CardioSource WorldNews September 2015 - Page 30

RANEXA® (ranolazine) Brief summary of full Prescribing Information. Please see full Prescribing Information. Rx Only. INDICATIONS AND USAGE: RANEXA® is indicated for the treatment of chronic angina. RANEXA may be used with betablockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ACE inhibitors, and angiotensin receptor blockers. DOSAGE AND ADMINISTRATION: Adult Dosage: Initiate RANEXA dosing at 500 mg twice daily and increase to 1000 mg twice daily, as needed, based on clinical symptoms. Take RANEXA with or without meals. Swallow RANEXA tablets whole; do not crush, break, or chew. The maximum recommended daily dose of RANEXA is 1000 mg twice daily. If a dose of RANEXA is missed, take the prescribed dose at the next scheduled time; do not double the next dose. Dose Modification: Dose adjustments may be needed when RANEXA is taken in combination with certain other drugs. Limit the maximum dose of RANEXA to 500 mg twice daily in patients on moderate CYP3A inhibitors such as diltiazem, verapamil, and erythromycin. Use of P-gp inhibitors, such as cyclosporine, may increase exposure to RANEXA. Titrate RANEXA based on clinical response. CONTRAINDICATIONS: RANEXA is contraindicated in patients: • Taking strong inhibitors of CYP3A • Taking inducers of CYP3A • With liver cirrhosis WARNINGS AND PRECAUTIONS QT Interval Prolongation: Ranolazine blocks IKr and prolongs the QTc interval in a doserelated manner. Clinical experience in an acute coronary syndrome population did not show an increased risk of proarrhythmia or sudden death. However, there is little experience with high doses (> 1000 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. Renal Failure Acute renal failure has been observed in some patients with severe renal impairment (creatinine clearance [CrCL] < 30 mL/min) while taking RANEXA. If acute renal failure develops (e.g., marked increase in serum creatinine associated with an increase in blood urea nitrogen [BUN]), discontinue RANEXA and treat appropriately. 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. ADVERSE REACTIONS Adverse Reactions from Clinical Trials 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 2,018 patients with chronic angina were treated with ranolazine in controlled clinical trials. Of the patients treated with RANEXA, 1,026 were enrolled in three double-blind, placebo-controlled, randomized studies (CARISA, ERICA, MARISA) of up to 12 weeks’ duration. In addition, upon study completion, 1,251 patients received treatment with RANEXA in open-label, long-term studies; 1,227 patients were exposed to RANEXA for more than 1 year, 613 patients for more than 2 years, 531 patients for more than 3 years, and 326 patients for more than 4 years. At recommended doses, about 6% of patients discontinued treatment with RANEXA because of an adverse event in controlled studies in angina patients compared to about 3% on placebo. The most common adverse events that led to discontinuation more frequently on RANEXA than placebo were dizziness (1.3% versus 0.1%), nausea (1% versus 0%), asthenia, constipation, and headache (each about 0.5% versus 0%). Doses above 1000 mg twice daily are poorly tolerated. In controlled clinical trials of angina patients, the most frequently reported treatment-emergent adverse reactions (> 4% and more common on RANEXA than on placebo) were dizziness (6.2%), headache (5.5%), constipation (4.5%), and nausea (4.4%). Dizziness may be dose-related. In open-label, long-term treatment studies, a similar adverse reaction profile was observed. The following additional adverse reactions occurred at an incidence of 0.5 to 4.0% in patients treated with RANEXA and were more frequent than the incidence observed in placebo-treated patients: Cardiac Disorders – bradycardia, palpitations Ear and Labyrinth Disorders – tinnitus, vertigo Eye Disorders – blurred vision Gastrointestinal Disorders – abdominal pain, dry mouth, vomiting, dyspepsia General Disorders and Administrative Site Adverse Events – asthenia, peripheral edema Metabolism and Nutrition Disorders – anorexia Nervous System Disorders – syncope (vasovagal) Psychiatric Disorders – confusional state Renal and Urinary Disorders – hematuria Respiratory, Thoracic, and Mediastinal Disorders – dyspnea Skin and Subcutaneous Tissue Disorders – hyperhidrosis Vascular Disorders – hypotension, orth