In this study, there was a significantly lower incidence of arrhyth- mias, including ventricular tachycardia, bradycardia, su- praventricular tachycardia, and new atrial fibrillation, in patients treated with ranolazine (80%) versus placebo Ranolazine does not require dose adjustment for age, sex, New York Heart Association class I IV heart failure, or diabetes mellitus. Plasma concentrations of ranolazine are increased by up to 50% in patients with Stage 4 CKD (creatinine clearance ,30 mL/min).892 The drug is contrain- dicated in patients with clinically significant hepatic impair- ment because of increased plasma concentrations and QT prolongation. In general, dosing in the elderly should start at the low end of the dosing range.883 Ranolazine is contraindicated in combination with potent inhibitors of the CYP3A4 pathway, including ketoconazole (3.2-fold increase in ranolazine plasma levels) and other azole antifungals, macrolide antibiotics, HIV (human immunodefi- ciency virus) protease inhibitors, grapefruit products or juice, diltiazem (1.8- to 2.3-fold increase in ranolazine plasma levels), itraconazole, clarithromycin, and certain HIV protease inhibi- tors. When administered with moderate inhibitors of CYP3A such as diltiazem, verapamil, aprepitant, erythromycin, flucona- zole, or grapefruit juice, the dose of ranolazine should be limited to 500 mg twice daily because of an approximately 2-fold increase in ranolazine plasma levels. No dose adjustment is required in patients treated with cimetidine or paroxetine. Co- administration of ranolazine (1000 mg twice daily) with simva- statin increases the plasma concentration of simvastatin and its active metabolite 2-fold. Digoxin plasma concentrations are increased 1.5-fold, but this interaction might not be clinically relevant with lower digoxin dosing (0.125 mg daily). Coadmin- istration of ranolazine with drugs that inhibit CYP2D6, with the exceptions of tricyclic antidepressants and some antipsychotics, does not require dosage adjustment. Ranolazine is well tolerated; the major adverse effects are constipation, nausea, dizziness, and headache. 