Ranexa

Ranexa (ranolazine) is an FDA-approved antianginal medication specifically indicated for the treatment of chronic angina pectoris. Unlike traditional antianginal agents, Ranexa operates through a unique mechanism of action, inhibiting the late sodium current in cardiac cells, which reduces intracellular calcium overload and myocardial oxygen demand without significantly affecting heart rate or blood pressure. This makes it a valuable therapeutic option, particularly as add-on therapy for patients who remain symptomatic despite treatment with conventional agents like beta-blockers, calcium channel blockers, or nitrates. Its efficacy in reducing angina frequency and improving exercise tolerance is well-supported by clinical evidence, offering a tailored approach to symptom management in a complex patient population.

Features

• Active ingredient: Ranolazine
• Available in extended-release tablet formulations (500 mg and 1000 mg)
• Unique mechanism: Selective inhibitor of late sodium current
• Does not cause clinically significant hemodynamic changes (e.g., heart rate or blood pressure reduction)
• Twice-daily dosing regimen for sustained effect
• Approved for use in combination with other antianginal medications

Benefits

• Reduces frequency of angina attacks and nitroglycerin use
• Improves exercise tolerance and time to onset of angina in patients with chronic stable angina
• Can be used safely in combination with other standard antianginal therapies
• Does not typically cause bradycardia or hypotension, making it suitable for patients intolerant to other agents
• May be beneficial in specific populations, such as those with diabetes or microvascular angina
• Provides an alternative mechanism of action when first-line therapies are insufficient or contraindicated

Common use

Ranexa is indicated for the treatment of chronic angina pectoris in patients who have not achieved an adequate response with other antianginal drugs. It is used as part of a comprehensive management plan that includes lifestyle modifications and other pharmacologic agents. It is not intended for use in the acute termination of angina attacks (i.e., it is not a “rescue” medication) and should not be used as monotherapy when initiating treatment for angina. Clinical studies have demonstrated its efficacy both as add-on therapy and in specific subpopulations, such as individuals with type 2 diabetes, where it may offer additional benefits.

Dosage and direction

The recommended starting dose of Ranexa is 500 mg taken orally twice daily. Based on clinical response and tolerability, the dose may be increased to a maximum of 1000 mg twice daily. Tablets should be swallowed whole and must not be crushed, chewed, or broken, as this alters the extended-release properties. Ranexa may be taken with or without food, but consistency in administration relative to meals is advised. Dose adjustments are recommended in patients with moderate to severe renal impairment (creatinine clearance <60 mL/min), with a maximum dose of 500 mg twice daily in such cases. Hepatic impairment is a contraindication for use.

Precautions

Patients should be advised that Ranexa may cause QT interval prolongation, although the risk of torsades de pointes appears low. ECG monitoring may be considered in susceptible individuals. Renal function should be assessed before initiation and periodically during treatment, as ranolazine is excreted renally. Use with caution in patients taking other drugs known to prolong the QT interval. Patients should be informed that Ranexa is not for aborting acute anginal episodes and that standard sublingual nitroglycerin should be used for this purpose. Dizziness or syncope may occur; patients should avoid driving or operating machinery until they know how Ranexa affects them.

Contraindications

Ranexa is contraindicated in patients with:

• Clinically significant hepatic impairment (Child-Pugh Class B or C)
• Hypersensitivity to ranolazine or any component of the formulation
• Concomitant use with strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, ritonavir)
• Concomitant use with CYP3A inducers (e.g., rifampin, phenobarbital, St. John’s wort)
• Preexisting QT prolongation or concomitant use of other QT-prolonging drugs (unless closely monitored)

Possible side effect

Common adverse reactions (≥4% and more frequent than placebo) include:

• Dizziness
• Headache
• Constipation
• Nausea

Less common but clinically significant side effects may include:

• QT interval prolongation
• Syncope
• Tinnitus or vertigo
• Blurred vision
• Urinary retention
• Hypotension (especially in volume-depleted patients)

Serious side effects are rare but may include severe QT prolongation and torsades de pointes, particularly in predisposed patients.

Drug interaction

Ranexa is primarily metabolized by CYP3A and CYP2D6 and is a moderate inhibitor of CYP3A, CYP2D6, and P-glycoprotein. Significant interactions include:

• Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin): Contraindicated—increased ranolazine exposure and QT prolongation risk.
• Moderate CYP3A inhibitors (e.g., diltiazem, verapamil): Use with caution; dose reduction may be needed.
• CYP3A inducers (e.g., rifampin, carbamazepine): Contraindicated—reduced ranolazine efficacy.
• CYP2D6 substrates (e.g., tricyclic antidepressants, antipsychotics): Increased levels of these drugs.
• Digoxin: Ranexa may increase digoxin levels; monitor concentrations.
• Simvastatin: Ranexa may increase simvastatin exposure; limit simvastatin dose to 20 mg daily.

Missed dose

If a dose of Ranexa is missed, the patient should take it as soon as remembered, unless it is nearly time for the next scheduled dose. In that case, the missed dose should be skipped, and the regular dosing schedule resumed. Doubling the dose to make up for a missed one is not recommended.

Overdose

Cases of Ranexa overdose have been reported, with symptoms including QT prolongation, nausea, vomiting, dizziness, and syncope. There is no specific antidote. Management should include supportive care, ECG monitoring for QT prolongation and arrhythmias, and symptomatic treatment. Hemodialysis is unlikely to be effective due to ranolazine’s high protein binding and extensive distribution.

Storage

Ranexa should be stored at room temperature (20–25°C or 68–77°F), with excursions permitted between 15–30°C (59–86°F). Keep the container tightly closed and protect from moisture and light. Keep out of reach of children and pets. Do not use beyond the expiration date printed on the packaging.

Disclaimer

This information is intended for educational purposes and does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting, changing, or stopping any medication. Individual patient responses may vary. Only a licensed medical professional can determine the appropriate use of Ranexa based on a patient’s specific health status and medical history.

Reviews

Clinical trials and post-marketing studies have consistently demonstrated Ranexa’s efficacy in reducing angina frequency and improving exercise tolerance. In the CARISA trial, Ranexa significantly increased exercise duration and time to angina onset compared to placebo. The ERICA trial showed a reduction in nitroglycerin use and angina attacks in patients with persistent symptoms despite conventional therapy. Real-world evidence supports its utility in complex cases, including patients with comorbidities such as diabetes. Overall, Ranexa is regarded as a well-tolerated and effective option for chronic angina management when used appropriately in indicated populations.