ADENOSINE (Generic for ADENOSCAN)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Prior to the administration of adenosine for paroxysmal supraventricular tachycardia (PSVT), appropriate vagal maneuvers should be instituted unless otherwise contraindicated (e.g., applying ice to the face of infants using caution not to hinder breathing, having an older child bear down).
-Prior to administration of adenosine as part of a cardiac nuclear stress test, screen all candidates for their suitability to receive the drug and have ready access to cardiac resuscitation equipment and trained medical staff.
Intravenous Administration
-Vials are for single-dose use; discard any unused portion.
-Administer undiluted as a rapid IV bolus (over 1 to 2 seconds).
-Inject into the most proximal injection site or central venous line. Stopcock or T-connector method recommended for rapid administration. Follow immediately with a rapid saline flush (at least 5 mL). May also be given directly into a peripheral vein.
-Elevate extremity after administration.

Other Injectable Administration
Intraosseous Administration
NOTE: Adenosine is not approved by the FDA for intraosseous administration.
-During cardiopulmonary resuscitation, the same dosage of adenosine may be given via the intraosseous route when IV access is not available. Administer a saline flush after the dose.

Fatal and nonfatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), and myocardial infarction (less than 1%) have occurred after adenosine infusion for cardiac stress testing. Transient or prolonged episodes of asystole have been reported with fatal outcomes in some cases. Rarely, ventricular fibrillation has been reported after adenosine administration, including both resuscitated and fatal events. At the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the electrocardiogram. They generally last only a few seconds without intervention, and may take the form of premature ventricular contractions (PVCs), premature atrial contractions (PACs), atrial fibrillation, sinus bradycardia (less than 1%), sinus tachycardia, skipped beats, and varying degrees of AV block. Such findings were seen in 55% of patients receiving adenosine for cardioversion. Atrial fibrillation typically began 1.5 to 3 minutes after initiation of adenosine, lasted for 15 seconds to 6 hours, and spontaneously converted to normal sinus rhythm. Adenosine can induce clinically significant increases in systolic and diastolic blood pressure. Most increases resolved spontaneously within several minutes, but in some cases, hypertension lasted for several hours. Flushing (18% to 44%) was among the most common adverse reactions reported with adenosine use in clinical trials. Other cardiovascular adverse reactions reported with adenosine during clinical trials include chest discomfort (40%), chest pain (unspecified), arrhythmias (1%), ventricular arrhythmia (less than 1%), first-degree AV block (3%), second-degree AV block (3%), third-degree AV block (less than 1%), palpitations (less than 1%), sinus exit block (less than 1%), sinus pause (less than 1%), ST-segment depression (3%), T-wave changes (less than 1%), hypertension (systolic blood pressure more than 200 mmHg) (less than 1%), hypotension (2% or less), and diaphoresis (less than 1%). Heart failure and torsade de pointes (TdP) were reported with postmarketing experience with adenosine. Discontinue adenosine in any patient who develops persistent or symptomatic high-grade AV block. Do not administer additional doses in patients who develop high-grade AV block after a single adenosine dose. Because of the very short half-life of adenosine, these effects are generally self-limiting. Discontinue adenosine in any patient who develops persistent or symptomatic hypotension.

Adenosine is a respiratory stimulant, and intravenous administration has been shown to increase minute ventilation and reduce arterial PCO2, causing respiratory alkalosis. Dyspnea/shortness of breath (12% to 28%), chest pressure (7%), hyperventilation, head pressure (less than 1%), and cough (less than 1%) have been reported with adenosine use during clinical trials. Bronchospasm, throat tightness, and respiratory arrest have been reported with postmarketing experience with adenosine. Discontinue adenosine in any patient who develops severe respiratory difficulties.

Genitourinary adverse reactions reported with adenosine in less than 1% of patients during clinical trials include vaginal pressure and urinary urgency.

