1
|
Xie H, Jiang L, Peng J, Hu H, Han M, Zhao B. Drug-induced pancreatitis: a real-world analysis of the FDA Adverse Event Reporting System and network pharmacology. Front Pharmacol 2025; 16:1564127. [PMID: 40308779 PMCID: PMC12040929 DOI: 10.3389/fphar.2025.1564127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Accepted: 04/04/2025] [Indexed: 05/02/2025] Open
Abstract
Background Drug-induced pancreatitis is a rare disease but frequently reported, owing to the vast number of medications. Aim To summarize potential drugs causing pancreatitis and to speculate on underlying mechanisms. Methods We extracted more than 60,000 reports of pancreatitis submitted to the U.S. Food and Drug Administration Adverse Event Reporting System (January 2004 to March 2023). Data on patient age, sex, weight, time to onset, and outcome (death et al.) were collected. Disproportionality analysis was used in data mining to identify associations between drugs and pancreatitis events. Seven databases, commonly used for network pharmacology analysis, were searched to identify potential targets. Results Of 867 drugs with 3 or more reports, 101 drugs met all criteria using disproportionality analysis and indicated a potential risk of pancreatitis. The risk of 40 drugs had not been previously noted in "UpToDate" database. Patients taking the drugs had a similar sex distribution, were mostly 45-64 years old, and were heavier (median, 88 kg; P < 0.0001). The median time to onset was 199 days (interquartile range, 27-731.5). Ponatinib (16.48%), tigecycline (14.12%) and valproic acid (13.41%) had higher fatality rates. Potential targets related to pancreatitis were identified in 50 of the 101 drugs. Conclusion Clinicians providing the 101 drugs for treatment should stay vigilant to detect pancreatitis early.
Collapse
Affiliation(s)
- Hao Xie
- Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Lin Jiang
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Junya Peng
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Haoyang Hu
- West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Meifen Han
- Department of Pharmacy, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Bin Zhao
- Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| |
Collapse
|
2
|
El Ouardi W, Benazzouz M. Acute Pancreatitis: An Unusual Side Effect of Adalimumab in Crohn's Disease Patient. CLINICAL MEDICINE INSIGHTS-CASE REPORTS 2025; 18:11795476251315000. [PMID: 39850596 PMCID: PMC11755513 DOI: 10.1177/11795476251315000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 12/20/2024] [Indexed: 01/25/2025]
Abstract
Background Drug-induced acute pancreatitis is a rare condition occurs at an incidence rate of 0.1-1.4% and represents a diagnostic challenge. TNFα inhibitors specially adalimumab is very rarely reported in the literature, primarily through case reports, as a potential cause of acute pancreatitis. Case presentation Our case report presents a case of a 23-year-old patient followed for Crohn disease in whom a diagnosis of acute pancreatitis induced by adalimumab was made. This diagnosis was confirmed after the elimination of other possible etiologies, and notably by the recurrence of pancreatitis after Adalimumab rechallenge. The occurrence of acute pancreatitis induced by TNFα inhibitors exposes to the risk of pancreatitis with other drugs in this class, hence the need to switch to another therapeutic class, which was Ustekinumab in our case. Conclusion Acute pancreatitis is an unusual complication of treatment with Adalimumab. Through our experience, based on solid scientific data, we want to draw the attention of clinicians to the reality of this complication. It should be considered in any patient on TNFα inhibitors who presents with acute pancreatitis without an obvious cause.
Collapse
Affiliation(s)
- Walid El Ouardi
- Resident in Gastroenterology, Faculty of Medicine and Pharmacy, Rabat, Morocco
| | - Mustapha Benazzouz
- Department of Gastroenterology, International University of Rabat/Riad Annakhil International Polyclinic, Rabat, Morocco
| |
Collapse
|
3
|
Akyildiz M, Geygel NC, Burhan EH, Gulumsek E, Avci BS, Ozturk HA, Arici FN, Bankir M, Saler T, Sumbul HE. Midostaurin-Associated acute pancreatitis. J Oncol Pharm Pract 2024:10781552241304755. [PMID: 39635990 DOI: 10.1177/10781552241304755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/07/2024]
Abstract
INTRODUCTION The multikinase inhibitor midostaurin is the first targeted drug for the treatment of AML FLT3. It reduces mortality by 23% more than standard chemotherapy group. Although it has many gastrointestinal side effects, there is no data in the literature regarding its association with acute pancreatitis. We wanted to present an acute pancreatitis case that developed after midostaurin treatment in our clinic. CASE REPORT A patient with AML FLT3 who developed abdominal pain, elevated amylase-lipase enzymes and increased volume around the pancreas on abdominal imaging after the addition of midostaurin to chemotherapy was hospitalized with a prediagnosis of acute pancreatitis. MANAGEMENT & OUTCOME Oral feeding was stopped, intravenous hydration was provided and anti-symptomatic treatment was given. The patient was discharged on the 4th day of hospitalization after the acute pancreatitis clinic resolved. DISCUSSION Drug induced acute pancreatitis is a rare clinical condition which is difficult to diagnose. It has a good prognosis and low mortality rate. The mechanisms of drug-induced pancreatitis include immunological reactions, direct toxic effect, accumulation of toxic metabolites, overstimulation of pancreatic acinar cells, ischemia, intravascular thrombosis and increased viscosity of pancreatic secretion. Although there are many gastrointestinal side effects of midostaurin, there are no clear data in the literature regarding the relationship with acute pancreatitis.
Collapse
Affiliation(s)
- Mert Akyildiz
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| | - Nebi Cankat Geygel
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| | - Esma Hazal Burhan
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| | - Erdinc Gulumsek
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| | - Begum Seyda Avci
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| | - Huseyin Ali Ozturk
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| | - Fatih Necip Arici
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| | - Mehmet Bankir
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| | - Tayyibe Saler
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| | - Hilmi Erdem Sumbul
- Department of Internal Medicine, University of Health Sciences - Adana Health Practice and Research Center, Adana, Turkey
| |
Collapse
|
4
|
Lin W, Zheng Q, Wang X, Lin X, Ni X, Pan J, Zippi M, Fiorino S, Hong W. The causality between use of glucocorticoids and risk of pancreatitis: a Mendelian randomization study. Front Immunol 2024; 15:1420840. [PMID: 39221257 PMCID: PMC11363070 DOI: 10.3389/fimmu.2024.1420840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 07/29/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND AND AIM To date, the association between glucocorticoid use and the risk of pancreatitis remains controversial. The aim of this study was the investigation of this possible relationship. METHODS We carried out a two-sample Mendelian randomization (MR) analysis using GWAS data from European ancestry, East Asian descendants and the FinnGen Biobank Consortium to evaluate this potential causal relationship. Genetic variants associated with glucocorticoid use were selected based on genome-wide significance (p < 5×10-8). RESULTS Our MR analysis of European ancestry data revealed no significant causal relationship between glucocorticoid use and AP (IVW: OR=1.084, 95% CI= 0.945-1.242, P=0.249; MR-Egger: OR=1.049, 95% CI= 0.686-1.603, P=0.828; weighted median: OR=1.026, 95% CI= 0.863-1.219, P=0.775) or CP (IVW: OR=1.027, 95% CI= 0.850-1.240, P=0.785; MR-Egger: OR= 1.625, 95% CI= 0.913-2.890, P= 0.111; weighted median: OR= 1.176, 95% CI= 0.909-1.523, P= 0.218). Sensitivity analyses, including MR-Egger and MR-PRESSO, indicated no evidence of pleiotropy or heterogeneity, confirming the robustness of our findings. Multivariable MR analysis adjusted for alcohol consumption, BMI, cholelithiasis and C-reactive protein levels supported these findings. Replicated analysis was performed on datasets from the FinnGen Biobank Consortium and East Asian descendants, and similar results were obtained. CONCLUSIONS This MR analysis suggests that there is no causal association between glucocorticoid use and the risk of pancreatitis.
Collapse
Affiliation(s)
- Wenfeng Lin
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Qiqi Zheng
- Department of Infection and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaorong Wang
- Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaolu Lin
- Department of Digestive Endoscopy Center, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou, Fujian, China
| | - Xixi Ni
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jingye Pan
- Department of Intensive Care Unit, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome, Italy
| | - Sirio Fiorino
- Unit of Internal Medicine, Budrio Hospital, Local Health Unit of Bologna, Bologna, Italy
| | - Wandong Hong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| |
Collapse
|
5
|
Wilhite K, Reid JM, Lane M. Risk of Pancreatitis With Incretin Therapies Versus Thiazolidinediones in the Veterans Health Administration. Ann Pharmacother 2024; 58:685-689. [PMID: 37881914 DOI: 10.1177/10600280231205490] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2023] Open
Abstract
BACKGROUND Incretin therapies, comprised of the dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have been increasingly utilized for the treatment of type 2 diabetes (T2DM). Previous studies have conflicting results regarding risk of pancreatitis associated with these agents-some suggest an increased risk and others find no correlation. Adverse event reporting systems indicate that incretin therapies are some of the most common drugs associated with reports of pancreatitis. OBJECTIVES This study aimed to compare the odds of developing pancreatitis in veterans with T2DM prescribed an incretin therapy versus thiazolidinediones (TZDs: pioglitazone and rosiglitazone) within the Veterans Health Administration (VHA). METHODS This was a retrospective cohort study analyzing veterans with T2DM first prescribed an incretin therapy or a TZD between January 1, 2011, and December 31, 2021. A diagnosis of pancreatitis within 365 days of being prescribed either therapy was counted as a positive case. Data was collected and analyzed utilizing VA's Informatics and Computing Infrastructure (VINCI) and an adjusted odds ratio was calculated. RESULTS The TZD cohort consisted of 42 912 patients compared with the incretin cohort of 304 811 patients. The TZD cohort had a pancreatitis incidence rate of 1.94 cases per 1000 patients. The incretin cohort had a incidence rate of 2.06 cases per 1000 patients. An adjusted odds ratio found no statistical difference of pancreatitis cases between the TZD and incretin cohorts (adjusted odds ratio [AOR] = 0.94, 95% CI [0.75, 1.18]). CONCLUSION AND RELEVANCE This retrospective cohort study of national VHA data found a relatively low incidence of pancreatitis in both cohorts, and an adjusted odds ratio found no statistical difference of pancreatitis in patients prescribed an incretin therapy compared with a control group. This data adds to growing evidence that incretin therapies do not seem to be associated with an increased risk of developing pancreatitis.
