Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 

During clinical development, 1,651 patients were exposed to regadenoson, with most receiving 0.4 mg as a rapid (≤ 10 seconds) intravenous injection. Most of these patients received regadenoson in two clinical studies that enrolled patients who had no history of bronchospastic lung disease as well as no history of a cardiac conduction block of greater than first-degree AV block, except for patients with functioning artificial pacemakers. In these studies (Studies 1 and 2), 2,015 patients underwent myocardial perfusion imaging after administration of regadenoson (N = 1,337) or ADENOSCAN (N = 678). The population was 26–93 years of age (median 66 years), 70% male and primarily Caucasian (76% Caucasian, 7% African American, 9% Hispanic, 5% Asian). Table 1 shows the most frequently reported adverse reactions. 

Overall, any adverse reaction occurred at similar rates between the study groups (80% for the regadenoson group and 83% for the ADENOSCAN group). Aminophylline was used to treat the reactions in 3% of patients in the regadenoson group and 2% of patients in the ADENOSCAN group. Most adverse reactions began soon after dosing, and generally resolved within approximately 15 minutes, except for headache which resolved in most patients within 30 minutes.

Table 1 Adverse Reactions in Studies 1 and 2 Pooled (Frequency ≥ 5%)

ECG Abnormalities

The frequency of rhythm or conduction abnormalities following regadenoson or ADENOSCAN is shown in Table 2 [see Warnings and Precautions (5.2)].

Table 2 Rhythm or Conduction Abnormalities* in Studies 1 and 2

*12-lead ECGs were recorded before and for up to 2 hours after dosing. †includes rhythm abnormalities (PACs, PVCs, atrial fibrillation/flutter, wandering atrial pacemaker, supraventricular or ventricular arrhythmia) or conduction abnormalities, including AV block.

Respiratory Abnormalities In a randomized, placebo-controlled trial of 999 patients with asthma (n = 532) or stable chronic obstructive pulmonary disease (n = 467), the overall incidence of pre-specified respiratory adverse reactions was greater in the regadenoson group compared to the placebo group (p < 0.001). Most respiratory adverse reactions resolved without therapy; a few patients received aminophylline or a short-acting bronchodilator. No differences were observed between treatment arms in the reduction of >15% from baseline at two-hours in FEV1 (Table3). 

Table 3 Respiratory Adverse Effects*

*All patients continued the use of their respiratory medications as prescribed prior to administration of regadenoson. 

†Patients may have reported more than one type of adverse reaction. Adverse reactions were collected up to 24 hours following drug administration. Pre-specified respiratory adverse reactions included dyspnea, wheezing, obstructive airway disorder, dyspnea exertional, and tachypnea. ‡Change from baseline at 2 hours.

Renal Impairment In a randomized, placebo-controlled trial of 504 patients (regadenoson n=334 and placebo n=170) with a diagnosis or risk factors for coronary artery disease and NKFK/DOQI Stage III or IV renal impairment (defined as GFR 15-59 mL/min/1.73 m2), no serious adverse events were reported through the 24-hour follow-up period. Inadequate Exercise Stress In an open-label, multi-center trial evaluating regadenoson administration following inadequate exercise stress, 1,147 patients were randomized into one of two groups. Each group underwent two regadenoson stress myocardial perfusion imaging (MPI) procedures. Group 1 received regadenoson 3 minutes following inadequate exercise in the first regadenoson stress (MPI 1). Group 2 rested 1 hour after inadequate exercise to allow hemodynamics to return to baseline prior to receiving regadenoson (MPI 1). Both groups returned for a second stress MPI 1-14 days later and received regadenoson without exercise (MPI 2). The most common adverse reactions are similar in type and incidence to those in Table 1above for both Groups. The timing of the administration of regadenoson following inadequate exercise did not alter the common adverse reaction profile. Table 4shows a comparison of cardiac events of interest for the two groups [see Warnings and Precautions (5.1)]. The cardiac events were numerically higher in Group 1. 

Table 4 Cardiac Events of Interest in Inadequate Exercise Stress Study