Ranolazine

What it is and how it works

Mechanism of Action The mechanism of action of ranolazine’s antianginal effects has not been determined. Ranolazine has anti-ischemic and antianginal effects that do not depend upon reductions in heart rate or blood pressure. It does not affect the rate-pressure product, a measure of myocardial work, at maximal exercise. Ranolazine at therapeutic levels can inhibit the cardiac late sodium current (I Na ). However, the relationship of this inhibition to angina symptoms is uncertain. The QT prolongation effect of ranolazine on the surface electrocardiogram is the result of inhibition of I Kr , which prolongs the ventricular action potential.

Mechanism class: Cytochrome P450 3A Inhibitors · P-Glycoprotein Inhibitors · Cytochrome P450 2D6 Inhibitors

Indications

Ranolazine extended-release tablets are indicated for the treatment of chronic angina. Ranolazine extended-release tablets may be used with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers. Ranolazine extended-release tablets are an antianginal indicated for the treatment of chronic angina.

Dosage and administration (summary)

500 mg twice daily and increase to 1,000 mg twice daily, based on clinical symptoms Dosing Information Initiate ranolazine extended-release tablets dosing at 500 mg twice daily and increase to 1000 mg twice daily, as needed, based on clinical symptoms. Take ranolazine extended-release tablets with or without meals. Swallow ranolazine extended-release tablets whole; do not crush, break, or chew. The maximum recommended daily dose of ranolazine extended-release tablets is 1000 mg twice daily. If a dose of ranolazine extended-release tablets is missed, take the prescribed dose at the next scheduled time; do not double the next dose.

Contraindications

Ranolazine is contraindicated in patients: • Taking strong inhibitors of CYP3A • Taking inducers of CYP3A • With liver cirrhosis • Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir) ( 4 , 7.1 ) • CYP3A inducers (e.g., rifampin, phenobarbital, St. John’s wort) ( 4 , 7.1 ) • Liver cirrhosis ( 4 , 8.6 )

Warnings and precautions

• QT interval prolongation: Can occur with ranolazine. Little data available on high doses, long exposure, use with QT interval-prolonging drugs, potassium channel variants causing prolonged QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation. • Renal failure: Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL<60 mL/min). If acute renal failure develops, discontinue ranolazine extended-release tablets.

Pregnancy

Pregnancy Risk Summary There are no available data on ranolazine use in pregnant women to inform any drug-associated risks. Studies in rats and rabbits showed no evidence of fetal harm at exposures 4 times the maximum recommended human dose (MRHD) (see Data) . In the U.S.

Storage and supply

Store ranolazine extended-release tablets at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) .

Source: Ranolazine (Ranolazine) — US FDA prescribing information, 2026-01-23, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.