Collapse
Affiliation(s)
- Kristen Wilhite
- Department of Pharmacy, Veterans Affairs Medical Center, Louisville, KY, USA
| | - Jennifer Meyer Reid
- Department of Pharmacy, Veterans Affairs Health Care System, Lexington, KY, USA
| | - Matthew Lane
- Department of Pharmacy, Veterans Affairs Health Care System, Lexington, KY, USA
| |
Collapse
|
6
|
Zhou Z, Yao X. Safety assessment of dapagliflozin: Real-world adverse event analysis based on the FAERS database from 2012 to 2023. Heliyon 2024; 10:e33306. [PMID: 39022025 PMCID: PMC11253505 DOI: 10.1016/j.heliyon.2024.e33306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 07/20/2024] Open
Abstract
Background Dapagliflozin possesses the capacity to cure a wide range of diseases, however, there are many adverse events (AEs) that have not yet been acknowledged or recorded. Aim Safety assessment of dapagliflozin based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to explore differences between the reported AEs to provide a overview of the safety profile of dapagliflozin. Methods We extracted data from the United States FAERS database, including from the fourth quarter of 2012 to the third quarter of 2023. Reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric average (EBGM) were used to evaluate the relationship between dapagliflozin and its associated AEs. Results A total of 13,593,946 case reports were gathered from the Food and Drug Administration Adverse Event Reporting System database for this investigation. Among these, there were 44,506 episodes of adverse events that were associated with dapagliflozin. Included in the analysis were 341 preferred words and 2 system organ classes that showed statistical significance according to all four methods simultaneously. The system organ classes encompassed illnesses related to metabolism and nutrition, as well as problems affecting the renal and urinary systems. PT levels were screened for adverse drug reaction signals including scrotal gangrene, scrotal cellulitis, perineal cellulitis, diabetic ketoacidosis, and pancreatitis. Conclusion The majority of our findings aligned with the specification, however, certain novel indicators of AEs such as acute pancreatitis were not accounted for. The analysis of the AE signals may provide support for clinical monitoring and risk identification of dapagliflozin. Due to the inherent limitations of FAERS data, well-designed studies are required to demonstrate the safety of dapagliflozin.
Collapse
Affiliation(s)
- Zhengxi Zhou
- Department of Urology, Ningbo Mingzhou Hospital, Zhejiang, China
| | - Xiaotian Yao
- The Division of Nephrology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| |
Collapse
|
7
|
Issa P, Agapakis D, Machaira K, Ioannis K, Kotronis G. Dapagliflozin-Induced Acute Pancreatitis: A Case Presentation and Review of the Literature. Cureus 2024; 16:e62757. [PMID: 39036218 PMCID: PMC11260201 DOI: 10.7759/cureus.62757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/19/2024] [Indexed: 07/23/2024] Open
Abstract
Acute pancreatitis has been considered a rare potential adverse effect of sodium-glucose co-transporter-2 inhibitors (SGLT-2is), a new class of medications recently approved for use as an add-on therapy in patients with poorly controlled type 2 diabetes mellitus as well as in individuals with heart failure (HF) and chronic kidney disease (CKD). SGLT-2i can effectively reduce cardiovascular mortality and the deterioration of renal function. There are only a few published cases of acute pancreatitis linked to SGLT-2i administration. Our case describes a 58-year-old male who presented to the emergency department with a clinical presentation of acute pancreatitis, with no known risk factors, who was recently started on therapy with dapagliflozin. Following thorough clinical and laboratory testing, the diagnosis of pancreatitis was associated with dapagliflozin. Upon discharge, dapagliflozin was discontinued with no further recurrence of epigastric pain.
Collapse
Affiliation(s)
- Panagiota Issa
- Department of Internal Medicine, Aghios Pavlos General Hospital, Thessaloniki, GRC
| | - Dimitrios Agapakis
- Department of Internal Medicine, Aghios Pavlos General Hospital, Thessaloniki, GRC
| | - Konstantina Machaira
- Department of Internal Medicine, Aghios Pavlos General Hospital, Thessaloniki, GRC
| | - Karageorgiou Ioannis
- Department of Internal Medicine, Aghios Pavlos General Hospital, Thessaloniki, GRC
| | - Georgios Kotronis
- Department of Internal Medicine, Aghios Pavlos General Hospital, Thessaloniki, GRC
- Diabetes Clinic, Aghios Pavlos General Hospital, Thessaloniki, GRC
| |
Collapse
|
8
|
Fazeli Farsani S, Iglay K, Zhang L, Niyonkuru C, Nessralla L, Girman CJ. Risk of acute pancreatitis among new users of empagliflozin compared to sulfonylureas in patients with type 2 diabetes: A post-authorization safety study. Pharmacoepidemiol Drug Saf 2024; 33:e5800. [PMID: 38719731 DOI: 10.1002/pds.5800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 02/01/2024] [Accepted: 04/04/2024] [Indexed: 06/09/2024]
Abstract
PURPOSE This study was undertaken to evaluate the potential risk of acute pancreatitis with empagliflozin in patients with type 2 diabetes (T2D) newly initiating empagliflozin. METHODS Data from two large US claims databases were analyzed in an observational study of patients with T2D receiving metformin who were newly prescribed empagliflozin versus sulfonylurea (SU). Because dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have been associated with the risk of acute pancreatitis in some studies, patients on these agents were excluded. Using pooled analyses of data from the two databases (2014-2021), patients initiating empagliflozin were matched 1:1 within database to patients initiating SU using propensity scores (PS) that incorporated relevant demographic and clinical characteristics. Prespecified sensitivity analyses were performed for design parameters. RESULTS The analyses identified 72 661 new users of empagliflozin and 422 018 new users of SUs, with both patient groups on concurrent metformin therapy. Baseline characteristics within treatment groups appeared to be similar across the 72 621 matched pairs. After mean follow-up of ~6 months, incidence rates of acute pancreatitis in the pooled matched cohort were 10.30 (95% confidence interval [CI] 9.29-11.39) events per 1000 patient-years (PY) for empagliflozin and 11.65 (95% CI 10.59-12.77) events per 1000 PY for SUs. On a background of metformin, patients newly initiating empagliflozin did not have an increased risk of acute pancreatitis compared with those initiating an SU (pooled PS matched hazard ratio 0.88 [0.76-1.02]) across 75621.42 PY of follow-up. CONCLUSIONS The results of this voluntary post-approval safety study provide additional evidence that the use of empagliflozin for the treatment of T2D is not associated with an increased risk of acute pancreatitis.
Collapse
Affiliation(s)
| | - Kristy Iglay
- Real World Evidence and Patient Outcomes, CERobs Consulting, LLC, Wrightsville Beach, North Carolina, USA
| | - Ling Zhang
- Global Integrated Evidence, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA
| | - Christian Niyonkuru
- Global Integrated Evidence, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA
| | - Laurieann Nessralla
- Global Patient Safety and Pharmacovigilence, Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, Connecticut, USA
| | - Cynthia J Girman
- Real World Evidence and Patient Outcomes, CERobs Consulting, LLC, Wrightsville Beach, North Carolina, USA
| |
Collapse
|
9
|
Zhu C, Wu H, Yang X, Gao J. The outcomes of COVID-19 and acute pancreatitis: a systematic review and meta-analysis. Transl Gastroenterol Hepatol 2024; 9:6. [PMID: 38317749 PMCID: PMC10838611 DOI: 10.21037/tgh-23-58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 11/16/2023] [Indexed: 02/07/2024] Open
Abstract
Background Coronavirus disease 2019 (COVID-19) was first reported in China at the end of 2019. Several case studies have documented a probable association between infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and acute pancreatitis (AP). The objective of this study was to provide a complete analysis of existing literature that compares the clinical outcomes of AP in patients with COVID-19 and those without COVID-19. The intention was to further our understanding of the involvement of SARS-CoV-2 in the development of pancreatitis. Methods Between January 2019 and December 2022, we searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus. Nine studies (3,160 patients) were included. In this meta-analysis, Stata 12.0. was utilized. The information provided in this study is presented following the MOOSE reporting checklist. Results Mortality [odds ratio (OR) =3.95, 95% confidence interval (CI): 2.87, 5.43, P<0.001], intensive care unit (ICU) administration (OR =3.74, 95% CI: 2.26, 6.20, P<0.001), mechanical ventilation (OR =4.84, 95% CI: 2.14, 10.96, P<0.001), severe pancreatitis (OR =2.71, 95% CI: 1.04, 7.04, P=0.042), etiology of idiopathic and unknown (OR =4.75, 95% CI: 1.80, 12.56, P=0.002), necrotizing pancreatitis (OR =1.88, 95% CI: 1.28, 2.76, P=0.001), and length of hospital stay [weighted mean difference (WMD) =5.10, 95% CI: 2.79, 7.41, P<0.001] were more significantly increased in AP cases with COVID-19 than those without it. Conclusions In conclusion, the findings of this study indicate a potential worsening of AP outcomes in patients affected by COVID-19.
Collapse
Affiliation(s)
- Caiyu Zhu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Haijuan Wu
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiangyu Yang
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jian Gao
- Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| |
Collapse
|
10
|
Haddadin R, Tonna RF, Iqbal H, Valenta J, Iraninezhad H. A Rare Case of Sodium-Glucose Cotransporter-2 Inhibitor-Induced Acute Pancreatitis. Cureus 2023; 15:e49369. [PMID: 38146577 PMCID: PMC10749287 DOI: 10.7759/cureus.49369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2023] [Indexed: 12/27/2023] Open
Abstract
Acute pancreatitis is an acute inflammatory process of the pancreas that requires hospital admission and treatment. There are many causes of pancreatitis, the most common being gallstone and alcohol-induced; other reasons include metabolic, infectious, and medication-induced. A new medication that has come to the market is empagliflozin, which is a sodium-glucose cotransporter-2 inhibitor that is common in managing type 2 diabetes mellitus and congestive heart failure. Although generally considered safe and effective, rare adverse effects have been reported. In this case, we present a 67-year-old female patient who presented with severe acute pancreatitis after two weeks of starting empagliflozin to treat her type 2 diabetes. This case report highlights the importance of considering rare adverse events associated with empagliflozin and the need for close monitoring of patients receiving this medication.
Collapse
Affiliation(s)
| | - Roger F Tonna
- Internal Medicine, MountainView Hospital, Las Vegas, USA
| | - Humzah Iqbal
- Internal Medicine, University of California San Francisco, Fresno, Fresno, USA
| | - Jordan Valenta
- Internal Medicine, MountainView Hospital, Las Vegas, USA
| | | |
Collapse
|
11
|
Ebhohon E, Khoshbin K, Shaka H. Rates and predictors of 30-day hospital readmissions in adults for drug-induced acute pancreatitis: A retrospective study from the United States National Readmission Database. J Gastroenterol Hepatol 2023; 38:1277-1282. [PMID: 36914611 DOI: 10.1111/jgh.16177] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 02/27/2023] [Accepted: 03/08/2023] [Indexed: 03/16/2023]
Abstract
BACKGROUND AND AIM Drug-induced acute pancreatitis (DIAP) linked to several medications is a diagnosis of exclusion and is associated with significant morbidity and mortality, contributing to the US healthcare cost burden. Existing studies on DIAP focus on the drug classes that can cause acute pancreatitis. Hence, our retrospective study aims to determine the rates and predictors for 30-day readmissions (30-DR) in patients with index hospitalization for DIAP. METHODS From the Nationwide Readmissions Database, we followed adults admitted for DIAP who were discharged alive for 30 days. During 30-DR, we evaluated the rates, predictors, and outcomes of DIAP. RESULTS Of the 4457 DIAP patients surviving at discharge, 12.5% were readmitted at 30 days. During readmissions, the predictors of 30-DR for DIAP were young age, the Charlson-Deyo Comorbidity Index of 2 and 3, protein-energy malnutrition, and dyslipidemia. During 30-DR, DIAP had a higher mortality rate (2.4% vs. 0.7%; P < 0.020), extended hospital stays (5.6 days vs. 4 days, 0.000), and higher hospital charges ($12 983.6 vs. $8 255.6; P 0.000). CONCLUSIONS DIAP has high 30-DR rates and poorer outcomes.
