General Articles

Adenosine

MEDICATION SAFETY ISSUES
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

U.S. BRAND NAMES — Adenocard®; Adenoscan®

PHARMACOLOGIC CATEGORY
Antiarrhythmic Agent, Class IV
Diagnostic Agent

DOSING: ADULTS
Paroxysmal supraventricular tachycardia (Adenocard®): I.V. (rapid, over 1-2 seconds, via peripheral line): Initial: 6 mg; if not effective within 1-2 minutes, 12 mg may be given; may repeat 12 mg bolus if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.
Recommended dosage adjustment for adenosine when administered via central line or with concurrent carbamazepine or dipyridamole (ACLS, 2005): Initial dose: 3 mg

Pharmacologic stress testing (Adenoscan®): I.V.: Continuous I.V. infusion via peripheral line: 140 mcg/kg/minute for 6 minutes using syringe or columetric infusion pump; total dose: 0.84 mg/kg. Thallium-201 is injected at midpoint (3 minutes) of infusion.

Acute vasodilator testing in pulmonary artery hypertension (unlabeled use) (Adenoscan®): I.V.: 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 250 mcg/kg/minute (McLaughlin, 2009); acutely assess vasodilator response

DOSING: PEDIATRIC — Rapid I.V. push (over 1-2 seconds) via peripheral line:

(For additional information see “Adenosine: Pediatric drug information”)

Paroxysmal supraventricular tachycardia (Adenocard®): Infants and Children:
Manufacturer’s recommendation:
Children <50 kg: Initial: 0.05-0.1 mg/kg (maximum initial dose: 6 mg). If conversion of PSVT does not occur within 1-2 minutes, may increase dose by 0.05-0.1 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, 2005): Treatment of SVT: I.V., I.O.: Initial: 0.1 mg/kg (maximum initial dose: 6 mg); if not effective within 1-2 minutes, administer 0.2 mg/kg; may repeat 0.2 mg/kg if needed (maximum single dose: 12 mg). Follow each dose with normal saline flush.

DOSING: ELDERLY — Refer to adult dosing. Elderly may be more sensitive to effects of adenosine.

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

Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)

DOSAGE FORMS: CONCISE
Injection, solution [preservative free]: 3 mg/mL (2 mL, 4 mL)
Adenocard®: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION — For rapid bolus I.V. use only; administer I.V. push over 1-2 seconds at a peripheral I.V. 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 (≥ 5 mL). Use of 2 syringes (one with adenosine dose and the other with NS flush) connected to a T-connector or stopcock is recommended (ACLS, 2005). Note: If administered via central line in adults, reduce initial dose to 3 mg (ACLS, 2005).

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COMPATIBILITY — Stable in D5LR, D5W, LR, NS.

USE
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

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

USE – UNLABELED / INVESTIGATIONAL
ACLS/PALS Guidelines (2005):
Stable, narrow-complex AV nodal or sinus nodal reentry tachycardias (eg, reentry SVT);
Unstable reentry SVT while preparations are made for synchronized direct-current cardioversion;
Undefined, stable, narrow-complex SVT as a combination therapeutic and diagnostic maneuver;
Stable, wide-complex tachycardias in patients with a recurrence of a known reentry pathway that has been previously defined

Adenoscan®: Acute vasodilator testing in pulmonary artery hypertension

ADVERSE REACTIONS SIGNIFICANT — Note: Frequency varies based on use; higher frequency of infusion-related effects, such as flushing and lightheadedness, were reported with continuous infusion (Adenoscan®).

>10%:
Cardiovascular: Facial flushing (18% to 44%)
Central nervous system: Headache (2% to 18%), lightheadedness (2% to 12%)
Gastrointestinal: GI discomfort (13%)
Neuromuscular & skeletal: Discomfort of neck, throat, jaw (<1% to 15%)
Respiratory: Chest pressure/discomfort (7% to 40%), dyspnea (12% to 28%)

1% to 10%:
Cardiovascular: AV block (infusion 6%; third degree <1%), ST segment depression (3%), hypotension (<1% to 2%), palpitation, chest pain
Central nervous system: Nervousness (2%), apprehension, dizziness
Gastrointestinal: Nausea (3%)
Neuromuscular & skeletal: Upper extremity discomfort (up to 4%), numbness (up to 2%), paresthesia (up to 2%)
Respiratory: Hyperventilation
Miscellaneous: Diaphoresis

