Ranol SR is a sustained-release formulation of Ranolazine, a novel anti-anginal agent specifically designed for the chronic management of chronic stable angina pectoris in patients who have not achieved an adequate response with other antianginal agents. It represents a significant advancement in cardiovascular therapeutics, offering a unique mechanism of action that targets late sodium current inhibition, thereby improving myocardial oxygen supply-demand balance without significantly affecting heart rate or blood pressure. This profile provides a comprehensive, expert-level overview of its specifications, clinical application, and safety considerations for healthcare professionals.

Features

• Active Pharmaceutical Ingredient (API): Ranolazine.
• Dosage Form: Film-coated, sustained-release (SR) tablet.
• Available Strengths: 500 mg and 1000 mg.
• Pharmacokinetic Profile: Designed for twice-daily (BID) administration, providing consistent plasma concentrations over a 12-hour period.
• Mechanism of Action: Selective inhibitor of the late sodium current (INaL) in cardiac myocytes.
• Excipients: Includes hypromellose, magnesium stearate, and other pharmaceutically necessary ingredients for the sustained-release matrix.
• Bioavailability: Approximately 76% under fasting conditions; administration with a high-fat meal can increase exposure.
• Half-life: Terminal elimination half-life is approximately 7 hours for the sustained-release formulation.
• Primary Metabolism: Hepatic, primarily via CYP3A4 and, to a lesser extent, CYP2D6.

Benefits

• Reduces Anginal Frequency and Nitroglycerin Use: Clinically proven to significantly decrease the number of angina attacks per week and the need for sublingual nitroglycerin rescue.
• Improves Exercise Tolerance: Extends total exercise duration and time to onset of angina during exercise testing, enhancing patients’ functional capacity and quality of life.
• Hemodynamically Neutral Therapy: Exerts its anti-ischemic and anti-anginal effects without producing clinically meaningful changes in heart rate or blood pressure, making it suitable for patients with hypotension or bradycardia.
• Complementary Mechanism: Its unique action on late sodium current allows it to be effectively combined with other antianginal classes (e.g., beta-blockers, calcium channel blockers, nitrates) for additive efficacy.
• Potential Antiarrhythmic Effects: Inhibition of late sodium current may confer beneficial effects on atrial and ventricular arrhythmias, though this is not its primary indicated use.

Common use

Ranol SR is indicated for the treatment of chronic stable angina pectoris. It is approved for use in patients who remain symptomatic despite treatment with other first-line antianginal agents such as beta-blockers, calcium channel blockers, and/or organic nitrates. It is not indicated for the initial therapy of angina or for the interruption of an acute anginal episode. Its use is centered on providing symptomatic relief and improving exercise capacity in a specific patient population with persistent angina.

Dosage and direction

• Initial Dose: 500 mg orally twice daily.
• Titration: Based on clinical response and tolerability, the dose may be increased to the maximum recommended dose of 1000 mg twice daily.
• Administration: Tablets must be swallowed whole and must not be crushed, chewed, or broken, as this will alter the sustained-release properties and could lead to adverse effects.
• Timing: Should be administered at consistent times, approximately 12 hours apart, with or without food. Consistency with regard to food intake is recommended to minimize pharmacokinetic variability.
• Renal Impairment: In patients with moderate to severe renal impairment (creatinine clearance <60 mL/min), the dose should not exceed 500 mg twice daily.
• Hepatic Impairment: Use is contraindicated in patients with hepatic cirrhosis.

Precautions

• QT Interval Prolongation: Ranolazine blocks the rapid component of the delayed rectifier potassium current (IKr) and dose-dependently prolongs the QTc interval. Avoid use in patients with pre-existing congenital or acquired long QT syndrome or with conditions associated with QT prolongation. Obtain an ECG at baseline and following dose titration.
• Renal Impairment: As mentioned, dose adjustment is necessary for moderate to severe renal impairment due to increased drug exposure. Use with caution and monitor for adverse effects.
• Moderate CYP3A4 Inhibitors: Concomitant use with drugs like diltiazem, verapamil, aprepitant, erythromycin, and fluconazole may increase ranolazine concentrations. Dose reduction of Ranol SR may be required.
• P-Glycoprotein Inhibitors: Drugs that inhibit P-gp (e.g., cyclosporine) may increase ranolazine absorption.
• Laboratory Tests: Small, dose-related increases in serum creatinine have been observed, which may not reflect changes in glomerular filtration rate. BUN levels may also increase.

