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U.S. Department of Health and Human Services

Safety

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Ranexa (ranolazine) Extended-Release Tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- November 2008

 

The detailed view includes drug products with safety labeling changes to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, or PATIENT PACKAGE INSERT/MEDICATION GUIDE sections. Deletions or editorial revisions made to these sections are not included in this summary. Read about the new physician labeling format.


 

Summary View

 

Sections Modified

Summary of Changes to Contraindications and Warnings

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

  • QT Interval Prolongation

ADVERSE REACTIONS

  • Clinical Trials Experience (see highlighted text)
    • ...Doses above 1000 mg twice daily are poorly tolerated...
    • ...Dizziness may be dose-related...
    • The following additional adverse reactions occurred at an incidence of 0.5 to 2.0% in patients treated with Ranexa...
      • Cardiac Disorders
        • bradycardia
      • Vascular Disorders
        • hypotension
        • orthostatic hypotension
    • Other (<0.5%) but potentially medically important adverse reactions observed more frequently in Ranexa than placebo treatment...
    • A large clinical trial in acute coronary syndrome patients was unsuccessful in demonstrating a benefit for Renexa...
  • Laboratory Abnormalities
    • Ranexa produces small reductions in hemoglobin A1c...
    • Ranexa produces elevations of serum creatinine by 0.1 mg/dL, regardless of previous renal function...

DRUG INTERACTIONS

  • Effects of Ranolazine on Other Drugs
    • Initial Section
    • Drugs Metabolized by CYP3A
      • ...Dose adjustments of simvastatin are not required when Ranexa is co-administered with simvastatin.

USE IN SPECIFIC POPULATIONS

  • Pregnancy
    • In animal studies, ranolazine at exposures 1.5 (rabbit) to 2 (rat) times the usual human exposure...
  • Use in Patients with Hepatic Impairment
  • Use in Patients with Heart Failure

NONCLINICAL TOXICOLOGY

  • Carcinogenesis, Mutagenesis, Impairment of Fertility

PATIENT COUNSELING INFORMATION

  • Patients should be advised...
    • to inform their physician if they are receiving...P-gp inhibitors (e.g., cyclosporine)...

CONTRAINDICATIONS

Ranexa is contraindicated in patients:

  • Taking strong inhibitors of CYP3A [see Drug Interactions (7.1)]
  • Taking inducers of CYP3A [see Drug Interactions (7.1)]
  • With clinically significant hepatic impairment [see Use in Specific Populations (8.6)]

WARNINGS AND PRECAUTIONS

QT Interval Prolongation:

Ranolazine blocks IKr 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 (> 1000 mg twice daily) or exposure, other QT-prolonging drugs, or potassium channel variants resulting in a long QT interval.