LAUSR

Loperamide misuse is associated with cardiotoxicity when used to achieve euphoria or to ameliorate opiate withdrawal symptoms, usually in doses (50–300mg daily) far in excess of recommended doses and with loperamide levels that are substantially greater than the therapeutic range, which is 0.24–3.1 ng/ml [1]. We report loperamide associated Torsades de Pointes (TdP), in the context of complete heart block, at marginally supratherapeutic dosing with documented loperamide and metabolite levels lower than previously reported. A 64-year-old man presented to the emergency department with syncope after six months of episodic lightheadedness. He had treated chronic diarrhea from Crohn’s disease with loperamide – 20mg daily. His only additional medication was simvastatin. Over months preceding presentation he displayed bradycardia to 36 beats per minute (bpm), right bundle branch block and left anterior fascicular block on electrocardiogram (ECG), but normal Holter monitoring. Presenting vitals were: heart rate 34 bpm; blood pressure 146/82mmHg; respiratory rate 20; SpO2 98% on 2L nasal cannula; afebrile. Physical examination demonstrated only bradycardia, an occipital hematoma, and laceration. An ECG showed complete heart block and QTc of 523 milliseconds (msec) (Figure 1). The patient lost consciousness and cardiac monitoring displayed polymorphic ventricular tachycardia, which terminated spontaneously (Figure 2). Serum electrolytes, renal and liver function, thyroid-stimulating hormone, and troponin were normal. The patient received intravenous magnesium and a transvenous pacemaker. On arrival, the serum loperamide and N-desmethylloperamide levels were 8.2 ng/ml and 9.8 ng/ml, respectively. An ECG on day two showed a QTc of 580 msec (ventricularpaced). After permanent pacemaker placement, the patient was discharged without further complication. To obtain central nervous system mu-opioid effects, individuals may overdose to overcome poor oral bioavailability, occasionally resulting in serious cardiotoxicity and sometimes death [1]. Cardiotoxicity with therapeutic dosing is rare. Loperamide is a potent inhibitor of cardiac delayed-rectifier potassium channels and sodium channels [2]. Cardiotoxicity is typically arrhythmic, presenting with syncope, ventricular tachycardia or sudden death, in the context of QT and sometimes QRS prolongation. A 2017U.S. Food and Drug Administration advisory described cardiotoxicity with loperamide misuse to manage diarrhea, and with therapeutic dosing in 11 cases, but without confirmatory drug levels [3]. Prescription dosing is 16mg daily; 32mg dosing may be used to treat diarrhea from ileostomies and short bowel syndrome [4]. Serum loperamide levels of 32–210 ng/ml have been reported in other cases of life-threatening cardiotoxicity [1,5]. This case highlights the risk for QTc prolongation and TdP with only marginally