Is regadenoson (adenosine receptor agonist) safe to use in patients with impaired renal function, specifically those with creatinine levels greater than 15?

Regadenoson Use in Severe Renal Impairment (Creatinine Clearance <15 mL/min)

Regadenoson is safe to use in patients with end-stage renal disease (ESRD), including those with creatinine clearance <15 mL/min or on dialysis, without dose adjustment. 1

FDA-Approved Safety Profile

The FDA drug label explicitly addresses regadenoson use in severe renal impairment and confirms no dose adjustment is necessary 1:

• Pharmacokinetic data demonstrate that while regadenoson clearance decreases with declining creatinine clearance, the maximum plasma concentrations and early-phase concentration-time profiles remain similar across all renal function groups 1
• The plasma concentration-time profiles are not significantly altered in the early stages after dosing when most pharmacologic effects occur, which is why dose adjustment is not required even in severe renal impairment 1
• Approximately 57% of regadenoson is excreted unchanged in urine, but the drug's clinical effects occur during the initial distribution phase (half-life 2-4 minutes), well before renal clearance becomes the limiting factor 1

Clinical Evidence in ESRD Populations

Multiple prospective studies confirm safety in patients with creatinine clearance <15 mL/min:

• The largest retrospective study of 277 consecutive ESRD patients (including dialysis patients) showed no medication-related hospitalizations, serious events, or deaths within 30 days, with hemodynamic responses identical to controls with normal renal function 2
• A prospective randomized controlled trial of 72 patients with stage 4 CKD (eGFR 15-29 mL/min) reported zero serious adverse events over 24 hours post-dose 3
• The first prospective evaluation in 146 ESRD patients (dialysis or GFR <15 mL/min) found no serious adverse events and no significant difference in composite adverse effects compared to controls (74% vs 75%, p=0.82) 4

Hemodynamic and Safety Monitoring

No special hemodynamic monitoring beyond standard protocols is required for ESRD patients 2, 4:

• Heart rate and blood pressure changes are comparable between ESRD and normal renal function groups (heart rate increase ~20 beats/min, systolic BP decrease ~11 mmHg) 2
• The incidence of ST-segment deviation, tachyarrhythmias, AV block, and hypotension shows no significant difference between ESRD and control groups 4
• Common adverse effects (headache, dyspnea, chest discomfort, nausea, flushing) occur at similar rates regardless of renal function 3, 4

Dialysis Considerations

For patients on hemodialysis, regadenoson can be administered without regard to dialysis timing 1, 5:

• While regadenoson is dialyzable in vitro, the drug's clinical effects occur within minutes of administration, well before dialysis would impact plasma levels 1
• The 2017 FDA label update specifically addressed ESRD use based on accumulated safety data 5

Key Clinical Pitfalls to Avoid

Do not withhold or delay regadenoson stress testing in patients with creatinine clearance <15 mL/min based on renal function alone 1, 2:

• The misconception that severe renal impairment contraindicates regadenoson stems from its renal excretion, but pharmacokinetic data show the early distribution phase (when clinical effects occur) is unaffected by renal function 1
• Unlike many renally-cleared medications that require dose reduction in ESRD, regadenoson's unique pharmacokinetic profile makes it safe at standard dosing 1, 5

Comparison to Other Renal Considerations

This differs markedly from other medications in renal impairment 6:

• NOACs require dose reduction or avoidance in severe renal impairment (CrCl <15 mL/min) due to accumulation risk 6
• Amantadine requires substantial dose reduction in renal insufficiency due to accumulation and neurotoxicity risk 6
• Regadenoson's safety profile in ESRD is exceptional because its therapeutic window occurs during initial distribution, not during the elimination phase 1