Can Ranexa (ranolazine) be taken in patients with acute kidney injury?

Ranexa Should Be Avoided in Acute Kidney Injury

Ranexa (ranolazine) should not be taken during acute kidney injury and must be discontinued if AKI develops, as the FDA label explicitly warns of acute renal failure risk in patients with severe renal impairment and mandates monitoring for worsening renal function. 1

FDA-Mandated Warnings and Monitoring Requirements

The FDA prescribing information contains critical safety warnings specific to renal impairment:

• Acute renal failure has been observed in patients with severe renal impairment (CrCL <30 mL/min) taking ranolazine 1
• If acute renal failure develops (marked increase in serum creatinine with elevated BUN), discontinue ranolazine immediately 1
• Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL <60 mL/min) for increases in serum creatinine accompanied by BUN elevation 1

Pharmacokinetic Evidence Supporting Avoidance

Ranolazine exposure increases significantly with declining renal function, even though renal excretion is minimal:

• Ranolazine AUC increases 1.72-fold in mild renal impairment, 1.80-fold in moderate impairment, and 1.97-fold in severe impairment compared to normal renal function 2
• Creatinine clearance is negatively correlated with ranolazine concentrations, indicating that factors beyond reduced GFR (such as altered drug metabolism in uremia) contribute to drug accumulation 2
• Less than 7% of ranolazine is excreted unchanged in urine, yet renal impairment still substantially increases drug levels through mechanisms including reduced hepatic clearance and altered protein binding 2

Clinical Case Evidence of Harm

A documented case report demonstrates the serious consequences of ranolazine use in the setting of renal dysfunction:

• An 88-year-old patient on ranolazine developed bradycardia, hyperkalemia (6.8 mEq/L), and acute renal injury (creatinine 1.6 mg/dL rising further over 24 hours) 3
• Discontinuation of ranolazine led to resolution of bradycardia, normalization of potassium, and return of renal function to baseline within 48 hours 3
• This represents a variant of BRASH syndrome (Bradycardia, Renal failure, AV blockade, Shock, Hyperkalemia) where ranolazine-induced renal failure caused hyperkalemia leading to cardiac conduction delays 3

Drug Stewardship Principles in AKI

General principles of medication management in AKI support ranolazine discontinuation:

• Patients with AKI should receive potentially nephrotoxic medications only if absolutely necessary and only for as long as needed 4
• Drug-induced AKI accounts for up to 25% of all AKI cases in critically ill patients, making medication review paramount 5
• Drug stewardship in AKI requires balancing changing risks and benefits, with AKI representing altered drug metabolism and unpredictable pharmacokinetics 4

Alternative Antianginal Management During AKI

While ranolazine is discontinued, chronic angina management should continue with safer alternatives:

• Beta-blockers remain safe and effective for angina control during AKI without the renal accumulation concerns of ranolazine 1
• Calcium channel blockers (particularly amlodipine) can be continued with appropriate dose adjustments based on hemodynamic status 1
• Nitrates (sublingual or long-acting) provide symptomatic relief without significant renal safety concerns 1

Critical Monitoring Parameters

If ranolazine was recently used before AKI diagnosis:

• Monitor for QT prolongation, as ranolazine blocks IKr and prolongs QTc in a dose-related manner, with risk amplified by drug accumulation in renal impairment 1
• Check serum potassium levels, as the combination of ranolazine and AKI can precipitate life-threatening hyperkalemia 3
• Assess for bradycardia and conduction abnormalities, which may worsen with ranolazine accumulation 3

Reintroduction Considerations After AKI Recovery

Ranolazine should only be restarted after complete AKI resolution with return to baseline renal function, and even then requires enhanced monitoring given the documented risk of recurrent renal injury 1, 2. The decision to restart must weigh the necessity of ranolazine versus safer antianginal alternatives, particularly in patients with residual renal impairment (CrCL <60 mL/min) who remain at elevated risk 1.