The A2B and A3 adenosine receptors have been implicated in the pathophysiology of bronchoconstriction in susceptible individuals (i.e., asthmatics). In in vitro studies, regadenoson has been shown to have little binding affinity for the A2B and A3 adenosine receptors.
The incidence adverse effects and of a drop of forced expiratory volume in 1 second (FEV 1) reduction > 15% from baseline after Rapiscan administration or placebo was assessed in three randomised, placebo-controlled clinical studies.1-3
- In the first study in 49 patients with moderate to severe COPD, no differences emerged between regadenoson and placebo repeated FEV1 the rate of new onset wheezing was 6% and 12% following Rapiscan and placebo dosing, respectively (p = 0.33). 1
- In the second study in 48 patients with mild to moderate asthma who had previously been shown to have bronchoconstrictive reactions to adenosine monophosphate, the rate of bronchoconstriction was the same (4%) following both Rapiscan and placebo dosing.2
- In the first two studies, dyspnoea was reported as an adverse reaction following Rapiscan dosing (61% for patients with COPD; 34% for patients with asthma) while no subjects experienced dyspnoea following placebo dosing.
- In the third study in 1,009 patients with mild or moderate asthma (n=537) and moderate or severe COPD (n=472) the incidence of FEV1 reduction >15% from baseline was 1.1% and 2.9% in patients with asthma (p=0.15) and 4.2% and 5.4% in patients with COPD (p=0.58) following Rapiscan and placebo dosing, respectively. Dyspnoea was reported more frequently following Rapiscan (18% for patients with COPD; 11% for patients with asthma) than placebo, but at a lower rate than reported during clinical development. A relationship between increased severity of disease and the increased incidence of dyspnoea was apparent in patients with asthma, but not in patients with COPD. The use of bronchodilator therapy for symptoms was not different between Rapiscan and placebo.
Dyspnoea did not correlate with a decrease in FEV1.
- Thomas GS, Tammelin BR, Schiffman GL, et al Safety of regadenoson, a selective adenosine A2A agonist, in patients with chronic obstructive pulmonary disease: A randomized, double-blind, placebo-controlled trial (RegCOPD trial). J Nucl Cardiol 2008;15(3):319-28 (View abstract)
- Leaker BR, O’Connor B, Hansel TT, et al. Safety of regadenoson, an adenosine A2A receptor agonist for myocardial perfusion imaging, in mild asthma and moderate asthma patients: A randomized, double-blind, placebo-controlled trial. J Nucl Cardiol 2008;15(3):329-36
- Prenner BM, Bukofzer S, Behm S, Feaheny K, McNutt BE "A randomized, double-blind, placebo-controlled study assessing the safety and tolerability of regadenoson in subjects with asthma or chronic obstructive pulomonary disease" J Nucl Cardiol. 2012 Aug;19(4):681-92. (view full text PDF)