Ranolazine Dosing for Chronic Angina
The recommended dosage for ranolazine in chronic angina is 500 mg orally twice daily initially, which can be escalated as needed to a maximum of 1000 mg twice daily based on clinical symptoms. 1, 2
Mechanism of Action and Clinical Effects
- Ranolazine works primarily through inhibition of the late sodium current (late INa), which prevents intracellular calcium overload during ischemia 1
- Unlike traditional antianginals, ranolazine exerts its effects without significantly reducing heart rate or blood pressure, making it particularly useful in patients with bradycardia or hypotension 1, 3
- Ranolazine has minimal effects on myocardial perfusion, with its antianginal effects attributed to decreased oxygen demand and improved left ventricular wall tension 1
Indications and Usage
- Ranolazine is indicated for the treatment of chronic angina pectoris as monotherapy or in combination with amlodipine, beta-blockers, or nitrates when angina is not adequately controlled with standard therapy 2
- It is particularly beneficial for patients who have failed to respond to standard antianginal therapy 4, 1
- Clinical trials have demonstrated that ranolazine increases exercise capacity and provides additional antianginal relief to patients with severe chronic angina already taking standard doses of atenolol, amlodipine, or diltiazem 5
Dosing Recommendations
- Start with 500 mg orally twice daily 4, 1, 2
- Titrate based on clinical response to a maximum of 1000 mg twice daily 4, 1, 2
- For patients taking moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin), limit ranolazine to 500 mg twice daily 2
- Extended-release formulation allows for twice-daily administration with maintained efficacy 3
Monitoring and Precautions
- Monitor for QT interval prolongation, which occurs in a dose-related manner 1, 2
- Use with caution in patients with renal impairment; monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL<60mL/min) 2
- If acute renal failure develops, discontinue ranolazine 2
Contraindications
- Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir) 2
- CYP3A inducers (e.g., rifampin, phenobarbital, St. John's wort) 2
- Liver cirrhosis or hepatic impairment 1, 2
Drug Interactions
- Moderate CYP3A inhibitors: Limit ranolazine to 500 mg twice daily 2
- P-gp inhibitors (e.g., cyclosporine): Ranolazine exposure increased; titrate based on clinical response 2
- CYP3A substrates: Limit simvastatin to 20 mg when used with ranolazine 2
- OCT2 substrates: Limit metformin to 1700 mg daily when used with ranolazine 1000 mg twice daily 2
- Drugs transported by P-gp (e.g., digoxin) or metabolized by CYP2D6 (e.g., tricyclic antidepressants) may need reduced doses 2, 3
Common Adverse Effects
- Most common adverse effects (>4% and more common than with placebo) include dizziness, headache, constipation, and nausea 2, 6
- Ranolazine causes dose-related QT interval prolongation, though torsades de pointes has not been observed at therapeutic doses 1
Clinical Outcomes
- In clinical trials, ranolazine has been shown to reduce angina attacks and nitroglycerin use by about 1 per week compared to placebo 5
- While ranolazine provides symptom relief, it has not been shown to significantly reduce major cardiovascular events, including cardiovascular death, myocardial infarction, or recurrent ischemia 4, 1