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