Adenosine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Adenoscan: 3 mg/mL (20 mL [DSC], 30 mL [DSC])

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

Solution, Intravenous [preservative free]:

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

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

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

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

Paroxysmal supraventricular tachycardia: Adenocard: Treatment of paroxysmal supraventricular tachycardia (PSVT); 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.

Guideline recommendations: The American College of Cardiology/American Heart Association/Heart Rhythm Society supraventricular tachycardia (SVT) guidelines recommends adenosine in the acute management of a variety of SVTs (eg, AV nodal reentrant tachycardia [AVNRT], AV reentrant tachycardia [AVRT]) (ACC/AHA/HRS [Page 2015]).

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

Use: Off Label

Fractional flow reserve testing (diagnostic aid)b

Data from 2 prospective single-center studies supports the use of adenosine (IV or intracoronary) for fractional flow reserve testing to determine the significance of a coronary artery lesion Rother 2016, Schlundt 2015. Additional trials may be necessary to further define the role of adenosine in this setting.

Monomorphic wide-complex tachycardia (stable)cyes

Data from a multicenter, retrospective, observational study suggests that adenosine may be beneficial in the therapeutic and diagnostic maneuver of stable regular monomorphic, wide-complex tachycardia Marill 2009. Additional data may be necessary to further define the role of adenosine in the management of this condition.

Based on the American Heart Association Adult Advanced Cardiovascular Life Support guidelines, adenosine given for the management of stable regular monomorphic, wide-complex tachycardias as a therapeutic (if supraventricular tachycardia [SVT]) and diagnostic maneuver is effective and recommended in this condition.

Narrow-complex regular tachycardia (stable)byes

Data from a randomized, double blind, controlled study supports the use of adenosine in the treatment of stable, narrow-complex regular tachycardias Dimarco 1990. Data from a prospective, uncontrolled, unblinded, pre-hospital study also supports the use of adenosine in the treatment of stable, narrow-complex regular tachycardias Furlong 1995. Additional trials may be necessary to further define the role of adenosine for this condition.

Based on the American Heart Association Adult Advanced Cardiovascular Life Support guidelines, adenosine given for stable, narrow-complex regular tachycardias that do not respond to vagal maneuvers is effective and recommended in the management of this condition.

Narrow-complex regular tachycardia (unstable)yes

Based on the American Heart Association Adult Advanced Cardiovascular Life Support guidelines, adenosine given for unstable narrow-complex regular tachycardias while preparations are made for synchronized direct-current cardioversion is effective and recommended in the management of this condition.

Pulmonary artery hypertension (acute vasodilator testing)yes

Based on the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) expert consensus document on pulmonary hypertension and the 5th World Symposium on Pulmonary Hypertension (WSPH) updated treatment algorithm of pulmonary arterial hypertension, adenosine (Adenoscan) given for acute vasodilator testing in pulmonary artery hypertension is an effective and acceptable alternative agent (inhaled nitric oxide is the gold standard).

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)

Dosage and Administration

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). A subsequent bolus dose of 18 mg (following an initial dose of 6 mg and a repeat bolus dose of 12 mg) has reportedly been used in patients with sustained SVTs (ACC/AHA/HRS [Page 2015]; Domanovits 1994).

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

Fractional flow reserve testing (diagnostic aid) (off-label use):

IV: 140 mcg/kg/minute as a continuous infusion during testing (Schlundt 2015)

Intracoronary: 40 mcg into the right coronary artery or 80 mcg into the left coronary artery; dilute dose in 10 mL of NS and administer rapidly through the guiding catheter (Röther 2016; Schlundt 2015)

Dosing: Geriatric

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

Dosing: Pediatric

Paroxysmal supraventricular tachycardia: Adenocard:

PALS Guidelines: Infants, Children and Adolescents: Rapid IV; IO: Initial: 0.1 mg/kg (maximum initial dose: 6 mg/dose); if not effective, increase to 0.2 mg/kg (maximum dose: 12 mg/dose) (PALS [Klienman 2010])

Manufacturer's labeling: Rapid IV:

Infants, Children, and Adolescents <50 kg: Initial dose: 0.05 to 0.1 mg/kg via peripheral or central line; maximum initial dose: 6 mg/dose; if not effective within 1 to 2 minutes, increase dose by 0.05 to 0.1 mg/kg increments every 1 to 2 minutes to a maximum single dose of 0.3 mg/kg or 12 mg, whichever is lower or until termination of PSVT

Children and Adolescents ≥50 kg: Initial: 6 mg via peripheral line, if not effective within 1 to 2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed. Note: In adults it has been suggested that the 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).

Reconstitution

Parenteral: IV: Doses ≥0.6 mg: Give undiluted.

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 (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).

Fractional flow reserve testing (off-label use): Intracoronary: Give rapidly followed by a 10 mL NS flush (Röther 2016; Schlundt 2015)

Adenoscan: For IV infusion only via peripheral line

Dietary Considerations

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

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: For patients requiring pharmacologic stress testing with adenosine, hold dipyridamole for 48 hours prior to testing. 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%, postmarketing, and/or case reports: Asystole (prolonged), atrial fibrillation, blurred vision, bradycardia, bronchospasm, burning sensation, cardiac arrest (fatal and nonfatal), increased intracranial pressure, injection site reaction, loss of consciousness, metallic taste, myocardial infarction, respiratory arrest, seizure, 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

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

What is this drug used for?

• It is used to treat certain types of abnormal heartbeats.
• It is used during a stress test of the heart.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Abdominal pain
• Flushing

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes
• Vision changes
• Shortness of breath
• Chest pain
• Severe dizziness
• Passing out
• Fast heartbeat
• Slow heartbeat
• Abnormal heartbeat
• Seizures
• Severe headache
• Neck pain
• Jaw pain
• Throat pain
• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.