Adenosine

Name: Adenosine

What are some things I need to know or do while I take Adenosine?

  • Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
  • Have an ECG checked often. Talk with your doctor.
  • High or low blood pressure may happen with adenosine. Have your blood pressure checked as you have been told by your doctor.
  • Avoid use of caffeine (for example, tea, coffee, cola) and chocolate.
  • If you are taking aminophylline, dipyridamole, theophylline, or any drug containing caffeine, talk with doctor. These drugs can affect how well this medicine works.
  • Heart attacks and very bad fast heartbeat have rarely happened with adenosine. Sometimes this has been deadly. Talk with the doctor.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
  • Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Dosage Forms and Strengths

Adenosine Injection, USP is supplied as 20 mL and 30 mL single-dose vials containing a sterile, nonpyrogenic, clear solution of Adenosine 3 mg per mL.

Adenosine Description

Adenosine is an endogenous nucleoside and is chemically described as 6-amino-9-beta-D-ribofuranosyl-9-H-purine. Adenosine has the following structural formula:

The molecular formula for Adenosine is C10H13N5O4 and its molecular weight is 267.24.

Adenosine, USP is a white crystalline powder. It is soluble in water and practically insoluble in alcohol. Solubility increases by warming and lowering the pH of the solution.

Each Adenosine Injection, USP vial contains a sterile, non-pyrogenic solution of Adenosine 3 mg per mL and sodium chloride 9 mg per mL in water for injection, with pH between 4.5 and 7.5.

Adenosine - Clinical Pharmacology

Mechanism of Action

Adenosine causes cardiac vasodilation which increases cardiac blood flow. Adenosine is thought to exert its pharmacological effects through activation of purine receptors (cell-surface A1 and A2 Adenosine receptors). Although the exact mechanism by which Adenosine receptor activation relaxes vascular smooth muscle is not known, there is evidence to support both inhibition of the slow inward calcium current reducing calcium uptake, and activation of adenylate cyclase through A2 receptors in smooth muscle cells. Adenosine may also lessen vascular tone by modulating sympathetic neurotransmission. The intracellular uptake of Adenosine is mediated by a specific transmembrane nucleoside transport system. Once inside the cell, Adenosine is rapidly phosphorylated by Adenosine kinase to Adenosine monophosphate, or deaminated by Adenosine deaminase to inosine. These intracellular metabolites of Adenosine are not vasoactive.

Myocardial uptake of thallium-201 is directly proportional to coronary blood flow. Since Adenosine significantly increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, Adenosine causes relatively less thallium-201 uptake in vascular territories supplied by stenotic coronary arteries i.e., a greater difference is seen after Adenosine between areas served by normal and areas served by stenotic vessels than is seen prior to Adenosine.

Pharmacodynamics

Hemodynamic Effects

Adenosine produces a direct negative chronotropic, dromotropic and inotropic effect on the heart, presumably due to A1-receptor agonism, and produces peripheral vasodilation, presumably due to A2-receptor agonism. The net effect of Adenosine in humans is typically a mild to moderate reduction in systolic, diastolic and mean arterial blood pressure associated with a reflex increase in heart rate. Rarely, significant hypotension and tachycardia have been observed [see Warnings and Precautions (5.4)].

Pharmacokinetics

Distribution

Intravenously administered Adenosine distributes 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.

Metabolism

Intracellular Adenosine is 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.

Elimination

While extracellular Adenosine is primarily cleared from plasma 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.

Specific Populations

Renal Impairment

As Adenosine does not require renal function for its activation or inactivation, renal impairment would not be expected to alter its effectiveness or tolerability.

Hepatic Impairment

As Adenosine does not require hepatic function for its activation or inactivation, hepatic impairment would not be expected to alter its effectiveness or tolerability.

Pharmacologic Category

  • Antiarrhythmic Agent, Miscellaneous
  • Diagnostic Agent

Pharmacology

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.

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.

Off Label Uses

Monomorphic wide-complex tachycardia (stable)

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 and the Pediatric Advanced 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)

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 and the Pediatric Advanced 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)

Based on the American Heart Association Adult Advanced Cardiovascular Life Support and the Pediatric Advanced 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)

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)

Dosing Geriatric

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

Dosing Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling. However, adenosine is not renally eliminated.

Adenosine Interactions

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • ADENOSINE/CARBAMAZEPINE
  • ADENOSINE/GATIFLOXACIN
  • ADENOSINE/PENTOXIFYLLINE

This is not a complete list of Adenosinedrug interactions. Ask your doctor or pharmacist for more information.

