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Introduction: Loperamide is an over-the-counter antidiarrheal acting on peripheral µ-opioid receptors. At therapeutic doses, it is safe; however, at supratherapeutic doses, it crosses the blood-brain barrier and blocks cardiac sodium and potassium channels, causing severe cardiotoxicity, including prolonged QT intervals and Torsades de Pointes (TdP). Misuse of loperamide for opioid withdrawal or euphoria has increased, underscoring the need for clinician awareness of its cardiac risks. Description: A 42-year-old woman with opioid use disorder presented after ingesting approximately 240 mg of loperamide. She was found unresponsive and required intubation. Initial evaluation revealed severe QTc prolongation (689 ms), sinus tachycardia, metabolic acidosis, and aspiration pneumonia. Despite aggressive electrolyte replacement and intravenous magnesium, she experienced recurrent TdP episodes. Initiation of intravenous isoproterenol successfully suppressed arrhythmias by maintaining her heart rate above 90 bpm. Her QTc interval gradually normalized (459 ms), allowing cessation of isoproterenol. She was discharged safely on Suboxone therapy for Opioid Use Disorder. Discussion: Loperamide overdose leads to severe cardiac toxicity due to its potent blockade of sodium and hERG potassium channels, resulting in prolonged QT intervals and life-threatening TdP. Effective management includes prompt recognition, magnesium administration, isoproterenol infusion, and pacing for refractory arrhythmias. Treatment should also include opioid addiction management to prevent recurrence. Clinicians should maintain high suspicion for loperamide misuse in unexplained arrhythmias. Artificial intelligence was utilized to support the drafting of the abstract in the preparation of this case report.