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Special Alerts
Adenosine: Safety Concern Regarding Compatibility of Prefilled Needleless Glass Syringes with Needleless I.V. Access Systems
May 2011
The U.S. Food and Drug Administration (FDA) is notifying healthcare professionals of reports of compatibility problems when prefilled needleless glass syringes are used with needleless I.V. access systems, specifically prefilled glass syringes containing amiodarone or adenosine. The syringes may malfunction, break, or become clogged when connecting to the needleless I.V. access system. In addition, the I.V. tubing or needleless connector may become damaged, thereby, requiring reestablishment of I.V. access and delaying the administration of potentially lifesaving medication.
The FDA is recommending that healthcare organizations that currently stock prefilled needleless glass syringes of amiodarone or adenosine consider stocking these medications in vials or prefilled plastic syringes as a back-up measure.
For more information, please refer to http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm234219.htm
Pronunciation
(a DEN oh seen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
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
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
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. Case reports of administration during pregnancy have indicated no adverse effects on fetus or newborn attributable to adenosine. ACLS guidelines suggest use is safe and effective in pregnancy.
Lactation
Excretion in breast milk unknown
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); use in patients with atrial fibrillation/flutter with underlying Wolff-Parkinson-White (WPW) syndrome (Fuster, 2006); asthma (ACLS, 2010)
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; has also been reported in patients with or without a history of atrial fibrillation undergoing myocardial perfusion imaging with adenosine infusion.
• Conduction disturbances: Adenosine decreases conduction through the AV node and may produce first-, second-, or third-degree heart block. Patients with pre-existing 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.
• 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, 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.
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); mild-to-moderate exacerbations have been reported following use in a limited number of patients with asthma. Per the ACLS guidelines, use considered contraindicated in 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 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 I.V. 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.
Adverse Reactions
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: Transient new arrhythmia (eg, atrial premature contractions, atrial fibrillation, PVCs) after cardioversion (55%), facial flushing (18% to 44%)
Central nervous system: Headache (2% to 18%), dizziness/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%), chest pain, palpitation
Central nervous system: Nervousness (2%), apprehension
Gastrointestinal: Nausea (3%)
Neuromuscular & skeletal: Upper extremity discomfort (≤4%), numbness (≤2%), paresthesia (≤2%)
Respiratory: Hyperventilation
Miscellaneous: Diaphoresis
<1%, postmarketing, and/or case reports (limited to important or life-threatening): Asystole (prolonged), atrial fibrillation, bradycardia, bronchospasm, burning sensation, blurred vision, hypertension (transient), injection site reaction, intracranial pressure increased, loss of consciousness, metallic taste, MI, respiratory arrest, seizure, torsade de pointes, ventricular fibrillation, ventricular tachycardia
Metabolism/Transport Effects
None known.
Drug Interactions
Caffeine: May diminish the therapeutic effect of Adenosine. Risk D: 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. Risk D: Consider therapy modification
Digoxin: May enhance the adverse/toxic effect of Adenosine. Risk C: Monitor therapy
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: Adenosine's therapeutic effect may be decreased if used concurrently with caffeine. Management: Avoid food or drugs with caffeine for at least 12 hours prior to pharmacologic stress testing.
Storage
Store at controlled room temperature of 15°C to 30°C (59°F to 86°F). Do not refrigerate; crystallization may occur (may dissolve by warming to room temperature).
Compatibility
Stable in D5LR, D5W, LR, NS.
Y-site administration: Compatible: Abciximab
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.
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
Dosage
Adenocard®: Rapid I.V. push (over 1-2 seconds) via peripheral line, followed by a normal saline flush:
Infants and Children:
Paroxysmal supraventricular tachycardia: Manufacturer's recommendation: I.V.:
<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.
≥50 kg: Refer to Adult dosing
Pediatric advanced life support (PALS, 2010): 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 (maximum single dose: 12 mg). Follow each dose with ≥5 mL normal saline flush.
Adults: Paroxysmal supraventricular tachycardia: I.V. (peripheral line; see Note): 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 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).
Adenoscan®:
Pharmacologic stress testing: Continuous I.V. infusion via peripheral line: 140 mcg/kg/minute for 6 minutes using syringe or volumetric 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): 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
Administration: I.V.
Adenocard®: 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 (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 (ACLS, 2010).
Adenoscan®: For I.V. infusion only via peripheral line
Administration: I.V. Detail
Do not mix with any other drug in syringe or solution.
Monitoring Parameters
ECG, heart rate, blood pressure
Dietary Considerations
Avoid dietary caffeine for at least 12 hours prior to pharmacologic stress testing.
Patient Education
Adenosine is administered in emergencies; patient education should be appropriate to the situation. May cause facial flushing. Report chest pain or pressure or difficulty breathing immediately.
