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Adenosine

Pronunciation

Pronunciation

(a DEN oh seen)

Index Terms

  • 9-Beta-D-Ribofuranosyladenine
  • Adenosine Phosphate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Adenocard: 6 mg/2 mL (2 mL); 12 mg/4 mL (4 mL)

Adenoscan: 3 mg/mL (20 mL, 30 mL)

Generic: 3 mg/mL (20 mL, 30 mL); 6 mg/2 mL (2 mL)

Solution, Intravenous [preservative free]:

Generic: 3 mg/mL (20 mL, 30 mL); 6 mg/2 mL (2 mL); 12 mg/4 mL (4 mL)

Brand Names: U.S.

  • Adenocard
  • Adenoscan

Pharmacologic Category

  • Antiarrhythmic Agent, Miscellaneous
  • Diagnostic Agent

Pharmacology

Antiarrhythmic actions: Slows conduction time through the AV node, interrupting the re-entry pathways through the AV node, restoring normal sinus rhythm

Myocardial perfusion scintigraphy: Adenosine also causes coronary vasodilation and increases blood flow in normal coronary arteries with little to no increase in stenotic coronary arteries; thallium-201 uptake into the stenotic coronary arteries will be less than that of normal coronary arteries revealing areas of insufficient blood flow.

Metabolism

Removed from systemic circulation primarily by vascular endothelial cells and erythrocytes (by cellular uptake); rapidly metabolized intracellularly; phosphorylated by adenosine kinase to adenosine monophosphate (AMP) which is then incorporated into high-energy pool; intracellular adenosine is also deaminated by adenosine deaminase to inosine; inosine can be metabolized to hypoxanthine, then xanthine and finally to uric acid.

Onset of Action

Rapid

Duration of Action

Very brief

Half-Life Elimination

<10 seconds

Use: Labeled Indications

Adenocard: Treatment of paroxysmal supraventricular tachycardia (PSVT) including that associated with accessory bypass tracts (Wolff-Parkinson-White syndrome); when clinically advisable, appropriate vagal maneuvers should be attempted prior to adenosine administration; not effective for conversion of atrial fibrillation, atrial flutter, or ventricular tachycardia

Note: While adenosine will not convert atrial fibrillation or atrial flutter, the transient AV-nodal block may aid in the identification of the arrhythmia by exposing the underlying atrial fibrillation or flutter electrocardiographic morphology.

Adenoscan: Pharmacologic stress agent used in myocardial perfusion thallium-201 scintigraphy

Use: Unlabeled

ACLS/PALS Guidelines (2010): Stable, narrow-complex regular tachycardias; unstable narrow-complex regular tachycardias while preparations are made for synchronized direct-current cardioversion; stable regular monomorphic, wide-complex tachycardia as a therapeutic (if SVT) and diagnostic maneuver

Adenoscan: Acute vasodilator testing in pulmonary artery hypertension

Contraindications

Hypersensitivity to adenosine or any component of the formulation; second- or third-degree AV block, sick sinus syndrome, or symptomatic bradycardia (except in patients with a functioning artificial pacemaker); known or suspected bronchoconstrictive or bronchospastic lung disease (Adenoscan), asthma (ACLS [Neumar, 2010]; Adenoscan prescribing information, 2014)

Dosing: Adult

Paroxysmal supraventricular tachycardia (Adenocard): IV (rapid, over 1 to 2 seconds, via peripheral line; see Note): Initial: 6 mg; if not effective within 1 to 2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed (maximum single dose: 12 mg). Follow each dose with 20 mL normal saline flush. Note: Initial dose of adenosine should be reduced to 3 mg if patient is currently receiving carbamazepine or dipyridamole, has a transplanted heart or if adenosine is administered via central line (ACLS 2010; Chang 2002).

Pharmacologic stress testing (Adenoscan): IV: Continuous IV infusion via peripheral line: 140 mcg/kg/minute for 6 minutes using syringe or volumetric infusion pump; total dose: 840 mcg/kg. Thallium-201 is injected at midpoint (3 minutes) of infusion.

