Regadenoson (Monograph)

Brand name: Lexiscan
Drug class: Cardiac Function
VA class: CV900
Chemical name: Adenosine, 2-[4-[(methylamino)carbonyl]-1H-pyrazol-1-yl]-, monohydrate
Molecular formula: C₁₅H₁₈N₈O₅ • H₂O
CAS number: 875148-45-1

Introduction

Pharmacologic stress test agent; A_2A adenosine receptor agonist.

Uses for Regadenoson

Radionuclide Myocardial Perfusion Imaging

Adjunct to radionuclide myocardial perfusion imaging in patients unable to undergo adequate stress testing with exercise.

Regadenoson Dosage and Administration

Administration

IV Administration

Administer by rapid (i.e., over approximately 10 seconds) IV injection into a peripheral vein. Use 22-gauge or larger catheter or needle.

After injection, immediately flush with 5 mL of 0.9% sodium chloride injection.

Administer radionuclide myocardial perfusion imaging agent 10–20 seconds after flush; may inject radionuclide directly into same catheter as regadenoson.

Some clinicians suggest BP monitoring every minute during infusion and 3–5 minutes into recovery. ECG monitoring also recommended.

Rate of Administration

Administer over approximately 10 seconds.

Dosage

Adults

Radionuclide Myocardial Perfusion Imaging

IV

0.4 mg (5 mL). (See Administration under Dosage and Administration.)

Special Populations

Hepatic Impairment

Dosage adjustment not necessary.

Renal Impairment

Dosage adjustment not necessary.

Geriatric Patients

Dosage adjustment not necessary.

Cautions for Regadenoson

Contraindications

• Second- or third-degree AV block (except in patients with a functioning artificial pacemaker).

• Sinus node dysfunction (except in patients with a functioning artificial pacemaker).

• Known hypersensitivity to regadenoson or any ingredient in the formulation.

Warnings/Precautions

Cardiovascular and Cerebrovascular Effects

Serious cardiovascular and cerebrovascular events, including myocardial ischemic events, rhythm and conduction abnormalities, hypotension, hypertension, and stroke, reported rarely. Ensure availability of cardiac resuscitation equipment and trained staff prior to administration.

Myocardial Ischemic Events

Risk of rare but serious adverse cardiovascular events, including MI and death, in patients receiving regadenoson as a cardiac stress testing agent during myocardial perfusion imaging; similar risk also observed with adenosine, another pharmacologic stress test agent.

Avoid use in patients with signs and symptoms of acute myocardial ischemia (e.g., unstable angina, cardiovascular instability).

If serious adverse reactions occur, may consider use of aminophylline, an adenosine antagonist, to shorten duration of increased coronary blood flow. However, do not use aminophylline in patients with regadenoson-associated seizures. (See Seizures under Cautions.)

Rhythm and Conduction Abnormalities

New-onset or recurrent supraventricular tachyarrhythmias, including atrial fibrillation with rapid ventricular response and atrial flutter, reported.

Risk of first-, second-, or third-degree AV block, or sinus bradycardia requiring intervention. (See Contraindications under Cautions.)

Profound sinus bradycardia (heart rate <40 beats/minute) considered a relative contraindication to regadenoson stress testing by some clinicians.

Hemodynamic and Associated Effects

Possible hypotension due to the vasodilating effects of the drug.

Risk of serious hypotension may be increased 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.

Clinically important increases in BP also possible; generally transient, resolving within 10–15 minutes.

Cerebrovascular events (e.g., syncope, TIA, hemorrhagic or ischemic stroke, seizures) possibly related to hemodynamic effects of regadenoson reported.

Respiratory Effects

Risk of dyspnea, bronchoconstriction, and respiratory compromise.

Ensure availability of appropriate bronchodilator therapy and resuscitative measures prior to administration in patients with known or suspected bronchoconstrictive disease, COPD, or asthma.

Some clinicians consider bronchospasm a contraindication to regadenoson stress testing.

Seizures

Risk of new-onset or recurrent seizures, including tonic-clonic seizures. In some cases, seizure activity may be prolonged and require emergency management.

Concomitant use of aminophylline may increase risk of seizures. (See Specific Drugs under Interactions.)

Sensitivity Reactions

Hypersensitivity

Risk of hypersensitivity reactions, possibly requiring resuscitative measures; manifestations have included anaphylaxis, angioedema, cardiac/respiratory arrest, decreased oxygen saturation, hypotension, throat tightness, urticaria, and rash. (See Contraindications under Cautions.)

