What is Ranexa (ranolazine) used for?

What is Ranexa (Ranolazine) Used For?

Ranexa is FDA-approved for the treatment of chronic angina pectoris, either as monotherapy or in combination with other antianginal medications when angina is not adequately controlled. 1

Primary Indication

• Ranolazine is specifically indicated for chronic stable angina that persists despite standard antianginal therapy. 1
• It can be used alongside beta-blockers, nitrates, calcium channel blockers, antiplatelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers. 1
• The American Heart Association recommends starting at 500 mg orally twice daily, escalating as needed to a maximum of 1000 mg twice daily for chronic angina that has failed standard therapy. 2

How It Works Differently

• Ranolazine works through a unique mechanism—inhibiting the late sodium current (late INa)—which prevents intracellular calcium overload during ischemia without affecting heart rate or blood pressure. 2, 3
• This neutral hemodynamic profile makes it particularly valuable when other antianginal agents are limited by bradycardia or hypotension. 2, 4, 3
• Unlike traditional antianginal drugs, ranolazine reduces oxygen demand and left ventricular wall tension without significantly altering myocardial perfusion. 2

Ideal Patient Populations

• Patients with chronic angina who cannot tolerate or have inadequate response to beta-blockers, calcium channel blockers, or nitrates. 2
• Patients with bradycardia or hypotension where traditional rate-lowering or blood pressure-lowering antianginals would be problematic. 2, 4
• Diabetic patients with chronic stable angina may derive additional benefit, as ranolazine reduces HbA1c levels (though it is not indicated as diabetes treatment). 2, 3
• Patients with left ventricular hypertrophy may experience greater efficacy compared to other antianginal drugs. 2, 3

Role in Treatment Algorithm

• The European Society of Cardiology recommends ranolazine as add-on therapy when symptoms remain inadequately controlled on beta-blockers and/or calcium channel blockers (Class IIa, Level B recommendation). 2, 4
• It can also be considered as part of initial treatment in properly selected patients. 2

Critical Limitations and Contraindications

• Ranolazine is absolutely contraindicated in patients with hepatic impairment or liver cirrhosis. 2, 4, 1
• While ranolazine improves angina symptoms and exercise tolerance, it does NOT reduce major cardiovascular outcomes, cardiovascular death, or myocardial infarction. 2, 4
• It causes dose-related QTc prolongation, though torsades de pointes has not been observed at therapeutic doses. 2, 4
• Ranolazine increases digoxin concentrations by 40-60% through P-glycoprotein inhibition—use with caution if co-administered. 2, 4
• Avoid strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) and grapefruit products, which can significantly increase ranolazine levels. 2, 4, 1

What Ranolazine Is NOT Used For

• Ranolazine is NOT effective for acute coronary syndrome or non-ST-elevation myocardial infarction—it provides symptom relief but does not reduce cardiovascular death or recurrent ischemia in these settings. 2
• It is not a first-line agent for chronic angina, but rather a second-line or adjunctive therapy. 2

Dosing Considerations

• Start at 500 mg twice daily and titrate to 1000 mg twice daily based on symptom response. 2
• Take with or without food; swallow tablets whole without crushing, breaking, or chewing. 1
• Dose adjustments needed in renal impairment (AUC increases up to 2-fold). 5