Reply to: “Torsade de Pointes Associated with High-dose Loperamide Ingestion”

DOI: 10.19102/icrm.2015.060402

JEANNA M. MARRAFFA, PharmD, Dabat, MICHAEL G. HOLLAND, MD, MICHAEL J. HODGMAN, MD

Upstate Medical University, Syracuse, New York, NY

KEYWORDS. Loperamide, drug abuse, QT prolongation, torsade de pointe.

The authors report no conflicts of interest for the published content.
Manuscript received January 30, 2015, final version accepted
March 16, 2015.

Address correspondence to: Jeanna M. Maffaffa, PharmD, DABAT,
Upstate Medical University, Syracuse, NY, E-mail: marraffj@upstate.edu

We read with great interest the recent article by Marzec et al.,¹ “Torsade de Pointes Associated with High-dose Loperamide.” Prescription opioid abuse is a major public health concern and an ongoing epidemic in the United States. According to the Centers for Disease Control and Prevention, unintentional poisoning is the leading cause of accidental death in the United States, with prescription opioid analgesics being most commonly involved.² To combat this epidemic, there have been numerous measures at both statewide and national levels to have tighter control on prescription opioid access and availability. Hydrocodone has recently been rescheduled to a Schedule II controlled substance. Pharmaceutical companies have changed their formulations of several sustained-release products to reduce their abuse potential and many states have implemented electronic prescription drug monitoring programs. These restrictions will likely lead to an increase in the use of illicit opioids such as heroin and the use of alternative pharmaceuticals. Loperamide, as Marzec et al.¹ point out, is widely available and inexpensive. At therapeutic doses, loperamide lacks central nervous system effects because of the P-glycoprotein efflux pump.³ Numerous online resources and blogs describe the abuse potential of loperamide. The combined use of a P-glycoprotein inhibitor such as quinine or quinidine, or just an excessive dose of loperamide, has been suggested to overcome the P-glycoprotein efflux pump.

We recently reported a case series comprising five patients and seven events of excessive doses of loperamide resulting in cardiac conduction abnormalities.⁴ Two of these five patients had torsade de pointes (TdP), and one of these patients has had several episodes of TdP and ventricular tachycardia after loperamide abuse. In addition to prolonged QT and TdP, some of our cases also exhibited prolongation of the QRS complex. All of our patients had resolution of their conduction abnormalities when loperamide was discontinued.⁴

These reports underscore the need for further investigation of the cardiac effects of high-dose loperamide. Further research into the mechanism of both QRS widening and QTc prolongation is warranted. Clinicians need to consider loperamide abuse in otherwise healthy patients with syncope or ventricular arrhythmias, especially those with a history of drug abuse or opioid dependence.

References

Marzec LN, Katz DF, Peterson PN, Thompson LE, Haigney MC, Krantz MJ. Torsade de pointes associated with high-dose loperamide ingestion. J Innov Cardiac Rhythm Manage 2015; 6:1897–1899. [CrossRef]
Centers for Disease Control and Prevention. Prescription painkiller overdoses. Available at: https://www.cdc.gov/vitalsigns/prescriptionpainkilleroverdoses/. Accessed: March 2015
Dufek MB, Knight BM, Bridges AS, Thakker DR. P-glycoprotein increases portal bioavailability of loperamide in mouse by reducing first-pass intestinal metabolism. Drug Metab Dispos 2013; 41:642–650. [CrossRef] [PubMed]
Marraffa JM, Holland MG, Sullivan RW, et al. Cardiac conduction disturbance after loperamide abuse. Clin Toxicol (Phila) 2014; 52:952–957. [CrossRef] [PubMed]