Review
Drug-Induced Acute Pancreatitis: An Evidence-Based Review

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The diagnosis of drug-induced acute pancreatitis often is difficult to establish. Although some medications have been shown to cause acute pancreatitis with a large body of evidence, including rechallenge, some medications have been attributed as a cause of acute pancreatitis merely by a single published case report in which the investigators found no other cause. In addition, some medications reported to have caused acute pancreatitis have obvious patterns of presentation, including the time from initiation to the development of disease (latency). There also appear to be patterns in the severity of disease. After reviewing the literature, we have classified drugs that have been reported to cause acute pancreatitis based on the published weight of evidence for each agent and the pattern of clinical presentation. Based on our analysis of the level of evidence, 4 classes of drugs could be identified. Class I drugs include medications in which at least 1 case report described a recurrence of acute pancreatitis with a rechallenge with the drug. Class II drugs include drugs in which there is a consistent latency in 75% or more of the reported cases. Class III drugs include drugs that had 2 or more case reports published, but neither a rechallenge nor a consistent latency period. Class IV drugs were similar to class III drugs, but only 1 case report had been published. Our analysis allows an evidence-based approach when suspecting a drug as causing acute pancreatitis.

Section snippets

Identification and Classification of Drugs

A MEDLINE search (1955–2006) of the English language literature for all cases with acute pancreatitis revealed 1214 case reports that allowed classification of 120 drugs. Search terms included “pancreatitis” and “drug-induced” or “medication-induced,” “drug,” and “medication.” The search was confined to human studies. Relevant bibliographies were included. The latest search date was July 1, 2006. Pharmaceutical and Food and Drug Administration data were not used for this analysis.

All published

Results

Based on our analysis of the level of evidence, 4 classes of drugs could be identified (Table 1). Class I drugs includes medications in which at least 1 case report described a recurrence of acute pancreatitis with a rechallenge with the drug. Class I drugs were subdivided further into class Ia and class Ib. Class Ia drugs are the drugs in which all potential causes of acute pancreatitis such as gallstones, hypertriglyceridemia, alcohol, hypercalcemia, and other medications were ruled out as a

Discussion

Although uncommon, defining a drug as causing acute pancreatitis poses a challenge to clinicians. To provide an evidence-based review of the literature, we chose to analyze this area by studying the patterns of drug-induced injury in published case reports. These reports allow the critical analysis of published information provided by the physician investigators and the editors of the journal. We did not use data from pharmaceutical or Food and Drug Administration reports because, in general,

Conclusions

We have classified 120 drugs that have been implicated in the scientific literature as causing pancreatitis (Table 2). The drugs are categorized based on the weight of evidence favoring this association. Two pieces of evidence link certain drugs to acute pancreatitis; recurrence of pancreatitis with rechallenge (class I drug) and a consistent latency between ingestion of the drug and the development of pancreatitis (class II drug). The evidence linking the remainder of the drugs to pancreatitis

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