Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Adenosine injection, USP is supplied as 20 mL and 30 mL vials of sterile, nonpyrogenic, preservative-free, solution in normal saline: 60 mg/20 mL (3 mg/mL) in a 20 mL single-dose, glass vial, packaged individually in a carton (NDC 23155-258-31) and in packages of ten (NDC 23155-258-41). 90 mg/30 mL (3 mg/mL) in a 30 mL single-dose, glass vial, packaged individually in a carton (NDC 23155-258-32) and in packages of ten (NDC 23155-258-42). 16.2 Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature] 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 Discard unused portion; PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 60 mg/20 mL label NDC 23155- 258 -31 ADENOSINE Injection USP 60 mg/20 mL (3 mg/mL) For Intravenous Infusion Only 20 mL Single-Dose Vial Rx only label-60mg-20ml; PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 60 mg/20 mL carton NDC 23155- 258 -31 ADENOSINE Injection USP 60 mg/20 mL (3 mg/mL) For Intravenous Infusion Only One 20 mL Single-Dose Vial Rx only 20 ml carton; PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 90 mg/30 mL label NDC 23155- 258 -32 ADENOSINE Injection USP 90 mg/30 mL (3 mg/mL) For Intravenous Infusion Only 30 mL Single-Dose Vial Rx only label-90mg-30ml; PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 90 mg/30 mL carton NDC 23155- 258 -32 ADENOSINE Injection USP 90 mg/30 mL (3 mg/mL) For Intravenous Infusion Only One 30 mL Single-Dose Vial Rx only 30 ml carton
- 16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Adenosine injection, USP is supplied as 20 mL and 30 mL vials of sterile, nonpyrogenic, preservative-free, solution in normal saline: 60 mg/20 mL (3 mg/mL) in a 20 mL single-dose, glass vial, packaged individually in a carton (NDC 23155-258-31) and in packages of ten (NDC 23155-258-41). 90 mg/30 mL (3 mg/mL) in a 30 mL single-dose, glass vial, packaged individually in a carton (NDC 23155-258-32) and in packages of ten (NDC 23155-258-42). 16.2 Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature] 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 Discard unused portion
- PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 60 mg/20 mL label NDC 23155- 258 -31 ADENOSINE Injection USP 60 mg/20 mL (3 mg/mL) For Intravenous Infusion Only 20 mL Single-Dose Vial Rx only label-60mg-20ml
- PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 60 mg/20 mL carton NDC 23155- 258 -31 ADENOSINE Injection USP 60 mg/20 mL (3 mg/mL) For Intravenous Infusion Only One 20 mL Single-Dose Vial Rx only 20 ml carton
- PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 90 mg/30 mL label NDC 23155- 258 -32 ADENOSINE Injection USP 90 mg/30 mL (3 mg/mL) For Intravenous Infusion Only 30 mL Single-Dose Vial Rx only label-90mg-30ml
- PACKAGE LABEL PRINCIPAL DISPLAY PANEL - 90 mg/30 mL carton NDC 23155- 258 -32 ADENOSINE Injection USP 90 mg/30 mL (3 mg/mL) For Intravenous Infusion Only One 30 mL Single-Dose Vial Rx only 30 ml carton
Overview
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 C 10 H 13 N 5 O 4 and its molecular weight is 267.24. Adenosine 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 USP 3 mg/mL and sodium chloride USP 9 mg/mL in water for injection, USP with pH between 4.5 and 7.5. structure
Indications & Usage
Adenosine, a pharmacologic stress agent, is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately ( 1 ) Adenosine injection, USP is indicated as an adjunct to thallium-201 myocardial perfusion scintigraphy in patients unable to exercise adequately.
