Omadacycline-Associated Pancreatic Injury: a Spectrum from Mild Interstitial to Recrudescent Pancreatitis with Pharmacovigilance Implications.

INTRODUCTION: Omadacycline is a novel aminomethylcycline antibiotic with an incompletely characterized safety profile, particularly regarding pancreatic toxicity. A single case of omadacycline-induced acute pancreatitis has been reported, yet multiple FDA Adverse Event Reporting System (FAERS) analyses have failed to detect a pancreatitis signal. We aimed to characterize the spectrum of omadacycline-associated pancreatic injury and to explore the pharmacovigilance implications of cases presenting with subtle or atypical imaging features. METHODS: We report three cases from an intensive care unit in which patients developed pancreatic enzyme elevation (> 3 × ULN) temporally associated with omadacycline. Alternative etiologies were systematically excluded. Causality was assessed using the Naranjo scale. A literature search of PubMed and Embase was also performed. RESULTS: All three patients exhibited predominant hyperlipasemia with CT-confirmed pancreatic injury spanning a severity spectrum. Case 1 (79F) showed lipase > 34 × ULN, peritoneal signs, and new pancreatic head enlargement with peripancreatic stranding (Naranjo 7); Case 2 (18M) had asymptomatic lipase elevation with diffuse glandular swelling and heterogeneous parenchymal density (Naranjo 5); Case 3 (73F) developed recrudescent focal pancreatitis during continued exposure, with tail involvement and perirenal fascial thickening (Naranjo 4). All improved after discontinuation. Common etiologies were excluded. The previously reported case showed an inverse pattern (imaging-dominant with mild enzyme elevation). Collectively, these four cases support upgrading omadacycline from Badalov Class IV to Class III. CONCLUSIONS: Omadacycline can cause a spectrum of pancreatic injury, from mild interstitial pancreatitis to recrudescent disease, with CT findings that may be unobtrusive and easily overlooked. This underrecognition likely contributes to underreporting, which may explain the absence of a FAERS pancreatitis signal. Clinicians should monitor lipase and amylase, maintain a low threshold for CT imaging when enzymes rise, and report suspected cases using specific MedDRA terms.