Ranolazine
An FDA-approved anti-anginal that inhibits the late sodium current in cardiac myocytes, reducing calcium overload during ischaemia. Originally proposed as a fatty-acid oxidation inhibitor, its main clinical action is now attributed to late-sodium-current blockade. It is not WADA-banned.
01 Overview
Ranolazine reduces the pathological late inward sodium current (late I-Na), which limits sodium-driven intracellular calcium overload during ischaemia, improving diastolic relaxation and myocardial perfusion. Unlike beta-blockers or calcium antagonists it does not meaningfully lower heart rate or blood pressure, making it useful in patients who cannot tolerate rate-limiting drugs.
It is approved for chronic stable angina, typically as add-on therapy. It prolongs the QT interval and has significant drug interactions through CYP3A metabolism. It is not on the WADA Prohibited List.
02 Mechanism
Selectively inhibits the late sodium current (late I-Na) in cardiomyocytes, reducing intracellular sodium and consequent calcium overload during ischaemia and improving diastolic function.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Starting dose | 500 mg | Oral | 500 mg twice daily (extended-release). |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Reduced angina frequencyDecreases anginal episodes and nitroglycerin use and increases exercise duration (MARISA, CARISA trials). | moderate | Clinical | |
| Anti-ischaemic without haemodynamic changeImproves ischaemia with minimal effect on heart rate or blood pressure. | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Dizziness and constipationDizziness, constipation, nausea and headache are the most frequent complaints. | Mild | Common | Clinical | |
| QT interval prolongationProlongs QTc; caution with other QT-prolonging drugs. | Moderate | Dose-dependent | Clinical | |
| Drug accumulation with CYP3A inhibitorsStrong CYP3A inhibitors (e.g. ketoconazole, diltiazem) markedly raise plasma levels. | Moderate | Interaction-dependent | Clinical |