Geriatric Considerations
Elderly patients may be more sensitive to the effects of this medication.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Short action is an advantage; has prolonged effects in patients taking dipyridamole or carbamazepine. In denervated transplanted hearts, the actions of adenosine are pronounced; adjust doses or choose alternative agent accordingly.
Cardiovascular Considerations
Adenosine may be effective in interrupting re-entrant tachycardias, both AV-nodal re-entrant tachycardias and supraventricular tachycardias secondary to accessory pathways. Adenosine acts via interruption of AV-nodal conduction and it is not uncommon to see heart block and sinus pause soon after adenosine administration. Cardiac denervation after cardiac transplantation may cause patients to be hypersensitive to the effects of adenosine. Patients will often experience shortness of breath and/or chest pain having unknown etiology. While adenosine will not convert atrial fibrillation or atrial flutter, the consequent AV-nodal conduction slowing (reduced ventricular rate), in this setting, may aid in the identification of the arrhythmia by making the atrial fibrillation or flutter electrocardiographic morphology more apparent.
Pulmonary Artery Hypertension: Adenosine as a continuous infusion may be used for acute vasodilator testing to identify those patients with PAH with a better prognosis and who will likely have a sustained response to oral calcium channel blockers (eg, high-dose extended-release nifedipine) which have been shown to increase survival (McLaughlin, 2009; Rich, 1992). Response to acute vasodilator testing is currently defined as a reduction in mean pulmonary artery pressure (mPAP) of ≥10 mm Hg, to a mPAP ≤40 mm Hg, with an unchanged or increased cardiac output (McLaughlin, 2009). Of note, acute vasodilator testing is not recommended and may be harmful in patients with significantly elevated left heart filling pressures.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common; may cause nervousness, anxiety, drowsiness, or emotional instability
Mental Health: Effects on Psychiatric Treatment
Use caution with carbamazepine and tricyclic antidepressants, may increase heart block. Postmarking experience reports seizures as a potential adverse reaction. Psychotropics have the potential to lower seizure threshold. Monitor for seizure activity.
Nursing: Physical Assessment/Monitoring
Requires use of infusion pump and continuous cardiac and hemodynamic monitoring during infusion. Emergency resuscitation equipment should be immediately available. Monitor for adverse reactions. Adenosine could produce bronchoconstriction in patients with asthma.
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® IV: 3 mg/mL (2 mL, 4 mL)
Adenoscan®: 3 mg/mL (20 mL, 30 mL)
References
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),” Circulation, 2003, 108(15):1871-909.
Delacrétaz E, “Clinical Practice: Supraventricular Tachycardia,” N Engl J Med, 2006, 354(10):1039-51.
Ellenbogen KA, Thames MD, DiMarco JP, et al, “Electrophysiological Effects of Adenosine in the Transplanted Human Heart. Evidence of Supersensitivity,” Circulation, 1990, 81(3):821-8.
Field JM, Hazinski MF, Sayre MR, et al, “Part 1: Executive Summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122 (18 Suppl 3):640-56.
Fuster V, Ryden LE, Cannom DS, et al, “ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: 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 Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation),” J Am Coll Cardiol, 2006, 48(4):149-246.
Harrison JK, Greenfield RA, and Wharton JM, “Acute Termination of Supraventricular Tachycardia by Adenosine During Pregnancy,” Am Heart J, 1992, 123(5):1386-8.
Henzlova MJ, Cerqueira MD, Mahmarian JJ, et al, “Stress Protocols and Tracers,” J Nuc Cardiol, 2006, 13(6):e80-90.
Kleinman ME, Chameides L, Schexnayder SM, et al, “Part 14: Pediatric Advanced Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122(18 Suppl 3):876-908.
McIntosh-Yellin NL, Drew BJ, and Scheinman MM, “Safety and Efficacy of Central Intravenous Bolus Administration of Adenosine for Termination of Supraventricular Tachycardia,” J Am Coll Cardiol, 1993, 22(3):741-5.
McLaughlin VV, Archer SL, Badesch DB, et al, “ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension. A Report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association,” Circulation, 2009, 119(16):2250-94.
Neumar RW, Otto CW, Link MS, et al, “Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122(18 Suppl 3):729-67.
Rich S, Kaufmann E, and Levy PS, “The Effect of High Doses of Calcium-channel Blockers on Survival in Primary Pulmonary Hypertension,” N Engl J Med, 1992, 327(2):76-81.
Schrader BJ, Inbar S, Kaufmann L, et al, “Comparison of the Effects of Adenosine and Nifedipine in Pulmonary Hypertension,” J Am Coll Cardiol, 1992, 19(5):1060-4.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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