Established Safety Profile

View information on Ranexa's safety profile below, including information on contraindications, warnings and precautions, adverse events, electrocardiographic safety data, and drug interactions.

Contraindications

• Do not use Ranexa with strong CYP3A inhibitors
  (eg, ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir).
• Do not use Ranexa with CYP3A inducers (eg, rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, and St. John’s wort).
• Do not use Ranexa in patients with significant hepatic impairment.

Warnings and precautions

• Ranexa blocks I_Kr and prolongs the QTc interval in a dose-related manner.
• Clinical experience did not show an increased risk of proarrhythmia or sudden death.
• 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.

Adverse events

• In controlled clinical trials of Ranexa, the most common adverse reactions during treatment with Ranexa (> 4% and more common than with 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 rate of discontinuation in controlled angina trials due to an adverse event was 6% for Ranexa and 3% for placebo.

Electrocardiographic safety data

• There were no apparent proarrhythmic effects in patients with acute coronary syndrome (ACS).
• In these high-risk patients, a large clinical trial was unsuccessful in demonstrating a benefit for Ranexa. Ranexa is not a treatment for ACS.

Drug interactions

• Limit maximum dose of Ranexa to 500 mg twice daily with moderate CYP3A inhibitors (eg, diltiazem, verapamil, aprepitant, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products).
• P-gp inhibitors (eg, cyclosporine): may need to lower the dose of Ranexa based on clinical response.
• Doses of drugs transported by P-gp (eg, digoxin) or metabolized by CYP2D6 (eg, tricyclic antidepressants and antipsychotics) may need to be reduced.

Hemodynamically neutral

• The anti-ischemic and antianginal effects of Ranexa do not depend upon reductions in heart rate or blood pressure. In controlled clinical trials Ranexa had minimal changes in mean heart rate (< 2 bpm) and systolic blood pressure
  (< 3 mm Hg).
  • Ranexa does not affect the rate-pressure product, a measure of myocardial work, at maximal exercise.
• The mechanism of action of ranolazine's antianginal effects has not been determined.
  • Ranexa at therapeutic levels can inhibit the cardiac late sodium current.
  • The relationship of this inhibition to angina symptoms is uncertain.