Ensure immediate availability of appropriate personnel and resuscitative equipment.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether regadenoson is distributed into milk. Interrupt nursing or discontinue drug. Based on pharmacokinetics of regadenoson, may consider interrupting nursing for 10 hours after drug administration.

Pediatric Use

Safety and efficacy not established in pediatric patients ≤18 years of age.

Geriatric Use

Similar adverse effect profile in patients ≥75 years of age and younger adults (i.e., patients <65 years of age); however, higher incidence of hypotension observed in older patients.

Population pharmacokinetic analysis indicate that age has minimal influence on pharmacokinetics of regadenoson; however, decreased renal clearance may occur with increasing age.

Hepatic Impairment

Effect of hepatic impairment on pharmacokinetics of regadenoson not established.

Renal Impairment

Reduced clearance is possible with increasing renal impairment. (See Special Populations under Pharmacokinetics.) However, serious adverse effects related to renal impairment generally have not been reported.

Pharmacokinetics of regadenoson not established in patients undergoing dialysis. Prolonged chest discomfort and nausea have been reported in at least one dialysis-dependent patient who received the drug.

Common Adverse Effects

Dyspnea, headache, flushing, chest discomfort, angina pectoris or ST-segment depression, dizziness, chest pain, nausea, abdominal discomfort, dysgeusia, warm feeling.

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Does not inhibit CYP1A2, 2C8, 2C9, 2C19, 2D6, or 3A4 in human liver microsomes; unlikely to alter pharmacokinetics of drugs metabolized by these CYP isoenzymes.

Specific Drugs

Regadenoson Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations achieved within 1–4 minutes following IV injection.

Elimination

Metabolism

Not fully elucidated; does not appear to be metabolized by CYP isoenzymes. No detectable metabolites have been identified.

Elimination Route

In healthy adults, approximately 57% of regadenoson is eliminated unchanged in urine (range: 19–77%); renal tubular secretion also involved.

Half-life

Initial phase: 2–4 minutes (onset of pharmacodynamic response).

Intermediate phase: Approximately 30 minutes (loss of pharmacodynamic effect).

Terminal phase: Approximately 2 hours (decrease in plasma concentrations).

Special Populations

Decreased clearance and increased half-life and AUC observed with increasing renal impairment. However, plasma concentration-time profile not substantially altered in early stages after dosing when most pharmacologic effects observed. (See Renal Impairment under Dosage and Administration.)

Increased clearance observed with increased body weight.

Minimal effects of age, gender, and race on regadenoson pharmacokinetics.

Stability

Storage

Parenteral

Injection

25°C (15–30°C permitted).

Actions

• Low affinity A_2A adenosine receptor agonist. Activation of the A_2A adenosine receptor induces coronary vasodilation and increases coronary blood flow.

• Increases blood flow in normal coronary arteries with little or no increase in stenotic arteries, resulting in a greater difference in radiopharmaceutical uptake in myocardium supplied by normal versus stenotic coronary arteries.

• Hemodynamic effects include reductions in BP and increases in heart rate.

• Binds to the A₁ adenosine receptor with at least tenfold lower affinity; no appreciable binding affinity for A_2B and A₃ receptors. A_2B and A₃ adenosine receptors have been implicated in the pathophysiology of bronchoconstriction in susceptible individuals (i.e., asthmatics). (See Respiratory Effects under Cautions.)

Advice to Patients

• Importance of informing patients about serious adverse effects associated with regadenoson, such as MI, arrhythmias, cardiac arrest, heart block, substantial changes in BP, bronchoconstriction, hypersensitivity reactions, seizures, and stroke.

• Importance of instructing patients to avoid consumption of any products containing methylxanthines (e.g., caffeinated coffee, tea, other caffeinated beverages, caffeine-containing drug products, aminophylline, theophylline) for at least 12 hours before scheduled radionuclide myocardial perfusion imaging.

• Importance of informing patients, prior to regadenoson administration, of the most common adverse effects that have been reported in association with use of regadenoson during myocardial perfusion imaging (e.g., shortness of breath, headache, flushing).

• Importance of informing patients with COPD or asthma to discuss their respiratory history and administration of pre- and post-study bronchodilator therapy with their clinician before scheduling a myocardial perfusion imaging study with regadenoson.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., aminophylline, theophylline), as well as any concomitant illnesses (e.g., COPD, asthma, seizure disorder).

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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