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KRISTIN ZERUMSKY, PHARM.D., is Assistant Professor of Pharmacy Practice and Science, School of Pharmacy, University of Maryland, Baltimore. BRIAN F. MCBRIDE, PHARM.D., is Clinical Pharmacology Research Fellow, John A. Oates Institute for Experimental Therapeutics, Division of Clinical Pharmacology, School of Medicine, Vanderbilt University, Nashville, TN.

Address correspondence to Dr. McBride at the Division of Clinical Pharmacology, Vanderbilt University Medical Center, 2215B Garland Avenue, 1275 Light Hall/MRB IV, Nashville, TN 37232-0575 (brian.mcbride{at}vanderbilt.edu).

Purpose. A review of the pharmacology, pharmacokinetics, clinical trials, safety, and efficacy of ranolazine is presented. Summary. Ranolazine has recently been approved as adjunctive treatment for chronic stable angina (CSA). Data suggest that ranolazine exerts its antiischemic effect through antagonism of the late sodium current and other cardiac ion channels. Peak plasma levels of ranolazine have been observed two to five hours following repeated dosing and are unaffected by food. In placebo-controlled and active-controlled clinical trials conducted with ranolazine, ranolazine has been effective in the treatment of patients with CSA. One trial demonstrated that monotherapy with extended-release ranolazine was effective against angina and ischemia in patients with CSA. Ranolazine improved exercise duration and time to onset of angina. In a trial in which ranolazine was given in combination with atenolol, diltiazem, or amlodipine, ranolazine produced clinically significant improvement in exercise duration and reduced the incidence of anginal attacks compared with placebo. Another trial demonstrated that extended-release ranolazine 1000 mg given twice daily reduced mean weekly angina episodes in patients with chronic angina. Ranolazine is generally well tolerated. In clinical trials, adverse effects were seen more in the ranolazine groups than in the placebo groups. Conclusion. Despite a lack of mortality data, ranolazine has demonstrated its efficacy and safety, either as monotherapy or in combination with other antianginal agents, in the management of CSA. Patients who fail optimal therapy with standard-of-care antianginal agents are the best candidates for treatment with ranolazine. Index terms: Amlodipine; Angina; Atenolol; Blood levels; Cardiac drugs; Combined therapy; Diltiazem; Dosage; Drug interactions; Food; Mechanism of action; Pharmacokinetics; Ranolazine; Toxicity