For the Consumer

Applies to adenosine: intravenous solution

Along with its needed effects, adenosine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking adenosine:

More common
  • Chest discomfort
  • difficult or labored breathing
  • lightheadedness or dizziness
  • throat, neck, or jaw discomfort
  • tightness in the chest
Less common
  • Chest pain
  • confusion
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • fainting
  • fast, slow, or irregular heartbeat
  • sweating
  • troubled breathing
  • unusual tiredness or weakness
Rare
  • Fast, irregular, pounding, or racing heartbeat or pulse
  • headache
  • nervousness
  • pounding in the ears

Some side effects of adenosine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Diarrhea
  • feeling of warmth
  • indigestion
  • loss of appetite
  • nausea or vomiting
  • passing of gas
  • redness of the face, neck, arms, and occasionally, upper chest
  • stomach pain, fullness, or discomfort
Rare
  • Area of decreased vision
  • cough
  • discomfort in the back, ears, or tongue
  • drowsiness
  • dry mouth
  • metallic taste
  • mood changes
  • shakiness in the legs, arms, hands, or feet
  • stuffy nose
  • trembling or shaking of the hands or feet

For Healthcare Professionals

Applies to adenosine: compounding powder, intravenous solution, sublingual spray

General

The most common adverse reactions are flushing, chest discomfort, dyspnea, facial flushing, headache, throat/neck/jaw discomfort, gastrointestinal discomfort, and lightheadedness/dizziness.[Ref]

Cardiovascular

Very common (10% or more): Flushing (44%), facial flushing (18%)
Common (1% to 10%): First degree atrioventricular block, second degree atrioventricular block, hypotension, arrhythmias, ventricular tachycardia
Uncommon (0.1% to 1%): Bradycardia, sinus tachycardia, palpitations
Very rare (less than 0.01%): Atrial fibrillation, ventricular fibrillation, Torsade de pointes, severe bradycardia
Frequency not reported: Myocardial infarction, ventricular arrhythmia, third degree atrioventricular block, sinus exit block, sinus pause, hypertension, skipped beats, atrial extrasystoles, ventricular extrasystoles
Postmarketing reports: Cardiac arrest/asystole, cardiac failure, tachycardia, prolonged asystole, transient increase in blood pressure[Ref]

Other

Very common (10% or more): Chest discomfort (40%)
Common (1% to 10%): ST segment depression, chest pressure
Uncommon (0.1% to 1%): Feeling of general discomfort/weakness/pain
Rare (less than 0.1%): Tinnitus, nipple discomfort
Frequency not reported: Chest pain, feeling of thoracic constriction/oppression, weakness, T wave changes, ear discomfort, tongue discomfort, heaviness in arms, pressure in groin
Postmarketing reports: ST segment elevation[Ref]

Respiratory

Very common (10% or more): Dyspnea (up to 28%)
Uncommon (0.1% to 1%): Hyperventilation
Rare (0.01% to 0.1%): Bronchospasm, nasal congestion
Very rare (less than 0.01%): Respiratory failure
Frequency not reported: Cough, throat tightness
Postmarketing reports: Respiratory arrest/apnea[Ref]

Nervous system

Very common (10% or more): Headache (up to 18%), lightheadedness/dizziness (12%)
Common (1% to 10%): Paresthesia, tingling in arms, numbness, burning sensation
Uncommon (0.1% to 1%): Metallic taste, head pressure
Rare (0.01% to 0.1%): Tremor, drowsiness
Very rare (less than 0.01%): Intracranial hypertension worsening
Frequency not reported: Scotomas, convulsions
Postmarketing reports: Cerebrovascular accident, intracranial hemorrhage, seizure, tonic clonic seizures, loss of consciousness/syncope[Ref]

Musculoskeletal

Very common (10% or more): Throat/neck/jaw discomfort (15%)
Common (1% to 10%): Upper extremity discomfort
Frequency not reported: Back discomfort, lower extremity discomfort, neck and back pain[Ref]

Gastrointestinal

Very common (10% or more): Gastrointestinal discomfort (13%)
Common (1% to 10%): Dry mouth, nausea
Frequency not reported: Abdominal discomfort
Postmarketing reports: Vomiting[Ref]

Psychiatric

Common (1% to 10%): Nervousness, apprehension
Frequency not reported: Emotional instability[Ref]

Dermatologic

Uncommon (0.1% to 1%): Sweating
Postmarketing reports: Angioedema, urticaria, rash[Ref]

Ocular

Uncommon (0.1% to 1%): Blurred vision[Ref]

Genitourinary

Rare (less than 0.1%): Urinary urgency
Frequency not reported: Vaginal pressure[Ref]

Local

Very rare (less than 0.01%): Injection site reaction
Postmarketing reports: Infusion site pain[Ref]

Hypersensitivity

Postmarketing reports: Hypersensitivity, anaphylaxis[Ref]

Some side effects of adenosine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

(web3)