Collapse
Affiliation(s)
- Ebehiwele Ebhohon
- Department of Internal Medicine, Lincoln Medical Center, Bronx, New York, USA
| | - Katayoun Khoshbin
- Department of Internal Medicine, John H. Stroger Hospital of Cook County, Chicago, Illinois, USA
| | - Hafeez Shaka
- Department of Internal Medicine, John H. Stroger Hospital of Cook County, Chicago, Illinois, USA
| |
Collapse
|
12
|
Pan J, Ye C, Zhou LZ, Li ZY, Wang J, He X, Chen SJ, Zhou GQ. The Spectrum of Tigecycline-Induced Pancreatitis in Clinical Characteristics, Diagnosis, and Management. Int J Gen Med 2023; 16:2971-2979. [PMID: 37465554 PMCID: PMC10350411 DOI: 10.2147/ijgm.s410542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 06/19/2023] [Indexed: 07/20/2023] Open
Abstract
Introduction Tigecycline-induced acute pancreatitis (AP) has been frequently increasingly reported in solid organ transplant patients. This review aimed to summarize the characteristics, possible mechanisms, and management of tigecycline-induced AP. Methods Case reports of tigecycline-induced AP published in Chinese or English were collected until February 2023 for retrospective analysis. Results Thirty-four patients from 29 articles were included. Fifteen patients (46.9%) had solid organ transplantation, and 4 patients (12.5%) had malignant tumors. Twenty-five patients (89.3%) received a recommended maintenance dose of tigecycline (50 mg q12 h). The median age was 50 years (range 9-87). Compared to the nontransplant patients, the median age of the transplant patients was significantly younger, 44 years (range 12.5-61) versus 57.5 years (range 9-87) (P=0.03). The median time of symptom onset was 7 days (range 2-29), and 91.2% (31/34) were less than 14 days. Typical initial symptoms included abdominal pain (90.6%), nausea (46.9%), vomiting (43.8%), and abdominal distention (21.9%). Most cases were accompanied by elevated levels of pancreatic enzymes. The main radiological features included edematous infiltrate and acute pancreatitis on computed tomography (CT) scan and abdominal ultrasound. Except for one patient who continued tigecycline treatment, all patients discontinued treatment and received symptomatic support such as fasting, acid suppression, and enzyme suppression. The median time to recover pancreatic enzymes to the normal range was 5 days (range 1-43), and the median time to relieve symptoms was 4 days (range 1-12). Four patients died, of whom two died of severe pancreatitis complications and two of cardiogenic shock and septicemia. Conclusion Tigecycline-induced AP was a rare and serious complication that occurred mainly within two weeks of the medication. This serious side effect should be kept in mind while treating severe infections especially in transplant recipients.
Collapse
Affiliation(s)
- Juan Pan
- Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, People’s Republic of China
| | - Chao Ye
- Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, People’s Republic of China
| | - Ling-Zhi Zhou
- Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, People’s Republic of China
| | - Zu-Yi Li
- Department of Pharmacy, Liuyang Hospital of Traditional Chinese Medicine, Changsha, Hunan, People’s Republic of China
| | - Juan Wang
- Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, People’s Republic of China
| | - Xin He
- Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, People’s Republic of China
| | - Shen-Jue Chen
- Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, People’s Republic of China
| | - Guang-Qing Zhou
- Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan, People’s Republic of China
| |
Collapse
|
13
|
Poloju A, Majety P, Groysman A. Pancreatitis in a 57-Year-Old Female Two Weeks After Initiation of Empagliflozin. AACE Clin Case Rep 2023; 9:104-107. [PMID: 37520757 PMCID: PMC10382614 DOI: 10.1016/j.aace.2023.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 04/02/2023] [Accepted: 04/10/2023] [Indexed: 07/18/2023] Open
Abstract
BACKGROUND/OBJECTIVE Pancreatitis is a common diagnosis requiring hospital admission, associated with significant costs. Although pancreatitis is an established side-effect with other diabetes medications, such as Glucagon like Peptide-1 Receptor Agonists and Dipeptidyl Peptidase 4 inhibitors, the association with SGLT2 inhibitors is not established. We present a patient with empagliflozin associated drug-induced acute pancreatitis (DIAP) and a review of published case reports. CASE REPORT A 57-year-old woman with T2DM presented to the hospital with severe abdominal pain. Her vital signs on presentation were temperature 98.3 F, blood pressure 139/79 mm Hg, pulse 62/min, and respiratory rate 15/min, saturating 99% on room air. Labs were notable for white blood cell count 12.8 (4.5-10.8 10∗3 μl), lipase- 36 (7-60 U/L), calcium- 9.4 (8.5-10.5 mg/dL), and triglycerides- 150 (35-150 mg/dL). Computed tomography abdomen showed induration of the peripancreatic fat, suggesting pancreatitis. No alcohol use was reported. DIAP and idiopathic pancreatitis were considered possible etiologies. Medication history revealed that the patient was started on empagliflozin 2 weeks before this admission. Empagliflozin was discontinued and she was discharged on metformin and glipizide. DISCUSSION Sodium Glucose Transporter 2 inhibitors (SGLT2) inhibitors are increasingly used for treating type 2 diabetes mellitus and heart failure. The association of these medications with pancreatitis, its timeline, and the underlying mechanisms are yet to be understood. This case is intended to add to the existing limited literature on this side effect. CONCLUSIONS With the increasing use of SGLT2 inhibitors, more cases of DIAP are being reported. Physicians need to consider SGLT2 inhibitors as a possible cause of pancreatitis after excluding other etiologies.
Collapse
Affiliation(s)
- Alekya Poloju
- Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin-Madison, Madison, Wisconsin
| | - Priyanka Majety
- Division of Endocrinology, Diabetes and Metabolism, Virginia Commonwealth University, Richmond, Virginia
| | - Anna Groysman
- Division of Endocrinology, Diabetes, and Metabolism, Atrius Health, Braintree, Massachusetts
| |
Collapse
|
14
|
Fredj H, Ben Ali H, Mokline A, Ben Saad M, Jami I, Gasri B, Messadi A. [Acute Pancreatitis Related to Tigecycline in ICU Burn Patients]. ANNALS OF BURNS AND FIRE DISASTERS 2023; 36:120-124. [PMID: 38681942 PMCID: PMC11041889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 01/04/2022] [Indexed: 05/01/2024]
Abstract
Drug-induced acute pancreatitis (AP) associated with tigecycline (TGC) is considered a rare complication (incidence between 1‰ and 1%). In this paper, we report five cases of AP occurring after the administration of TGC in septic patients hospitalized in intensive burn care in Tunisia over 9 years. The diagnosis of AP was based on clinical and/or biological signs. Among 303 cases treated with TGC, AP occurred with an incidence of 1.65%. The mean age was 28±6 years. Only one patient had a history of chronic alcoholism. The prescribed dose was 200 mg as a loading dose, followed by 100 mg twice a day. The time to onset of symptoms after initiation of TGC was 5.4 days [2-7]. PA was suspected due to abdominal pain associated with nausea and vomiting (n=2), occlusive syndrome (n=1) and fortuitously increased pancreatic enzymes in 2 patients under mechanical ventilation. The mean lipase level at diagnosis was 447 IU ± 135 IU (4.5 to 10 times the normal). All the aetiologies of AP were ruled out, including gallstones, hypercalcemia, hypertriglyceridemia, trauma and infections. The mean time to symptom resolution after stopping TGC was 4±2 days [5-7] and to the normalization of pancreatic enzymes it was 9 days [2-20 days]. In conclusion, clinical and biological monitoring was necessary in patients treated with TGC in order to avoid severe forms, especially in at-risk patients.
Collapse
Affiliation(s)
- H. Fredj
- Service de Réanimation des Brûlés, Centre de Traumatologie et des Grands Brûlés, Tunis, Tunisie
- Faculté de Médecine de Tunis, Université de Tunis El Manar, Tunis, Tunisie
| | - H. Ben Ali
- Service de Réanimation des Brûlés, Centre de Traumatologie et des Grands Brûlés, Tunis, Tunisie
- Faculté de Médecine de Tunis, Université de Tunis El Manar, Tunis, Tunisie
| | - A. Mokline
- Service de Réanimation des Brûlés, Centre de Traumatologie et des Grands Brûlés, Tunis, Tunisie
- Faculté de Médecine de Tunis, Université de Tunis El Manar, Tunis, Tunisie
| | - M. Ben Saad
- Service de Réanimation des Brûlés, Centre de Traumatologie et des Grands Brûlés, Tunis, Tunisie
| | - I. Jami
- Service de Réanimation des Brûlés, Centre de Traumatologie et des Grands Brûlés, Tunis, Tunisie
| | - B. Gasri
- Service de Réanimation des Brûlés, Centre de Traumatologie et des Grands Brûlés, Tunis, Tunisie
| | - A.A. Messadi
- Service de Réanimation des Brûlés, Centre de Traumatologie et des Grands Brûlés, Tunis, Tunisie
- Faculté de Médecine de Tunis, Université de Tunis El Manar, Tunis, Tunisie
| |
Collapse
|
15
|
Yuki M, Taira H, Inden T. Development of acute pancreatitis after oral administering a praziquantel, pyrantel pamoate, and febantel combination in a dog: A case report. Heliyon 2023; 9:e17225. [PMID: 37484301 PMCID: PMC10361369 DOI: 10.1016/j.heliyon.2023.e17225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 06/09/2023] [Accepted: 06/10/2023] [Indexed: 07/25/2023] Open
Abstract
Oral praziquantel, pyrantel pamoate, and febantel combination (PPFC) is a highly safe anthelmintic treatment commonly administered for the purpose of canine gastrointestinal parasites with mild adverse effects such as anorexia, vomiting, lethargy, or diarrhea. A 12-year-old castrated Chihuahua was brought to our hospital for a periodic health examination. Although his general physical examination showed no abnormalities, blood test results showed increase in the liver enzyme, lipase activity, total bile acid, total cholesterol, and triglyceride concentration. Moreover, the dog had underlying tricuspid regurgitation that was not treated. PPFC was prescribed on the suspicion of gastrointestinal tract parasites. Following the oral administration of PPFC at home, anorexia and lethargy were found, and vomiting and diarrhea were noted after 30 h. The dog was diagnosed with acute pancreatitis based on clinical course of the disease and subsequent pathology results. Although intravenous drip was initiated upon hospitalization, the treatment was discontinued owing to financial reasons. The onset of acute pancreatitis can be considered an adverse effect of PPFC. Although the association between PPFC administration and the onset of acute pancreatitis could not be clarified in this case, the onset of acute pancreatitis may have been associated with a decrease in liver function and/or increase in the false activity of lipase. PPFC has been considered highly safe in dogs, although care should be taken when administering medications to dogs suspected of having an underlying disorder.