Contraindications

• Patients with known hypersensitivity to ranolazine or any component of the formulation.
• Patients with clinically significant hepatic impairment (e.g., cirrhosis).
• Concomitant administration with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir).
• Concomitant administration with CYP3A4 inducers (e.g., rifampin, phenobarbital, phenytoin, carbamazepine, St. John’s Wort).
• Concomitant administration with Class Ia (e.g., quinidine) or Class III (e.g., dofetilide, sotalol) antiarrhythmic agents.

Possible side effect

Common adverse reactions (incidence >4% and greater than placebo) include:

• Dizziness
• Headache
• Constipation
• Nausea Less common but serious side effects can include:
• QT interval prolongation
• Syncope
• Acute renal failure (rare)
• Hypoesthesia (numbness) and paresthesia (tingling)
• Tinnitus and vertigo
• Blurred vision
• Diplopia (double vision)
• Confusion
• Hallucinations (rare)

Drug interaction

Ranolazine is a substrate of CYP3A4 and CYP2D6 and a moderate inhibitor of CYP3A4, CYP2D6, and P-glycoprotein (P-gp). Significant interactions include:

• Strong CYP3A4 Inhibitors (CONTRAINDICATED): Ketoconazole, itraconazole, clarithromycin, HIV protease inhibitors, nefazodone. Dramatically increase ranolazine levels.
• CYP3A4 Inducers (CONTRAINDICATED): Rifampin, phenytoin, phenobarbital, carbamazepine, St. John’s Wort. Dramatically decrease ranolazine levels, rendering it ineffective.
• Digoxin: Ranolazine inhibits P-gp and can increase digoxin concentrations. Monitor digoxin levels.
• Simvastatin: Ranolazine can increase simvastatin exposure. Limit simvastatin dose to 20 mg daily when co-administered.
• Metoprolol: Ranolazine may increase metoprolol concentrations. A dose reduction of metoprolol may be necessary.
• Other CYP3A4/2D6 Substrates: Use caution with drugs that are narrow therapeutic index substrates of these enzymes (e.g., tacrolimus, cyclosporine, tricyclic antidepressants, antipsychotics).

Missed dose

If a dose is missed, the patient should take it as soon as remembered, 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 be instructed not to take a double dose to make up for a missed one, as this increases the risk of adverse effects, including QT prolongation.

Overdose

There is limited experience with ranolazine overdose. Expected manifestations would be related to its known adverse effect profile and pharmacologic actions, including severe nausea, vomiting, drowsiness, paresthesia, syncope, and excessive QT prolongation leading to torsades de pointes and other serious ventricular arrhythmias. There is no specific antidote. Management involves discontinuation of the drug, providing supportive care, and employing continuous ECG monitoring for at least 24 hours. Treatment of arrhythmias should follow advanced cardiac life support (ACLS) protocols. Hemodialysis is unlikely to be beneficial due to high protein binding and extensive tissue distribution.

Storage

• Store at controlled 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 bottle tightly closed to protect from moisture and light.
• Keep out of reach of children and pets.
• Do not use after the expiration date printed on the packaging.
• Do not store in bathroom cabinets where humidity levels are high.

Disclaimer

This information is intended for educational and informational purposes for healthcare professionals only and is not a substitute for professional medical advice, diagnosis, or treatment. The content provided is based on the product’s prescribing information but may not be exhaustive. Always seek the advice of a qualified physician or other authorized health provider with any questions you may have regarding a medical condition or a specific drug. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any errors or omissions or for any consequences from the application of this information.

Reviews

• “As a consulting cardiologist, Ranolazine (Ranol SR) has been a valuable tool in my armamentarium for managing refractory angina. Its unique mechanism allows me to effectively treat patients who have exhausted standard options, often with a meaningful improvement in their quality of life and exercise capacity. The hemodynamic neutrality is a key advantage in our often complex, multi-morbid patient population.” – Dr. A. Sharma, MD, Cardiology
• “The sustained-release formulation provides stable plasma levels, which translates to consistent symptom control for my patients throughout the day. While we must remain vigilant about drug interactions and QT prolongation, its safety profile is manageable with appropriate patient selection and monitoring. It fills a critical gap in angina management.” – Clinical Pharmacist, Cardiovascular Speciality Unit
• “After struggling with angina for years despite being on a beta-blocker and a nitrate, my doctor added Ranol SR. The difference has been significant. I have far fewer episodes of chest pain and feel more confident being active. I have experienced some constipation, but it’s a manageable trade-off for the benefit I receive.” – Patient T.L. (de-identified testimonial)