Recommended Dosage and Management of Ranolazine for Chronic Angina
The recommended dosage of ranolazine for chronic angina is to start at 500 mg twice daily and increase to 1000 mg twice daily based on clinical response and symptom control. 1, 2
Dosing and Administration
- Initial dose: 500 mg twice daily
- Titration: May increase to 1000 mg twice daily based on clinical symptoms
- Formulation: Extended-release tablets (500 mg, 1000 mg)
- Administration: Can be taken with or without food (food has no effect on absorption) 3
Patient Selection and Clinical Considerations
Ranolazine is indicated as:
- Add-on therapy when angina is not adequately controlled with standard treatments
- Particularly useful in patients with:
- Bradycardia and/or hypotension (due to neutral hemodynamic profile)
- Left ventricular hypertrophy
- Diabetes mellitus (may reduce HbA1c levels)
- Microvascular angina
- Left ventricular systolic dysfunction (LVEF <40%) when beta-blockers or calcium channel blockers are contraindicated 1
Contraindications
Ranolazine is contraindicated in:
- Patients taking strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir)
- Patients taking CYP3A inducers (e.g., rifampin, phenobarbital, St. John's wort)
- Patients with liver cirrhosis 1, 2
Drug Interactions
Dose Adjustments Required:
- Moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin): Limit ranolazine to 500 mg twice daily
- P-gp inhibitors (e.g., cyclosporine): Titrate ranolazine based on clinical response
- CYP3A substrates: Limit simvastatin to 20 mg when used with ranolazine
- OCT2 substrates: Limit metformin to 1700 mg daily when used with ranolazine 1000 mg twice daily 2
Use with Caution:
- Digoxin (ranolazine increases digoxin concentration by 40-60%)
- Drugs metabolized by CYP2D6 (e.g., tricyclic antidepressants)
- Drugs that prolong QT interval (especially dofetilide) 1, 3
Monitoring and Follow-up
Baseline Assessment:
- ECG to evaluate QTc interval
- Renal function
- Hepatic function
- Medication review for potential interactions 1
Follow-up Monitoring:
- ECG after dose adjustments (monitor for QT prolongation)
- Symptom assessment for side effect management
- Periodic renal function tests in at-risk patients
- Monitor for clinical response (reduction in angina frequency) 1
Side Effects and Management
Common side effects include:
- Constipation (increase fluid intake, dietary fiber, consider mild laxatives)
- Nausea
- Dizziness
- Headache
- QTc interval prolongation 1, 4
Special Populations
- Renal impairment: AUC increases up to 2-fold with advancing degree of renal impairment; monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL<60mL/min) 2, 3
- Elderly: Efficacy and tolerability not affected by old age 5
- Comorbid conditions: Efficacy and tolerability not affected by heart failure or diabetes mellitus 5
Clinical Efficacy Considerations
- Ranolazine provides modest but significant improvements in exercise duration and reduction in angina frequency
- Prevents approximately one angina attack per week when added to ongoing therapy 6
- Antianginal effect does not depend on changes in heart rate or blood pressure 3, 4
Common Pitfalls to Avoid
- Failure to recognize QT interval prolongation risk: Monitor ECG, especially in patients with pre-existing QT prolongation, electrolyte abnormalities, bradycardia, or heart failure
- Overlooking drug interactions: Many medications interact with ranolazine through CYP3A4, CYP2D6, and P-glycoprotein pathways
- Not adjusting dose in renal impairment: Monitor renal function and discontinue if acute renal failure develops 1, 2