Collapse
|
16
|
Paramythiotis D, Karlafti E, Veroplidou K, Fafouti M, Kaiafa G, Netta S, Michalopoulos A, Savopoulos C. Drug-Induced Acute Pancreatitis in Hospitalized COVID-19 Patients. Diagnostics (Basel) 2023; 13:1398. [DOI: https:/doi.org/10.3390/diagnostics13081398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2025] Open
Abstract
Coronavirus disease-19 (COVID-19), caused by SARS-CoV-2, is a systemic disease that affects not only the respiratory system, but also other systems, including gastrointestinal. A great number of different drugs have been used on hospitalized patients for the management of COVID-19, and acute pancreatitis (AP) has been reported as a complication or side effect of these drugs. The development of drug-induced acute pancreatitis (DIAP) follows a complex of pathophysiological mechanisms, and particular risk factors play a key role. Diagnosis of DIAP depends on specific criteria, and based on these, a drug may be characterized as having a definite, probable or possible connection with AP. The aim of this review is to present the medications that are used for COVID-19 management and are associated with AP in hospitalized patients. The list of these drugs mainly includes corticosteroids, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), antiviral agents, antibiotics, monoclonal antibodies, estrogens and anesthetic agents. Moreover, the prevention of the development of DIAP is vital, especially for critically ill patients who may receive multiple drugs. DIAP management is mainly non-invasive and the first step concerns the exception of the suspicious drug from patients therapy.
Collapse
Affiliation(s)
- Daniel Paramythiotis
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Eleni Karlafti
- Emergency Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Kalliopi Veroplidou
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Maria Fafouti
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Georgia Kaiafa
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Smaro Netta
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Antonios Michalopoulos
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Christos Savopoulos
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| |
Collapse
|
17
|
Paramythiotis D, Karlafti E, Veroplidou K, Fafouti M, Kaiafa G, Netta S, Michalopoulos A, Savopoulos C. Drug-Induced Acute Pancreatitis in Hospitalized COVID-19 Patients. Diagnostics (Basel) 2023; 13:1398. [PMID: 37189499 PMCID: PMC10137519 DOI: 10.3390/diagnostics13081398] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 03/28/2023] [Accepted: 03/29/2023] [Indexed: 05/17/2023] Open
Abstract
Coronavirus disease-19 (COVID-19), caused by SARS-CoV-2, is a systemic disease that affects not only the respiratory system, but also other systems, including gastrointestinal. A great number of different drugs have been used on hospitalized patients for the management of COVID-19, and acute pancreatitis (AP) has been reported as a complication or side effect of these drugs. The development of drug-induced acute pancreatitis (DIAP) follows a complex of pathophysiological mechanisms, and particular risk factors play a key role. Diagnosis of DIAP depends on specific criteria, and based on these, a drug may be characterized as having a definite, probable or possible connection with AP. The aim of this review is to present the medications that are used for COVID-19 management and are associated with AP in hospitalized patients. The list of these drugs mainly includes corticosteroids, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), antiviral agents, antibiotics, monoclonal antibodies, estrogens and anesthetic agents. Moreover, the prevention of the development of DIAP is vital, especially for critically ill patients who may receive multiple drugs. DIAP management is mainly non-invasive and the first step concerns the exception of the suspicious drug from patients therapy.
Collapse
Affiliation(s)
- Daniel Paramythiotis
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Eleni Karlafti
- Emergency Department, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Kalliopi Veroplidou
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Maria Fafouti
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Georgia Kaiafa
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Smaro Netta
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Antonios Michalopoulos
- First Propaedeutic Department of Surgery, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Christos Savopoulos
- First Propaedeutic Department of Internal Medicine, AHEPA University General Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| |
Collapse
|
18
|
Abstract
OBJECTIVE Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis. METHODS The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis. RESULTS Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83 y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34 d). In 6 cases, "de-challenge" followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely. CONCLUSION Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.
Collapse
|
19
|
He S, Ikner TP, Taylor BV, Aguiar T, Thakur NP, Chakravorty S. Mirtazapine-associated acute pancreatitis in a patient with insomnia and co-occurring psychiatric disorders. J Natl Med Assoc 2022; 114:617-620. [PMID: 36114064 DOI: 10.1016/j.jnma.2022.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Revised: 07/21/2022] [Accepted: 08/24/2022] [Indexed: 12/15/2022]
Abstract
We report the case of an African American patient who developed drug-associated acute pancreatitis without hypertriglyceridemia, after being treated with mirtazapine for major depressive disorder (MDD). Acute pancreatitis is characterized by rapid inflammation and autodigestion of the pancreas, which may become life-threatening. Although heavy alcohol use and gallstones are the most common causes of acute pancreatitis, some medications are also known to cause drug-induced acute pancreatitis. This report describes a 47-year-old African American female with a history of MDD, insomnia, posttraumatic stress disorder (PTSD), and alcohol use disorder, who was prescribed mirtazapine. A literature search implicated mirtazapine as a rare cause of drug-induced acute pancreatitis. Some reports have suggested that mirtazapine-associated acute pancreatitis may be due to hypertriglyceridemia. This case report instead presents with a normal lipid panel, which is consistent with the majority of prior reports, and it is noteworthy for introducing an alternative mechanism. The Naranjo Adverse Drug Reaction (ADR) Probability Scale calculated an ADR of 5, indicating mirtazapine as the probable cause of the patient's drug-associated acute pancreatitis.
Collapse
Affiliation(s)
- Sean He
- Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.
| | - Taylor P Ikner
- University of Pennsylvania College of Liberal and Professional Studies, USA
| | | | - Taylor Aguiar
- Hackensack Meridian School of Medicine, Nutley, NJ, USA
| | - Nina P Thakur
- University of New England College of Osteopathic Medicine, Biddleford, ME 04005, USA
| | - Subhajit Chakravorty
- Cpl. Michael J Crescenz VA Medical Center, Philadelphia, PA 19104, USA; Perelman School of Medicine, Philadelphia, PA 19104, USA
| |
Collapse
|
20
|
Wilson JL, Steinberg E, Racz R, Altman RB, Shah N, Grimes K. A network paradigm predicts drug synergistic effects using downstream protein-protein interactions. CPT Pharmacometrics Syst Pharmacol 2022; 11:1527-1538. [PMID: 36204824 PMCID: PMC9662203 DOI: 10.1002/psp4.12861] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 08/05/2022] [Accepted: 08/11/2022] [Indexed: 11/16/2022] Open
Abstract
In some cases, drug combinations affect adverse outcome phenotypes by binding the same protein; however, drug-binding proteins are associated through protein-protein interaction (PPI) networks within the cell, suggesting that drug phenotypes may result from long-range network effects. We first used PPI network analysis to classify drugs based on proteins downstream of their targets and next predicted drug combination effects where drugs shared network proteins but had distinct binding proteins (e.g., targets, enzymes, or transporters). By classifying drugs using their downstream proteins, we had an 80.7% sensitivity for predicting rare drug combination effects documented in gold-standard datasets. We further measured the effect of predicted drug combinations on adverse outcome phenotypes using novel observational studies in the electronic health record. We tested predictions for 60 network-drug classes on seven adverse outcomes and measured changes in clinical outcomes for predicted combinations. These results demonstrate a novel paradigm for anticipating drug synergistic effects using proteins downstream of drug targets.
Collapse
Affiliation(s)
- Jennifer L. Wilson
- Department of BioengineeringUniversity of California Los AngelesLos AngelesCaliforniaUSA
| | - Ethan Steinberg
- Center for Biomedical Informatics ResearchStanford UniversityPalo AltoCaliforniaUSA
| | - Rebecca Racz
- Division of Applied Regulatory ScienceUS Food and Drug AdministrationSilver SpringMarylandUSA
| | - Russ B. Altman
- Department of BioengineeringStanford UniversityPalo AltoCaliforniaUSA,Department of GeneticsStanford UniversityPalo AltoCaliforniaUSA
| | - Nigam Shah
- Center for Biomedical Informatics ResearchStanford UniversityPalo AltoCaliforniaUSA
| | - Kevin Grimes
- Department of Chemical and Systems BiologyStanford UniversityPalo AltoCaliforniaUSA
| |
Collapse
|
21
|
Bassi R, Prakash P, Balakrishnan E, Cockey G. Blame it on the Drug: A Rare Case of Recurrent Doxycycline-Induced Pancreatitis. Cureus 2022; 14:e29171. [PMID: 36258981 PMCID: PMC9568648 DOI: 10.7759/cureus.29171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/14/2022] [Indexed: 11/17/2022] Open
Abstract
Doxycycline is a broad-spectrum bacteriostatic antibiotic that belongs to the tetracycline class. It is a relatively safe medication with reported side effects being gastrointestinal symptoms, bone and teeth discoloration, photosensitivity, and renal toxicity. Acute pancreatitis (AP) is an uncommon adverse effect with only a few reported cases in the literature. Despite tetracyclines being labeled as a probable causative agent of drug-induced pancreatitis (DIP), doxycycline has been rarely implicated. Herein we present the case of a 65-year-old patient who developed recurrent doxycycline-induced pancreatitis after she was inadvertently started on the medication for community-acquired pneumonia. The most common causes of pancreatitis were ruled out during her hospital admission and she was subsequently diagnosed with DIP. She was successfully treated with the cessation of the offending agent and with supportive therapy. It is critical that clinicians are aware of the possible association between doxycycline and pancreatitis to further aid in the prompt diagnosis and treatment of this condition.
Collapse
|
22
|
Mitrovic M, Tadic B, Jankovic A, Rankovic I, Kovac JD. Fatal gastrointestinal bleeding associated with acute pancreatitis as a complication of Covid-19: a case report. J Int Med Res 2022; 50:3000605221098179. [PMID: 35538708 PMCID: PMC9102154 DOI: 10.1177/03000605221098179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Clinical manifestations of Covid-19 vary widely among patients. Recent studies suggest that up to 15% of patients with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections develop gastrointestinal symptoms. The location of virus-host cell receptors angiotensin-converting enzyme 2 and transmembrane serine protease 2 has an important role in the pathophysiology and presentation of disease. They are expressed in the respiratory tract, as well as other organs and tissues including exocrine and endocrine pancreatic cells. These cells are therefore a possible target for the virus, which could explain the relationship between SARS-CoV-2 infection and pancreatic injury. We report a disastrous collateral effect of the Covid-19 pandemic on a 33-year-old man with chronic renal insufficiency and asymptomatic SARS-CoV-2 infection, who developed acute pancreatitis. Inflammation progressed rapidly toward necrosis and the development of a peripancreatic pseudoaneurysm which subsequently ruptured, causing death.
