Recommended Use and Dosage of Ranolazine for Chronic Angina
Ranolazine should be considered as add-on therapy in patients with inadequate control of angina symptoms while on treatment with beta-blockers and/or calcium channel blockers, or as part of initial treatment in properly selected patients, with a recommended starting dose of 500 mg twice daily, which can be increased to 1000 mg twice daily based on clinical response. 1, 2
Indications and Place in Therapy
Ranolazine is an antianginal medication indicated for the treatment of chronic angina. Its position in the treatment algorithm is as follows:
- First-line therapy: Beta-blockers and/or calcium channel blockers are recommended as initial treatment for most patients with chronic coronary syndrome 1
- Second-line/Add-on therapy: Ranolazine should be considered when:
Dosing Recommendations
- Initial dose: 500 mg orally twice daily 2
- Maximum dose: Can be increased to 1000 mg twice daily based on clinical symptoms 2
- Administration: Extended-release tablets should be taken with or without food 2
Mechanism of Action
Ranolazine works differently from traditional antianginals:
- It inhibits the late sodium current in cardiac cells
- Does not significantly affect heart rate or blood pressure (hemodynamically neutral) 1, 3
- Improves diastolic function by reducing intracellular calcium overload 3
Efficacy
- Provides modest but significant improvements in exercise duration and reduction in angina frequency 3, 4
- Effective as adjunctive therapy in patients whose angina is not adequately controlled with conventional therapy 5
- May be particularly beneficial in patients with:
Contraindications and Precautions
Ranolazine is contraindicated in:
- Patients taking strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir) 2
- Patients taking CYP3A inducers (e.g., rifampin, phenobarbital, St. John's wort) 2
- Patients with liver cirrhosis 2
- Combination with non-dihydropyridine calcium channel blockers or other strong CYP3A4 inhibitors is not recommended 1
Important Drug Interactions
- Moderate CYP3A inhibitors (e.g., diltiazem, verapamil): Limit ranolazine to 500 mg twice daily 2
- P-glycoprotein inhibitors (e.g., cyclosporine): May increase ranolazine exposure 2
- Digoxin: Ranolazine increases digoxin concentration 1, 2
- Simvastatin: Limit to 20 mg when used with ranolazine 2
- Metformin: Limit to 1700 mg daily when used with ranolazine 1000 mg twice daily 2
Monitoring and Safety Considerations
QT interval prolongation: Ranolazine can prolong the QT interval in a dose-dependent manner 1, 2
Renal function: Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCl <60 mL/min) 2
Common side effects (>4%):
Special Populations
- Elderly: Efficacy and tolerability not significantly affected by age 5
- Heart failure: Can be used in patients with left ventricular systolic dysfunction 3
- Diabetes: May provide additional benefit due to favorable effects on glycemic control 1, 3
Clinical Pearls
- Unlike traditional antianginals, ranolazine does not significantly affect heart rate or blood pressure, making it suitable for patients with bradycardia or hypotension 1, 4
- While ranolazine is effective for symptom relief, it does not appear to significantly improve the underlying disease substrate or reduce major adverse cardiovascular events 1
- The QT prolongation seen with ranolazine at therapeutic doses has not been associated with increased risk of torsades de pointes in clinical trials 4
By following these recommendations, ranolazine can be effectively and safely used as part of a comprehensive approach to managing chronic angina.