Increased Risk of Acute Pancreatitis with Codeine Use in Patients with a History of Cholecystectomy

Background Codeine has a spasmodic effect on sphincter of Oddi and is suspected to cause acute pancreatitis in patients with a history of cholecystectomy. Aims To assess the association between codeine use and acute pancreatitis in patients with a previous cholecystectomy. Methods We conducted a retrospective nested case-control study using the 2005-2015 MarketScan (R) Commercial Claims and Encounters Database. The cohort included patients aged 18-64; cohort entry began 365 days after cholecystectomy. Odds ratios (ORs) and 95% CIs for acute pancreatitis hospitalization were estimated comparing use of codeine with non-use of codeine. In a secondary analysis, use of codeine was compared with an active comparator: use of non-steroidal anti-inflammatory drugs (NSAIDs). Results Of the 664,083 patients included in the cohort, 1707 patients were hospitalized for acute pancreatitis (incidence 1.1 per 1000 person-years) and were matched to 17,063 controls. Compared with non-use of codeine, use of codeine was associated with an increased risk of acute pancreatitis (OR 2.67; 95% CI 1.63, 4.36), particularly elevated in the first 15 days of codeine use (OR 5.37; 95% CI 2.70, 10.68). Compared with use of NSAIDs, use of codeine was also associated with an increased risk of acute pancreatitis (OR 2.64; 95% CI 1.54, 4.52). Conclusion Codeine is associated with an increased risk of acute pancreatitis in patients who have previously undergone cholecystectomy; greater clinician awareness of this association is needed.