Oral LD50 is 185 mg/kg in rats.^L42780

Due to its actions on opioid receptors, loperamide has been misused and abused to self-manage opioid withdrawal symptoms and to induce euphoria.A251610, A251625 However, loperamide is associated with a risk of experiencing a range of adverse effects, often life-threatening, if taken for non-therapeutic reasons or at doses higher than the recommended dose.^L42790 Loperamide overdose can lead to a range of cardiac and non-cardiac effects. Chronic ingestion of doses ranging from 70 mg to 1600 mg daily - which is four to 100 times the recommended dose - resulted in life-threatening cardiac adverse reactions, including QT/QTc and QRS interval prolongation, Torsades de Pointes, Brugada syndrome and other ventricular arrhythmias, syncope, cardiac arrest, and death. These cases included instances of loperamide misuse and abuse. In case of cardiac effects, it is recommended that loperamide is discontinued and therapies to manage and prevent cardiac arrhythmias are initiated.^L42790 Cases of loperamide overdose may cause opioid toxic effects including CNS depression (e.g. altered mental status, stupor, coordination disorders, somnolence, miosis, muscular hypertonia, respiratory depression), hypotension, urinary retention, and paralytic ileus.^L42790 Naloxone may reverse the opioid-related toxicity, including CNS and respiratory depression, and hypotension, associated with loperamide overdosage.^L42790