Acute vasodilator testing in pulmonary artery hypertension (off-label use) (Adenoscan): IV: Initial: 50 mcg/kg/minute increased by 50 mcg/kg/minute every 2 minutes to a maximum dose of 500 mcg/kg/minute (Schrader, 1992) or to a maximum dose of 350 mcg/kg/minute(ACCF/AHA [McLaughlin, 2009]; ESC/ERS/ISHLT [Galie 2009]; Zuo 2012); acutely assess vasodilator response

Dosing: Geriatric

Refer to adult dosing. Elderly may be more sensitive to effects of adenosine.

Dosing: Pediatric

Rapid IV push (over 1 to 2 seconds) via peripheral line, followed by a normal saline flush:

Paroxysmal supraventricular tachycardia (Adenocard): Infants and Children: IV:

Manufacturer's labeling:

Children <50 kg: Initial: 0.05 to 0.1 mg/kg (maximum initial dose: 6 mg). If conversion of PSVT does not occur within 1 to 2 minutes, may increase dose by 0.05 to 0.1 mg/kg. May repeat until sinus rhythm is established or to a maximum single dose of 0.3 mg/kg or 12 mg. Follow each dose with normal saline flush.

Children ≥50 kg: Refer to adult dosing.

Pediatric advanced life support (PALS, 2010): Treatment of SVT: IV, I.O.: Initial: 0.1 mg/kg (maximum initial dose: 6 mg); if not effective within 1 to 2 minutes, administer 0.2 mg/kg (maximum single dose: 12 mg). Follow each dose with ≥5 mL normal saline flush.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling. However, adenosine is not renally eliminated.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling. However, adenosine is not hepatically eliminated.

Administration

Adenocard: For rapid bolus IV use only; administer IV push over 1 to 2 seconds at a peripheral IV site as proximal as possible to trunk (not in lower arm, hand, lower leg, or foot); follow each bolus with a rapid normal saline flush (infants and children ≥5 mL; adults 20 mL). Use of 2 syringes (one with adenosine dose and the other with NS flush) connected to a T-connector or stopcock is recommended. If administered via central line in adults, reduce initial dose to 3 mg (ACLS 2010; Chang 2002).

Adenoscan: For IV infusion only via peripheral line

Dietary Considerations

Avoid dietary caffeine for at least 12 hours prior to pharmacologic stress testing.

Compatibility

Stable in D5LR, D5W, LR, NS.

Storage

Store between 15°C and 30°C (59°F and 86°F). Do not refrigerate; crystallization may occur (may dissolve by warming to room temperature).

Drug Interactions

Caffeine and Caffeine Containing Products: May diminish the therapeutic effect of Adenosine. Management: Monitor for decreased effect of adenosine if patient is receiving caffeine. Discontinue caffeine in advance of scheduled diagnostic use of adenosine whenever possible. Consider therapy modification

CarBAMazepine: May enhance the adverse/toxic effect of Adenosine. Specifically, the risk of higher degree heart block may be increased. Management: Consider using a lower initial dose of adenosine in patients who are receiving carbamazepine. Consider therapy modification

Digoxin: May enhance the adverse/toxic effect of Adenosine. Monitor therapy

Dipyridamole: May enhance the adverse/toxic effect of Adenosine. Specifically, cardiovascular effects of adenosine may be enhanced. Adenosine dose reduction may be needed. Management: Reduction of the initial dose of adenosine may be warranted. Consider therapy modification

Nicotine: May enhance the AV-blocking effect of Adenosine. Nicotine may enhance the tachycardic effect of Adenosine. Monitor therapy

Theophylline Derivatives: May diminish the therapeutic effect of Adenosine. Consider therapy modification

Adverse Reactions

Note: Frequency varies based on use and is not always defined; higher frequency of infusion-related effects, such as flushing and lightheadedness/dizziness, were reported with continuous infusion (Adenoscan).

