About Gilead’s Ranolazine Diabetes Program
TERISA is one of several Gilead studies evaluating the role of ranolazine in patients with chronic angina and/or type 2 diabetes. Results of a Phase 2 study and post-hoc analyses of previous clinical trials with ranolazine suggest that ranolazine may reduce HbA1c when added to antidiabetic therapy. Gilead is now conducting three Phase 3 clinical trials in patients with type 2 diabetes, which will determine the effects of ranolazine on glycemic control as monotherapy and in combination with other antidiabetic therapies. Top-line results from these three trials are expected in late 2013.
Ranolazine is an investigational medication for type 2 diabetes and has not been proven safe and efficacious for this indication.
About RanexaRanexa is an extended-release tablet approved as a treatment for chronic angina. Ranexa may be used in combination with beta-blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ACE inhibitors and angiotensin receptor blockers. Ranexa was approved in the United States in January 2006. In 2008, the U.S. Ranexa indication was updated to include first-line treatment for chronic angina. Ranexa at therapeutic levels can inhibit the cardiac late sodium current. However, the mechanism of Ranexa’s antianginal effects has not been determined. The relationship between the inhibition of the late sodium current and angina symptoms is uncertain. Important Safety Information Contraindications
- Ranexa is contraindicated in patients:
- Taking strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir)
- Taking inducers of CYP3A (e.g., rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, and St John’s wort)
- With liver cirrhosis
- Ranexa blocks lKr 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, with other QT-prolonging drugs, with 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.
- The most common adverse reactions (> 4% and more common than with placebo) during treatment with Ranexa were dizziness, headache, constipation, and nausea.
- Begin treatment with 500 mg twice daily and increase to the maximum recommended dose of 1000 mg twice daily, based on clinical symptoms. Swallow tablets whole; do not crush, break, or chew.
- Limit the dose of Ranexa to 500 mg twice daily in patients on moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products).
- Inducers and strong inhibitors of CYP3A: Do not use Ranexa (see Contraindications).
- Moderate CYP3A inhibitors: Limit Ranexa to 500 mg twice daily (see Dosage and Administration).
- P-gp inhibitors (e.g., cyclosporine): Ranexa exposure increased; titrate Ranexa based on clinical response.
- CYP3A substrates: Limit simvastatin to 20 mg when used with Ranexa. 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 Ranexa.
- Drugs transported by P-gp (e.g., digoxin) or metabolized by CYP2D6 (e.g., tricyclic antidepressants and antipsychotics): Doses of these drugs may need to be reduced.