INTERACTIONS Methylxanthines interfere with the activity of adenosine injection ( 7.1 , 10 ) Nucleoside transport inhibitors such as dipyridamole can increase the activity of adenosine injection ( 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 <span class="opacity-50 text-xs">[see Overdosage (10) ]</span> . The vasoactive effects of adenosine injection 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 Injection 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 <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2) ]</span> .
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 injection [see Warnings and Precautions (5.7) ] 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 )
AND 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 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 if patient develops severe respiratory difficulties ( 5.3 ) Hypotension . Significant hypotension can occur. Discontinue adenosine 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 seizures in association with adenosine ( 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 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. Appropriate resuscitative measures should be available <span class="opacity-50 text-xs">[see Overdosage ( 10 )]</span> .
5.2 Sinoatrial and Atrioventricular Nodal Block Adenosine 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 administration (first-degree heart block developed in 3%, second-degree in 3%, and third-degree in 0.8% of patients) <span class="opacity-50 text-xs">[see Clinical Trials Experience ( 6.1 )]</span> . Use adenosine 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 in any patient who develops persistent or symptomatic high-grade AV block.
5.3 Bronchoconstriction Adenosine administration can cause dyspnea, bronchoconstriction, and respiratory compromise. Adenosine 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 in any patient who develops severe respiratory difficulties. Resuscitative measures should be available prior to adenosine administration <span class="opacity-50 text-xs">[see Clinical Trials Experience ( 6.1 ), Overdosage ( 10 ), and Clinical Pharmacology ( 12.2 )]</span>.
5.4 Hypotension Adenosine 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 in any patient who develops persistent or symptomatic hypotension.
5.5 Cerebrovascular Accident Hemorrhagic and ischemic cerebrovascular accidents have occurred. Hemodynamic effects of adenosine including hypotension or hypertension can be associated with these adverse reactions <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.4 ) and ( 5.9 )]</span> .
5.6 Seizures New-onset or recurrence of convulsive seizures has occurred following adenosine. Some seizures are prolonged and require emergent anticonvulsive management. Aminophylline may increase the risk of seizures associated with adenosine. Methylxanthine use is not recommended in patients who experience seizures in association with adenosine administration <span class="opacity-50 text-xs">[see Overdosage ( 10 )]</span>.
5.7 Hypersensitivity, including Anaphylaxis 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 <span class="opacity-50 text-xs">[see Post-Marketing Experience ( 6.2 )]</span>.
5.8 Atrial Fibrillation Adenosine 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, lasted for 15 seconds to 6 hours, and spontaneously converted to normal sinus rhythm <span class="opacity-50 text-xs">[see Post-Marketing Experience ( 6.2 )]</span> .
5.9 Hypertension 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 <span class="opacity-50 text-xs">[see Clinical Trials Experience ( 6.1 )]</span> .
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 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. Appropriate resuscitative measures should be available <span class="opacity-50 text-xs">[see Overdosage ( 10 )]</span> .
5.2 Sinoatrial and Atrioventricular Nodal Block Adenosine 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 administration (first-degree heart block developed in 3%, second-degree in 3%, and third-degree in 0.8% of patients) <span class="opacity-50 text-xs">[see Clinical Trials Experience ( 6.1 )]</span> . Use adenosine 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 in any patient who develops persistent or symptomatic high-grade AV block.
5.3 Bronchoconstriction Adenosine administration can cause dyspnea, bronchoconstriction, and respiratory compromise. Adenosine 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 in any patient who develops severe respiratory difficulties. Resuscitative measures should be available prior to adenosine administration <span class="opacity-50 text-xs">[see Clinical Trials Experience ( 6.1 ), Overdosage ( 10 ), and Clinical Pharmacology ( 12.2 )]</span>.
5.4 Hypotension Adenosine 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 in any patient who develops persistent or symptomatic hypotension.
5.5 Cerebrovascular Accident Hemorrhagic and ischemic cerebrovascular accidents have occurred. Hemodynamic effects of adenosine including hypotension or hypertension can be associated with these adverse reactions <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.4 ) and ( 5.9 )]</span> .
5.6 Seizures New-onset or recurrence of convulsive seizures has occurred following adenosine. Some seizures are prolonged and require emergent anticonvulsive management. Aminophylline may increase the risk of seizures associated with adenosine. Methylxanthine use is not recommended in patients who experience seizures in association with adenosine administration <span class="opacity-50 text-xs">[see Overdosage ( 10 )]</span>.
5.7 Hypersensitivity, including Anaphylaxis 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 <span class="opacity-50 text-xs">[see Post-Marketing Experience ( 6.2 )]</span>.
5.8 Atrial Fibrillation Adenosine 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, lasted for 15 seconds to 6 hours, and spontaneously converted to normal sinus rhythm <span class="opacity-50 text-xs">[see Post-Marketing Experience ( 6.2 )]</span> .
5.9 Hypertension 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 <span class="opacity-50 text-xs">[see Clinical Trials Experience ( 6.1 )]</span> .