Acute pancreatitis (AP) is Characterized by acute inflammation of the pancreas and classified into interstitial Oedematous pancreatitis and necrotizing pancreatitis. Common clinical symptoms are upper abdominal pain, nausea, vomiting, fever, and elevated serum pancreatic enzymes. Although AP is mild to moderate in severity in the majority of patients, some develop persistent organ failure. The most frequent causes of AP are gallstones and excessive alcohol consumption. Drugs are responsible for 5% of AP incidents.

The vast majority of reported drug-induced AP cases may have an idiosyncratic character; the onset of drug-induced AP is thought to be immune mediated. Early diagnosis and discontinuation of the offending drug can reduce complications. Classically, there have been several studies on drugs inducing AP but little information about drugs that are most frequently responsible for AP in a real-world setting.

A recent publication (International Journal of Toxicology 2019, Vol. 38(6) 487-492), describes its Pharmacovigilance and report tools to screen for potential associations among adverse drug events. Identifying the drugs most frequently implicated in the occurrence of AP could improve prescribing practice.

Based on the Japanese Adverse Drug Event Report (JADER) database and based on the a spontaneous reporting database of the Pharmaceuticals and Medical Devices Agency (PMDA), the authors conducted a comprehensive nationwide overview of the risk of drug-induced AP and identification of drugs most frequently implicated in the occurrence of AP.

The mechanisms of drug-induced AP include pancreatic duct constriction, cytotoxic and metabolic effects, the accumulation of a toxic metabolite or intermediary, and hypersensitivity reactions.

1. Mainly, intrinsic drug toxicity and idiosyncratic reactions treated with drugs are involved in the pathogenesis of drug-induced AP. The mechanism of intrinsic drug toxicity is dose dependent, develops in the short term, and is consistent from person to person regarding the frequency of development.

2. Alternatively, idiosyncratic reactions are not dose dependent,are unpredictable, and the period of development depends on the person. Idiosyncratic reactions can be categorized into

   1. those secondary to hypersensitivity reactions: Hypersensitivity reactions tend to occur with a latency of within 1 month after exposure. When a patient is reexposed to a drug that caused hypersensitivity, the drug reaction is reproduced in a shorter time period than before.

   2. those caused by the accumulation of a toxic metabolite

   3. or an injurious intermediary substance.

In conclusion, analysis of real-world data suggests that the peak age at onset was in the 60s, the most frequent treatment period until AP was within 1 month. The highest incidence was noted in patients in their 60s, which is consistent with a study that there is an association between increased risk of AP and polypharmacy. the most implicated drug categories were corticosteroids and antivirals.

https://journals.sagepub.com/doi/full/10.1177/1091581819870717