Collapse
Affiliation(s)
- Milica Mitrovic
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Center of Serbia, Belgrade, Serbia
| | - Boris Tadic
- Clinic for Digestive Surgery, Department of HBP Surgery, University Clinical Center of Serbia, Belgrade, Serbia.,Department of Surgery with Anesthesiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Aleksandra Jankovic
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Center of Serbia, Belgrade, Serbia
| | - Ivan Rankovic
- Clinic for Gastroenterology and Hepatology, University Clinical Center of Serbia, Belgrade, Serbia
| | - Jelena Djokic Kovac
- Center for Radiology and Magnetic Resonance Imaging, University Clinical Center of Serbia, Belgrade, Serbia.,Department of Radiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| |
Collapse
|
23
|
Freitas M, Lima Capela T, Macedo Silva V, Arieira C, Cúrdia Gonçalves T, Dias de Castro F, Moreira MJ, Firmino-Machado J, Cotter J. Finding Predictors of Azathioprine-Induced Pancreatitis in Patients With Inflammatory Bowel Disease. Pancreas 2022; 51:288-294. [PMID: 35584388 DOI: 10.1097/mpa.0000000000002012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES Azathioprine (AZA)-induced pancreatitis (AIP) is a common, idiosyncratic adverse effect whose incidence and risk factors data in inflammatory bowel disease (IBD) patients are not fully clarified. We aimed to establish the incidence, clinical course and identify risk factors for AIP. METHODS A retrospective study including all IBD patients on AZA between January 2013 and July 2020 was conducted. Patients with AIP were considered. RESULTS Azathioprine-induced pancreatitis occurred in 33 patients (7.5%; 442 patients on AZA). The mean time receiving AZA until AIP was 25 days, with a mean dose of 88 mg. All patients had a mild course of disease, which resolved with suspension of AZA and with no complications. Smoking (P = 0.02), single daily dose of AZA (P < 0.001), and concomitant budesonide (P = 0.001) were risk factors for AIP. In multivariate analysis, concomitant treatment with budesonide (odds ratio, 5.3; P = 0.002) and single daily dose of AZA (odds ratio, 3.8; P = 0.002) were the only predictors of AIP. CONCLUSIONS Although AIP was a relatively common adverse effect, it presented a mild course in all patients. Smoking, concomitant use of budesonide, and single-dose regimen of AZA should be avoided in IBD patients treated with AZA.
Collapse
|
24
|
Barrett AD, Pitts MA, Myers EM, Johnson JL. Probable Dapagliflozin-Associated Acute Pancreatitis. Diabetes Spectr 2022; 35:232-238. [PMID: 35668880 PMCID: PMC9160563 DOI: 10.2337/ds21-0025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Ashlee D. Barrett
- Advanced Vital Care Pharmacy: Home Infusion and Infusion Services, Amarillo, TX
- Southwestern Oklahoma State University College of Pharmacy, Weatherford, OK
| | - Mason A. Pitts
- Southwestern Oklahoma State University College of Pharmacy, Weatherford, OK
- Stillwater Medical Center, Stillwater, OK
| | - Elizabeth M. Myers
- Southwestern Oklahoma State University College of Pharmacy, Weatherford, OK
- Jackson County Memorial Hospital, Altus, OK
| | - Jeremy L. Johnson
- Department of Pharmacy Practice, Southwestern Oklahoma State University College of Pharmacy, Weatherford, OK
- Department of Internal Medicine, Oklahoma State University Center for Health Sciences, Tulsa, OK
- Corresponding author: Jeremy L. Johnson,
| |
Collapse
|
25
|
Kamath A, Acharya SD, Rao RR, Ullal SD. Assessment of pancreatitis associated with tocilizumab use using the United States Food and Drug Administration Adverse Event Reporting System database. Sci Rep 2021; 11:18818. [PMID: 34552181 PMCID: PMC8458491 DOI: 10.1038/s41598-021-98325-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 09/07/2021] [Indexed: 01/05/2023] Open
Abstract
Tocilizumab (TCZ) is used to treat rheumatoid arthritis and other systemic inflammatory disorders. There is some evidence suggesting the occurrence of pancreatitis following TCZ use. We aimed to determine the reporting of pancreatitis following TCZ use in comparison with other drugs using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database. We extracted adverse event reports submitted to FAERS during 2013-2019. A reporting odds ratio (ROR) with the lower bound 95% confidence interval (CI) > 1 and a lower limit of a two-sided 95% interval of information component (IC025) more than zero was considered significant. Following deduplication, 3,383,910 adverse event reports were available; 144 (0.004%) reports were of pancreatic adverse events associated with TCZ use, and 15,907 (0.47%) associated with other drugs. Of the 144 cases, 74 (51.39%) received concomitant medications with pancreatotoxic potential. The likelihood of reporting of pancreatic events, compared with any other adverse event, with TCZ use was 1.32 times higher than that with other drugs. The lower bound of the 95% CI of the ROR and IC remained above the criteria of significance throughout the study period, except 2013. The findings suggest disproportionately high reporting of pancreatitis in patients receiving TCZ as compared with other drugs. This marginally high reporting is not likely to be of immediate clinical concern and needs to be interpreted cautiously.
Collapse
Affiliation(s)
- Ashwin Kamath
- Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India.
| | - Sahana D Acharya
- Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India
| | - Rashmi R Rao
- Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India
| | - Sheetal D Ullal
- Department of Pharmacology, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India
| |
Collapse
|
26
|
Jevtic D, Dumic I, Nordin T, Singh A, Sulovic N, Radovanovic M, Jecmenica M, Milovanovic T. Less Known Gastrointestinal Manifestations of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: A Systematic Review of the Literature. J Clin Med 2021; 10:4287. [PMID: 34575398 PMCID: PMC8467470 DOI: 10.3390/jcm10184287] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 09/12/2021] [Accepted: 09/14/2021] [Indexed: 12/14/2022] Open
Abstract
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life threatening severe cutaneous drug reaction. Most patients develop eosinophilia, a rash, a fever, lymphadenopathy and variable visceral organ involvement 2-6 weeks following exposure to the inciting medication. Unlike other severe cutaneous drug reactions, internal organ involvement that leads to high mortality is a unique feature of DRESS syndrome. While the liver is the most common internal organ involved, literally every other visceral organ can be affected in this syndrome. The lesser-known gastrointestinal manifestations of this syndrome include esophagitis, gastritis, enteritis, colitis, pancreatitis and a late autoimmune sequela due to pancreatic injury such as fulminant type 1 diabetes mellitus, autoimmune type 1 diabetes mellitus and type 2 diabetes mellitus. While these entities are less common, they are associated with equally severe complications and adverse patient outcomes. In this review, we synthetize data on these rare manifestations using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The liver, the most common visceral organ involved, has been described as part of DRESS elsewhere and is not included in the scope of this article.
Collapse
Affiliation(s)
- Djordje Jevtic
- School of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (D.J.); (N.S.); (T.M.)
| | - Igor Dumic
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (T.N.); (M.R.)
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54702, USA
| | - Terri Nordin
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (T.N.); (M.R.)
- Department of Family Medicine, Mayo Clinic Health System, Eau Claire, WI 54702, USA
| | - Amteshwar Singh
- Department of Hospital Medicine, Johns Hopkins University, Baltimore, MD 21205, USA;
- Department of Hospital Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Nadezda Sulovic
- School of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (D.J.); (N.S.); (T.M.)
| | - Milan Radovanovic
- Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA; (T.N.); (M.R.)
- Department of Hospital Medicine, Mayo Clinic Health System, Eau Claire, WI 54702, USA
| | - Mladen Jecmenica
- Gastroenterology Fellowship Program, The Wright Center for Graduate Medical Education, Scranton, PA 18501, USA;
| | - Tamara Milovanovic
- School of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (D.J.); (N.S.); (T.M.)
- Department of Gastroenterology and Hepatology, Clinical Center of Serbia, 11000 Belgrade, Serbia
| |
Collapse
|
27
|
Genova E, Stocco G, Decorti G. Induced pluripotent stem cells as an innovative model to study drug induced pancreatitis. World J Gastroenterol 2021; 27:5796-5802. [PMID: 34629803 PMCID: PMC8475012 DOI: 10.3748/wjg.v27.i35.5796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/27/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
Drug-induced pancreatitis is a gastrointestinal adverse effect concerning about 2% of drugs. The majority of cases are mild to moderate but severe episodes can also occur, leading to hospitalization or even death. Unfortunately, the mechanisms of this adverse reaction are still not clear, hindering its prevention, and the majority of data available of this potentially life-threatening adverse effect are limited to case reports leading to a probable underestimation of this event. In particular, in this editorial, special attention is given to thiopurine-induced pancreatitis (TIP), an idiosyncratic adverse reaction affecting around 5% of inflammatory bowel disease (IBD) patients taking thiopurines as immunosuppressants, with a higher incidence in the pediatric population. Validated biomarkers are not available to assist clinicians in the prevention of TIP, also because of the inaccessibility of the pancreatic tissue, which limits the possibility to perform dedicated cellular and molecular studies. In this regard, induced pluripotent stem cells (iPSCs) and the exocrine pancreatic differentiated counterpart could be a great tool to investigate the cellular and molecular mechanisms underlying the development of this undesirable event. This particular type of stem cells is obtained by reprogramming adult cells, including fibroblasts and leukocytes, with a set of transcription factors known as the Yamanaka's factors. Maintaining unaltered the donors' genetic heritage, iPSCs represent an innovative model to study the mechanisms of adverse drug reactions in individual patients' tissues not easily obtainable from human probands. Indeed, iPSCs can differentiate under adequate stimuli into almost any somatic lineage, opening a new world of opportunities for researchers. Several works are already available in the literature studying liver, central nervous system and cardiac cells derived from iPSCs and adverse drug effects. However, to our knowledge no studies have been performed on exocrine pancreas differentiated from iPSCs and drug-induced pancreatitis, so far. Hence, in this editorial we focus specifically on the description of the study of the mechanisms of TIP by using IBD patient-specific iPSCs and exocrine pancreatic differentiated cells as innovative in vitro models.
Collapse
Affiliation(s)
- Elena Genova
- Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste 34137, Italy
| | - Gabriele Stocco
- Department of Life Sciences, University of Trieste, Trieste 34127, Italy
| | - Giuliana Decorti
- Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste 34137, Italy
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste 34127, Italy
| |
Collapse
|
28
|
Albugami MM, Ahmed M, Shihah AB. Ceftriaxone-Induced Pancreatitis. Can J Hosp Pharm 2021; 74:291-293. [PMID: 34248170 DOI: 10.4212/cjhp.v74i3.3157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Muneerah M Albugami
- , MD, is with the Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Mohamed Ahmed
- , MPharm, MRPharmS, BCPS, is with the Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Abdulelah Bin Shihah
- , MD, is with the Department of Family Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| |
Collapse
|
29
|
|
30
|
Ciobanu C, Jadav RS, Colon Ramos A, Sequeira Gross HG, Brazzarola C. Heroin-Induced Acute Pancreatitis. Cureus 2021; 13:e15470. [PMID: 34262808 PMCID: PMC8260205 DOI: 10.7759/cureus.15470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/05/2021] [Indexed: 12/01/2022] Open
Abstract
Heroin-induced pancreatitis (HIP) is rare with only a few cases reported previously in the literature and the pathophysiology mechanism is yet to be investigated. We present two cases of acute pancreatitis (AP) in the setting of acute heroin (diacetylmorphine) intoxication. Both patients presented with nausea, vomiting and severe abdominal pain after intranasal heroin use. On laboratory analysis were found to have elevated serum lipase, positive urine toxicology for opioids, without any other obvious causes for AP. Both patients had a full recovery with supportive treatment. As a general approach, drug-induced pancreatitis is a diagnosis of exclusion and a high index of suspicion is required when the most common etiologies are ruled out.
