Ranolazine: uses, appearance and warnings

Ranolazine extended-release tablets is 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 is an antianginal indicated for the treatment of chronic angina.

Ranolazine extended-release tablets is supplied as film-coated, oblong-shaped, extended-release tablets in the following strengths: 500 mg tablets are Yellow color, with RAN500 on one side and plain on other side 1,000 mg tablets are Yellow color, with RAN1000 on one side and plain on other side Extended-release tablets: 500 mg, 1,000 mg.

Ranolazine extended-release tablets is supplied as film-coated, oblong-shaped, extended-release tablets in the following strengths: 500 mg tablets are Yellow color, with RAN500 on one side and plain on other side 1,000 mg tablets are Yellow color, with RAN1000 on one side and plain on other side Ranolazine extended-release tablets are available in: Strength NDC Unit-of-Use Bottle (60 Tablets) 500 mg 60290-055-01 Carton of 60 tablets (6 blister cards of 10 tablets) 500 mg 60290-055-03 Unit-of-Use Bottle (60 Tablets) 1,000 mg 60290-056-01 Carton of 60 tablets (6 blister cards of 10 tablets) 1,000 mg 60290-056-03 Store at 20° to 25°C (68° to 77°F), excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Ranolazine extended-release tablets is contraindicated in patients: Taking strong inhibitors of CYP3A [see Drug Interactions (7.1) ] Taking inducers of CYP3A [see Drug Interactions (7.1) ] With liver cirrhosis [see Use in Specific Populations (8.6) ] 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 )

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. ( 5.1 ) 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. ( 5.2 ) 5.1 QT Interval Prolongation Ranolazine blocks I Kr and prolongs the QTc interval in a dose-related manner. Clinical experience in an acute coronary syndrome population did not show an increased risk of proarrhythmia or sudden death [see Clinical Studies (14.2) ]. However, there is little experience with high doses (>1,000 mg twice daily) or exposure, other QT- prolonging drugs, potassium channel variants resulting in a long QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation. 5.2 Renal Failure Acute renal failure has been observed in some patients with severe renal impairment (creatinine clearance [CrCL] <30 mL/min) while taking ranolazine extended-release tablets. If acute renal failure develops (e.g., marked increase in serum creatinine associated with an increase in blood urea nitrogen [BUN]), discontinue ranolazine extended-release tablets and treat appropriately [see Use in Specific Populations (8.7) ]. Monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (CrCL <60 mL/min) for increases in serum creatinine accompanied by an increase in BUN.

Most common adverse reactions (>4% and more common than with placebo) are dizziness, headache, constipation, nausea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Umedica Laboratories USA Inc. at 1-855-288-5777 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 2018 patients with chronic angina were treated with ranolazine in controlled clinical trials. Of the patients treated with ranolazine extended-release tablets, 1026 were enrolled in three double- blind, placebo-controlled, randomized studies (CARISA, ERICA, MARISA) of up to 12 weeks’duration. …

Moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin): Limit ranolazine extended-release tablets to 500 mg twice daily. ( 7.1 ) P-gp inhibitors (e.g., cyclosporine): Ranolazine exposure increased. Titrate ranolazine extended-release tablets based on clinical response. ( 7.1 ) CYP3A substrates: Limit simvastatin to 20 mg when used with ranolazine extended-release tablets. Doses of other sensitive CYP3A substrates (e.g., lovastatin) and CYP3A substrates with narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus) may need to be reduced with ranolazine extended-release tablets. ( 7.2 ) OCT2 substrates: Limit the dose of metformin to 1700 mg daily when used with ranolazine extended-release tablets 1,000 mg twice daily. Doses of other OCT2 substrates may require adjusted doses. …