Ranolazine is indicated for the management of chronic angina. It can be used in combination with beta-blockers, nitrates, calcium channel blockers, antiplatelet agents, lipid-lowering drugs, ACE inhibitors, and angiotensin receptor blockers. It has been shown to reduce angina episodes in patients with coronary artery disease who are on maximum doses of amlodipine. Because Ranolazine may prolong the QT interval, it should be reserved for patients who have not responded adequately to other antianginal therapies. The improvement in angina frequency and exercise tolerance appears to be less pronounced in women compared to men.

Ranolazine exerts anti-ischemic and antianginal effects without significantly affecting heart rate or blood pressure. Its exact mechanism of action is not fully understood. At therapeutic concentrations, Ranolazine inhibits the late sodium current (INa) in cardiac cells; however, the direct relationship between this effect and relief of angina symptoms remains unclear. The prolongation of the QT interval observed on ECG is attributed to inhibition of the IKr current, which extends the ventricular action potential.

Absorption: Cmax is reached within approximately 2–5 hours.

Half-life: Approximately 6–22 hours.

Distribution: Across a concentration range of 0.25 to 10 µg/mL, Ranolazine is about 62% bound to plasma proteins.

Metabolism and Excretion: Ranolazine is primarily metabolized by CYP3A and, to a lesser extent, by CYP2D6. It undergoes extensive and rapid metabolism in the liver and intestines, with less than 5% excreted unchanged in urine and feces. After a single oral dose of Ranolazine solution, approximately 75% of the dose is eliminated via urine and 25% via feces.

Ranolazine is usually initiated at 500 mg twice daily and may be increased to 1000 mg twice daily as needed based on clinical symptoms. It can be taken with or without food. Tablets should be swallowed whole and must not be crushed, broken, or chewed. The maximum recommended dose is 1000 mg twice daily. If a dose is missed, the next dose should be taken at the scheduled time; do not double the dose.

Pediatric Use: The safety and effectiveness of this medicine have not been established in pediatric patients.

CYP3A Inhibitors: Avoid using Ranolazine together with strong CYP3A inhibitors. When used with moderate CYP3A inhibitors (such as diltiazem, verapamil, erythromycin), the maximum dose of Ranolazine should be limited to 500 mg twice daily.

CYP3A Inducers: Ranolazine should not be used with CYP3A inducers.

P-gp Inhibitors (e.g., Cyclosporin): Dose reduction of Ranolazine may be required based on clinical response.

Drugs transported by P-gp or metabolized by CYP2D6 (e.g., digoxin, TCAs): Lower doses of these medications may be necessary when co-administered with Ranolazine.

Ranolazine is contraindicated in patients:

• With pre-existing QT interval prolongation
• With hepatic impairment
• Taking medications known to prolong QT interval
• Taking strong or moderate CYP3A inhibitors such as ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir, including diltiazem

• Cardiac Disorders: bradycardia, palpitations
• Ear and Labyrinth Disorders: tinnitus, vertigo
• Gastrointestinal Disorders: abdominal pain, dry mouth, vomiting
• General Disorders and Administration Site Conditions: peripheral edema
• Respiratory, Thoracic, and Mediastinal Disorders: dyspnea
• Vascular Disorders: hypotension, orthostatic hypotension

Pregnancy Category C. There are no adequate and well-controlled studies evaluating the effects of ranolazine on the developing fetus or in pregnant women. Ranolazine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is not known whether ranolazine is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, a decision should be made whether to discontinue breastfeeding or discontinue the drug, considering the importance of the medication to the mother.

Ranolazine prolongs the QTc interval in a dose-dependent manner by blocking IKr current. Clinical data in patients with acute coronary syndrome did not demonstrate an increased risk of proarrhythmia or sudden cardiac death.

Co-administration of ranolazine with digoxin increases digoxin plasma levels (approximately 1.5-fold), and dose adjustment of digoxin may be required. Similarly, doses of other P-gp substrates may need to be reduced. Caution is advised when ranolazine is used with P-gp inhibitors such as ritonavir or cyclosporine.

Excessive oral doses of Ranolazine may lead to dose-dependent increases in dizziness, nausea, and vomiting. High intravenous exposure can also result in symptoms such as double vision (diplopia), abnormal sensations (paresthesia), confusion, and fainting (syncope). In cases of overdose, along with general supportive care, continuous ECG monitoring may be required. As Ranolazine is approximately 62% bound to plasma proteins, hemodialysis is not likely to be effective in removing it.

Other Anti-anginal & Anti-ischaemic drugs

Store below 30°C in a cool, dry place. Protect from light and moisture. Keep out of reach of children.