Collapse
Affiliation(s)
| | - Raja Shekar Jadav
- Cardiovascular Disease, Mayo Clinic, Rochester, USA
- Internal Medicine, St. Barnabas Hospital, Bronx, USA
| | | | | | - Carlos Brazzarola
- Internal Medicine, St. Barnabas Hospital (SBH) Health System, Bronx, USA
| |
Collapse
|
31
|
Tang H, Yang K, Li X, Song Y, Han J. Pancreatic safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus: A systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 2021; 29:161-172. [PMID: 32017292 DOI: 10.1002/pds.4943] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2019] [Revised: 11/07/2019] [Accepted: 11/25/2019] [Indexed: 12/26/2022]
Abstract
PURPOSE This study aimed to systematically evaluate the association between sodium-glucose cotransporter 2 (SGLT2) inhibitors and pancreatic safety in patients with type 2 diabetes mellitus (T2DM). METHODS Electronic databases were searched before September 2019 to include randomized controlled trials (RCTs) of SGLT2 inhibitors that reported any event on pancreatitis or pancreatic cancer among patients with T2DM. Peto odds ratio (OR) with 95% confidence interval (CI) was used to pool the data. The GRADE framework was introduced to assess the quality of evidence. RESULTS Of the 35 trials involving 44 912 patients with T2DM included, 41 events of acute pancreatitis (19 trials; 32 932 patients), 72 events of overall pancreatitis (including acute pancreatitis, chronic pancreatitis, or nonspecific pancreatitis; 26 trials; 36 688 patients), and 40 events of pancreatic cancer (18 trials; 27 806 patients) were reported during a median follow-up of 52 weeks. SGLT2 inhibitors were not associated with an increased risk of acute pancreatitis compared to controls (placebo or other active drugs; Peto OR, 1.13; 95% CI, 0.60-2.13; moderate quality evidence). A similar result was found for risk of overall pancreatitis (Peto OR, 1.08; 95% CI, 0.67-1.75; moderate quality evidence) and pancreatic cancer (Peto OR, 1.34; 95% CI, 0.71-2.54; very low-quality evidence). CONCLUSIONS Moderate quality evidence from RCTs shows no significantly increased risk of acute pancreatitis associated with SGLT2 inhibitors, while there is very low-quality evidence suggesting no significant association between SGLT2 inhibitors and pancreatic cancer among patients with T2DM.
Collapse
Affiliation(s)
- Huilin Tang
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indiana
| | - Keming Yang
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indiana
| | - Xin Li
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indiana
| | - Yiqing Song
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indiana
| | - Jiali Han
- Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indiana.,Melvin and Bren Simon Cancer Center, Indiana University, Indiana
| |
Collapse
|
32
|
Sánchez-Aldehuelo R, García García de Paredes A, Rojo Lázaro D, Martínez Ortega A, García de la Filia Molina I, López-Durán S, Rodríguez-Gandía MÁ, López-Sanromán A, Albillos A. Outcomes of drug-induced acute pancreatitis: a ten-year experience of an academic center. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2020; 113:276-279. [PMID: 33256421 DOI: 10.17235/reed.2020.7443/2020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND drug-induced pancreatitis is an unexplored entity. METHODS a retrospective cohort study was performed at a referral center. Patients with drug-induced acute pancreatitis between 2008 and 2018 were included. Baseline patient characteristics, involved drugs, clinical course and recurrence were analyzed. RESULTS drug-induced pancreatitis represented 2.8 % of acute pancreatitis (47/1,665) and 18 different drugs were involved (thiopurines 61.8 %). The latency period was less than one month in 87.2 % of cases. Pancreatitis was mild in 89.3 % and recurrence risk was 2.3 %. CONCLUSION drugs are a rare cause of pancreatitis, which mostly occurs within the first month of treatment, is usually mild and is associated with a low risk of recurrence.
Collapse
Affiliation(s)
| | | | - Diego Rojo Lázaro
- Digestive Diseases and Hepatology Service, Hospital Universitario Ramón y Cajal
| | | | | | - Sergio López-Durán
- Digestive Diseases and Hepatology Service, Hospital Universitario Ramón y Cajal, España
| | | | | | - Agustín Albillos
- Digestive Diseases and Hepatology , Hospital Universitario Ramón y Cajal
| |
Collapse
|
33
|
Ardolino L, Moylan E. PEGylated Liposomal Doxorubicin Rechallenge following Doxorubicin-induced Pancreatitis. CURRENT PROBLEMS IN CANCER: CASE REPORTS 2020. [DOI: 10.1016/j.cpccr.2020.100001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
|
34
|
Gameil MA, Elsebaie AH. Mildly symptomatic liraglutide-induced acute pancreatitis in a patient with type 2 diabetes mellitus: a case report. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2020. [DOI: 10.1186/s43162-020-00026-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Abstract
Background
Acute pancreatitis (AP) represents a serious clinical challenge as it can threaten the patient’s life if it is missed or improperly managed. Liraglutide is one of the glucagon-like peptide 1 receptor agonists (GLP1-RA) which represent a novel class of antidiabetic medications in the Egyptian market. Hereby, we report a case of liraglutide-induced acute pancreatitis with atypical presentation.
Case presentation
A 53-year-old Egyptian male patient with diabetes presented to the emergency department with abdominal discomfort and vomiting without significant abdominal pain. Serum lipase and amylase were elevated more than three folds the upper normal limit (NUL 300 and 110 U/L respectively); abdominal ultrasonography was inconclusive, but contrast-enhanced computed tomography was diagnostic. A diagnosis of liraglutide-induced AP was built after exclusion of other causes. After admission, his medications were modified and improved clinically after 1 week.
Conclusion
Mildly symptomatic AP in diabetic patients is a clinical challenge as it can be missed. Therefore, in certain clinical situations, AP should be suspected in patients administrating liraglutide particularly for those with autonomic neuropathy.
Collapse
|
35
|
El-Gohary Y, Mansfield S, Staszak J, Abdelhafeez A, Talbot L, Pui CH, Gold R, Murphy AJ, Davidoff AM. Management of pancreatic pseudocysts in pediatric oncology patients. J Pediatr Surg 2020; 55:1727-1731. [PMID: 31954554 DOI: 10.1016/j.jpedsurg.2019.12.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 11/05/2019] [Accepted: 12/02/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND Management of children with pancreatic pseudocysts has historically been adopted from the adult experience where pancreatic pseudocysts greater than 6 cm are unlikely to resolve without intervention. We reviewed the clinical course of pediatric oncology patients with pancreatic pseudocysts. METHODS A retrospective review of patients treated over a 15-year period was performed. Variables evaluated included cancer type, medications administered, clinical and imaging characteristics of the pancreatic pseudocysts, treatment and outcome. RESULTS A total of 132 patients with a median age of 13 (IQR, 9-17) years were identified with pancreatitis. Thirty-one (23.5%) patients developed a pancreatic pseudocyst, of which 84% were associated with PEG-asparaginase treatment. The median pseudocyst size was 7.6 (IQR, 4.4-9.9) cm with 59% being greater than 6 cm. Twenty-two (71%) patients with a pancreatic pseudocyst underwent successful conservative management, while only 9 (29%) required procedural intervention including six percutaneous drainage, one of whom recurred and required surgical cyst-enteric drainage. Two other patients had primary surgical cyst-enteric drainage and one patient underwent endoscopic retrograde cholangiopancreatography with stenting. The indication for intervention was worsening pain rather than pseudocyst imaging characteristics, size or serum amylase/lipase. CONCLUSION Most medication-induced pancreatic pseudocysts in children being treated for cancer, regardless of pseudocyst size, can be managed non-operatively or with transgastric percutaneous drainage. The need for intervention can be safely dictated by patient symptoms. LEVEL OF EVIDENCE III.
Collapse
Affiliation(s)
- Yousef El-Gohary
- Department of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA
| | - Sara Mansfield
- Department of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA
| | - Jessica Staszak
- Division of Pediatric Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38105, USA
| | - Abdelhafeez Abdelhafeez
- Department of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA; Division of Pediatric Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38105, USA
| | - Lindsay Talbot
- Department of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA; Division of Pediatric Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38105, USA
| | - Ching-Hon Pui
- Department of Oncology, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA
| | - Robert Gold
- Department of Radiology, University of Tennessee Health Science Center, Memphis, TN, USA
| | - Andrew J Murphy
- Department of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA; Division of Pediatric Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38105, USA
| | - Andrew M Davidoff
- Department of Surgery, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN 38105, USA; Division of Pediatric Surgery, Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38105, USA.
| |
Collapse
|
36
|
Taguchi Y, Turki T. Universal Nature of Drug Treatment Responses in Drug-Tissue-Wide Model-Animal Experiments Using Tensor Decomposition-Based Unsupervised Feature Extraction. Front Genet 2020; 11:695. [PMID: 32973862 PMCID: PMC7469919 DOI: 10.3389/fgene.2020.00695] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 06/05/2020] [Indexed: 01/10/2023] Open
Abstract
Gene expression profiles of tissues treated with drugs have recently been used to infer clinical outcomes. Although this method is often successful from the application point of view, gene expression altered by drugs is rarely analyzed in detail, because of the extremely large number of genes involved. Here, we applied tensor decomposition (TD)-based unsupervised feature extraction (FE) to the gene expression profiles of 24 mouse tissues treated with 15 drugs. TD-based unsupervised FE enabled identification of the common effects of 15 drugs including an interesting universal feature: these drugs affect genes in a gene-group-wide manner and were dependent on three tissue types (neuronal, muscular, and gastroenterological). For each tissue group, TD-based unsupervised FE enabled identification of a few tens to a few hundreds of genes affected by the drug treatment. These genes are distinctly expressed between drug treatments and controls as well as between tissues in individual tissue groups and other tissues. We also validated the assignment of genes to individual tissue groups using multiple enrichment analyses. We conclude that TD-based unsupervised FE is a promising method for integrated analysis of gene expression profiles from multiple tissues treated with multiple drugs in a completely unsupervised manner.
