Ranolazine is a unique anti-anginal agent that works by inhibiting the late sodium current without significant hemodynamic effects. Unlike other anti-anginals, it does not significantly reduce heart rate or blood pressure, making it suitable as add-on therapy for chronic stable angina when conventional agents are inadequate.
Evidence rating moderate. Most-documented uses: reduces angina frequency and nitroglycerin use, no significant effect on heart rate or blood pressure, add-on therapy when conventional anti-anginals insufficient. 10 sources indexed (2017–2023), with 3 interaction records on file.
The science
How it works, mechanistically.
Core mechanism
Selectively inhibits the late phase of the inward sodium current (late INa) in cardiomyocytes. During ischemia, late INa is enhanced, causing intracellular sodium overload and subsequent calcium overload via the Na+/Ca2+ exchanger. Ranolazine reduces this sodium and calcium overload, improving diastolic relaxation and reducing myocardial oxygen consumption without affecting heart rate or blood pressure.
Class
Late Sodium Current Inhibitor
Dosing
Dosing & protocol.
Common range
500 mg twice daily, titrated up to 1000 mg twice daily (as prescribed by your physician)
Recommended form
Extended-release oral tablet (do not crush or chew)
Can be taken with or without food; high-fat meals increase absorption by ~20% but this is not clinically significant; CYP3A4 substrate, avoid grapefruit juice
St. John's Wort is a clinically important inducer of CYP3A4 and P-glycoprotein. Ranolazine is extensively metabolized by CYP3A and is also linked to transporter-mediated drug interactions, so induction can reduce ranolazine exposure and antianginal benefit. Starting or stopping St. John's Wort can make symptom control less predictable.
Recommendation: Avoid St. John's Wort while taking ranolazine. If you have already combined them, tell your prescriber, especially if angina, exercise tolerance, or palpitations changed. Do not try to fix this by spacing doses because enzyme induction persists throughout the day.
Ranolazine usually causes modest QT prolongation, but torsades de pointes has been reported when risk factors stack. Low potassium is a major modifiable risk factor for drug-induced torsades. Potassium supplementation is only appropriate when potassium is low or intake is inadequate and should be monitored.
Recommendation: Keep potassium in the normal range while using ranolazine, especially if you take diuretics or have vomiting or diarrhea. Do not start potassium supplements without clinician monitoring, and report fainting, near-fainting, or new sustained palpitations promptly.
Ranolazine can prolong the QT interval, and torsades risk rises when magnesium is low. Maintaining normal magnesium helps stabilize repolarization and supports potassium balance. Oral magnesium is preventive support for deficiency risk, not a substitute for emergency treatment of an arrhythmia.
Recommendation: Maintain adequate magnesium intake while taking ranolazine, especially if you use diuretics, PPIs, or have chronic diarrhea. Ask your prescriber about checking magnesium if you have arrhythmia symptoms or risk factors, and avoid high-dose magnesium if kidney function is reduced unless monitored.
Cempaka Putri DKS, Andrianto A, Al-Farabi MJ et al.. Efficacy of Ranolazine to Improve Diastolic Performance in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-analysis. European cardiology. 2023
Gong M, Zhang Z, Fragakis N et al.. Role of ranolazine in the prevention and treatment of atrial fibrillation: A meta-analysis of randomized clinical trials. Heart rhythm. 2017
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
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