Can regadenoson (adenosine receptor agonist) be used in patients with impaired renal function?

From the Guidelines

Regadenoson can be safely used in patients with renal failure, as it does not require dose adjustment in renal impairment or end-stage renal disease, with a standard dose of 0.4 mg administered as a rapid intravenous injection, followed by a saline flush 1.

Key Considerations

• Regadenoson has minimal renal clearance, with approximately 57% eliminated through the kidneys, making it advantageous in renal patients who may have impaired drug clearance.
• The drug has a short half-life of 2-3 minutes, and its effects are primarily terminated through redistribution rather than excretion.
• Regadenoson is selective for the A2A adenosine receptor, which causes coronary vasodilation with fewer side effects compared to non-selective adenosine receptor agonists.

Monitoring and Precautions

• Patients should still be monitored for potential side effects such as headache, shortness of breath, and flushing, but these are generally well-tolerated and short-lived due to the drug's brief duration of action.
• Clinicians should apply the concept of benefit-to-risk ratio when considering testing, taking into account the patient's ability to exercise, body habitus, cardiac medication use, and ECG interpretability 1.

Comparison with Other Agents

• Regadenoson is preferred over adenosine in renal failure patients due to its pharmacokinetic profile and selective receptor agonism.
• Other pharmacologic stress agents, such as dobutamine, may have different considerations and precautions in patients with renal failure 1.

From the FDA Drug Label

Specific Populations Renally Impaired Patients: The disposition of regadenoson was studied in 18 patients with various degrees of renal function and in 6 healthy subjects With increasing renal impairment, from mild (CLcr 50 to < 80 mL/min) to moderate (CLcr 30 to < 50 mL/min) to severe renal impairment (CLcr < 30 mL/min), the fraction of regadenoson excreted unchanged in urine and the renal clearance decreased, resulting in increased elimination half-lives and AUC values compared to healthy subjects (CLcr ≥ 80 mL/min) However, the maximum observed plasma concentrations as well as volumes of distribution estimates were similar across the groups. The plasma concentration- time profiles were not significantly altered in the early stages after dosing when most pharmacologic effects are observed. No dose adjustment is needed in patients with renal impairment

Regadenoson can be used in patients with renal failure, as the drug label states that no dose adjustment is needed in patients with renal impairment. However, it is essential to note that the pharmacokinetics of regadenoson in patients on dialysis has not been assessed 2.

From the Research

Regadenoson Use in Renal Failure

• Regadenoson is predominantly renally metabolized, and its use in patients with chronic kidney disease has been the subject of active post-marketing clinical research 3.
• Studies have shown that regadenoson can be used in patients with renal failure, including those with end-stage renal disease (ESRD) 4, 5.
• However, patients with severe chronic kidney disease (CKD) may experience more frequent gastrointestinal adverse effects (AE) from regadenoson, and aminophylline use following regadenoson may reduce the incidence of regadenoson-related AE 6.
• The safety and tolerability of regadenoson have been evaluated in subjects with stage 3 or 4 CKD, and no serious adverse events or deaths were reported over 24-h post-dose 7.
• Regadenoson was not associated with any serious or unexpected adverse events in subjects with stage 3 or 4 CKD, but the overall adverse event incidence was higher with regadenoson than placebo 7.

Adverse Effects and Safety

• The most common adverse events reported by subjects receiving regadenoson include headache, dyspnea, chest discomfort, nausea, flushing, and dizziness 7.
• ESRD patients may have excess incidences of diarrhea and fewer events of dizziness compared to controls 5.
• There were no significant differences in the incidence of ST-segment deviation, tachyarrhythmias, atrioventricular block, or hypotension between ESRD patients and controls 5.
• Aminophylline use was associated with greater absolute risk reduction in gastrointestinal AE among patients with severe CKD compared to controls 6.