Regadenoson Associated Side Effect Reversal: Safety and Efficacy of IV Theophylline

307 Objectives: Regadenoson is a selective A2A adenosine receptor agonist used for pharmacological stress in patients unable to perform exercise stress testing or have abnormal ECG findings, such as left bundle branch block. Despite this selectivity, side effects occur in 80% of patients and 89% of patients with asthma consisting of dyspnea, arrhythmias, chest tightness, dizziness and headache. Due to these side effects, aminophylline, a non-selective adenosine receptor antagonist is considered a safe and effective reversal agent. Due to nationwide drug shortages, aminophylline has been in limited supply.Theophylline, also an adenosine receptor antagonist has been reported to be a potential substitute for aminophylline, though limited safety and efficacy exist. The aim of this investigation was to demonstrate the safety and efficacy of intravenous (IV) theophylline to reverse regadenoson associated side effects. Methods: In this single center, retrospective, observational study, electronic medical records were evaluated from March 2013 to May 2013 and again April 2018 to September 2018 at the University of Colorado hospital. These time periods were determined by aminophylline shortage time periods. Patients were included if they were ≥ 18 years old, had a pharmacologic stress test using regadenoson, and required an antidote for reversal of regadenoson associated side effects. IV Theophylline was prepared by inpatient pharmacy to a concentration of 0.8 mg/mL with a total volume of 100 mL D5W. Once prepared, IV theophylline bags were stable at room temperature for 60 days. Per protocol 50 mL (40 mg) of IV theophylline was withdrawn and administered at 40 mg/min, slow IV push over 1 minute. If needed, an additional 40 mg (50 mL) could be re-administered for continued symptoms. A new theophylline bag was required for each patient. Study endpoints consisted of characterizing specific regadenoson-associated side effect(s) requiring IV theophylline, resolution status of regadenoson-associated side effect (complete resolution, partial resolution, no resolution, unknown), and theophylline-associated side effects. Descriptive statistics were used to evaluate study endpoints. This study received exempt status by the Colorado Multiple Institutional Review Board. Results: A total of 122 patients met inclusion, the majority of whom were male (63%) with a mean age of 64 ± 13 years. Twenty six patients (21%) had a history of end stage renal disease, 18 (14.7%) had asthma, 13 (10.7%) had COPD, and 22 (18%) had heart failure with a reduced ejection fraction. The most common regadenoson-associated side effect requiring IV theophylline was headache (n=59), followed by nausea/vomiting (n=49), abdominal cramping (n=31), chest tightness (n=27), shortness of breath (n=20), dizziness (n=14), lightheadedness (n=8), hypotension (n=7), flushing (n=6), other (n=25). The majority (80.3%) of patients had complete resolution of symptoms following administration of IV theophylline (n=98), 9.8% had partial resolution (n=12), 0.8% (n=1) had no resolution, and 9% (n=11) were unknown. There were no documented side effects from IV theophylline administration. Conclusions: During periods of drug shortages, IV theophylline is a reasonable alternative to aminophylline for reversal of regadenoson associated side-effect experienced during pharmacologic stress testing.