6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling. 9) ] The most common (incidence ≥ 5%) adverse reactions to regadenoson injection are dyspnea, headache, flushing, chest discomfort, dizziness, angina pectoris, chest pain, and nausea ( 6 ).
To report SUSPECTED ADVERSE REACTIONS, contact Hospira, Inc. gov/medwatch . 1 Clinical Trials Experience 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.
4 mg as a rapid (≤ 10 seconds) intravenous injection. Most of these patients received regadenoson injection 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 injection (N = 1,337) or adenosine injection (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 injection group and 83% for the adenosine injection group). Aminophylline was used to treat the reactions in 3% of patients in the regadenoson injection group and 2% of patients in the adenosine injection 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. 2) ] . Table 2 Rhythm or Conduction Abnormalities 12-lead ECGs were recorded before and for up to 2 hours after dosing.
in Studies 1 and 2 Regadenoson Injection N/N evaluable (%) Adenosine Injection N/N evaluable (%) Rhythm or conduction abnormalities includes rhythm abnormalities (PACs, PVCs, atrial fibrillation/flutter, wandering atrial pacemaker, supraventricular or ventricular arrhythmia) or conduction abnormalities, including AV block.
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 FEV 1 (Table 3).
Table 3 Respiratory Adverse Effects All patients continued the use of their respiratory medications as prescribed prior to administration of regadenoson injection. Asthma Cohort Chronic Obstructive Pulmonary Disease (COPD) Cohort Regadenoson Injection (N = 356) Placebo (N = 176) Regadenoson Injection (N = 316) Placebo (N = 151) Overall Pre-specified Respiratory Adverse Reaction 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. 7% FEV 1 reduction>15% Change from baseline at 2 hours.
73 m 2 ), 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 injection administration following inadequate exercise stress, 1,147 patients were randomized into one of two groups.
Each group underwent two regadenoson injection stress myocardial perfusion imaging (MPI) procedures. Group 1 received regadenoson injection 3 minutes following inadequate exercise in the first regadenoson injection stress (MPI 1). Group 2 rested 1 hour after inadequate exercise to allow hemodynamics to return to baseline prior to receiving regadenoson injection (MPI 1).
Both groups returned for a second stress MPI 1–14 days later and received regadenoson injection without exercise (MPI 2). The most common adverse reactions are similar in type and incidence to those in Table 1 above for both Groups.
The timing of the administration of regadenoson injection following inadequate exercise did not alter the common adverse reaction profile. 1) ] . The cardiac events were numerically higher in Group 1. Table 4 Cardiac Events of Interest in Inadequate Exercise Stress Study Cardiac Event A clinically significant cardiac event was defined as any of the following events found on the Holter ECG/12-lead ECG within one hour after regadenoson administration : ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation, Torsade de Pointes, ventricular flutter) ; ST-T depression (≥ 2 mm) ; ST-T elevation (≥ 1 mm) ; AV block (2:1 AV block, AV Mobitz I, AV Mobitz II, complete heart block) ; sinus arrest > 3 seconds in duration Or a Treatment Emergent Adverse Event (TEAE) per the MedDRA SMQ (narrow Scope) for myocardial infarction Or a TEAE preferred term (PT) of angina unstable within 24 hours of regadenoson administration.
2 Post-Marketing Experience The following adverse reactions have been reported from worldwide marketing experience with regadenoson. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
8) ] have been reported. Some events required intervention with fluids and/or aminophylline [see Overdosage (10) ] . QTc prolongation shortly after regadenoson injection administration has been reported. 9) ] . Gastrointestinal Abdominal pain, occasionally severe, has been reported a few minutes after regadenoson injection administration, in association with nausea, vomiting, or myalgias; administration of aminophylline, an adenosine antagonist, appeared to lessen the pain.
Diarrhea and fecal incontinence have also been reported following regadenoson injection administration. 4) ] . Musculoskeletal Musculoskeletal pain has occurred, typically 10–20 minutes after regadenoson injection administration; the pain was occasionally severe, localized in the arms and lower back and extended to the buttocks and lower legs bilaterally.
Administration of aminophylline appeared to lessen the pain. Respiratory Respiratory arrest, dyspnea and wheezing have been reported following regadenoson injection administration.