Dosage & Administration
Recommended dose is 0.14 mg/kg/min infused over six minutes as a continuous peripheral intravenous infusion (total dose of 0.84 mg/kg) ( 2 ) The recommended adenosine injection dose is 0.14 mg/kg/min infused over six minutes (total dose of 0.84 mg/kg) (Table 1). Administer adenosine injection only as a continuous peripheral intravenous infusion Inject Thallium-201 at the midpoint of the adenosine injection infusion (i.e., after the first three minutes of adenosine injection) Thallium-201 is physically compatible with adenosine injection and may be injected directly into the adenosine injection infusion set Inject Thallium-201 as close to the venous access as possible to prevent an inadvertent increase in the dose of adenosine injection (the contents of the intravenous tubing) being administered Visually inspect adenosine injection for particulate matter and discoloration prior to administration. Do not administer adenosine injection if it contains particulate matter or is discolored. There are no data on the safety or efficacy of alternative adenosine injection infusion protocols. The safety and efficacy of adenosine injection administered by the intracoronary route have not been established. Table 1 Dosage Chart for Adenosine Injection Patient Weight (kilograms) Infusion Rate (mL per minute over 6 minutes for total dose of 0.84 mg/kg) 45 2.1 50 2.3 55 2.6 60 2.8 65 3 70 3.3 75 3.5 80 3.8 85 4 90 4.2 The nomogram displayed in Table 1 was derived from the following general formula: formula
Warnings & Precautions
Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction. Fatal cardiac events have occurred. Avoid use in patients with symptoms or signs of acute myocardial ischemia. Appropriate resuscitative measures should be available ( 5.1 ) Sinoatrial (SA) and Atrioventricular (AV) Nodal Block. First-, second- or third-degree AV block, or sinus bradycardia can occur. Discontinue adenosine injection if patient develops persistent or symptomatic high-grade AV block ( 5.2 ) Bronchoconstriction. Can induce dyspnea, bronchoconstriction, and respiratory compromise, especially in patients with obstructive pulmonary disease. Discontinue adenosine injection if patient develops severe respiratory difficulties ( 5.3 ) Hypotension. Significant hypotension can occur. Discontinue adenosine injection if patient develops persistent or symptomatic hypotension ( 5.4 ) Cerebrovascular Accidents. Hemorrhagic and ischemic cerebrovascular accidents have occurred ( 5.5 ) Seizures. New onset or recurrence of convulsive seizures have occurred. Use of methylxanthines (e.g., caffeine, aminophylline and theophylline) is not recommended in patients who experience a seizures in association with adenosine injection ( 5.6 ) Hypersensitivity. Dyspnea, throat tightness, flushing, erythema, rash, and chest discomfort have occurred. Have personnel and resuscitative equipment immediately available ( 5.7 ) Atrial Fibrillation. Reported in patients with or without a history of atrial fibrillation ( 5.8 ) Hypertension. Clinically significant increases in systolic and diastolic pressure have been observed ( 5.9 ) 5.1 Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction Fatal and nonfatal cardiac arrest, sustained ventricular tachycardia (requiring resuscitation), and myocardial infarction have occurred following adenosine injection infusion. Avoid use in patients with symptoms or signs of acute myocardial ischemia, for example, unstable angina or cardiovascular instability; these patients may be at greater risk of serious cardiovascular reactions to adenosine injection. Appropriate resuscitative measures should be available [see Overdosage (10) ]. 5.2 Sinoatrial and Atrioventricular Nodal Block Adenosine injection exerts a direct depressant effect on the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia. In clinical trials, approximately 6% of patients developed AV block following adenosine injection administration (first-degree heart block developed in 3%, second-degree in 3%, and third-degree in 0.8% of patients) [see Clinical Trials Experience (6.1) ]. Use adenosine injection with caution in patients with pre-existing first-degree AV block or bundle branch block. Do not use in patients with high-grade AV block or sinus node dysfunction (except in patients with a functioning artificial pacemaker). Discontinue adenosine injection in any patient who develops persistent or symptomatic high-grade AV block. 