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

Warning(s)

Special Alerts:

[Posted 10/11/2013] ISSUE: The FDA is warning health care professionals of the rare but serious risk of heart attack and death with use of the cardiac nuclear stress test agents Lexiscan (regadenoson) and Adenoscan (adenosine). FDA has approved changes to the drug labels to reflect these serious events and updated recommendations for use of these agents. At this time, data limitations prevent FDA from determining if there is a difference in risk of heart attack or death between Lexiscan and Adenoscan.

The Warnings & Precautions section of the Lexiscan and Adenoscan labels previously contained information about the possible risk of heart attack and death with use of these drugs. However, recent reports of serious adverse events in the FDA Adverse Event Reporting System (FAERS) database and the medical literature prompted approval changes to the drug labels to include updated recommendations for use.

BACKGROUND: Lexiscan and Adenoscan are FDA approved for use during cardiac nuclear stress tests in patients who cannot exercise adequately. Lexiscan and Adenoscan help identify coronary artery disease. They do this by dilating the arteries of the heart and increasing blood flow to help identify blocks or obstructions in the heart’s arteries. Lexiscan and Adenoscan cause blood to flow preferentially to the healthier, unblocked or unobstructed arteries, which can reduce blood flow in the obstructed artery. In some cases, this reduced blood flow can lead to a heart attack, which can be fatal.

RECOMMENDATION: Screen all nuclear stress test candidates for their suitability to receive Lexiscan or Adenoscan. Avoid using these drugs in patients with signs or symptoms of unstable angina or cardiovascular instability, as these patients may be at greater risk for serious cardiovascular adverse reactions. Cardiac resuscitation equipment and trained staff should be available before administering Lexiscan or Adenoscan.

For more information visit the FDA website at: and .

Introduction

Antiarrhythmic and adjunct diagnostic agent; endogenous nucleoside.1 2 3 4 17 24 31

Uses for Adenosine

Supraventricular Tachyarrhythmias

Initial treatment for 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, narrow-complex supraventricular tachycardias (SVTs).7 26 31

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

Diagnosis and/or initial treatment of regular,26 28 narrow-complex tachycardias.3 28

Initial treatment of stable, wide-complex tachycardias of supraventricular origin+ 28 31 or those with previously defined reentry pathway.31

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Consider adenosine in patients with unstable narrow-complex reentry SVT while preparing synchronized cardioversion; do not delay cardioversion to administer adenosine or to establish IV access.31 (See Cardiovascular Effects under Cautions.)

Do not use in atrial fibrillation or flutter; adenosine does not convert rhythms other than PSVT, (e.g., atrial flutter, atrial fibrillation, ventricular tachycardia) to normal sinus rhythm.1 4 14 24 31 Risk of serious arrhythmias and/or hypotension in patients with preexcited arrhythmias.18 19 26 27 29 (See Cardiovascular Effects under Cautions.)

Contraindicated in patients with atrial fibrillation or flutter associated with Wolff-Parkinson-White syndrome; risk of dramatically accelerating ventricular rate.28 31

Drug of choice for SVT in infants and children.31 Attempt appropriate vagal maneuvers in those with probable SVT; do not delay chemical or electrical cardioversion.31 If IV access is immediately available, administer adenosine by rapid IV injection.3 31 Implement electrical (synchronized) cardioversion in unstable patients and in those without immediate IV access.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 Effects under Cautions.)

Thallium Stress Test

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

Diagnosis of Tachycardias

Adjunct to vagal maneuvers and clinical assessment to establish a specific diagnosis of undefined,31 stable, narrow-complex SVT.15 16 31

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

Adenosine Dosage and Administration

Administration

Administer by IV injection 1 31 or infusion.17

For ACLS during CPR, may be 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

Administer by rapid IV (“bolus”) injection into a peripheral vein.1 31

To ensure the drug reaching 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

Over 1–3 seconds.1 31

IV Infusion

Administer by continuous infusion into a peripheral vein.2 17

Rate of Administration

Administer calculated dose 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

CPR: Initially, 0.1 mg/kg (maximum single dose of 6 mg).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

CPR: Initially, 0.1 mg/kg (maximum single dose of 6 mg).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, a 12-mg dose may be administered1 31 and repeated 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

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

The appropriate rate of infusion corrected for total body weight may be determined using the following table:

Infusion Rate Corrected for Total Body Weight.2

Patient Weight (kg)

Infusion Rate (mL/min)

