Ranexa (ranolazine) is an FDA-approved antianginal medication indicated for the treatment of chronic angina pectoris. It functions 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 both as monotherapy and in combination with other antianginal agents, particularly for patients who remain symptomatic despite standard treatments or who cannot tolerate hemodynamic side effects. Its distinct pharmacologic profile offers a complementary approach to angina management in a broad patient population.

Features

• Active ingredient: Ranolazine
• Available as extended-release tablets: 500 mg and 1000 mg
• Unique mechanism: Late sodium current inhibition
• Does not cause clinically significant hemodynamic changes (heart rate, BP)
• Twice-daily dosing regimen
• Approved for use in combination with amlodipine, beta-blockers, or nitrates

Benefits

• Reduces frequency of angina attacks and nitroglycerin use
• Improves exercise tolerance and time to onset of angina
• Suitable for patients with contraindications to or intolerance of traditional antianginal agents
• May be used safely in combination with other cardiovascular medications
• Does not require titration for heart rate or blood pressure effects
• Provides symptomatic relief without negative inotropic effects

Common use

Ranexa is indicated for the treatment of chronic angina in patients who have not achieved an adequate response with other antianginal drugs. It is commonly prescribed as part of a comprehensive antianginal regimen that may include beta-blockers, calcium channel blockers, or nitrates. The medication is particularly useful in patients who cannot tolerate the hemodynamic effects of traditional antianginal agents or who continue to experience symptoms despite optimal doses of first-line therapies. Clinical studies have demonstrated its efficacy in reducing both angina frequency and nitroglycerin consumption while improving exercise performance.

Dosage and direction

The recommended starting dose of Ranexa is 500 mg twice daily, with or without meals. 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. Dose adjustments are recommended in patients with moderate to severe hepatic impairment, with a maximum dose of 500 mg twice daily in these populations. No initial dose adjustment is necessary for renal impairment, but careful monitoring is advised.

Precautions

Ranexa should be used with caution in patients with pre-existing QT interval prolongation or who are taking other drugs that prolong the QT interval. Electrocardiographic monitoring should be considered in these patients. Hepatic impairment significantly increases ranolazine exposure; dosage reduction is required in patients with moderate to severe hepatic impairment (Child-Pugh Class B or C). Renal impairment does not significantly affect ranolazine pharmacokinetics, but patients with severe renal impairment (creatinine clearance <30 mL/min) should be monitored closely. The safety and effectiveness in patients under 18 years have not been established.

Contraindications

Ranexa is contraindicated in patients with clinically significant hepatic impairment (Child-Pugh Class C), in patients taking strong CYP3A inhibitors (including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir), and in patients taking CYP3A inducers (such as rifampin, phenobarbital, phenytoin, carbamazepine, and St. John’s wort). Concomitant use with Class Ia or III antiarrhythmics (except amiodarone) is also contraindicated due to the potential for additive effects on QT interval prolongation.

Possible side effects

The most common adverse reactions (occurring in >4% of patients and more frequently than placebo) include dizziness, headache, constipation, and nausea. Other reported side effects include dry mouth, vomiting, asthenia, and peripheral edema. QT interval prolongation has been observed in a dose-related manner, though the clinical significance of this effect remains uncertain. Serious but rare adverse events include syncope, hypotension, and renal failure. Patients should be advised to report any persistent or severe side effects to their healthcare provider.

Drug interaction

Ranexa is primarily metabolized by CYP3A and to a lesser extent by CYP2D6. Significant interactions occur with:

• Strong CYP3A inhibitors: Contraindicated (increase ranolazine levels 3-fold)
• Moderate CYP3A inhibitors: Limit Ranexa to 500 mg twice daily
• CYP3A inducers: Contraindicated (decrease ranolazine levels)
• CYP2D6 substrates: May increase levels of drugs metabolized by CYP2D6
• Digoxin: Moderate increase in digoxin levels (monitor levels)
• Simvastatin: 2-fold increase in simvastatin exposure (limit to 20 mg daily)
• Metformin: Moderate increase in metformin exposure (monitor glycemic control)
• Antihypertensive drugs: Additive effects possible

Missed dose

If a dose of Ranexa is missed, patients should take it as soon as they remember, unless it is almost 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 dose. Consistent twice-daily administration is important for maintaining therapeutic drug levels and optimal angina control.

Overdose

Cases of Ranexa overdose have been reported with doses up to 9000 mg. Symptoms may include QT prolongation, nausea, vomiting, dizziness, diplopia, syncope, and hypotension. There is no specific antidote for ranolazine overdose. Management should include supportive care with ECG monitoring for at least 24 hours. Hemodialysis is unlikely to be effective due to ranolazine’s high protein binding and extensive tissue distribution. Gastric lavage or activated charcoal may be considered if presented soon after ingestion.

Storage

Ranexa tablets should be stored at room temperature (20°C to 25°C/68°F to 77°F) with excursions permitted between 15°C and 30°C (59°F and 86°F). Keep the medication in its original container, tightly closed, and protected from moisture and light. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging. Proper disposal of unused medication should follow local regulations or medication take-back programs.

Disclaimer

This information is provided 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 professional. Individual patient responses may vary, and treatment decisions should be based on the healthcare provider’s assessment of the patient’s specific medical condition, contraindications, and potential drug interactions. Patients should not adjust their dosage or discontinue treatment without consulting their physician.

Reviews

Clinical trials have demonstrated Ranexa’s efficacy in reducing angina frequency and improving exercise tolerance. In the CARISA trial, ranolazine significantly increased exercise duration and time to angina onset compared to placebo. The ERICA trial showed a significant reduction in angina attacks and nitroglycerin use when added to amlodipine therapy. Real-world evidence supports its effectiveness in diverse patient populations, including elderly patients and those with multiple comorbidities. Many clinicians report satisfactory results in patients who were previously refractory to conventional antianginal therapies, though individual responses vary. Long-term safety data from the MERLIN-TIMI 36 trial showed no increase in mortality or sudden cardiac death with ranolazine use.