5.3 Bronchoconstriction Adenosine injection administration can cause dyspnea, bronchoconstriction, and respiratory compromise. Adenosine injection should be used with caution in patients with obstructive lung disease not associated with bronchoconstriction (e.g., emphysema, bronchitis). Do not use in patients with bronchoconstriction or bronchospasm (e.g., asthma). Discontinue adenosine injection in any patient who develops severe respiratory difficulties. Resuscitative measures should be available prior to adenosine injection administration [see Clinical Trials Experience (6.1) , Overdosage (10) , and Clinical Pharmacology (12.2) ]. 5.4 Hypotension Adenosine injection is a potent peripheral vasodilator and can induce significant hypotension. The risk of serious hypotension may be higher in patients with autonomic dysfunction, hypovolemia, stenotic valvular heart disease, pericarditis or pericardial effusions, or stenotic carotid artery disease with cerebrovascular insufficiency. Discontinue adenosine injection in any patient who develops persistent or symptomatic hypotension. 5.5 Cerebrovascular Accident Hemorrhagic and ischemic cerebrovascular accidents have occurred. Hemodynamic effects of adenosine injection including hypotension or hypertension can be associated with these adverse reactions. [see Warnings and Precautions (5.4) and ( 5.9 )]. 5.6 Seizures New-onset or recurrence of convulsive seizures has occurred following adenosine injection. Some seizures are prolonged and require emergent anticonvulsive management. Aminophylline may increase the risk of seizures associated with adenosine injection. Methylxanthine use is not recommended in patients who experience seizures in association with adenosine injection administration [see Overdosage (10) ]. 5.7 Hypersensitivity Dyspnea, throat tightness, flushing, erythema, rash, and chest discomfort have occurred. Symptomatic treatment may be required. Have personnel and appropriate treatment available. Resuscitative measures may be necessary if symptoms progress. [see Post-Marketing Experience (6.2) ]. 5.8 Atrial Fibrillation Adenosine injection can cause atrial fibrillation in patients with or without a history of atrial fibrillation. Atrial fibrillation typically began 1.5 to 3 minutes after initiation of adenosine injection, lasted for 15 seconds to 6 hours, and spontaneously converted to normal sinus rhythm [see Post-Marketing Experience (6.2) ]. 5.9 Hypertension Adenosine injection 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 [see Clinical Trials Experience (6.1) ].
Contraindications
Second- or third-degree AV block (except in patients with a functioning artificial pacemaker) ( 4 ) Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker) ( 4 ) Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma) ( 4 ) Known hypersensitivity to adenosine injection ( 4 ) Adenosine injection is contraindicated in patients with: Second- or third-degree AV block (except in patients with a functioning artificial pacemaker) [see Warnings and Precautions (5.2) ] Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker) [see Warnings and Precautions (5.2) ] Known or suspected bronchoconstrictive or bronchospastic lung disease (e.g., asthma) [see Warnings and Precautions (5.3) ] Known hypersensitivity to adenosine [see Warnings and Precautions (5.7) ]
Adverse Reactions
Most common adverse reactions (incidence greater than or equal to 10%) are: flushing; chest discomfort; shortness of breath; headache; throat, neck or jaw discomfort; gastrointestinal discomfort; and dizziness ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . The following adverse reactions are discussed in more detail in other sections of the prescribing information: Fatal Cardiac Arrest, Ventricular Arrhythmias, and Myocardial Infarction [see Warnings and Precautions (5.1) ] Sinoatrial and Atrioventricular Nodal Block [see Warnings and Precautions (5.2) ] Bronchoconstriction [see Warnings and Precautions (5.3) ] Hypotension [see Warnings and Precautions (5.4) ] Cerebrovascular Accident [see Warnings and Precautions (5.5) ] Seizures [see Warnings and Precautions (5.6) ] Hypersensitivity [see Warnings and Precautions (5.7) ] Atrial fibrillation [see Warnings and Precautions (5.8) ] Hypertension [see Warnings and Precautions (5.9) ] 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following adverse reactions, with an incidence of at least 1%, were reported with adenosine injection among 1,421 patients in clinical trials. 