A Comprehensive Monograph on Ranolazine

Executive Summary

Ranolazine is a piperazine derivative classified as an antianginal agent, occupying a unique position in the therapeutic landscape for cardiovascular disease.[1] First approved by the U.S. Food and Drug Administration (FDA) in 2006, it is indicated for the treatment of chronic stable angina, a condition affecting millions worldwide and causing significant disability.[1] Marketed under brand names such as Ranexa and Aspruzyo Sprinkle, Ranolazine can be used as monotherapy or as an adjunctive treatment with traditional antianginal agents like beta-blockers, calcium channel blockers, and nitrates.[1]

The primary mechanism of action that distinguishes Ranolazine from conventional therapies is its selective inhibition of the late inward sodium current (INaL​) in cardiac myocytes.[5] During myocardial ischemia, this aberrant current leads to intracellular sodium and subsequent calcium overload, causing diastolic dysfunction and increased myocardial oxygen consumption. By blocking

INaL​, Ranolazine mitigates this ionic imbalance, thereby exerting its anti-ischemic effects without significantly altering heart rate or blood pressure—a key point of differentiation from hemodynamically active agents.[1] Ancillary mechanisms, including the partial inhibition of fatty acid oxidation, further contribute to its metabolic-modulating profile by shifting the heart towards more oxygen-efficient glucose utilization.[8]