Loperamide toxicity: recommendations for patient monitoring and management

References

• Lee VR, Vera A, Alexander A, et al. Loperamide misuse to avoid opioid withdrawal and to achieve a euphoric effect: high doses and high risk. Clin Toxicol. 2019;57:175–180.
   PubMed Web of Science ®Google Scholar
• Abuse NI on D. Overdose Death Rates. [cited 2018 Dec 4]. Available from: https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates.
   Google Scholar
• Canada PHA of, Canada PHA of. National report: Apparent opioid-related deaths in Canada (released September 2018). aem. [cited 2018 Dec 4]. Available from: https://www.canada.ca/en/public-health/services/publications/healthy-living/national-report-apparent-opioid-related-deaths-released-september-2018.html.
   Google Scholar
• United Nations Office on Drugs and Crime, World Drug Report 2017. (ISBN: 978-92-1-148291-1, eISBN:978-92-1-060623-3, United Nations publication, Sales No. E.17.XI.6).
   Google Scholar
• Shee CD, Pounder RE. Loperamide, diphenoxylate, and codeine phosphate in chronic diarrhoea. Br Med J. 1980;280(6213):524.
   PubMed Web of Science ®Google Scholar
• Baker DE. Loperamide: A pharmacological review. Rev Gastroenterol Disord. 2007;7(SUPPL. 3):S11–S18.
   PubMedGoogle Scholar
• Reynolds IJ, Gould RJ, Snyder SH. Loperamide: blockade of calcium channels as a mechanism for antidiarrheal effects. J Pharmacol Exp Ther. 1984;231(3):628–632.
   PubMed Web of Science ®Google Scholar
• Kannan P, Brimacombe KR, Zoghbi SS, et al. N-desmethyl-Loperamide is selective for P-glycoprotein among three ATP-binding cassette transporters at the blood-brain barrier. Drug Metab Dispos. 2010;38(6):917.
   PubMed Web of Science ®Google Scholar
• Sadeque AJ, Wandel C, He H, et al. Increased drug delivery to the brain by P-glycoprotein inhibition. Clin Pharmacol Ther. 2000;68(3):231–237.
   PubMed Web of Science ®Google Scholar
• Seneca N, Zoghbi SS, Shetty HU, et al. Effects of ketoconazole on the biodistribution and metabolism of [11C]loperamide and [11C]N-desmethyl-loperamide in wild-type and P-gp knockout mice. Nuclear Med Biol. 2010;37(3):335–345.
   PubMed Web of Science ®Google Scholar
• Wu PE, Juurlink DN. Clinical review: loperamide toxicity. Ann Emerg Med. 2017;70(2):245–252.
   PubMed Web of Science ®Google Scholar
• Kim K-A, Chung J, Jung D-H, et al. Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol. 2004;60(8):575–581.
   PubMed Web of Science ®Google Scholar
• Swank KA, Wu E, Kortepeter C, et al. Adverse event detection using the FDA post-marketing drug safety surveillance system: Cardiotoxicity associated with loperamide abuse and misuse. J Am Pharma Assoc. 2017;57(2):S63–S67.
   PubMed Web of Science ®Google Scholar
• Bhutta TI, Tahir KI. Loperamide poisoning in children. Lancet. 1990;335(8685):363.
   PubMed Web of Science ®Google Scholar
• Litovitz T, Clancy C, Korberly B, et al. Surveillance of loperamide ingestions: an analysis of 216 poison center reports. J Toxicol: Clin Toxicol. 1997;35(1):11–19.
   PubMed Web of Science ®Google Scholar
• Mégarbane B, Alhaddad H. P-glycoprotein should be considered as an additional factor contributing to opioid-induced respiratory depression in paediatrics: the buprenorphine example. Br J Anaesthesia. 2013;110(5):842.
   PubMed Web of Science ®Google Scholar
• Minton NA, Smith PG. Loperamide toxicity in a child after a single dose. Br Med J (Clin Res Ed). 1987;294(6584):1383.
   PubMed Web of Science ®Google Scholar
• Daniulaityte R, Carlson R, Falck R, et al. I just wanted to tell you that loperamide WILL WORK”: A web-based study of extra-medical use of loperamide. Drug Alcohol Dependence. 2013;130(1-3):241–244.
