Drug-Induced Acute Pancreatitis in Adults: Focus on Antimicrobial and Antiviral Drugs, a Narrative Review
Angelo Del Gaudio et al
Acute pancreatitis (AP) is an acute inflammation of the pancreas caused by the activation of digestive enzymes in the pancreatic tissue. The main causes of AP are cholelithiasis and alcohol abuse; less commonly, it can be caused by drugs, with a prevalence of up to 5%. Causal associations between drugs and pancreatitis are largely based on case reports or case series with limited evidence. We reviewed the available data on drug-induced AP, focusing on antimicrobial drugs and antivirals, and discussed the current evidence in relation to the classification systems available in the literature. We found 51 suspected associations between antimicrobial and antiviral drugs and AP. The drugs with the most evidence of correlation are didanosine, protease inhibitors, and metronidazole. In addition, other drugs have been described in case reports demonstrating positive rechallenge. However, there are major differences between the various classifications available, where the same drug being assigned to different probability classes. It is likely that the presence in multiple case reports of an association between acute pancreatitis and a drug should serve as a basis for conducting prospective randomized controlled trials to improve the quality of the evidence.
acute pancreatitis; drug-induced acute pancreatitis; antimicrobial drugs
Acute pancreatitis (AP) is an acute inflammation of the pancreas resulting from intrapancreatic activation of digestive enzymes. This condition can lead to pancreatic necrosis, organ failure, and multiple organ dysfunction, with a mortality rate of 1–5% [1,2]. In addition, acute pancreatitis may be associated with significant short- and long-term morbidity, with recurrent symptoms and, in severe cases, exocrine and/or endocrine pancreatic failure . The diagnosis of AP requires the identification of two of the following criteria: (1) abdominal pain suggestive of pancreatitis, (2) serum amylase or lipase levels at least three times the upper normal limit, and (3) imaging findings consistent with pancreatitis on computed tomography (CT) or magnetic resonance imaging (MRI) [1,4,5]. It is clear that the first two criteria alone are sufficient for diagnosis; thus, imaging can be performed later to better identify complications of acute pancreatitis. AP can be classified into mild, moderate, and severe forms according to the Atlanta criteria .
Mild acute pancreatitis is not associated with local or systemic complications and often resolves within the first week. Usually, mild AP does not result in organ failure. It is the most common form. Moderate AP is associated with local complications or exacerbation of concomitant diseases; transient organ failure may occur. In contrast, severe acute pancreatitis is defined by persistent organ failure (i.e., organ failure > 48 h). Local complications include pancreatic and peripancreatic necrosis (sterile or infected), peripancreatic fluid collections, pseudocysts, and parietal necrosis (sterile or infected) . The main causes of AP are cholelithiasis and alcohol abuse, which account for more than 80% of cases [6,7]. Less commonly, it can also be caused by medications, with a prevalence ranging from 2 to 5.3% [3,7]. In this narrative review, we focused on the role of pharmacologic agents in causing acute pancreatitis, particularly antimicrobial and antiviral agents, considering the widespread use of these therapies and the absence of specific work on these types of drugs in the literature.