Blurred vision, xerostomia, otalgia, nasal congestion, scotomata, and tongue discomfort have been reported in less than 1% of patients receiving adenosine.

Gastrointestinal discomfort (13%), throat, neck, or jaw discomfort (15%), nausea (3%), tightness in throat, groin pressure (less than 1%), and metallic taste (less than 1%) have been reported with adenosine use during clinical trials. Nausea and vomiting have been reported with postmarketing experience with adenosine.

New-onset or recurrence of convulsive seizures has occurred after adenosine injection. Some seizures are prolonged and require emergency management. Hemorrhagic and ischemic cerebrovascular accidents (e.g., stroke, intracranial bleeding) have also been reported with adenosine use and may be associated with the hemodynamic effects of adenosine. Headache (2% to 18%), lightheadedness/dizziness (2% to 12%), paresthesias (2%), numbness (1%), apprehension, nervousness (2%), burning sensation, heaviness in arms, upper extremity discomfort (4%), lower extremity discomfort (less than 1%), neck and back pain (less than 1%), weakness (less than 1%), drowsiness (less than 1%), tremor (less than 1%), and emotional lability (less than 1%) have been reported with adenosine use during clinical trials. Headache and dizziness were more common during infusion for cardiac stress testing than injection for cardioversion. Loss of consciousness has been reported with postmarketing experience with adenosine.

Hypersensitivity (dyspnea, throat tightness, flushing, erythema, rash, chest discomfort), injection site reaction, and infusion-related reactions (i.e., pain) have been reported with postmarketing use of adenosine for cardiac stress testing. Symptomatic treatment may be required for hypersensitivity reactions. Resuscitative measures may be necessary if symptoms progress.

Adenosine is contraindicated in patients with known adenosine hypersensitivity. Dyspnea, throat tightness, flushing, erythema, rash, and chest discomfort have occurred after adenosine administration. Symptomatic treatment may be required. Have personnel and appropriate treatment available. Resuscitative measures may be necessary if symptoms progress.

Adenosine will not effectively terminate atrioventricular node-independent tachycardias (e.g., atrial flutter, ectopic atrial tachycardia, atrial fibrillation). Do not administer for wide QRS complex tachycardia unless it is clear the underlying rhythm is not atrial fibrillation or atrial flutter with associated antegrade accessory pathway conduction. Adenosine can be life-threatening for atrial fibrillation with an antegrade accessory pathway. Adenosine is also not effective in converting ventricular tachycardia to normal sinus rhythm.

Adenosine is contraindicated in patients with sinus node disease, such as sick sinus syndrome or symptomatic bradycardia, and in patients with second- or third-degree AV block, except in patients with a functioning artificial pacemaker. Use adenosine with caution in patients with pre-existing first-degree AV block or bundle-branch block. Discontinue adenosine in any patient who develops persistent or symptomatic high-grade AV block. Do not administer additional doses in patients who develop high-grade AV block after a single adenosine dose.

Adenosine is a potent peripheral vasodilator and can induce significant hypotension. The risk of serious hypotension may be higher in patients with autonomic neuropathy, hypovolemia, stenotic valvular heart disease, pericarditis or pericardial effusion, or stenotic carotid artery disease with cerebrovascular insufficiency. Discontinue adenosine in any patient who develops persistent or symptomatic hypotension.

Fatal and nonfatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), and myocardial infarction have occurred after adenosine infusion. Avoid use in patients with symptoms or signs of acute myocardial infarction, for example, unstable angina or cardiovascular instability; these patients may be at greater risk of serious cardiovascular reactions to adenosine. Ensure appropriate resuscitative measures are available.

