What are the indications for Ranolazine (ranolazine)?

Indications for Ranolazine

Ranolazine is indicated for the treatment of chronic angina and may be used in combination with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers. 1

Primary Indication

• Ranolazine is FDA-approved as an antianginal medication specifically for the treatment of chronic stable angina pectoris 1
• It is intended for use when angina is not adequately controlled with other antianginal agents, as an adjunctive therapy 2

Place in Therapy

• Ranolazine can be used with beta-blockers for prevention of angina when initial treatment with beta-blockers alone is not successful (American Heart Association/American College of Cardiology class IIa A indication) 3
• It is particularly useful when angina persists despite treatment with traditional first-line therapies (beta-blockers, long-acting nitrates, and calcium channel blockers) 3
• Ranolazine may be considered when hemodynamic side effects from other antianginal medications are problematic, as it exerts antianginal effects without significantly affecting heart rate or blood pressure 4, 5

Mechanism Supporting Its Use

• Ranolazine works primarily through inhibition of the late sodium current (late INa), which prevents intracellular calcium overload during ischemia 4
• This mechanism reduces oxygen demand and left ventricular wall tension without affecting hemodynamic parameters 4
• The antianginal effect occurs without significant changes in heart rate, blood pressure, or myocardial perfusion 4, 5

Special Populations That May Benefit

• Patients with diabetes and chronic stable angina may particularly benefit from ranolazine treatment, as it has been shown to reduce glycated hemoglobin (HbA1c) levels 6, 4
• Patients with left ventricular hypertrophy might experience greater efficacy with ranolazine compared to other antianginal drugs 6
• Ranolazine may be useful in cases of bradycardia and/or hypotension due to its neutral hemodynamic profile 6

Important Contraindications and Precautions

• Ranolazine is contraindicated in patients with:
  • Hepatic impairment or liver cirrhosis 6, 7, 1
  • Concurrent use of strong CYP3A inhibitors 1
  • Concurrent use of CYP3A inducers 1
• Dose limitation to 500 mg twice daily is recommended in patients:
  • Taking moderate CYP3A inhibitors such as diltiazem, verapamil, and erythromycin 1
  • With severe renal impairment (CrCl <30 ml/min) 7
• Caution is advised when using ranolazine in patients taking digoxin, as ranolazine may increase digoxin concentration by 40-60% through P-glycoprotein inhibition 7, 8

Clinical Efficacy Considerations

• Ranolazine has been shown to improve exercise duration and reduce the frequency of angina episodes and nitroglycerin consumption in clinical trials 2
• However, ranolazine does not improve outcomes in patients with chronic stable angina, regardless of ventricular function 6
• It has not been shown to reduce major cardiovascular events, including cardiovascular death and myocardial infarction, in patients with non-ST-segment elevation acute coronary syndrome 6, 2

Dosing Information

• Initial dose: 500 mg twice daily 1
• May be increased to 1000 mg twice daily based on clinical symptoms 1
• Maximum recommended daily dose: 1000 mg twice daily 1
• Should be taken with or without meals 1
• Tablets should be swallowed whole; not crushed, broken, or chewed 1

By understanding the specific indication and appropriate place in therapy for ranolazine, clinicians can optimize its use for patients with chronic stable angina who have not achieved adequate symptom control with traditional antianginal medications.