Drug-induced acute pancreatitis: Pathophysiology, imaging, clinical pharmacology, and causality assessment: An evidence-informed narrative review

Background: Drug-induced acute pancreatitis (DIAP) is an uncommon but important adverse drug event. Diagnosis continues to be difficult due to the similarity of clinical, laboratory, and radiological findings to more common causes of acute pancreatitis such as gallstones, alcohol-induced pancreatitis, hypertriglyceridemia, hypercalcemia, pancreatic-biliary obstruction, cancer, infections, injuries and post-endoscopic retrograde cholangio-pancreatography (ERCP)-induced pancreatitis. Wrong diagnosis can result in repeated pancreatic injury on re-exposure or inappropriate termination of treatment.
Objective: This evidence-informed narrative review seeks to synthesize existing evidence about DIAP from pathophysiologic, radiologic, pharmacologic, and causality evaluation points of views, especially on clinical practice.
Methods: Structured literature search was carried out in PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Priority was placed on acute pancreatitis guidelines, updated Atlanta classifications, systematic reviews, evidence-based DIAP classifications, pharmacoepidemiologic and pharmacovigilance studies, cohorts, case-control studies, and case series with sufficient diagnostic and etiologic evidence.
Findings to note: DIAP should be understood as a diagnosis made using a probabilistic approach rather than a temporal association. Proposed mechanisms include direct acinar cell injury, mitochondrial injury, oxidative stress, immune mediated damage, microvascular ischemia, duct or sphincter involvement, and metabolic injury indirectly caused by the medicine. Even though various medicines have been associated with DIAP, the quality of evidence is highly variable. Imaging has an important role in ruling out causes and excluding biliary, ductal, structural, or malignant conditions.
Conclusion: Diagnosis of DIAP demands demonstration of pancreatitis, elimination of common causes, drug chronology, analysis of latency and rechallenge, evaluation of drug literature, patient susceptibility and multi-disciplinary opinion.