A Rare Cause of Pancreatitis

Abstract

SESSION TITLE: Student/Resident Case Report Poster - Obstructive Lung Diseases SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Roflumilast, a selective phosphodiesterase-4 inhibitor, is a well tolerated medication in the prevention of chronic obstructive pulmonary disease (COPD) exacerbations in patients with moderate to severe COPD. Roflumilast has infrequently been described as a cause of pancreatitis. We present a patient with Roflumilast induced pancreatitis, which resolved after discontinuation. CASE PRESENTATION: A 59 year old male with GOLD III COPD, started on Roflumilast three weeks earlier, presented to the emergency department with acute onset epigastric pain associated with nausea and vomiting. Exam revealed a diaphoretic male in moderate distress with diminished breath sounds, and epigastric tenderness without rebound, or rigidity. Laboratory values include lipase of 24,289 unit/L with an elevation in amylase and total bilirubin, as well as a normal lipid and hepatitis profile and IgG4 level. Ultrasound noted gallbladder wall edema without stones or sludge. Computed tomography revealed pancreatic enlargement and fat stranding. Roflumilast was discontinued and supportive management, including intravenous fluids, anti-emetics and pain control were provided. Symptoms and elevated lab values resolved within one week of discontinuation. DISCUSSION: Roflumilast has an overall low incidence of adverse events. Compared to placebo, the incidence of severe adverse events was less in both the 500 mcg and 250 mcg treatment groups. With the most common adverse effect being diarrhea, Roflumilast is tolerated well in patients with moderate to severe COPD. However acute pancreatitis has been described in a small subset of patients. In one benefit-harm assessment, acute pancreatitis had an incidence rate of 0.077 per 1000 person-years. In a separate double blind placebo-controlled study, the incidence was equal to that of the placebo. While rare, the FDA does recognize pancreatitis as a possible severe gastrointestinal adverse effect. Of the patients who developed pancreatitis, increased mortality was noted in those receiving treatment doses of 500 mcg, suggesting a possible dose-dependent relationship on mortality from Roflumilast induced pancreatitis. While there is no proven mechanism for the cause, Roflumilast may cause pathology via duct constriction, accumulation of toxic metabolites or hypersensitivity. The associated elevation of cAMP, an intended effect within the lung parenchyma, may play a role in the side-effects experienced elsewhere in the body. CONCLUSIONS: Drug induced pancreatitis, though rare, is a potential fatal side effect of Roflumilast. While the incidence is low, the potential side effect and possible dose-related mortality relationship cannot be ignored. As with all new medications, a meticulous risk-benefit ratio should be analyzed and discussed before starting Roflumilast in all patients. Reference #1: Yu, T. et al. Benefits and Harms of Roflumilast in Moderate to Severe COPD.” Thorax 69.7 (2013):616-22 DISCLOSURE: The following authors have nothing to disclose: Noah Reisman, Lelia Logue, Saleem Shahzad No Product/Research Disclosure Information