Researchers report first documented case of loperamide misuse linked with acute pancreatitis

Given loperamide's mu agonism, Christopher A. Bouvette, University of Oklahoma College of Medicine, Oklahoma City, Oklahoma, and colleagues suspected that supratherapeutic doses induce sphincter of Oddi dysfunction and predispose to pancreatitis.

Loperamide was originally listed as a Schedule II drug in 1977, since then, loperamide has been deregulated and became nonprescription in 1988. Loperamide misuse has mirrored the progression of America's opioid epidemic, most frequently presenting with cardiac complications.

Epidemiologic studies have shown increasing reports of loperamide misuse for euphoria or as a methadone equal. Misuse dysregulates cardiac myocytes and is often manifested by ventricular dysrhythmias.

The case concerns a 32-year-old man with an extensive history of gastric and duodenal ulcers presented to an outside facility with a 4-month history of fluctuating abdominal pain. Six years previously, the patient had multiple emergent laparotomies and antrectomy with Roux-en-Y gastrojejunostomy for penetrating duodenal ulcers related to nonsteroidal anti-inflammatory drug use.

Initially, he attributed current pain to his previous operations and dyspepsia, although 72 hours of 10/10 abdominal pain, weakness, and fatigue ultimately prompted presentation. He did not report recent abdominal trauma or instrumentation. His only active medication was scheduled omeprazole and as-needed acetaminophen. He reported no active alcohol, illicit drug use, or tobacco.

On arrival, the patient was normotensive and afebrile, and heart rates ranged from 45 to 55 beats/min. An electrocardiogram revealed transient episodes of asymptomatic bradycardia with a corrected QT interval of 577 milliseconds. Physical examination included midline abdominal wall surgical scars.

An abdominal/pelvic computed tomography scan revealed severe obstipation, acute pancreatitis, loculated peripancreatic/perigastric/left retroperitoneal fluid collections, and severe compression of the splenic vein with splenomegaly. The patient received supportive care for pancreatitis, including opioid analgesia and intravenous fluids.

There was a clinical improvement in the patient after endoscopic retrograde pancreatography. Autoimmune pancreatitis panel (IgG4) and genetic panel (CFTR, SPINK1, PRSS1, and CTRC) were sent and returned within normal limits. Upon further discussion with the patient, he disclosed taking up to 150 loperamide, 2 mg tablets, daily for the last 6 months.

It was suspected that these longstanding supratherapeutic loperamide doses may have led to sphincter Oddi dysfunction with resulting pancreatitis. Following stabilization, the patient was discharged to an inpatient substance misuse rehabilitation centre.

"We aim to provide an interesting hypothesis for this patient's presentation," the researchers wrote. "We hope to provide a heightened awareness of potential patterns of misuse."

"Furthermore, in patients with a clinical picture of opioid misuse, evidence of ventricular dysregulation, and now perhaps pancreatitis, providers may have heightened suspicion for loperamide misuse," they concluded.

Reference:

DOI: https://doi.org/10.7326/aimcc.2023.0874