Advertisement

Loperamide Abuse Associated With Cardiac Dysrhythmia and Death

      Loperamide is an over-the-counter antidiarrheal with μ-opioid agonist activity. Central nervous system opioid effects are not observed after therapeutic oral dosing because of poor bioavailability and minimal central nervous system penetration. However, central nervous system opioid effects do occur after supratherapeutic oral doses. Recently, oral loperamide abuse as an opioid substitute has been increasing among patients attempting to self-treat their opioid addiction. Ventricular dysrhythmias and prolongation of the QRS duration and QTc interval have been reported after oral loperamide abuse. We describe 2 fatalities in the setting of significantly elevated loperamide concentrations.
      To read this article in full you will need to make a payment
      ACEP Member Login
      ACEP Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Baker D.E.
        Loperamide: a pharmacological review.
        Rev Gastroenterol Disord. 2007; 7: S11-S18
        • 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: 11-19
        • 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 Depend. 2013; 130: 241-244
        • Marraffa J.M.
        • Holland M.G.
        • Sullivan R.W.
        • et al.
        Cardiac conduction disturbance after loperamide abuse.
        Clin Toxicol (Phila). 2014; 52: 952-957
        • MacDonald R.
        • Heiner J.
        • Villarreal J.
        • et al.
        Loperamide dependence and abuse.
        BMJ Case Rep. 2015;
        • Enakpene E.O.
        • Riaz I.B.
        • Shirazi F.M.
        • et al.
        The long QT teaser: loperamide abuse.
        Am J Med. 2015; 128: 1083-1086
        • Spinner H.L.
        • Lonardo N.W.
        • Mulamalla R.
        • et al.
        Ventricular tachycardia associated with high-dose chronic loperamide use.
        Pharmacotherapy. 2015; 35: 234-238
        • Eggleston W.
        • Nacca N.
        • Marraffa J.M.
        Loperamide toxicokinetics: serum concentrations in the overdose setting.
        Clin Toxicol (Phila). 2015; 53: 495-496
        • Naestoft J.
        • Larsen N.E.
        Quantitative determination of clonazepam and its metabolites in human plasma by gas chromatography.
        J Chromatogr. 1974; 93: 113-122
        • Pérez de los Cobos J.
        • Martin S.
        • Etcheberrigaray A.
        • et al.
        A controlled trial of daily versus thrice-weekly buprenorphine administration for the treatment of opioid dependence.
        Drug Alcohol Depend. 2000; 59: 223-233
        • Harris D.S.
        • Mendelson J.E.
        • Lin E.T.
        • et al.
        Pharmacokinetics and subjective effects of sublingual buprenorphine, alone or in combination with naloxone: lack of dose proportionality.
        Clin Pharmacokinet. 2004; 43: 329-340
        • Emerich D.F.
        • Snodgrass P.
        • Pink M.
        • et al.
        Central analgesic actions of loperamide following transient permeation of the blood brain barrier with Cereport (RMP-7).
        Brain Res. 1998; 801: 259-266
        • Ericsson C.D.
        • Johnson P.C.
        Safety and efficacy of loperamide.
        Am J Med. 1990; 88: 10S-14S
        • Korey A.
        • Zilm D.H.
        • Sellers E.M.
        Dependence liability of two antidiarrheals, nufenoxole and loperamide.
        Clin Pharmacol Ther. 1980; 27: 659-664
        • Fletcher P.
        • Steffen R.
        • DuPont H.
        Benefit/risk considerations with respect to OTC-descheduling of loperamide.
        Arzneimittelforschung. 1995; 45: 608-613
        • Jaffe J.
        • Kanzler M.
        • Green J.
        Abuse potential of loperamide.
        Clin Pharmacol Ther. 1980; 28: 812-819
        • Schinkel A.H.
        • Wagenaar E.
        • Mol C.A.
        • et al.
        P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs.
        J Clin Invest. 1996; 97: 2517-2524
        • Sadeque A.J.
        • Wandel C.
        • He H.
        • et al.
        Increased drug delivery to the brain by P-glycoprotein inhibition.
        Clin Pharmacol Ther. 2000; 68: 231-237
        • Harmer A.R.
        • Valentin J.-P.
        • Pollard C.E.
        On the relationship between block of the cardiac Na+ channel and drug-induced prolongation of the QRS complex.
        Br J Pharmacol. 2011; 164: 260-273
        • Berger S.I.
        • Ma’ayan A.
        • Iyengar R.
        Systems pharmacology of arrhythmias.
        Sci Signal. 2010; 3: ra30
        • Ekins S.
        • Balakin K.V.
        • Savchuk N.
        • et al.
        Insights for human ether-a-go-go-related gene potassium channel inhibition using recursive partitioning and Kohonen and Sammon mapping techniques.
        J Med Chem. 2006; 49: 5059-5071
        • Johansen S.S.
        • Jensen J.L.
        Liquid chromatography–tandem mass spectrometry determination of loperamide and its main metabolite desmethylloperamide in biological specimens and application to forensic cases.
        J Chromatogr B Analyt Technol Biomed Life Sci. 2004; 811: 31-36
        • Sklerov J.
        • Levine B.
        • Moore K.A.
        • et al.
        Tissue distribution of loperamide and N-desmethylloperamide following a fatal overdose.
        J Anal Toxicol. 2005; 29: 750-754
        • Mowry J.B.
        • Spyker D.A.
        • Brooks D.E.
        • et al.
        2014 Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 32nd annual report.
        Clin Toxicol (Phila). 2015; 53: 962-1147
        • Bronstein A.C.
        • Spyker D.A.
        • Cantilena L.R.
        • et al.
        2011 Annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 29th annual report.
        Clin Toxicol (Phila). 2012; 50: 911-1164