Ranolazine for Chronic Angina
Recommended Dosage
Start ranolazine at 500 mg orally twice daily and titrate to 1000 mg twice daily based on symptom response. 1, 2
- The FDA-approved dosing regimen begins with 500 mg twice daily, with escalation to the maximum dose of 1000 mg twice daily as needed for symptom control 2
- Titration should be guided by clinical angina symptom response rather than fixed time intervals 1
Treatment Approach and Patient Selection
Use ranolazine as add-on therapy when beta-blockers and/or calcium channel blockers provide inadequate symptom control (ESC Class IIa, Level B recommendation). 1
Ideal Patient Populations
Ranolazine is particularly advantageous in specific clinical scenarios:
- Patients with bradycardia or hypotension who cannot tolerate rate-lowering or blood pressure-lowering agents, since ranolazine has a hemodynamically neutral profile without significantly affecting heart rate or blood pressure 1, 3
- Diabetic patients with chronic stable angina, as ranolazine reduces glycated hemoglobin (HbA1c) levels, though it is not indicated as diabetes treatment 3
- Patients with left ventricular hypertrophy, who may experience greater efficacy compared to other antianginal drugs 1, 3
Mechanism of Action
Ranolazine inhibits the late sodium current (late INa), preventing intracellular calcium overload during ischemia and reducing left ventricular wall tension and oxygen demand 1, 3
This unique mechanism distinguishes it from traditional antianginal agents by providing symptom relief without hemodynamic effects 1, 3
Absolute Contraindications
Do not use ranolazine in patients with liver cirrhosis or hepatic impairment. 1, 3, 2
Additional contraindications include:
- Strong CYP3A inhibitors (ketoconazole, clarithromycin, nelfinavir) 2
- CYP3A inducers (rifampin, phenobarbital, St. John's wort) 2
Critical Drug Interactions Requiring Dose Adjustments
When Using Ranolazine WITH Other Medications:
- Moderate CYP3A inhibitors (diltiazem, verapamil, erythromycin): Limit ranolazine to 500 mg twice daily 2
- P-glycoprotein inhibitors (cyclosporine): Titrate ranolazine based on clinical response due to increased exposure 2
When Using Other Medications WITH Ranolazine:
- Simvastatin: Limit to 20 mg daily when combined with ranolazine 2
- Metformin: Limit to 1700 mg daily when used with ranolazine 1000 mg twice daily 2
- Digoxin: Reduce dose as ranolazine increases digoxin concentration by 40-60% through P-glycoprotein inhibition 3, 2, 4
- Other CYP3A substrates (lovastatin, cyclosporine, tacrolimus, sirolimus): May require dose reduction 2
- CYP2D6 substrates (tricyclic antidepressants): May require dose reduction 2
Expected Clinical Benefits and Limitations
Ranolazine reduces angina frequency and nitroglycerin use but does NOT reduce major cardiovascular events, cardiovascular death, myocardial infarction, or improve mortality. 1, 3
This is a critical limitation: ranolazine provides symptom relief only, without prognostic benefit 1, 3
Safety Monitoring
QTc Prolongation
- Ranolazine causes dose-related QTc prolongation, but torsades de pointes has not been observed at therapeutic doses 1, 3, 5
- Exercise caution in patients with baseline QT prolongation, family history of long QT syndrome, or concomitant use of QT-prolonging drugs 2
Renal Function
- Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCl <60 mL/min) 2
- Discontinue ranolazine if acute renal failure develops 2
Common Adverse Effects
The most common adverse reactions (>4% and more common than placebo) are dizziness, headache, constipation, and nausea 2, 5