Collapse
Affiliation(s)
- Yh. Taguchi
- Department of Physics, Chuo University, Tokyo, Japan
| | - Turki Turki
- Department of Computer Science, King Abdulaziz University, Jeddah, Saudi Arabia
| |
Collapse
|
37
|
Weissman S, Aziz M, Perumpail RB, Mehta TI, Patel R, Tabibian JH. Ever-increasing diversity of drug-induced pancreatitis. World J Gastroenterol 2020; 26:2902-2915. [PMID: 32587438 PMCID: PMC7304112 DOI: 10.3748/wjg.v26.i22.2902] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2020] [Revised: 03/27/2020] [Accepted: 05/28/2020] [Indexed: 02/06/2023] Open
Abstract
With over 100000 hospital admissions per annum, acute pancreatitis remains the leading gastrointestinal cause of hospitalization in the United States and has far-reaching impact well beyond. It has become increasingly recognized that drug-induced pancreatitis (DIP), despite accounting for less than 3% of all cases, represents an important and growing though often inconspicuous cause of acute pancreatitis. Nevertheless, knowledge of DIP is often curtailed by the limited availability of evidence needed to implicate given agents, especially for non-prescription medications. Indeed, the majority of available data is derived from case reports, case series, or case control studies. Furthermore, the mechanism of injury and causality for many of these drugs remain elusive as a definitive correlation is generally not established (< 10% of cases). Several classification systems have been proposed, but no single system has been widely adopted, and periodic updates are required in light of ongoing pharmacologic expansion. Moreover, infrequently prescribed medications or those available over-the-counter (including herbal and other alternative remedies) are often overlooked as a potential culprit of acute pancreatitis. Herein, we review the ever-increasing diversity of DIP and the potential mechanisms of injury with the goal of raising awareness regarding the nature and magnitude of this entity. We believe this manuscript will aid in increasing both primary and secondary prevention of DIP, thus ultimately facilitating more expedient diagnosis and a decrease in DIP-related morbidity.
Collapse
Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack University-Palisades Medical Center, North Bergen, NJ 07047, United States
| | - Muhammad Aziz
- Department of Medicine, University of Toledo Medical Center, Toledo, OH 43614, United States
| | - Ryan B Perumpail
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
| | - Tej I Mehta
- Department of Interventional Radiology, Johns Hopkins University Hospital, Baltimore, MD 21205, United States
| | - Rutwik Patel
- Department of Medicine, Hackensack University-Palisades Medical Center, North Bergen, NJ 07047, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342 and David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
| |
Collapse
|
38
|
Chen Q, Li J, Ma J, Yang X, Ni M, Zhang Y, Li X, Lin Z, Gong F. Fibroblast growth factor 21 alleviates acute pancreatitis via activation of the Sirt1-autophagy signalling pathway. J Cell Mol Med 2020; 24:5341-5351. [PMID: 32233059 PMCID: PMC7205819 DOI: 10.1111/jcmm.15190] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 01/22/2020] [Accepted: 02/23/2020] [Indexed: 01/18/2023] Open
Abstract
Fibroblast growth factor 21 (FGF21), a metabolic hormone with pleiotropic effects on glucose and lipid metabolism and insulin sensitivity, alleviates the process of acute pancreatitis (AP). However, its mechanism remains elusive. The pathological and physiological characteristics of FGF21 are observed in both patients with AP and cerulein‐induced AP models, and the mechanisms of FGF21 in response to AP are investigated by evaluating the impact of autophagy in FGF21‐treated mice and cultured pancreatic cells. Circulating levels of FGF21 significantly increase in both AP patients and cerulein‐induced AP mice, which is accompanied by the change of pathology in pancreatic injury. Replenishment of FGF21 distinctly reverses cerulein‐induced pancreatic injury and improves cerulein‐induced autophagy damage in vivo and in vitro. Mechanically, FGF21 acts on pancreatic acinar cells to up‐regulate Sirtuin‐1 (Sirt1) expression, which in turn repairs impaired autophagy and removes damaged organs. In addition, blockage of Sirt1 accelerates cerulein‐induced pancreatic injury and weakens the regulative effect in FGF21‐activated autophagy in mice. These results showed that FGF21 protects against cerulein‐induced AP by activation of Sirtuin‐1‐autophagy axis.
Collapse
Affiliation(s)
- Qiongzhen Chen
- College of Life and Environmental Science, Wenzhou University, Wenzhou, China
| | - Jinmeng Li
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Junfeng Ma
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Xiaoning Yang
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Ming Ni
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Yali Zhang
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Xiaokun Li
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Zhuofeng Lin
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| | - Fanghua Gong
- School of Pharmacy, Wenzhou Medical University, Wenzhou, China
| |
Collapse
|
39
|
Lorenze A, Hsueh W, Nasr J. Beta-sitosterol-induced Acute Pancreatitis: A Case Report and Review of the Literature. Cureus 2020; 12:e7407. [PMID: 32226701 PMCID: PMC7098410 DOI: 10.7759/cureus.7407] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 03/25/2020] [Indexed: 11/05/2022] Open
Abstract
While drug-induced pancreatitis from corticosteroids has been well described in the medical literature, the exact mechanism is unclear. We present the first reported case of drug-induced pancreatitis from beta-sitosterol, a naturally occurring plant sterol structurally similar to cholesterol, obtained primarily through Western diet and supplementation. A 57-year-old male with a history of situs inversus and benign prostatic hyperplasia presented from an outside facility with a two-day history of worsening epigastric pain radiating to the right upper quadrant. Lipase was markedly elevated at 572 U/L. CT scan and ultrasound of the abdomen were remarkable for acute pancreatitis with acute necrotic collections and normal appearing gallbladder and bile ducts without the presence of gallstones. The patient was managed with aggressive intravenous hydration and supportive management and had resolution of symptoms. At his follow-up appointment, the patient disclosed that he had started a new herbal supplement, beta-sitosterol, on the morning after his symptoms began. Abdominal magnetic resonance cholangiopancreatography obtained at follow-up appointment showed interval resolution of pancreatitis and normal biliary anatomy. In the absence of classical risk factors for acute pancreatitis, a diagnosis of drug-induced pancreatitis secondary to beta-sitosterol was made. The patient was advised to avoid beta-sitosterol, and thus continued to remain asymptomatic. We describe the first reported case of drug-induced pancreatitis from beta-sitosterol, a common phytosterol found in many over the counter supplements worldwide. After a thorough workup to exclude other causes, our case demonstrates consistent resolution of symptoms and pancreatic enzymes along with normal imaging following discontinuation of the offending agent.
Collapse
Affiliation(s)
- Alyssa Lorenze
- Pediatrics, West Virginia University School of Medicine, Ruby Memorial Hospital, Morgantown, USA
| | - William Hsueh
- Gastroenterology, West Virginia University, Morgantown, USA
| | - John Nasr
- Gastroenterology, West Virginia University, Morgantown, USA
| |
Collapse
|
40
|
Weissman S, Amrutiya V, Saleem S, Mehta TI, Aziz M, Lo A, Elias S, Sotiriadis J, Takakura K, Pandol SJ, Tabibian JH. Herbal supplement-induced acute pancreatitis: An unfamiliar culprit. Pancreatology 2020; 20:297-299. [PMID: 31864812 DOI: 10.1016/j.pan.2019.12.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2019] [Accepted: 12/12/2019] [Indexed: 02/07/2023]
Affiliation(s)
- Simcha Weissman
- Department of Medicine, Hackensack Meridian Health, Palisades Medical Center, North Bergen, NJ, USA.
| | - Viralkumar Amrutiya
- Department of Medicine, Hackensack Meridian Health, Palisades Medical Center, North Bergen, NJ, USA
| | - Saad Saleem
- Department of Medicine, University of Nevada, Los Vegas, NV, United States
| | - Tej I Mehta
- Department of Medicine, South Dakota University Sanford School of Medicine, Sioux Falls, SD, USA
| | - Muhammad Aziz
- Department of Medicine, University of Toledo Medical Center, Toledo, OH, United States
| | - Abraham Lo
- Department of Medicine, Hackensack Meridian Health, Palisades Medical Center, North Bergen, NJ, USA
| | - Sameh Elias
- Department of Medicine, Hackensack Meridian Health, Palisades Medical Center, North Bergen, NJ, USA
| | - John Sotiriadis
- Division of Gastroenterology and Hepatology, Hackensack Meridian Health, Palisades Medical Center, North Bergen, NJ, USA
| | - Kazuki Takakura
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Stephen J Pandol
- Division of Gastroenterology, Department of Medicine, Ceders-Sinai Medical Center, Los Angeles, CA, USA
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA, USA
| |
Collapse
|
41
|
Dapagliflozin-Induced Acute Pancreatitis: A Case Report and Review of Literature. Case Rep Endocrinol 2020; 2020:6724504. [PMID: 32123591 PMCID: PMC7044483 DOI: 10.1155/2020/6724504] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 01/29/2020] [Accepted: 02/01/2020] [Indexed: 12/28/2022] Open
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are increasingly used as add-on therapy in patients with poorly controlled type 2 diabetes mellitus (T2DM). Although pancreatitis is not a known side effect of SGLT-2 inhibitors, there have been case reports of SGLT-2 inhibitor use being associated with pancreatitis. Case Presentation. A 51-year-old male with a history of type 2 diabetes, dyslipidemia, and status-post cholecystectomy presented to the emergency room with a four-day history of periumbilical pain radiating to the back. He denied any history of recent alcohol intake or prior episodes of pancreatitis. On physical examination, his abdomen was diffusely tender to palpation without guarding or rebound. Initial labs were notable for a leukocyte count of 9.3 × 109/L, creatinine level of 0.72 mg/dL, calcium level of 9.5 mg/dL, lipase level of 262 U/L, and triglyceride level of 203 mg/dL. His last HbA1c was 8.5%. CT scan of his abdomen and pelvis showed findings consistent with acute pancreatitis with no biliary ductal dilatation. Careful review of his medications revealed the patient was recently started on dapagliflozin five days prior to admission in addition to his longstanding regimen of insulin detemir, sitagliptin, metformin, and rosuvastatin. His symptoms resolved after discontinuation of sitagliptin and dapagliflozin. A year later, due to increasing HbA1c levels, a decision was made to rechallenge the patient with dapagliflozin, after which he developed another episode of acute pancreatitis. His symptoms resolved upon cessation of dapagliflozin. Conclusion. This case highlights the possible association of SGLT-2 inhibitors and pancreatitis. Patients should be informed about the symptoms of acute pancreatitis and advised to discontinue SGLT-2 inhibitors in case such symptoms occur.
Collapse
|
42
|
Abstract
Drug-induced pancreatitis is a disease that is receiving increasing attention. This article reviews the advances in the incidence, risk factors, pathogenesis, diagnosis, treatment and prevention of drug-induced pancreatitis by reviewing the literature on drug-induced pancreatitis, especially in the literature of the latest 10 years. The incidence of drug-induced pancreatitis is relatively low, however, there is an increasing trend with the widespread use of drugs, and the incidence seems to be related to regional distribution. There is currently lack of data on the epidemiology of drug-induced pancreatitis in China. In recent years, research on the pathogenesis of drug-induced pancreatitis has made some progress, but further research is needed. Drug-induced pancreatitis is a diagnosis of exclusion. With further understanding and research, a new diagnostic approach has been proposed. Pharmacogenomics is expected to help prevent and perform an individual treatment of drug-induced pancreatitis.