Avoid adenosine for cardioversion in patients with bronchoconstriction or acute bronchospasm (e.g., asthma). Use adenosine with caution in patients with obstructive lung disease not associated with bronchoconstriction (e.g., emphysema, bronchitis). Adenosine is a respiratory stimulant (probably through activation of carotid chemoreceptors) and intravenous administration has been shown to increase minute ventilation and reduce arterial PCO2, causing respiratory alkalosis. Use of adenosine in patients with asthma has resulted in mild to moderate exacerbation of their symptoms. In addition, respiratory compromise has occurred during adenosine infusion in patients with chronic obstructive pulmonary disease (COPD). Discontinue adenosine if a patient develops severe respiratory difficulties. The use of adenosine for myocardial perfusion imaging is contraindicated in patients with bronchoconstrictive or bronchospastic lung disease (e.g., asthma).

When used for cardioversion in pediatric patients with a heart transplant, reduce the adenosine dose to one-fifth to one-third the usual dose. In the denervated posttransplantation heart, both the sinus and atrioventricular nodes are 3 to 5 times more sensitive to adenosine.

Description: Adenosine, a ubiquitous, endogenous purine nucleotide, is available commercially for use as an antiarrhythmic agent in the management of reentrant paroxysmal supraventricular tachycardias (PSVT) including those associated with Wolff-Parkinson-White (WPW) syndrome. Because of its unique chemical structure, adenosine cannot be categorized as an antiarrhythmic agent using the Vaughn-Williams classification scheme. Although adenosine is not effective in converting ventricular tachycardia, except in the rare case of exercise-induced VT in an otherwise healthy heart, it is an effective "diagnostic aid" in determining the underlying rhythm in wide complex tachycardias. In this case, adenosine is preferred over verapamil because its effects are so transient that life-threatening hypotension does not ensue. Adenosine is equal in effectiveness to verapamil in converting PSVT, but adenosine is less toxic. Adenosine is not effective in managing basic atrial arrhythmias such as atrial flutter, atrial fibrillation, or atrial ectopic foci. A unique feature of adenosine is its extraordinarily short half-life (less than 10 seconds), which necessitates administration via rapid intravenous bolus. Adenosine is FDA-approved for use in pediatric patients as young as neonates.

For the treatment of stable reentry supraventricular tachycardia or paroxysmal supraventricular tachycardia (PSVT), including PSVT in patients with Wolff-Parkinson-White (WPW) syndrome:
Intravenous or Intraosseous* dosage:
Neonates: 0.1 mg/kg rapid IV/IO bolus followed immediately by a saline flush. If conversion does not occur within 1 to 2 minutes, give an additional 0.2 mg/kg rapid IV/IO bolus followed by a saline flush. An initial dose of 0.05 to 0.1 mg/kg IV, with the dose increased in 0.05 to 0.1 mg/kg increments, up to 0.3 mg/kg IV is FDA-approved. However, studies have shown that initial doses of 0.05 mg/kg/dose and 0.1 mg/kg/dose terminate the arrhythmia in less than 10% and less than 37% of pediatric patients who received these doses, respectively. The median effective dose was approximately 0.2 mg/kg in neonates and infants, leading some experts to recommend higher initial doses of 0.2 mg/kg/dose.
Infants, Children, and Adolescents weighing less than 50 kg: 0.1 mg/kg rapid IV/IO bolus followed immediately by a saline flush. If conversion does not occur within 1 to 2 minutes, give an additional 0.2 mg/kg rapid IV/IO bolus followed by a saline flush. An initial dose of 0.05 to 0.1 mg/kg IV, with the dose increased in 0.05 to 0.1 mg/kg increments, up to 0.3 mg/kg IV (Max: 12 mg/dose) is FDA-approved. However, studies have shown that initial doses of 0.05 mg/kg/dose and 0.1 mg/kg/dose terminate the arrhythmia in less than 10% and less than 37% of pediatric patients who received these doses, respectively. The median effective dose was approximately 0.2 mg/kg in infants and 0.1 to 0.15 mg/kg in children, leading some experts to recommend higher initial doses of 0.2 mg/kg/dose.
Children and Adolescents weighing 50 kg or more: 6 mg rapid IV/IO bolus followed immediately by a saline flush. If conversion does not occur within 1 to 2 minutes, give an additional 12 mg rapid IV/IO bolus followed by a saline flush. May repeat the 12 mg dose once if needed.

