What is the recommended dosage of Isolazine (Ranolazine) for angina pectoris?

Recommended Dosage of Ranolazine for Angina Pectoris

Ranolazine should be initiated at 500 mg twice daily and increased to 1000 mg twice daily based on clinical symptoms for the treatment of chronic angina pectoris. 1

Initial Dosing and Titration

• Start with 500 mg twice daily of the extended-release formulation 1
• Titrate to 1000 mg twice daily if needed, based on symptom response 1
• The medication is available as 500 mg and 1000 mg extended-release tablets 1

Dosing Considerations in Special Populations

• For patients taking moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin), limit ranolazine to 500 mg twice daily 1
• Reduce dosage in patients with renal impairment (CrCL <60 mL/min) and monitor renal function after initiation and periodically 1
• Contraindicated in patients with liver cirrhosis 1
• Contraindicated with strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) 1
• Contraindicated with CYP3A inducers (e.g., rifampin, phenobarbital) 1

Place in Therapy for Angina Management

• Ranolazine is indicated for the treatment of chronic angina pectoris 1
• It may be considered when angina persists despite treatment with a beta-blocker (or alternative first-line agent) 2
• The European Society of Cardiology (ESC) guidelines classify ranolazine as a second-line agent that "may be considered when angina persists despite treatment with a beta-blocker (or alternative)" with a Class IIb recommendation level 2
• Unlike first-line agents, ranolazine does not significantly affect heart rate or blood pressure, making it useful in patients with bradycardia or hypotension 2, 3

Efficacy and Clinical Outcomes

• Ranolazine effectively reduces angina attacks from an average of 5.3 to 0.8 per week in real-world settings 4
• It decreases nitrate use from 3.4 to 0.4 applications per week 4
• Improves exercise capacity in 94% of patients 4
• Improves quality of life in patients with stable angina 4, 5
• However, ranolazine does not significantly improve cardiovascular outcomes or mortality compared to placebo (low quality evidence) 5

Common Side Effects and Safety

• Most common adverse reactions (>4% and more common than placebo) include dizziness (6.2%), headache (5.5%), constipation (4.5%), and nausea (4.4%) 1
• Can cause QT interval prolongation in a dose-related manner 1
• May cause acute renal failure in patients with severe renal impairment 1
• Increases risk of non-serious adverse events compared to placebo (moderate quality evidence) 5

Monitoring Recommendations

• Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment 1
• Be aware of potential drug interactions, particularly with CYP3A inhibitors and substrates 1
• Limit simvastatin to 20 mg when used with ranolazine 1
• Limit metformin to 1700 mg daily when used with ranolazine 1000 mg twice daily 1

Ranolazine offers an alternative for patients who cannot tolerate or have inadequate response to first-line agents like beta-blockers, with its unique mechanism of action and neutral hemodynamic profile being particularly valuable in certain patient populations.