Ranolazine-Induced Confusion: Might Hurt More Than Angina

Abstract

SESSION TITLE: Student/Resident Case Report Poster - Cardiovascular Disease II SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Confusion and delirium in the hospitalized elderly patients are under-diagnosed medical emergencies associated with increased morbidity, mortality and health care expenditure. Ranolazine is an antianginal medication approved for chronic stable angina when symptoms persist despite using first line medications. This case highlights ranolazine as a cause of delirium in an elderly patient. CASE PRESENTATION: An 84-year-old man with coronary artery disease (CAD) and chronic exertional angina was admitted for management of NSTEMI. Home medications were aspirin, clopidogrel, rosuvastatin, metoprolol, tamsulosin, furosemide, insulin, lisinopril, isosorbide mononitrate and pantoprazole. Based on findings of cardiac catheterization it was decided to medically manage his CAD and angina. He was started on ranolazine extended release 500mg twice daily, as metoprolol dose could not be increased due to heart rate restriction. Next day, he was confused and inattentive. On exam, he was pain-free, afebrile, and breathing comfortably with normal oxygen saturation. He was lethargic, oriented to person and place but not time and had tactile hallucinations. There were no focal neurological deficits. Delirium was diagnosed based on Confusion Assessment Method algorithm. Blood work did not reveal any metabolic or electrolyte abnormalities. There was no hepatic dysfunction and creatinine clearance was around 50 mL/min/1.73m2. Urinalysis was not suggestive of infection. Computerized tomography ruled out brain hemorrhage. Ranolazine was the only medication added during this hospitalization and was a ‘probable’ cause of delirium based on the Naranjo adverse drug reaction algorithm (score of 6). Ranolazine was discontinued and within 24 hours his delirium improved and mental status returned to his baseline. DISCUSSION: Ranolazine is a relatively new medication that acts by selective inhibition of the myocardial late inward sodium channel. Common side effects are dizziness, constipation, nausea and headache, occurring more frequent in the elderly (>65 years). Neurological side effects were rarely reported in clinical studies and were dose dependent. The possibility of its action on neuronal sodium channels underlying the mechanism of neurological side effects has been hypothesized. To our best knowledge there were two other similar reports, but one patient had renal dysfunction and the other was on a medication that reduced the hepatic metabolism of ranolazine. In our patient without any hepatic dysfunction, delirium was noted with a lower dose of ranolazine. CONCLUSIONS: It is very important for clinicians to be aware of such neurological adverse effects, especially in elderly patients receiving higher doses and with coexisting renal or hepatic dysfunction, to prevent misdiagnosis and further complications. Reference #1: Mishra et al. A rare debilitating neurological adverse effect of ranolazine due to drug interaction with clarithromycin. Indian J Pharmacol. 2014;46:547-548. DISCLOSURE: The following authors have nothing to disclose: Srikanth Yandrapalli, Pratik Mondal, Venkat Lakshmi Kishan Vuddanda, Lakshmi Asritha Gollapudi, Deepthi Gandhiraj, Sachin Sule No Product/Research Disclosure Information