Pharmacology Update

Regadenoson Injection (Lexiscan™)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.

Regadenoson, the first selective A2A adenosine receptor agonist, has been approved for use as a pharmacologic stress agent for nuclear medicine stress testing (radionuclide myocardial perfusion imaging). Currently available pharmacologic stress agents include adenosine and dipyridamole, which are FDA approved for this indication, and dobutamine which is used off label. Regadenoson injection was developed by CV Therapeutics and will be marketed by Astellas Pharma US Inc as "Lexiscan."

Indications

Regadenoson is indicated as a pharmacologic stress agent for radionuclide myocardial perfusion imaging in patients unable to undergo adequate exercise stress.1

Dosage

The recommended dose is 0.4 mg (5 ml) by rapid intravenous injection to be followed by saline flush and radiopharmaceutical.1

Regadenoson is supplied as single-use vial and syringes containing 0.4 mg/5 ml.

Potential Advantages

Regadenoson appears to be associated with less flushing, chest pain, and dyspnea compared to adenosine.1,2,3 It can be administered by a rapid intravenous injection compared to continuous infusion required for adenosine and dipyridamole.

Potential Disadvantages

Headache and increase in heart rate (>100 bpm) appears more likely with regadenoson compared to adenosine.1 As with adenosine, the labeling contains warnings/precautions regarding SA and AV nodal block, hypotension, and bronchoconstriction. Similar to adenosine, it should be used with caution in patients with asthma or COPD and resuscitative measures should be available. It also has potential drug-drug interactions with methylxanthine (eg, caffeine) and dipyridamole.1

Comments

Regadenoson is an A2A selective adenosine receptor agonist that produces coronary vasodilation and increases coronary blood flow. This selectivity may reduce the potential for AV nodal block and bronchospasm. The efficacy and safety of regadenoson and adenosine were compared in two randomized, double-blind studies (n = 2015) with known or suspected coronary artery disease in whom pharmacologic stress myocardial perfusion imaging was indicated.1,2 Each patient received an initial scan with a radionuclide gated single photon emission computer tomography (SPECT) protocol with adenosine and was then randomized to regadenoson or adenosine for a second scan with the same protocol. The primary endpoint was the agreement rate between agents. In the first study the agreement rates (± SE) were 61 ± 3 % for adenosine and adenosine and 62 ± 2% for adenosine and regadenoson. For the second study, the rates were 64 ± 4% and 63 ± 3% respectively. Generally, increase in heart rate was greater with regadenoson but symptom scores of flushing, chest pain, and dyspnea was less compared to adenosine.2 The cost of regadenoson was not available at the time of this review.

Clinical Implications

Currently available pharmacologic stress agents approved are adenosine and dipyridamole. A large number of studies indicate that these agents have high sensitivity (approximately 90%) for detecting coronary heart disease.4 Regadenoson offers some potential advantages in terms of administration (rapid intravenous injection vs. infusion). It has a longer half-life (2-4 minutes) than adenosine (5 seconds) but shorter than dipyridamole (40-60 minutes). Whether the greater A2A selectivity becomes a real clinical advantage remains to be established.

References

1. Lexiscan Product Information. Astellas Pharma US, Inc. April 2008.

2. Iskandrian AB, et al. J Nucl Cardiol. 2007;14(5):645-658.

3. Hendel RC, et al. J Am Coll Cardiol. 2005;46(11):2069-2075.

4. Patel RN, et al. South Med J. 2007;100:1006-1014.