Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations

Dianna Wolfe; Salmaan Kanji; Fatemeh Yazdi; Pauline Barbeau; Danielle Rice; Andrew Beck; Claire Butler; Leila Esmaeilisaraji; Becky Skidmore; David Moher; Brian Hutton

doi:10.1371/journal.pone.0231883

Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations

PLoS One. 2020 Apr 17;15(4):e0231883. doi: 10.1371/journal.pone.0231883. eCollection 2020.

Authors

Dianna Wolfe¹, Salmaan Kanji^{1

2}, Fatemeh Yazdi¹, Pauline Barbeau¹, Danielle Rice¹, Andrew Beck¹, Claire Butler¹, Leila Esmaeilisaraji¹, Becky Skidmore¹, David Moher^{1

3}, Brian Hutton^{1

3}

Affiliations

¹ Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
² Department of Pharmacy, The Ottawa Hospital, Ottawa, Ontario, Canada.
³ School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Abstract

Objective: A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations.

Methods: A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency.

Results: Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis.

Discussion: Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations.

Registration: CRD42017060473.

Publication types

Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Acute Disease
Databases, Factual
Drug-Related Side Effects and Adverse Reactions
Humans
Pancreatitis / chemically induced
Pancreatitis / pathology*
Pharmaceutical Preparations / classification*

Substances

Pharmaceutical Preparations

Grants and funding

This work was supported by a team grant (awarded to authors DM and BH) from the Canadian Institutes of Health Research through the Drug Safety and Effectiveness Network (https://cihr-irsc.gc.ca/e/39389.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.