>10%:

Cardiovascular: Cardiac arrhythmia (transient and new arrhythmia after cardioversion; eg, atrial premature contractions, atrial fibrillation, premature ventricular contractions; 55%), chest pressure (and discomfort; 7% to 40%)

Central nervous system: Headache (2% to 18%), dizziness (≤12%)

Dermatologic: Facial flushing (18% to 44%)

Gastrointestinal: Gastrointestinal distress (13%)

Neuromuscular & skeletal: Neck discomfort (includes throat, jaw; <1% to 15%)

Respiratory: Dyspnea (12% to 28%)

1% to 10%:

Cardiovascular: Atrioventricular block (infusion 6%; third-degree <1%), depression of ST segment on ECG (3%), hypotension (<1% to 2%), chest pain, palpitations

Central nervous system: Nervousness (2%), paresthesia (≤2%), numbness (1%), apprehension

Dermatologic: Diaphoresis

Gastrointestinal: Nausea (3%)

Neuromuscular & skeletal: Upper extremity discomfort (≤4%)

Respiratory: Hyperventilation

<1% (Limited to important or life-threatening): Atrial fibrillation, blurred vision, bradycardia, bronchospasm, cardiac arrest, increased intracranial pressure, injection site reaction, myocardial infarction, respiratory arrest, torsades de pointes, transient hypertension, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia

Warnings/Precautions

Concerns related to adverse effects:

• Atrial fibrillation/flutter: There have been reports of atrial fibrillation/flutter when administered to patients with paroxysmal supraventricular tachycardia (PSVT) and may be especially problematic in patients with PSVT and underlying Wolff-Parkinson-White syndrome; has also been reported in patients with or without a history of atrial fibrillation undergoing myocardial perfusion imaging with adenosine infusion.

• Cardiovascular events (Adenoscan): Cardiac arrest (fatal and nonfatal), myocardial infarction (MI), cerebrovascular accident (hemorrhagic and ischemic), and sustained ventricular tachycardia (requiring resuscitation) have occurred following Adenoscan use. Avoid use in patients with signs or symptoms of unstable angina, acute myocardial ischemia, or cardiovascular instability due to possible increased risk of significant cardiovascular consequences. Appropriate measures for resuscitation should be available during use.

• Conduction disturbances: Adenosine decreases conduction through the AV node and may produce first-, second-, or third-degree heart block. Patients with preexisting SA nodal dysfunction may experience prolonged sinus pauses after adenosine; use caution in patients with first-degree AV block or bundle branch block; use is contraindicated in patients with high-grade AV block, sinus node dysfunction, or symptomatic bradycardia (unless a functional artificial pacemaker is in place). Rare, prolonged episodes of asystole have been reported, with fatal outcomes in some cases. Discontinue adenosine in any patient who develops persistent or symptomatic high-grade AV block.

• Hypersensitivity: Hypersensitivity reactions (including dyspnea, pharyngeal edema, erythema, flushing, rash, or chest discomfort) have been reported following Adenoscan administration.

• Hypertension: Systolic and diastolic pressure increases have been observed with Adenoscan infusion. In most instances, blood pressure increases resolved spontaneously within several minutes; occasionally, hypertension lasted for several hours.

• Hypotension: May produce profound vasodilation with subsequent hypotension. When used as a bolus dose (PSVT), effects are generally self-limiting (due to the short half-life of adenosine). However, when used as a continuous infusion (pharmacologic stress testing), effects may be more pronounced and persistent, corresponding to continued exposure. Use infusions with caution in patients with autonomic dysfunction, carotid stenosis (with cerebrovascular insufficiency), hypovolemia, pericarditis, pleural effusion and/or stenotic valvular heart disease; discontinue infusion in patients who develop persistent or symptomatic hypotension.

• Proarrhythmic effects: Monitor for proarrhythmic effects (eg, polymorphic ventricular tachycardia) during and shortly after administration/termination of arrhythmia. The benign transient occurrence of atrial and ventricular ectopy is common upon termination of arrhythmia.

