The antidiarrheal over-the-counter drug loperamide is increasingly being used to control opioid withdrawal or for opioid abuse. Taking many times above the normally recommended dose is dangerous with cardiovascular, respiratory, and neurological adverse events. Cytochrome P-450 (CYP)2C8, CYP3A, and P-glycoprotein inhibitors can increase the plasma and central nervous system concentrations and radically alter the risk profile of loperamide. Online forums suggest using over-the-counter metabolic enzyme blockers to enhance the effects. Public health options include switching over-the-counter loperamide to blister packs (the FDA-preferred method), making loperamide only available by prescription, or moving the product behind the pharmacy counter. Although naloxone may ameliorate the neurological and respiratory adverse events, it is ineffective at reversing loperamide-induced arrhythmias. Even magnesium might provide less efficacy in loperamide-induced Torsade de Pointes necessitating the use of cardiac pacing and electrical cardioversion.