Indications for Ranolazine
Ranolazine is indicated for the treatment of chronic angina pectoris, either as monotherapy or in combination with other antianginal agents including beta-blockers, nitrates, calcium channel blockers, antiplatelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers. 1
Primary Indication
- Ranolazine is FDA-approved specifically for chronic stable angina in patients who continue to experience symptoms despite standard antianginal therapy 1
- The drug can be used as add-on therapy when angina remains inadequately controlled on beta-blockers and/or calcium channel blockers, or as part of initial treatment in properly selected patients 2
Dosing Strategy
- Initiate ranolazine at 500 mg orally twice daily, then escalate to 1000 mg twice daily based on clinical response and symptom control 2, 1
- The maximum recommended dose is 1000 mg twice daily 1
- Tablets must be swallowed whole and can be taken with or without food 1
Specific Clinical Scenarios Where Ranolazine Is Particularly Useful
Hemodynamic Limitations
- Ranolazine is especially valuable in patients with bradycardia or hypotension who cannot tolerate standard antianginal agents because it exerts antianginal effects without significantly affecting heart rate or blood pressure 2, 3
Comorbid Conditions
- Patients with diabetes and chronic stable angina may derive additional benefit, as ranolazine reduces glycated hemoglobin (HbA1c) levels, though it is not indicated as a diabetes treatment 2, 3
- Patients with left ventricular hypertrophy might experience greater efficacy with ranolazine compared to other antianginal drugs 2, 3
Important Limitations
- Ranolazine does NOT reduce major cardiovascular events, cardiovascular death, or myocardial infarction 2
- It is NOT indicated for acute coronary syndrome or unstable angina, as trials showed symptom relief but no reduction in cardiovascular death, myocardial infarction, or recurrent ischemia 2, 4
- The drug provides symptomatic relief only—improving exercise tolerance and reducing angina frequency—but does not improve mortality outcomes 2
Absolute Contraindications
- Liver cirrhosis or hepatic impairment 2, 3, 1
- Concurrent use with strong CYP3A inhibitors (ketoconazole, clarithromycin, nelfinavir) 1
- Concurrent use with CYP3A inducers (rifampin, phenobarbital, St. John's wort) 1
Critical Dose Adjustments
- Limit maximum dose to 500 mg twice daily when used with moderate CYP3A inhibitors such as diltiazem, verapamil, or erythromycin 1
- Use caution and titrate based on clinical response when co-administered with P-glycoprotein inhibitors like cyclosporine 2, 1
- Monitor digoxin levels closely, as ranolazine increases digoxin concentration 2, 3
Key Safety Considerations
- Ranolazine causes dose-related QT interval prolongation (mean increase of 2.4 ms), though torsades de pointes has not been observed at therapeutic doses 2, 5
- Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCl <60 mL/min), as acute renal failure has been observed in severe renal impairment 1
- Most common adverse effects (>4%) include dizziness, headache, constipation, and nausea 1
Clinical Evidence Supporting Use
- In the CARISA trial, ranolazine increased trough exercise duration by 115.6 seconds versus 91.7 seconds with placebo (P=0.01) and reduced angina attacks and nitroglycerin use by approximately one episode per week 6
- Long-term safety data from the ROLE program showed 76.7% of patients remained on therapy after 2 years, with annual mortality of 2.8-3.0%, which was lower than predicted by risk models 5