Adenosine

Adenosine
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi

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Overview

Adenosine is an adenosine receptor agonist and antiarrhythmic that is FDA approved for the {{{indicationType}}} of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White syndrome).. Common adverse reactions include chest discomfort, flushing, abdominal discomfort, pain of head and neck region, dizziness, headache, and dyspnea.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Paroxysmal Supraventricular Tachycardia

• Adenocard (adenosine injection) should be given as a rapid bolus by the peripheral intravenous route. To be certain the solution reaches the systemic circulation, it should be administered either directly into a vein or, if given into an IV line, it should be given as close to the patient as possible and followed by a rapid saline flush.

Adult Patients

• The dose recommendation is based on clinical studies with peripheral venous bolus dosing. Central venous (CVP or other) administration of Adenocard has not been systematically studied.

• Dosing Information

• Initial dose: 6 mg given as a rapid intravenous bolus (administered over a 1-2 second period).
• Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1-2 minutes, 12 mg should be given as a rapid intravenous bolus. This 12 mg dose may be repeated a second time if required.

Pediatric Patients with a Body Weight < 50 kg

• Dosing Information

• Give 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.
• Repeat administration: If conversion of PSVT does not occur within 1-2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.

Pediatric Patients with a Body Weight ≥ 50 kg

• Administer the adult dose.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Supraventricular Tachycardia

• Developed by: ACCF/AHA

• Class of Recommendation: Class I

• Strength of Evidence: Category B

• Dosing Information

• 6 mg, followed by 12 mg as needed

Non–Guideline-Supported Use

Preventing Graft Occlusion Following Aortocoronary Bypass Surgery

• Dosing Information

• Intraoperative administration of blood cardioplegia containing containing 0.5–2 mM adenosine. Patients receiving adenosine cardioplegia were also given an infusion of adenosine (200 microg/kg/min) 10 minutes before and 15 minutes after removal of the aortic crossclamp.

Percutaneous Transluminal Angioplasty

• Dosing Information

• 20 mg in 50 milliliters (mL) saline infused at a rate of 2 mg/minute

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Adenosine in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Supraventricular Tachycardia

• Developed by: ACCF/AHA

• Class of Recommendation: Class IIa

• Strength of Evidence: Category B

• Dosing Information

• 0.05–0.3 mg/kg

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Adenosine in pediatric patients.

Contraindications

• Second- or third-degree A-V block (except in patients with a functioning artificial pacemaker)
• Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker)
• Hypersensitivity to adenosine

Warnings

• Heart Block

• Adenocard (adenosine injection) exerts its effect by decreasing conduction through the A-V node and may produce a short lasting first-, second- or third-degree heart block. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of Adenocard should not be given additional doses. Because of the very short half-life of adenosine, these effects are generally self-limiting. Appropriate resuscitative measures should be available.

• Transient or prolonged episodes of asystole have been reported with fatal outcomes in some cases. Rarely, ventricular fibrillation has been reported following Adenocard administration, including both resuscitated and fatal events. In most instances, these cases were associated with the concomitant use of digoxin and, less frequently with digoxin and verapamil. Although no causal relationship or drug-drug interaction has been established, Adenocard should be used with caution in patients receiving digoxin or digoxin and verapamil in combination.

• Arrhythmias at Time of Conversion

• 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, atrial premature contractions, atrial fibrillation, sinus bradycardia, sinus tachycardia, skipped beats, and varying degrees of A-V nodal block. Such findings were seen in 55% of patients.

• Bronchoconstriction

• Adenocard (adenosine injection) is a respiratory stimulant (probably through activation of carotid body chemoreceptors) and intravenous administration in man has been shown to increase minute ventilation (Ve) and reduce arterial PCO2 causing respiratory alkalosis.

• Adenosine administered by inhalation has been reported to cause bronchoconstriction in asthmatic patients, presumably due to mast cell degranulation and histamine release. These effects have not been observed in normal subjects. Adenocard has been administered to a limited number of patients with asthma and mild to moderate exacerbation of their symptoms has been reported. Respiratory compromise has occurred during adenosine infusion in patients with obstructive pulmonary disease. Adenocard should be used with caution in patients with obstructive lung disease not associated with bronchoconstriction (e.g., emphysema, bronchitis, etc.) and should be avoided in patients with bronchoconstriction or bronchospasm (e.g., asthma). Adenocard should be discontinued in any patient who develops severe respiratory difficulties.