   PubMed Web of Science ®Google Scholar
• Google Trends 2019. Google Trends. [cited 2018 Dec 4]. Available from: https://g.co/trends/FDVVW.
   Google Scholar
• Vakkalanka JP, Charlton NP, Holstege CP. Epidemiologic Trends in Loperamide Abuse and Misuse. Ann Emergency Med. 2017;69(1):73–78.
   PubMed Web of Science ®Google Scholar
• Powell JW, Presnell SE. Loperamide as a potential drug of abuse and misuse: fatal overdoses at the Medical University of South Carolina. J Forensic Sci. 2019.
   PubMed Web of Science ®Google Scholar
• Kang J, Compton DR, Vaz RJ, et al. Proarrhythmic mechanisms of the common anti-diarrheal medication loperamide: revelations from the opioid abuse epidemic. Naunyn-Schmiedeberg's Arch Pharmacol. 2016;389(10):1133–1137.
   Google Scholar
• Sheng J, Tran PN, Li Z, et al. Characterization of loperamide-mediated block of hERG channels at physiological temperature and its proarrhythmia propensity. J Pharmacol Toxicol Methods. 2017;88:109–122.
   PubMed Web of Science ®Google Scholar
• Vaz RJ, Kang J, Luo Y, et al. Molecular determinants of loperamide and N-desmethyl loperamide binding in the hERG cardiac K + channel. Bioorg Med Chem Lett. 2018;28(3):446–451.
   PubMed Web of Science ®Google Scholar
• Achilli T-M, McCalla S, Meyer J, et al. Multilayer spheroids to quantify drug uptake and diffusion in 3D. Mol Pharmaceutics. 2014;11(7):2071–2081.
   PubMed Web of Science ®Google Scholar
• Klein MG, Haigney MCP, Mehler PS, et al. Potent inhibition of hERG channels by the over-the-counter antidiarrheal agent loperamide. JACC. 2016;2(7):784–789.
   Google Scholar
• Olofinsan KA, Ajala‐Lawal RA, Ajiboye TO. Loperamide-induced cardiotoxicity in rats: Evidence from cardiac and oxidative stress biomarkers. J Biochem Mole Toxicol. 0(0):e22278.
   Google Scholar
• Eggleston W, Clark KH, Marraffa JM. Loperamide abuse associated with cardiac dysrhythmia and death. Ann Emerg Med. 2017;69(1):83–86.
   PubMed Web of Science ®Google Scholar
• Marraffa JM, Holland MG, Sullivan RW, et al. Cardiac conduction disturbance after loperamide abuse. Clin Toxicol. 2014;52(9):952–957.
   Web of Science ®Google Scholar
• Bishop-Freeman SC, Feaster MS, Beal J, et al. Loperamide-Related Deaths in North Carolina. J Anal Toxicol. 2016;40(8):677–686.
   PubMed Web of Science ®Google Scholar
• Eggleston W, Nacca N, Marraffa JM. Loperamide toxicokinetics: serum concentrations in the overdose setting. Clin Toxicol. 2015;53(5):495–496.
   PubMed Web of Science ®Google Scholar
• Olson KR. Activated charcoal for acute poisoning: one toxicologist’s journey. J Med Toxicol. 2010;6(2):190–198.
   PubMedGoogle Scholar
• Panchal AR, Berg KM, Kudenchuk PJ, et al. 2018 American Heart Association Focused Update on Advanced Cardiovascular Life Support Use of Antiarrhythmic Drugs During and Immediately After Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2018;138(23):e740–e749.
   PubMed Web of Science ®Google Scholar
• Enakpene EO, Riaz IB, Shirazi FM, et al. The long QT teaser: loperamide abuse. Am J Med. 2015;128(10):1083–1086.
   PubMed Web of Science ®Google Scholar
• Johnson D, Eppler J, Giesbrecht E, et al. Effect of multiple-dose activated charcoal on the clearance of high-dose intravenous aspirin in a porcine model. Ann Emerg Med. 1995;26(5):569–574.
   PubMed Web of Science ®Google Scholar