Loperamide Cardiac Toxicity: Pathophysiology, Presentation, and Management

Loperamide is a nonprescription medication commonly used to treat diarrhea. Although it is an opioid, it is very poorly absorbed and well tolerated, with no systemic toxicity at standard doses. In recent years, however, loperamide has been ingested in very large quantities, sometimes with concomitant medications intended to enhance absorption and/or passage across the blood-brain barrier. Most people who misuse loperamide do so for its euphoric effects or to treat symptoms of opioid withdrawal. In addition to the risks of central opioid toxicity, this practice can result in potentially fatal cardiac dysrhythmias, because very high concentrations of loperamide alter the cardiac action potential. Patients will often present with recurrent, unexplained syncope accompanied with marked electrocardiographic abnormalities including QT-interval prolongation, widening of the QRS complex, and dysrhythmias such as torsades de pointes. Treatment involves early identification and discontinuation of loperamide, reversal of central opioid effects if present, and interventions aimed at addressing any cardiac conduction abnormalities. In addition, if there is an underlying opioid use disorder, efforts should be made to refer to specialised addictions care and initiate opioid agonist therapy when appropriate. We review the pharmacology of loperamide and the clinical presentation, pathophysiology, and suggested management of loperamide cardiac toxicity.