11% of the adverse reactions occurred several hours after adenosine injection administration. 8% of the adverse reactions began with adenosine injection infusion and persisted for up to 24 hours. The most common (incidence greater than or equal to 10%) adverse reactions to adenosine injection are flushing, chest discomfort, shortness of breath, headache, throat, neck or jaw discomfort, gastrointestinal discomfort, and dizziness (Table 2). Table 2 Adverse Reactions in Clinical Trials (Frequency Greater Than or Equal To 1%) Adverse Reactions Adenosine N=1,421 Flushing 44% Chest discomfort 40% Dyspnea 28% Headache 18% Throat, neck or jaw discomfort 15% Gastrointestinal discomfort 13% Lightheadedness/dizziness 12% Upper extremity discomfort 4% ST segment depression 3% First-degree AV block 3% Second-degree AV block 3% Paresthesia 2% Hypotension 2% Nervousness 2% Arrhythmias 1% Adverse reactions to adenosine injection of any severity reported in less than 1% of patients include: Body as a Whole: back discomfort, lower extremity discomfort, weakness Cardiovascular System: myocardial infarction, ventricular arrhythmia, third-degree AV block, bradycardia, palpitation, sinus exit block, sinus pause, T-wave changes, hypertension (systolic blood pressure greater than 200 mm Hg) Respiratory System: cough Central nervous System: drowsiness, emotional instability, tremors Genital/Urinary System: Vaginal pressure, urgency Special Senses: blurred vision, dry mouth, ear discomfort, metallic taste, nasal congestion, scotomas, tongue discomfort 6.2 Post-Marketing Experience The following adverse reactions have been reported from marketing experience with adenosine injection. Because these reactions are reported voluntarily from a population of uncertain size, are associated with concomitant diseases and multiple drug therapies and surgical procedures, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac Disorders: cardiac arrest, atrial fibrillation, cardiac failure, myocardial infarction, tachycardia, ventricular arrhythmia Gastrointestinal Disorders: nausea and vomiting General Disorders and Administration Site Conditions: chest pain, injection site reaction, infusion site pain Immune System Disorders: hypersensitivity Nervous System Disorders: cerebrovascular accident including intracranial hemorrhage, seizure activity including tonic-clonic (grand mal) seizures, loss of consciousness Respiratory, Thoracic and Mediastinal Disorders: bronchospasm, respiratory arrest, throat tightness
Drug Interactions
Methylxanthines interfere with the activity of adenosine ( 7.1 , 10 ) Nucleoside transport inhibitors such as dipyridamole can increase the activity of adenosine ( 7.1 ) 7.1 Effects of Other Drugs on Adenosine Injection The vasoactive effects of adenosine are inhibited by adenosine receptor antagonists, (such as methylxanthines (e.g., caffeine, aminophylline, and theophylline). The safety and efficacy of adenosine injection in the presence of these agents has not been systematically evaluated [see Overdosage (10) ]. The vasoactive effects of adenosine are potentiated by nucleoside transport inhibitors such as dipyridamole. The safety and efficacy of adenosine in the presence of dipyridamole has not been systematically evaluated. Whenever possible, drugs that might inhibit or augment the effects of adenosine should be withheld for at least five half-lives prior to the use of adenosine injection. 7.2 Effects of Adenosine on Other Drugs Adenosine injection has been given with other cardioactive drugs (such as beta adrenergic blocking agents, cardiac glycosides, and calcium channel blockers) without apparent adverse interactions, but its effectiveness with these agents has not been systematically evaluated. Because of the potential for additive or synergistic depressant effects on the SA and AV nodes, however, adenosine injection should be used with caution in the presence of these agents [see Warnings and Precautions (5.2) ].
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