regadenoson (Rx)

>10%

Dyspnea (28%)

Headache (26%)

Rhythm conduction abnormalities (26%)

Flushing (16%)

PVCs (14%)

Chest Discomfort (13%)

Angina or ST segment depression (12%)

1-10%

Dizziness (8%)

Chest pain (7%)

PACs (7%)

Nausea (6%)

Ventricular conduction abnormalities (6%)

Abdominal discomfort (5%)

Dysgeusia (5%)

Feeling hot (5%)

First-degree AV block (3%)

<1%

Anaphylaxis, angioedema, cardiac arrest, respiratory arrest/distress, throat tightness, and urticaria/rashes, atrial fibrillation, seizures, cardiovascular accidents (stroke)

Postmarketing reports

Cardiovascular: Myocardial infarction, cardiac arrest, ventricular arrhythmias, supraventricular tachyarrhythmias including atrial fibrillation with rapid ventricular response (new-onset or recurrent), atrial flutter, heart block (including third-degree block), asystole, marked hypertension, symptomatic hypotension in association with transient ischemic attack, seizures and syncope

Central nervous system: Tremor, seizure, transient ischemic attack, and cerebrovascular accident including intracranial hemorrhage

Contraindications

Second- or third-degree AV block, or sinus node dysfunction (unless patient has a functioning artificial pacemaker installed)

Cautions

Appropriate bronchodilator therapy and resuscitative measures should be available prior to and following therapy; adhere to recommended duration of injection; longer injection times may increase duration and magnitude of increase in coronary blood flow

QT prolongation has occurred shortly after administration in postmarketing surveillance

Adenosine receptor agonists can depress the SA and AV nodes and may cause first-, second- or third-degree AV block, or sinus bradycardia requiring intervention

Anaphylaxis, angioedema, cardiac or respiratory arrest, respiratory distress, decreased oxygen saturation, hypotension, throat tightness, urticaria, and rashes have occurred

Adenosine receptor agonists may cause dyspnea, bronchoconstriction, and respiratory compromise; caution with asthma or bronchoconstrictive disease; appropriate bronchodilator therapy and resuscitative measures should be available prior to and following therapy administration

Nucleoside transport inhibitors (eg, dipyridamole) and potentiate the vasoactive effects of regadenoson; withhold for 5 half-lives before regadenoson administration

Methylxanthines (eg, caffeine, theophylline) are adenosine receptor antagonists and inhibit regadenoson’s vasoactive effects; withhold methylxanthines for 5 half-lives before regadenoson administration

Aminophylline may increase risk of seizures associated with regadenoson injection; aminophylline may increase risk of seizures associated with therapy; methylxanthine use is not recommended in patients who experience a seizure in association with this drug

May lower seizure threshold; new-onset or recurrence of convulsive seizures has occurred following regadenoson injection; some seizures are prolonged and require emergent anticonvulsive management

Hemorrhagic and ischemic cerebrovascular accidents have occurred; effects of including hypotension or hypertension may be associated with these adverse reactions

New-onset or recurrent atrial fibrillation with rapid ventricular response and atrial flutter reported

Adenosine receptor agonists induce arterial vasodilation and hypotension; risk of serious hypotension may be higher in patients with autonomic dysfunction, hypovolemia, left main coronary artery stenosis, stenotic valvular heart disease, pericarditis or pericardial effusions, or stenotic carotid artery disease with cerebrovascular insufficiency; in post-marketing experience, syncope, transient ischemic attacks and seizures have been observed

Administration of adenosine receptor agonists may result in clinically significant increases in blood pressure in some patients; in post-marketing experience, cases of potentially clinically significant hypertension have been reported, particularly with underlying hypertension and when low-level exercise was included in the myocardial perfusion imaging

Myocardial ischemia

• Fatal and nonfatal myocardial infarction (MI), ventricular arrhythmias, and cardiac arrest reported; 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 reaction
• Cardiac resuscitation equipment and trained staff should be available before administering therapy; adhere to recommended duration of injection; as noted in an animal study, longer injection times may increase duration and magnitude of increase in coronary blood flow
• If serious reactions occur, consider use of aminophylline, an adenosine antagonist, to shorten duration of increased coronary blood flow induced by the drug

Risk for myocardial infarction and death

• Avoid use for cardiac nuclear stress tests in patients with signs or symptoms of acute myocardial ischemia (eg, unstable angina, cardiovascular instability); use may increase risk of fatal MI
• Screen all nuclear stress test candidates for risks

Pregnancy

There are no available data on use in pregnant women to inform a drug-associated risk

Animal data

• In animal reproduction studies, adverse developmental outcomes were observed with the administration to pregnant rats and rabbits during organogenesis only at doses that produced maternal toxicity

Lactation

There is no information on presence of regadenoson in human milk, effects on breastfed infant, or on milk production; because of the potential risk of serious cardiac reactions in breastfed infant, advise the nursing mother to pump and discard breast milk for 10 hours after administration of the drug

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Low affinity agonist for the A2A adenosine receptor

Activation of the A2A adenosine receptor produces coronary vasodilation and increases coronary blood flow