• Seizures: Seizures (new-onset or recurrent) have been reported following Adenoscan administration; risk may be increased with concurrent use of aminophylline. Use of any methylxanthine (eg aminophylline, caffeine, theophylline) is not recommended in patients experiencing seizures associated with Adenoscan administration.

Disease-related concerns:

• Arrhythmia (wide-complex tachycardia): Avoid use in irregular or polymorphic wide-complex tachycardias; may cause degeneration to ventricular fibrillation (ACLS, 2010).

• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.

• Heart transplant recipients: Use with extreme caution in heart transplant recipients; adenosine may cause prolonged asystole; reduction of initial adenosine dose is recommended (ACLS, 2010); considered by some to be contraindicated in this setting (Delacrétaz, 2006).

• Pulmonary artery hypertension: Acute vasodilator testing (not an approved use): Use with extreme caution in patients with concomitant heart failure (LV systolic dysfunction with significantly elevated left heart filling pressures) or pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis; significant decompensation has occurred with other highly selective pulmonary vasodilators resulting in acute pulmonary edema.

• Respiratory disease: Avoid use in patients with bronchoconstriction or bronchospasm (eg, asthma); dyspnea, bronchoconstriction, and respiratory compromise have occurred during use. Per the ACLS guidelines and the manufacturer of Adenoscan, use considered contraindicated in patients with asthma. Use caution in patients with obstructive lung disease not associated with bronchoconstriction (eg, emphysema, bronchitis). Immediately discontinue therapy if severe respiratory difficulty is observed. Appropriate measures for resuscitation should be available during use.

• Wolff-Parkinson-White (WPW) syndrome: Adenosine should not be used in patients with WPW syndrome and preexcited atrial fibrillation/flutter since ventricular fibrillation may result (AHA/ACC/HRS [January, 2014]).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Caffeine: Pharmacologic stress testing: Since caffeine antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use; avoid dietary caffeine for at least 12 hours prior to pharmacologic stress testing (Henzlova, 2006).

• Carbamazepine: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2010).

• Dipyridamole: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2010); withhold dipyridamole-containing medications for at least 24 hours prior to pharmacologic stress testing (Henzlova, 2006)

• Drugs which slow AV node conduction: Use with caution in patients receiving other drugs which slow AV node conduction (eg, digoxin, verapamil).

• Theophylline (includes aminophylline): Pharmacologic stress testing: Since theophylline antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use whenever possible.

Special populations:

• Elderly: Use with caution in the elderly; may be at increased risk of hemodynamic effects, bradycardia, and/or AV block.

Dosage form specific issues:

• Adenocard: Transient AV block is expected. When used in PSVT, at the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the ECG. Administer as a rapid bolus, either directly into a vein or (if administered into an IV line), as close to the patient as possible (followed by saline flush). Dose reduction recommended when administered via central line (ACLS, 2010).

Other warnings/precautions:

• Appropriate use: ECG monitoring is required during use. Equipment for resuscitation and trained personnel experienced in handling medical emergencies should always be immediately available. Adenosine does not convert atrial fibrillation/flutter to normal sinus rhythm; however, may be used diagnostically in these settings if the underlying rhythm is not apparent.

Monitoring Parameters

ECG, heart rate, blood pressure; consult individual institutional policies and procedures

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Adenosine is an endogenous substance and adverse fetal effects would not be anticipated. Adenosine is recommended for the acute treatment of SVT in pregnant women. The usual recommended doses may be used, although higher doses may be needed in some cases (Page [ACC/AHA/HRS 2015]). ACLS guidelines suggest use is safe and effective in pregnancy (ACLS [Neumar 2010]).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience abdominal pain, flushing, or headache. Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), angina, severe dizziness, passing out, tachycardia, bradycardia, abnormal heartbeat, seizures, severe headache, neck pain, jaw pain, or throat pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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