Notes from the Field: Cardiac Dysrhythmias After Loperamide Abuse — New York, 2008–2016

Abstract

Loperamide is an over-the-counter antidiarrheal with opioidreceptor agonist properties. Recommended over-the-counter doses (range = 2-8 mg daily) do not produce opioid effects in the central nervous system because of poor oral bioavailability and P-glycoprotein efflux* of the medication (1); recent reports suggest that large doses (50-300 mg) of loperamide produce euphoria, central nervous system depression, and cardiotoxicity (2-4). Abuse of loperamide for its euphoric effect or for selftreatment of opioid withdrawal is increasing (5). Cases of loperamide abuse reported to the Upstate New York Poison Center and New York City Poison Control Center were analyzed for demographic, exposure, clinical, and laboratory characteristics. Cases of intentional loperamide abuse reported to the National Poison Database System (NPDS) also were analyzed for demographic, dose, formulation, and outcome information.A New York case of loperamide abuse was defined as any call to the Upstate New York Poison Center or New York City Poison Control Center reporting intentional loperamide abuse during January 1, 2008-March 31, 2016. An NPDS loperamide abuse case was defined as any exposure reported to NPDS citing intentional loperamide abuse during January 1, 2008-March 31, 2016.Among the 22 New York loperamide abuse cases identified, 18 patients were male. Median patient age was 30 years (range = 19-48 years). Electrocardiogram abnormalities included QTc prolongation in 15 (68%) patients, QRS prolongation in nine (41%) patients, and ventricular dysrhythmia in eight (36%) patients. The average reported daily dose was 358 mg (range = 34-1,200 mg). Previous opioid abuse was reported by 15 patients, previous treatment with methadone or buprenorphine (a partial opioid agonist used to treat opioid addiction) by eight patients, and chronic abuse by 13 patients. Opioid withdrawal symptoms after cessation of loperamide were reported by nine patients. Serum loperamide concentrations were obtained from four patients and ranged from 77-210 ng/mL, representing 25-875 times the therapeutic range of 0.24-3.1 ng/mL (6).A total of 179 NPDS cases were identified, approximately half of which were reported after January 1, 2014 (Figure). Notes from the FieldAmong the 179 cases, 137 (77%) of the patients were male, the median patient age was 26 years (range = 7-87 years), and 154 (86%) were admitted to or treated in a health care facility. The average loperamide dose was 196.5 mg (range = 2-1,200 mg), and nearly all cases (95%) involved tablets or capsules. Cardiac conduction disturbances were reported in 24 (13%) patients, ventricular tachycardia or fibrillation in 16 (9%) patients, other dysrhythmias in 10 (6%) patients, and other electrocardiogram changes in five (3%) patients. Outcome was reported for 132 patients and was coded as moderate (pronounced or prolonged systemic symptoms, non-life threatening) or major (life-threatening symptoms or residual disability) for 66 patients (50%). Four (3%) deaths were reported.These cases support the reported ass...

Loperamide: A Readily Available but Dangerous Opioid Substitute

“…Although the elimination half‐life is approximately 11 hours, the FDA is aware that in gross overdoses, the terminal half‐life can be prolonged to 41 hours . Doubling the dose of loperamide approximately doubles the concentration from 0.24 ng/mL with 2 mg, 0.62 ng/mL with 4 mg, 1.2 ng/mL with 8 mg, and 3.1 ng/mL with 16 mg . The plasma protein binding of loperamide is about 95%…”

“…Case reports have described combining loperamide with OTC cimetidine, omeprazole, quinine, or grapefruit juice to boost the effect of the drug . These drugs might have CYP or P‐gp inhibitory effects that can make the effects of loperamide more dangerous …”

“…Gastrointestinal μ‐opioid receptor stimulation from loperamide reduces local acetylcholine and prostaglandin release, slowing peristalsis. When used as directed (2–8 mg OTC, 2–16 mg prescription), it has a strong safety profile because of its poor innate bioavailability, high first‐pass metabolism, and P‐glycoprotein (P‐gp) efflux that minimizes extraintestinal effects …”

“…As late as 2007, reviews of loperamide were still touting that it was free of abuse potential . However, in 2008 the National Poison Database System began to register the intentional use of loperamide therapy in the 50‐ to 300‐mg range for the purposes of attenuating opioid withdrawal symptoms or to experience opioid euphoric effects . The frequency of these cases has increased dramatically since then .…”

“…However, in 2008 the National Poison Database System began to register the intentional use of loperamide therapy in the 50‐ to 300‐mg range for the purposes of attenuating opioid withdrawal symptoms or to experience opioid euphoric effects . The frequency of these cases has increased dramatically since then . This article describes why patients are self‐medicating with very large loperamide doses, pharmacokinetic parameters of loperamide that can worsen the risk of adverse events, the most common adverse events that arise with excessive doses, possible public health solutions, and treatment recommendations for the adverse events.…”