<1% (Limited to important or life-threatening): Asystole (prolonged), atrial fibrillation (upon termination of PSVT), back discomfort, bradycardia, bronchospasm, burning sensation, blurred vision, hypertension (transient), injection site reaction, intracranial pressure increased, lower extremity discomfort, metallic taste, pressure in groin, respiratory arrest, seizure, torsade de pointes, ventricular fibrillation, ventricular tachycardia CONTRAINDICATIONS — Hypersensitivity to adenosine or any component of the formulation; second- or third-degree AV block or sick sinus syndrome (except in patients with a functioning artificial pacemaker); use in patients with atrial fibrillation/flutter with underlying Wolff-Parkinson-White (WPW) syndrome is considered to be contraindicated (Fuster, 2006) In addition to the above, Adenoscan® should be avoided in patients with known or suspected bronchoconstrictive or bronchospastic lung disease. 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. Conduction disturbances: Adenosine decreases conduction through the AV node and may produce first-, second-, or third-degree heart block. Patients with pre-existing S-A nodal dysfunction may experience prolonged sinus pauses after adenosine; use caution in patients with first-degree AV block or bundle branch block; avoid use of adenosine for pharmacologic stress testing in patients with high-grade AV block or sinus node dysfunction (unless a functional pacemaker is in place). Rare, prolonged episodes of asystole have been reported, with fatal outcomes in some cases. 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), uncorrected hypovolemia, pericard

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itis, pleural effusion and/or stenotic valvular heart disease. 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.

Disease-related concerns: 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, 2005); considered by some to be contraindicated in this setting (Delacretaz, 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); mild-to-moderate exacerbations have been reported following use in a limited number of patients with asthma. Use caution in patients with obstructive lung disease not associated with bronchoconstriction (eg, emphysema, bronchitis); respiratory compromise has occurred during use. Wolff-Parkinson-White (WPW) syndrome: Use in patients with atrial fibrillation/flutter with underlying WPW syndrome is considered to be contraindicated since ventricular fibrillation may result (Fuster, 2006).

Concurrent drug therapy issues: Caffeine: Pharmacologic stress testing: Since caffeine antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use; avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing. Carbamazepine: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Dipyridamole: Concomitant use potentiates the effects of adenosine; reduction of initial adenosine dose is recommended when used for SVT (ACLS, 2005). Drugs which slow AV node conduction: Use with caution in patients receiving other drugs which slow AV node conduction (eg, digoxin, verapamil). Theophylline: Pharmacologic stress testing: Since theophylline antagonizes the activity of adenosine, withhold for 5 half-lives prior to adenosine use whenever possible.

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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 I.V. line), as close to the patient as possible (followed by saline flush).

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.

DRUG INTERACTIONS
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. Risk D: Consider therapy modification

Dipyridamole: May enhance the therapeutic effect of Adenosine. Dose reduction of adenosine may be needed. Management: Reduction of the initial dose of adenosine may be warranted. Risk D: Consider therapy modification

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

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

ETHANOL / NUTRITION / HERB INTERACTIONS — Food: Avoid food or drugs with caffeine. Adenosine’s therapeutic effect may be decreased if used concurrently with caffeine. Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Reports of administration during pregnancy have indicated no adverse effects on fetus or newborn attributable to adenosine.

LACTATION — Excretion in breast milk unknown

DIETARY CONSIDERATIONS — Avoid dietary caffeine for 12-24 hours prior to pharmacologic stress testing.

MONITORING PARAMETERS — ECG, heart rate, blood pressure

CANADIAN BRAND NAMES — Adenocard®; Adenoscan®; Adenosine Injection, USP

INTERNATIONAL BRAND NAMES — Adenocard (BR); Adenocor (AU, BE, BG, CZ, DK, EE, EG, ES, FI, GB, HN, HU, IE, IL, KP, LU, MY, NO, PE, PL, PT, SE, TH, TW, UY, VE, ZA); Adenocur (NL); Adenoject (IN); Adenoscan (ES, HK); Adenosin Ebewe (PL); Adenosina Biol (AR, PY); Adenozer (TW); Adrekar (AT, DE); Cardiovert (PH); Fosfobion (PL); Krenosin (FR, IT, LU, MX); Krenosine (CH); Soladen (PL); Tricor (CN)

MECHANISM OF ACTION — Slows conduction time through the AV node, interrupting the re-entry pathways through the AV node, restoring normal sinus rhythm

PHARMACODYNAMICS / KINETICS
Onset of action: Rapid

Duration: Very brief

Metabolism: Blood and tissue to inosine then to adenosine monophosphate (AMP) and hypoxanthine

Half-life elimination: <10 seconds