Re: Dysrhythmias with Loperamide Used for Opioid Withdrawal

We read the article, “Dysrhythmias with Loperamide Used for Opioid Withdrawal” by Vithalani et al¹ with great interest. As they elegantly highlighted, the opioid abusing population is young and facile with access to Web-based resources. This has opened up multiple channels through which people around the globe can freely exchange drug or medication-related information, including the unlabeled use of medications to combat opioid withdrawal and to achieve an opioid “high.” Such user-generated content, which represents a rich source of unsolicited, unfiltered, and anonymous self disclosures of drug misuse from hard-to-reach populations of illicit drug users represent a promising avenue to study drug abuse trends.² In addition to the acute management highlighted in the article, a patient with loperamide induced QT prolongation may also benefit from a psychiatry and cardiology/electrophysiology consultation.

This bears import as such patients also tend to be concomitantly prescribed psychotropic medications for comorbid psychiatric conditions, many of which are known to cause QT prolongation.³ Sudden cessation of psychotropic medications can be deleterious with adverse psychiatric consequences. We recently managed a patient whose loperamide overdose was thought to have precipitated the salvoes of nonsustained polymorphic ventricular tachycardia captured on telemetry. It was discovered that this patient was misusing loperamide while also on QT prolonging psychotropic medications. Our psychiatry colleagues recommended medication adjustments that minimized ongoing exposure to QT prolonging psychotropic medications without incurring a risk of significant withdrawal.

Cardiology/electrophysiology service should also be consulted promptly. In addition to acute management of QT prolongation, drug-acquired long QT can represent a formefruste of congenital long QT syndrome. Compared with 4% of control population, patients with drug-induced QT prolongation have 10% to 12% incidence of congenital long QT syndrome mutations. Although genetic screening of the patient may be considered, Electrocardiogram (EKG) screening of first-degree family members has been recommended by the Heart Rhythm Society guidelines.⁴

Lastly, one of the most common reasons for withdrawal of medications from the market or abandonment of drug development relates to cardiac toxicity. Notably, terfenadine was pulled off the markets for similar concerns of cardiac toxicity with IKr blockade. New drugs are routinely screened for IKr blocking potential by the Food and Drug Administration (FDA).⁵ If the concern for loperamide related cardiac side effects continues to rise, there may need to be containment of access (for example, by moving it to behind the pharmacy counter) or consideration of removal from the market.

In summary, the opioid epidemic is propelling loperamide, once considered a benign over-the-counter medication, into a medication ripe for misuse. Online forums have become a new source of information for patients looking for alternate options to manage opioid withdrawal or achieve opioid-related euphoria. Case reports highlighting potentially life-threatening consequences of loperamide misuse are on the rise, highlighting the urgent need for widespread education of health care personnel about this concerning new trend. In addition, associations like cardiac toxicity with loperamide abuse in high-risk populations need to be borne in mind while assessing patients in clinic and emergency department visits where multidisciplinary team approach with primary care providers, cardiologists and psychiatrists can lend better care. Furthermore, recognition of this body of literature might also portend regulatory consequences.