventricular tachycardia in an infant. Ann Emerg Med. 1996; 28:356-8. [IDIS 372678] [PubMed 8780485]

22. Burkhart KK. Respiratory failure following adenosine administration. Am J Emerg Med. 1993; 11:249-50. [PubMed 8489671]

23. Hintringer F, Pürerfellner H, Aichinger J. Supraventricular tachycardia. N Engl J Med. 1995; 333:323-4. [IDIS 351812] [PubMed 7596389]

24. Wilbur SL, Marchlinski FE. Adenosine as an antiarrhythmic agent. Am J Cardiol. 1997; 79(12A):30-7. [IDIS 391432] [PubMed 9223361]

25. Robins K, Lyons G. Supraventricular tachycardia in pregnancy. Br J Anaesthesia. 2004; 92:140-3.

26. Blomström-Lundqvist C, Scheinman MM, Aliot EM et al. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias.). J Am Coll Cardiol 2003;42:1493–531.

27. Astellas Pharma US, Inc: Personal communication.

28. Reviewers’ comments (personal observations).

29. Mallet ML. Proarrhythmic effects of adenosine: a review of the literature. Emerg Med J. 2004; 21:408-10. [PubMed 15208219]

30. Adenosine. In: Briggs GG, Freeman RK, Yaffe SJ. Drug in pregnancy and lactation: a reference guide to fetal and neonatal risk. 7th ed. Philadelphia: Lippincott Williams & Wilkins; 2005:33-5.

31. The American Heart Association. Guidelines 2005 for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2005; 112(Suppl I): IV1-211.

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]

39. Astellas Pharma US, Inc. Regadenoson (Lexiscan) injection prescribing information. Northbrook, IL; 2014 Sep.

HID. Trissel LA. Handbook on injectable drugs. 14th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2007:13-14.

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