Ranolazine is an anti-angina agent with many metabolites creating the potential for off-target effects. The U.S. Food and Drug Administration (FDA) reviews sometimes contain clinically relevant data not found in other sources.

We reanalyzed data in an FDA review of the placebo-controlled MERLIN trial of ranolazine to display differences in adverse event rates graphically.

Rates of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)-related adverse events (eg, angioedema, dry cough, renal impairment, hypotension, anemia, and serum potassium > 5.5 mmol/L) were higher in patients receiving ranolazine and an ACEI or ARB. Rates of adverse events that should be decreased by ACEI/ARBs (eg, hypokalemia, hypertension, and serum potassium < 3.5 mmol/L) were lower in patients receiving ranolazine and an ACEI or ARB compared to rates in patients receiving placebo and an ACEI or ARB.

Ranolazine potentiates the effects of ACEIs and ARBs. Clinicians should monitor for this potentiation when initiating treatment with ranolazine and an ACEI or ARB.