Is Ranexa (ranolazine) 500 mg twice daily appropriate for an adult with chronic stable angina?

Is Ranexa 500 mg BID Appropriate?

Yes, ranolazine 500 mg twice daily is the correct starting dose for adults with chronic stable angina, as recommended by the FDA and major cardiology guidelines. 1

Dosing Strategy

• Start at 500 mg twice daily and titrate up to 1000 mg twice daily based on clinical response and tolerability. 2, 1
• The maximum recommended dose is 1000 mg twice daily. 2, 1
• Dose escalation should be guided by symptom control and adverse effect profile. 1

Place in Therapy

Ranolazine is a second-line agent, not first-line therapy. The European Society of Cardiology recommends it only after optimizing beta-blockers and/or calcium channel blockers (Class IIa, Level B). 2, 3

When to Use Ranolazine:

• Add-on therapy when angina persists despite optimal first-line treatment with beta-blockers and/or calcium channel blockers. 2, 3
• Alternative therapy in patients who cannot tolerate beta-blockers or calcium channel blockers due to bradycardia or hypotension, since ranolazine has a neutral hemodynamic profile. 2, 4
• Preferred agent in patients with type 2 diabetes and chronic stable angina, as it reduces HbA1c levels while controlling angina. 2, 4

Absolute Contraindications

Before prescribing, verify the patient does NOT have:

• Liver cirrhosis (absolute contraindication). 2, 3, 1
• Concurrent use of strong CYP3A inhibitors (ketoconazole, clarithromycin, nelfinavir). 1
• Concurrent use of CYP3A inducers (rifampin, phenobarbital, St. John's wort). 1

Dose Adjustments for Drug Interactions

Critical dose limitation: If the patient is taking moderate CYP3A inhibitors (diltiazem, verapamil, erythromycin), limit ranolazine to 500 mg twice daily maximum—do not escalate to 1000 mg. 1

Important Drug Interactions to Monitor:

• Digoxin: Ranolazine increases digoxin levels by 40-60%; reduce digoxin dose and monitor levels. 2, 1
• Simvastatin: Limit to 20 mg daily when used with ranolazine. 1
• Metformin: Limit to 1700 mg daily when used with ranolazine 1000 mg twice daily. 1

Monitoring Requirements

• Renal function: Monitor creatinine clearance at initiation and periodically in patients with moderate to severe renal impairment (CrCl <60 mL/min). 1
• QTc interval: Ranolazine causes dose-dependent QTc prolongation, though torsades de pointes has not been observed at therapeutic doses. 2, 1
• Discontinue if acute renal failure develops. 1

Clinical Outcomes: Set Realistic Expectations

Important limitation: Ranolazine improves angina symptoms and exercise tolerance but does not reduce mortality, myocardial infarction, or need for revascularization. 2, 3

• It provides symptom relief without prognostic benefit. 2, 3
• All patients should still receive short-acting nitroglycerin for acute symptom relief and prophylaxis. 3

Special Populations Where Ranolazine Excels

• Bradycardia or hypotension: Ranolazine does not lower heart rate or blood pressure, making it ideal when other antianginals are contraindicated. 2, 4
• Left ventricular hypertrophy: May have greater efficacy compared to other antianginals. 2, 4
• Diabetes with angina: Reduces HbA1c while controlling symptoms. 2, 4
• Atrial fibrillation with angina: Can be added to beta-blockers for dual benefit. 2

Common Adverse Effects

The most common side effects (>4% and more than placebo) are:

• Dizziness 1, 5
• Headache 1, 5
• Constipation 1, 5
• Nausea 1, 5

These are generally mild and do not require discontinuation in most patients. 5