For wide-complex tachycardia diagnosis* and conversion of wide-complex tachycardia of supraventricular origin* in hemodynamically stable patients:
Intravenous or Intraosseous* dosage:
Infants, Children, and Adolescents: 0.1 mg/kg (Max: 6 mg) rapid IV/IO bolus followed immediately by a saline flush. If necessary, give a second dose of 0.2 mg/kg (Max: 12 mg) rapid IV/IO bolus followed by a saline flush. Consider adenosine only if the rhythm is regular and the QRS is monomorphic. Do not use in patients with Wolff-Parkinson-White syndrome and wide-complex tachycardia.

Maximum Dosage Limits:
-Neonates
0.3 mg/kg/dose IV/IO.
-Infants
0.3 mg/kg/dose IV/IO.
-Children
Weighing less than 50 kg: 0.3 mg/kg/dose IV/IO (Max: 12 mg).
Weighing 50 kg or more: 12 mg/dose IV/IO, with maximum total dosage up to 30 mg per PSVT episode.
-Adolescents
Weighing less than 50 kg: 0.3 mg/kg/dose IV/IO (Max: 12 mg).
Weighing 50 kg or more: 12 mg/dose IV/IO, with maximum total dosage up to 30 mg per PSVT episode.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Endogenous Role
Adenosine is a metabolic product of adenosine monophosphate (which also occurs as a diphosphorylated (ADP) or triphosphorylated (ATP) compound) and is found in all human cells. During periods of hypoxia, nucleotidases in the cardiac myocytes increase the concentration of adenosine in the cell by inducing the hydrolysis of AMP. Endogenous adenosine may be involved in mediating the balance between oxygen delivery and oxygen consumption in the heart. Adenosine's vasodilatory, antiadrenergic, and negative chronotropic properties act to decrease cardiac oxygen demand, possibly protecting the myocardium during hypoxic episodes.

Pharmacologic Mechanism of Action
Adenosine slows the conduction time through the AV node, interrupts the reentry pathways through the AV node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff-Parkinson-White Syndrome. Adenosine produces electrophysiologic changes by stimulating adenosine-sensitive potassium channels in the atrial and sinoatrial node, causing an outward flow of potassium from the cardiac myocytic membrane, which acts to induce sinus bradycardia. Thus, the drug hyperpolarizes atrial tissues, reducing the duration of the atrial action potential. Adenosine reduces the diastolic depolarization phase of the sinoatrial nodal pacemaker cells, but, unlike calcium-channel blocking agents, adenosine does not affect the upstroke phase of the action potential of sinus-node cells. The drug does, however, reduce the upstroke phase of the action potential of atrioventricular ("N") cells, resulting in atrioventricular nodal blockade and reduction of accessory-pathway antegrade refractoriness. The ionic mechanism of the drug's action on the atrioventricular node is unknown.

Methylxanthines competitively block the effects of adenosine, but the activity of adenosine is not antagonized by atropine. Dipyridamole, a nucleoside transport blocking agent, inhibits the cellular uptake of adenosine, thereby enhancing its effects. There appear to be no clinically significant adverse reactions when adenosine is administered concomitantly with other cardioactive agents, including digitalis, quinidine, beta-adrenergic blocking agents, calcium-channel blocking agents, and angiotensin-converting agent inhibitors.

Pharmacokinetics: Adenosine is administered intravenously. Adenosine is rapidly cleared from circulation by cellular uptake, mainly by erythrocytes and vascular endothelial cells. Rapid metabolism of adenosine results in an extremely short plasma half-life (less than 10 seconds with intravenous doses). Due to this short half-life, it is not known how adenosine is excreted.

Affected cytochrome P450 isoenzymes: none