Ranexa: Advanced Angina Management for Stable Coronary Artery Disease
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Ranexa (ranolazine) is an antianginal medication indicated for the treatment of chronic angina pectoris in patients with stable coronary artery disease. As a late sodium current inhibitor, it operates via a unique mechanism distinct from traditional antianginal agents like beta-blockers or calcium channel blockers. It is typically prescribed when symptoms are not adequately controlled by first-line therapies, offering an adjunctive or alternative option to reduce angina frequency and improve exercise tolerance. Ranexa does not lower heart rate or blood pressure significantly, making it a suitable choice for patients who cannot tolerate hemodynamic effects of other antianginal medications.
Features
- Active ingredient: Ranolazine
- Available in extended-release tablet formulations (500 mg and 1000 mg)
- Unique mechanism: Selective inhibition of the late sodium current in cardiac cells
- Twice-daily dosing regimen for sustained effect
- Not associated with significant hemodynamic changes (e.g., heart rate or blood pressure reduction)
- FDA-approved for chronic angina management
Benefits
- Reduces frequency of angina attacks and nitroglycerin use
- Improves exercise tolerance and time to onset of angina in patients with stable coronary artery disease
- May be used safely in combination with other antianginal agents (e.g., beta-blockers, calcium channel blockers, nitrates)
- Suitable for patients with contraindications or intolerance to traditional antianginal therapies
- Does not exhibit negative chronotropic or inotropic effects, preserving cardiac output
- May improve glycemic parameters in diabetic patients due to metabolic effects
Common use
Ranexa is prescribed for the management of chronic angina pectoris in adults with stable coronary artery disease who remain symptomatic despite standard antianginal therapy. It is commonly used as add-on treatment when beta-blockers, calcium channel blockers, or nitrates provide insufficient symptom control or cannot be tolerated. The medication is particularly valuable in patients with comorbidities such as diabetes, heart failure, or conduction abnormalities where traditional antianginal agents may be problematic. Clinical studies demonstrate its efficacy in reducing both angina frequency and nitroglycerin rescue use while improving exercise performance.
Dosage and direction
The recommended initial 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 not crushed, chewed, or broken, as this would alter the extended-release properties. Administration with or without food is acceptable, though consistency in timing relative to meals is recommended. Dose adjustments are necessary in patients with hepatic impairment, renal impairment (creatinine clearance <30 mL/min), or when co-administered with certain CYP3A inhibitors. Titration should occur at intervals of no less than 2-4 weeks to assess therapeutic response and side effects.
Precautions
Ranexa should be used cautiously in patients with pre-existing QT interval prolongation or those taking other medications that prolong the QT interval. Regular ECG monitoring may be warranted, particularly during dose titration. Hepatic impairment (moderate to severe) requires dose reduction or avoidance due to decreased metabolism. Renal impairment (CrCl <30 mL/min) necessitates a maximum dose of 500 mg twice daily. Patients should be advised that Ranexa is not intended for the treatment of acute angina attacks, for which sublingual nitroglycerin remains the standard rescue medication. Dizziness or syncope may occur, particularly upon initiation; patients should exercise caution when operating machinery or driving until they understand how the medication affects them.
Contraindications
Ranexa is contraindicated in patients with clinically significant hepatic impairment (Child-Pugh Class C cirrhosis). Concomitant use with strong CYP3A inhibitors (including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir) is prohibited due to the risk of significantly increased ranolazine concentrations. Use with potent CYP3A inducers (such as rifampin, phenobarbital, phenytoin, carbamazepine, or St. John’s wort) is also contraindicated. The medication should not be used in patients with a known hypersensitivity to ranolazine or any component of the formulation.
Possible side effects
The most commonly reported adverse reactions (≥4% and more frequent than placebo) include dizziness, headache, constipation, and nausea. Other potential side effects include:
- QT interval prolongation (dose-dependent)
- Syncope or presyncope
- vomiting
- asthenia
- dry mouth
- abdominal pain
- peripheral edema
- tinnitus or vertigo
- palpitations
- dyspnea
- blurred vision
- confusion or memory impairment
Serious but rare adverse effects include acute renal failure, thrombocytopenia, and hallucinations. Most side effects are mild to moderate in severity and often diminish with continued therapy or dose adjustment.
Drug interaction
Ranexa is primarily metabolized by CYP3A and to a lesser extent by CYP2D6, making it susceptible to numerous drug interactions:
- Strong CYP3A inhibitors: Contraindicated (e.g., ketoconazole, clarithromycin)
- Moderate CYP3A inhibitors: Dose limitation to 500 mg twice daily (e.g., diltiazem, verapamil, erythromycin)
- CYP3A inducers: Contraindicated (e.g., rifampin, carbamazepine)
- CYP2D6 substrates: Ranexa may increase concentrations of drugs metabolized by CYP2D6 (e.g., tricyclic antidepressants, antipsychotics, beta-blockers)
- Digoxin: Ranexa may increase digoxin levels (monitor concentrations)
- Simvastatin: Ranexa may increase simvastatin exposure (limit simvastatin to 20 mg daily)
- Transporters: May inhibit P-gp (e.g., digoxin) and OCT2 (e.g., metformin)
Missed dose
If a dose of Ranexa is missed, patients should take it as soon as they remember, 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. Patients should not take a double dose to make up for a missed one. Consistency in administration is important to maintain stable drug concentrations and antianginal efficacy.
Overdose
Cases of Ranexa overdose have been reported with doses up to 9000 mg. Symptoms may include severe nausea, vomiting, drowsiness, paresthesia, syncope, and QT prolongation. There is no specific antidote for ranolazine overdose. Management should include supportive care with continuous ECG monitoring for at least 24 hours due to the drug’s long half-life (approximately 7 hours). Gastric lavage or activated charcoal may be considered if presented soon after ingestion. Hemodialysis is unlikely to be effective due to ranolazine’s high protein binding and extensive tissue distribution.
Storage
Ranexa tablets 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 medication in its original container, tightly closed, and protected from light and moisture. Do not store in bathrooms or other areas with high humidity. Keep out of reach of children and pets. Properly discard any expired or unused medication according to local regulations.
Disclaimer
This information is intended for educational purposes only and does not constitute medical advice. Ranexa is a prescription medication that should be used only under the supervision of a qualified healthcare provider. Individual response to therapy may vary, and patients should follow their physician’s instructions regarding use, monitoring, and dose adjustments. The full prescribing information should be consulted for complete details regarding indications, contraindications, warnings, and precautions.
Reviews
Clinical trials and post-marketing experience demonstrate that Ranexa provides meaningful angina relief for many patients who have not achieved adequate control with conventional antianginal therapies. In the CARISA trial, Ranexa significantly increased exercise duration and reduced angina frequency compared to placebo. The ERICA trial showed a significant reduction in nitroglycerin use and angina attacks. Many clinicians report particular value in complex patients with multiple comorbidities where traditional antianginal options are limited. Some patients note improved quality of life due to reduced angina frequency and increased activity tolerance. However, gastrointestinal side effects and dizziness may limit tolerability in some individuals, requiring careful dose titration.