45

2.1

50

2.3

55

2.6

60

2.8

65

3.0

70

3.3

75

3.5

80

3.8

85

4.0

90

4.2

This table was derived from the following general formula:2

infusion rate (mL/min) = [0.14 mg/kg/min × total body weight (kg)] / [adenosine concentration (3 mg/mL)]

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: Maximum single dose is 0.3 mg/kg or 12 mg.1

Children ≥50 kg: Maximum single dose is 12 mg.1

Intraosseous

CPR: Maximum initial dose is 6 mg; maximum repeat dose is 12 mg.31

Adults

Supraventricular Tachyarrhythmias
PSVT
IV

Maximum single dose is 12 mg.1

Special Populations

Hepatic Impairment

Adenosine does not require hepatic function for therapeutic effect or inactivation; hepatic dysfunction not expected to alter efficacy or tolerability.1 2

Renal Impairment

Adenosine does not require renal function for therapeutic effect or inactivation; renal dysfunction not expected to alter efficacy or tolerability.1 2

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 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

Warnings

Cardiovascular Effects

When administered by continuous IV infusion, risk of fatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), nonfatal MI, mainly in patients with unstable angina.2 28

Risk of first-, second-, or third-degree heart block, sinus bradycardia, and, rarely, sinus pause (with continuous IV infusion) due to direct depressant effects on SA and AV nodes.1 2 28 Use IV infusion with caution in patients with preexisting first-degree AV block or bundle branch block.2 Avoid additional doses (using IV injection)1 or discontinue IV infusion2 in patients who develop persistent or symptomatic high-level AV block.1 2

Frequent development of new arrhythmias (VPCs, atrial premature complexes, atrial fibrillation, sinus bradycardia, sinus tachycardia, skipped beats, and varying degrees of AV nodal block) at the time of conversion to normal sinus rhythm with administration of IV injection.1 2 7 8 12 28 29 Generally, these arrhythmias last only a few seconds and resolve without intervention,1 although transient or prolonged episodes of asystole, sometimes fatal, may occur following IV injection.1 Risk of ventricular fibrillation with IV injection (both resuscitated and fatal events).1 29 In most cases, these adverse effects occur in patients receiving concomitant therapy with digoxin or, less frequently, digoxin and verapamil; a causal relationship, however, not established.1 (See Specific Drugs under Interactions.)

Some clinicians state that adenosine should not be used in patients with wide-complex tachycardias of unknown origin because of the risk of inducing potentially serious arrhythmias, including atrial fibrillation with a rapid ventricular rate or prolonged asystole with severe hypotension in preexcited tachycardias (e.g., atrial flutter);18 19 26 28 the drug also may induce ventricular fibrillation29 in patients with severe coronary artery disease.26

Prolonged systemic hemodynamic effects generally do not occur with administration of rapid IV injection (in usual doses).1 3 28 However, persistent hypotension following IV injection may be more likely when the arrhythmia is not terminated.3

Risk of marked hypotension with large doses of continuous infusion.1 2 Use IV infusion with caution in patients with autonomic dysfunction, stenotic valvular heart disease, pericarditis or pericardial effusions, stenotic carotid artery disease with cerebrovascular insufficiency, or uncorrected hypovolemia.2 Discontinue infusion in patients who develop persistent or symptomatic hypotension.2

Possible increased systolic and diastolic blood pressures with continuous IV infusion;2 usually transient, but may last for several hours.2

Cardiac denervation in those who have undergone cardiac transplantation may enhance sensitivity to the bradycardic effects of the drug.3 28

Appropriate resuscitative measures should be readily available.1 28

Respiratory Effects

Risk of mild to moderate exacerbation of symptoms (i.e., bronchoconstriction) in patients with asthma; such effects have not been observed in healthy individuals.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 since respiratory compromise may occur during IV infusion.1 2 Discontinue the drug in patients who develop severe respiratory difficulty.1 2

Transient dyspnea2 3 14 or urge to breathe deeply (rarely requiring intervention) may occur with IV infusion.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 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

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

Reduce initial adenosine dose to 3 mg in adults31

Methylxanthines (caffeine, theophylline)

Inhibition of adenosine vasoactive effects1 2 3 4 20 24 27

Increased doses of adenosine may be required1 7 20 24 31

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 common adverse effects of adenosine, such as transient flushing, shortness of breath, and chest pressure.1 2 24

  • Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, caffeine-containing foods or beverages,27 as well as any concomitant illnesses.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.

* 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, 2004-2014, Selected Revisions November 26, 2013. 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. Deerfield, IL; 2005 Jul.

2. Astellas Pharma US, Inc. Adenoscan IV (adenosine injection) prescribing information. Deerfield, IL; 2005 Jul.

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.

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

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