Adverse Reactions

Clinical Trials Experience

Cardiovascular

Facial flushing (18%), headache (2%), sweating, palpitations, chest pain, hypotension (less than 1%).

Digestive

Nausea (3%), metallic taste, tightness in throat, pressure in groin (less than 1%).

Neurologic

Lightheadedness (2%), dizziness, tingling in arms, numbness (1%), apprehension, blurred vision, burning sensation, heaviness in arms, neck and back pain (less than 1%).

Respiratory

Shortness of breath/dyspnea (12%), chest pressure (7%), hyperventilation, head pressure (less than 1%).

Postmarketing Experience

Cardiovascular

Prolonged asystole, ventricular tachycardia, ventricular fibrillation, transient increase in blood pressure, bradycardia, atrial fibrillation, and Torsade de Pointes

Neurologic

Seizure activity, including tonic clonic (grand mal) seizures, and loss of consciousness.

Respiratory

Bronchospasm

Drug Interactions

• Intravenous Adenocard (adenosine injection) has been effectively administered in the presence of other cardioactive drugs, such as quinidine, beta-adrenergic blocking agents, calcium channel blocking agents, and angiotensin converting enzyme inhibitors, without any change in the adverse reaction profile. Digoxin and verapamil use may be rarely associated with ventricular fibrillation when combined with Adenocard (see Warnings). Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, Adenocard should be used with caution in the presence of these agents. The use of Adenocard in patients receiving digitalis may be rarely associated with ventricular fibrillation.

• The effects of adenosine are antagonized by methylxanthines such as caffeine and theophylline. In the presence of these methylxanthines, larger doses of adenosine may be required or adenosine may not be effective. Adenosine effects are potentiated by dipyridamole. Thus, smaller doses of adenosine may be effective in the presence of dipyridamole. Carbamazepine has been reported to increase the degree of heart block produced by other agents. As the primary effect of adenosine is to decrease conduction through the A-V node, higher degrees of heart block may be produced in the presence of carbamazepine.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category C

• Animal reproduction studies have not been conducted with adenosine; nor have studies been performed in pregnant women. As adenosine is a naturally occurring material, widely dispersed throughout the body, no fetal effects would be anticipated. However, since it is not known whether Adenocard can cause fetal harm when administered to pregnant women, Adenocard should be used during pregnancy only if clearly needed.

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Adenosine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Adenosine during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Adenosine with respect to nursing mothers.

Pediatric Use

• No controlled studies have been conducted in pediatric patients to establish the safety and efficacy of Adenocard for the conversion of paroxysmal supraventricular tachycardia (PSVT). However, intravenous adenosine has been used for the treatment of PSVT in neonates, infants, children and adolescents.

Geriatic Use

• Clinical studies of Adenocard did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, Adenocard in geriatric patients should be used with caution since this population may have a diminished cardiac function, nodal dysfunction, concomitant diseases or drug therapy that may alter hemodynamic function and produce severe bradycardia or AV block.

Gender

There is no FDA guidance on the use of Adenosine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Adenosine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Adenosine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Adenosine in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Adenosine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Adenosine in patients who are immunocompromised.

Administration and Monitoring

Administration

• Intravenous

Monitoring

There is limited information regarding Monitoring of Adenosine in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Adenosine in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• The half-life of Adenocard (adenosine injection) is less than 10 seconds. Thus, adverse effects are generally rapidly self-limiting.

Management

• Treatment of any prolonged adverse effects should be individualized and be directed toward the specific effect. Methylxanthines, such as caffeine and theophylline, are competitive antagonists of adenosine.

Chronic Overdose

There is limited information regarding Chronic Overdose of Adenosine in the drug label.

Pharmacology

Adenosine
Systematic (IUPAC) name
(2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
Identifiers
CAS number	58-61-7
ATC code	C01EB10
PubChem	60961
DrugBank	DB00640
Chemical data
Formula	Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox
Mol. mass	267.241 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	Rapidly cleared from circulation via cellular uptake
Protein binding	No
Metabolism	Rapidly converted to inosine and adenosine monophosphate
Half life	cleared plasma <30 seconds – half-life <10 seconds
Excretion	can leave cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid
Therapeutic considerations
Pregnancy cat.	C
Legal status	POM(UK) [[Prescription drug|Template:Unicode-only]](US)
Routes	Intravenous, injection

Mechanism of Action

• Adenocard (adenosine injection) slows conduction time through the AV node, can interrupt 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.