Collapse
|
43
|
Anwar SM, Aqsa A, Shaukat R. Losartan-induced Pancreatitis. Cureus 2019; 11:e6253. [PMID: 31893179 PMCID: PMC6937474 DOI: 10.7759/cureus.6253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Drug-induced acute pancreatitis (DIAP) is a rare gastrointestinal condition but well-known in the medical literature. The medications have been classified into four subgroups (Classes I-IV) depending upon the propensity of the cases discussed in the literature, interval time period between drug initiation to pancreatitis, and reaction to the drug with reintroduction. Our clinical case is one such example where losartan was described as the agent of recurrent pancreatitis after excluding all other possible causes with laboratory and imaging studies.
Collapse
Affiliation(s)
- Shamsuddin M Anwar
- Internal Medicine, Staten Island University Hospital, Staten Island, USA
| | - Anum Aqsa
- Internal Medicine, Staten Island University Hospital, Staten Island, USA
| | - Rameez Shaukat
- Internal Medicine, Staten Island University Hospital, Staten Island, USA
| |
Collapse
|
44
|
Luskin KT, Bosso JV, Simon RA. Intranasal ketorolac-induced pancreatitis as a complication of modified oral aspirin desensitization in a patient with aspirin-exacerbated respiratory disease. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2019; 8:1147-1148. [PMID: 31678291 DOI: 10.1016/j.jaip.2019.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 09/24/2019] [Accepted: 10/10/2019] [Indexed: 10/25/2022]
Affiliation(s)
- Kathleen T Luskin
- Division of Allergy, Asthma and Immunology, Scripps Clinic, San Diego, Calif
| | - John V Bosso
- Penn Medicine, Penn AERD Center, Philadelphia, Pa.
| | - Ronald A Simon
- Division of Allergy, Asthma and Immunology, Scripps Clinic, San Diego, Calif
| |
Collapse
|
45
|
Computed tomography findings of ceftriaxone-associated biliary pseudocholelithiasis in adults. Jpn J Radiol 2019; 37:826-831. [DOI: 10.1007/s11604-019-00893-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 10/15/2019] [Indexed: 01/01/2023]
|
46
|
Niinomi I, Hosohata K, Oyama S, Inada A, Wakabayashi T, Iwanaga K. Pharmacovigilance Assessment of Drug-Induced Acute Pancreatitis Using a Spontaneous Reporting Database. Int J Toxicol 2019; 38:487-492. [DOI: 10.1177/1091581819870717] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Acute pancreatitis (AP) is associated with risks of morbidity and mortality. The incidence of AP recently increased compared to that traditionally reported in the literature. Objective: The purpose of this study was to evaluate the possible association between AP and drugs using the Japanese Adverse Drug Event Report (JADER) database, which is a spontaneous reporting database of adverse drug events. Methods: Adverse event reports submitted to the JADER database between 2004 and 2017 were analyzed. Disproportionality analysis was performed by calculating the reporting odds ratio (ROR) with 95% confidence intervals for signal detection. Results: A total of 3,443 reports (0.17% of all adverse events) were identified as drug-induced AP, in which 431 different drugs were involved. Acute pancreatitis was frequently reported in men (58.5%) in their 60s (19.1%); 40.6% developed AP within 4 weeks after the treatment. Among the most frequently reported drugs, signals were detected for prednisolone, ribavirin, sitagliptin, mesalazine, tacrolimus, and l-asparaginase, which are well-known causes of AP. Telaprevir, donepezil, and ustekinumab also generated signals. As for drugs with high RORs, l-asparaginase and alogliptin were noteworthy. Conclusion: Most of the identified drugs were already known to induce AP, but the likelihood of the reporting of AP varied among the drugs. Our results should raise physicians’ awareness of drugs associated with AP, but further investigation of these medications is warranted.
Collapse
Affiliation(s)
- Iku Niinomi
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan
| | - Keiko Hosohata
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan
| | - Saki Oyama
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan
| | - Ayaka Inada
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan
| | - Tomohito Wakabayashi
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan
| | - Kazunori Iwanaga
- Education and Research Center for Clinical Pharmacy, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan
| |
Collapse
|
47
|
Barbosa SC, Cabrera P, Guerra B, Roman CF. Valproic acid induced necrohemorragic pancreatitis: Case report and diagnostic approach in uncommon pancreatitis. Int J Surg Case Rep 2019; 60:126-129. [PMID: 31220680 PMCID: PMC6584841 DOI: 10.1016/j.ijscr.2019.05.052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Accepted: 05/26/2019] [Indexed: 12/24/2022] Open
Abstract
Is convenient to consider a medication induced necrohemorragic pancreatitis in patients without clear causative agent. Because progressive increase in AP incidence and the impact on morbidity and mortality is crucial determine an etiologic diagnosis in order to proceed to appropriate therapeutic interventions as for recurrence prevention. The valproic acid is a strong AP inducer (class Ia) in its evidence based classification and review of literature on medication induced AP, with the biomolecular evidence of pancreatic injury. An adequate initial approach with a complete clinical history and pharmacological background, good physical examination, and pertinent extension of laboratory tests are necessary in order to achieve a proper AP etiology. The etiologic diagnosis algorithm for AP proposed could be considered as a diagnostic exclusion tool, and is easy to apply for a timely therapeutic approach in medication induced AP. Background Acute pancreatitis (AP) is one of the most frequent gastrointestinal alterations in the United States. Medication induced AP has been undervalued in the surgical environment as etiologic entity of necrohemorragic pancreatitis (NHP). A case of NHP induced by valproic acid (VA) is presented, and an exclusion diagnostic algorithm is proposed. Case report A 29-year-old female with past medical history of migraine controlled with VA was admitted to our institute for acute abdominal pain and peritoneal irritation. An exploratory laparotomy was performed, finding pancreatic necrosis and a diagnosis of NHP was determined. The most frequent etiologies for AP were discarded. An exclusion diagnostic algorithm was performed reaching VA as etiologic gent. The treatment consisted on medication withdrawal, oral restriction, parenteral nutrition, hydration, analgesia and peritoneal wash-outs with a positive outcome. Conclusion Is convenient to consider a medication induced AP in patients without clear causative agent, such as the VA case presented. An etiological diagnosis algorithm of exclusion is proposed, for an adequate therapeutic approach in medication induced PNH. Algorithm validation is required.
Collapse
Affiliation(s)
| | - Paulo Cabrera
- Fundacion Cardioinfantil, General Surgery Department, Bogota, Colombia
| | - Bayron Guerra
- Fundacion Cardioinfantil, General Surgery Department, Bogota, Colombia
| | - Carlos F Roman
- Fundacion Cardioinfantil, General Surgery Department, Bogota, Colombia
| |
Collapse
|
48
|
Weis S, Heindl M, Carvalho T, Jentho E, Lorenz J, Sommerer I, Mössner J, Hoffmeister A. Azithromycin does not improve disease severity in acute experimental pancreatitis. PLoS One 2019; 14:e0216614. [PMID: 31075097 PMCID: PMC6510415 DOI: 10.1371/journal.pone.0216614] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Accepted: 04/24/2019] [Indexed: 12/31/2022] Open
Abstract
Acute pancreatitis is a severe systemic disease triggered by a sterile inflammation and initial local tissue damage of the pancreas. Immune cells infiltrating into the pancreas are main mediators of acute pancreatitis pathogenesis. In addition to their antimicrobial potency, macrolides possess anti-inflammatory and immunomodulatory properties which are routinely used in patients with chronic airway infections and might also beneficial in the treatment of acute lung injury. We here tested the hypothesis that the macrolide antibiotic azithromycin can improve the course of acute experimental pancreatitis via ameliorating the damage imposed by sterile inflammation, and could be used as a disease specific therapy. However, our data show that azithromycin does not have influence on caerulein induced acute pancreatitis in terms of reduction of organ damage, and disease severity. Furthermore Infiltration of immune cells into the pancreas or the lungs was not attenuated by azithromycin as compared to controls or ampicillin treated animals with acute experimental pancreatitis. We conclude that in the chosen model, azithromycin does not have any beneficial effects and that its immunomodulatory properties cannot be used to decrease disease severity in the model of caerulein-induced pancreatitis in mice.
Collapse
Affiliation(s)
- Sebastian Weis
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany
- Institute for Infectious Disease and Infection Control, Jena University Hospital, Jena, Germany
- Division of Gastroenterology, University Hospital Leipzig, Leipzig, Germany
| | - Mario Heindl
- Division of Gastroenterology, University Hospital Leipzig, Leipzig, Germany
| | - Tania Carvalho
- Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Elisa Jentho
- Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany
| | - Jana Lorenz
- Division of Gastroenterology, University Hospital Leipzig, Leipzig, Germany
| | - Ines Sommerer
- Division of Gastroenterology, University Hospital Leipzig, Leipzig, Germany
| | - Joachim Mössner
- Division of Gastroenterology, University Hospital Leipzig, Leipzig, Germany
| | - Albrecht Hoffmeister
- Division of Gastroenterology, University Hospital Leipzig, Leipzig, Germany
- * E-mail:
| |
Collapse
|
49
|
Gunawan F, Fayyaz B, Mihardja TO. Etanercept - A culprit agent in acute pancreatitis? J Community Hosp Intern Med Perspect 2019; 9:147-149. [PMID: 31044047 PMCID: PMC6484468 DOI: 10.1080/20009666.2019.1593783] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 03/07/2019] [Indexed: 01/07/2023] Open
Abstract
Drugs are responsible for 3%-5% of acute pancreatitis cases. There are a lot of medications that are known to cause acute pancreatitis, however only one case has been reported so far on Etanercept. This is a case about 62-year old female with history of Rheumatoid arthritis (RA) was started on Etanercept to control her severe RA symptoms. Three weeks later, she presented with abdominal pain, nausea, vomiting and found to have acute pancreatitis based on clinical symptoms and elevated pancreatic enzymes. A thorough workup for the cause of pancreatitis was done and all were unrevealing. There was no history of alcohol use, abdominal trauma or any gastroenterology procedures. Ultrasound and CT abdomen ruled out hepatobiliary abnormalities. Lipid profile and electrolytes including calcium were also found to be normal. As all the workup was unremarkable, it was thought that drug-induced acute pancreatitis was likely the case. Etanercept was the only medication that was started recently, which made it the likely culprit and therefore it was stopped. Patient continued to improve and was discharged after medical stabilization. Her rheumatologist started her on Abatacept and she has remained symptom-free since then. Our case is interesting as it is the second case of etanercept induced acute pancreatitis. Furthermore, recent animal trials have demonstrated that etanercept potentially has a protective and/or therapeutic role in acute pancreatitis. However, no human studies regarding this topic have been performed. Due to limited data, a clear explanation behind these paradoxical actions of etanercept is still lacking.
Collapse
|
50
|
Jung M, Kim J, Lee JY, Kim M, Kim SH, Ahn K. Trimethoprim-sulfamethoxazole induces acute pancreatitis associated with drug-specific cytotoxic T lymphocytes. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2019; 7:336-338. [DOI: 10.1016/j.jaip.2018.06.009] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2018] [Revised: 05/30/2018] [Accepted: 06/11/2018] [Indexed: 01/27/2023]
|