Trade Names:Ranexa- Tablets, ER 500 mg- Tablets, ER 1,000 mg
Mechanism of action unknown. Ranolazine has antianginal and anti-ischemic effects that do not depend upon reductions in heart rate or BP.
T max is 2 to 5 h. Mean steady-state C max is 2,600 ng/mL (range, 400 to 6,100 ng/mL), and is usually attained within 3 days of twice-daily dosing. Bioavailability from oral solution is about 76%.
Protein binding is approximately 62%.
Extensively metabolized in the gut and the liver with less than 5% excreted unchanged. Primarily metabolized by CYP3A and, to a lesser extent, by CYP2D6.
Apparent terminal half-life is 7 h. Approximately 75% is excreted in the urine and 25% in the feces.
Plasma levels increase up to 50%.Hepatic Function Impairment
Increased plasma levels in patients with mild and moderate hepatic function impairment.
Treatment of chronic angina.
Patients taking strong CYP3A inhibitors; patients taking CYP3A inducers; clinically important hepatic function impairment.
PO 500 mg twice daily. May increase to 1,000 mg twice daily, based on symptoms (max, 2,000 mg/day).Dose ModificationAdults
PO Limit the max dosage to 500 mg twice daily in patients receiving diltiazem, verapamil, and other moderate CYP3A inhibitors. Down-titrate the dose based on clinical response in patients receiving P-glycoprotein inhibitors (eg, cyclosporine).
Store tablets at controlled room temperature (59° to 86°F).
Studies have not been conducted; however, ranolazine may inhibit metabolism of these agents, necessitating a decrease in dose of CYP2D6 substrates.Drugs metabolized by CYP3A (eg, simvastatin)
Plasma levels may be increased by ranolazine; however, dosage adjustments do not appear to be necessary.Drugs transported by P-glycoprotein (eg, digoxin)
Plasma levels may be elevated by ranolazine. Dosage adjustment may be needed.Inducers of CYP3A (carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine) and P-glycoprotein (eg, rifampin, St. John's wort)
Ranolazine plasma concentrations may be decreased. Avoid coadministration with ranolazine.Inhibitors of CYP2D6 (eg, paroxetine)
Ranolazine plasma concentrations may be increased. However, ranolazine dosage adjustment does not appear to be necessary.Moderate CYP3A inhibitors (eg, aprepitant, diltiazem, erythromycin, fluconazole, grapefruit juice or grapefruit-containing products, verapamil)
Ranolazine plasma concentrations may be increased. Limit the ranolazine dosage to 500 mg twice daily.P-glycoprotein inhibitors (eg, cyclosporine)
Ranolazine plasma concentrations may be increased. Down-titrate the ranolazine dose based on clinical response.Strong CYP3A inhibitors (eg, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir)
Ranolazine plasma concentrations may be increased. Coadministration with ranolazine is contraindicated.
None well documented.
Bradycardia, hypotension, orthostatic hypotension, palpitations (2% or less); dose-related QTc interval prolongation.
Dizziness, headache (6%).
Tinnitus, vertigo (2% or less).
Constipation (5%); nausea (4%); abdominal pain, dry mouth, vomiting (2% or less).
Leukopenia, pancytopenia, thrombocytopenia.
Dyspnea (2% or less).
Peripheral edema (2% or less).
Obtain baseline and follow-up ECGs to evaluate effects of ranolazine on QT interval. Monitor BP after initiating therapy in patients with severe renal function impairment.
Category C .
Safety and efficacy not established.
Use caution when selecting dose, usually starting at the lower end of the dosing range, reflecting the greater frequency of hepatic and renal function impairment and comorbidity.
Plasma concentrations may be increased up to 50%.
Plasma concentrations may increase in patients with mild and moderate hepatic function impairment by 30% and 60%, respectively. Contraindicated in patients with clinically significant hepatic function impairment.
Ranolazine prolongs the QTc interval in a dose-related manner. There is little experience with dosages above 1,000 mg twice daily, high exposure, other QT-prolonging drugs, or potassium channel variants resulting in a long QT interval.
Ranolazine has been reported to promote tumor formation and progression to malignancy in mice.
Confusion, diplopia, dizziness, nausea, paresthesia, syncope, vomiting.
Copyright © 2009 Wolters Kluwer Health.