• Adenocard is antagonized competitively by methylxanthines such as caffeine and theophylline, and potentiated by blockers of nucleoside transport such as dipyridamole. Adenocard is not blocked by atropine.

Structure

• Adenosine is an endogenous nucleoside occurring in all cells of the body. It is chemically 6-amino-9-β-D-ribofuranosyl-9-H-purine and has the following structural formula:

This image is provided by the National Library of Medicine.

• Adenosine is a white crystalline powder. It is soluble in water and practically insoluble in alcohol. Solubility increases by warming and lowering the pH. Adenosine is not chemically related to other antiarrhythmic drugs. Adenocard® (adenosine injection) is a sterile, nonpyrogenic solution for rapid bolus intravenous injection. Each mL contains 3 mg adenosine and 9 mg sodium chloride in Water for Injection. The pH of the solution is between 4.5 and 7.5.

• The Ansyr® plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life.

• Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.

Pharmacodynamics

• The intravenous bolus dose of 6 or 12 mg Adenocard (adenosine injection) usually has no systemic hemodynamic effects. When larger doses are given by infusion, adenosine decreases blood pressure by decreasing peripheral resistance.

Pharmacokinetics

• Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. This process involves a specific transmembrane nucleoside carrier system that is reversible, nonconcentrative, and bidirectionally symmetrical. Intracellular adenosine is rapidly metabolized either via phosphorylation to adenosine monophosphate by adenosine kinase, or via deamination to inosine by adenosine deaminase in the cytosol. Since adenosine kinase has a lower Km and Vmax than adenosine deaminase, deamination plays a significant role only when cytosolic adenosine saturates the phosphorylation pathway. Inosine formed by deamination of adenosine can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. Adenosine monophosphate formed by phosphorylation of adenosine is incorporated into the high-energy phosphate pool. While extracellular adenosine is primarily cleared by cellular uptake with a half-life of less than 10 seconds in whole blood, excessive amounts may be deaminated by an ecto-form of adenosine deaminase. As Adenocard requires no hepatic or renal function for its activation or inactivation, hepatic and renal failure would not be expected to alter its effectiveness or tolerability.

Nonclinical Toxicology

• Carcinogenesis, Mutagenesis, Impairment of Fertility

• Studies in animals have not been performed to evaluate the carcinogenic potential of Adenocard (adenosine injection). Adenosine was negative for genotoxic potential in the Salmonella (Ames Test) and Mammalian Microsome Assay.

• Adenosine, however, like other nucleosides at millimolar concentrations present for several doubling times of cells in culture, is known to produce a variety of chromosomal alterations. Fertility studies in animals have not been conducted with adenosine.

Clinical Studies

• In controlled studies in the United States, bolus doses of 3, 6, 9, and 12 mg were studied. A cumulative 60% of patients with paroxysmal supraventricular tachycardia had converted to normal sinus rhythm within one minute after an intravenous bolus dose of 6 mg Adenocard (some converted on 3 mg and failures were given 6 mg), and a cumulative 92% converted after a bolus dose of 12 mg. Seven to sixteen percent of patients converted after 1-4 placebo bolus injections. Similar responses were seen in a variety of patient subsets, including those using or not using digoxin, those with Wolff-Parkinson-White syndrome, males, females, blacks, Caucasians, and Hispanics.

• Adenosine is not effective in converting rhythms other than PSVT, such as atrial flutter, atrial fibrillation, or ventricular tachycardia, to normal sinus rhythm.

How Supplied

• Adenocard® (adenosine injection) is supplied as a sterile non-pyrogenic solution in normal saline.

NDC 0469-8234-12 Product Code 823412

6 mg/2 mL (3 mg/mL) in 2 mL (fill volume) Ansyr® plastic disposable syringe, in a package of ten.

NDC 0469-8234-14 Product Code 823414

12 mg/4 mL (3 mg/mL) in 4 mL (fill volume) Ansyr® plastic disposable syringe, in a package of ten.

• Store at controlled room temperature 15º-30ºC (59º-86ºF).

• DO NOT REFRIGERATE as crystallization may occur. If crystallization has occurred, dissolve crystals by warming to room temperature. The solution must be clear at the time of use.

• Contains no preservatives. Discard unused portion.

• May require needle or blunt. To prevent needle-stick injuries, needles should not be recapped, purposely bent or broken by hand.

Storage

There is limited information regarding Adenosine Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Adenosine in the drug label.

Precautions with Alcohol

• Alcohol-Adenosine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• Adenocard®

Look-Alike Drug Names

• N/A

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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