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Li D, Wang H, Qin C, Du D, Wang Y, Du Q, Liu S. Drug-Induced Acute Pancreatitis: A Real-World Pharmacovigilance Study Using the FDA Adverse Event Reporting System Database. Clin Pharmacol Ther 2024; 115:535-544. [PMID: 38069538 DOI: 10.1002/cpt.3139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Accepted: 12/04/2023] [Indexed: 01/04/2024]
Abstract
Timely identification and discontinuation of culprit-drug is the cornerstone of clinical management of drug-induced acute pancreatitis (AP), but the comprehensive landscape of AP culprit-drugs is still lacking. To provide the current overview of AP culprit-drugs to guide clinical practice, we reviewed the adverse event (AE) reports associated with AP in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from 2004 to 2022, and summarized a potential AP culprit-drug list and its corresponding AE report quantity proportion. The disproportionality analysis was used to detect adverse drug reaction (ADR) signals for each drug in the drug list, and the ADR signal distribution was integrated to show the risk characteristic of drugs according to the ADR signal detection results. In the FAERS database, a total of 62,206 AE reports were AP-related, in which 1,175 drugs were reported as culprit-drug. On the whole, metformin was the drug with the greatest number of AE reports, followed by quetiapine, liraglutide, exenatide, and sitagliptin. Drugs used in diabetes was the drug class with the greatest number of AE reports, followed by immunosuppressants, psycholeptics, drugs for acid-related disorders, and analgesics. In disproportionality analysis, 595 drugs showed potential AP risk, whereas 580 drugs did not show any positive ADR signal. According to the positive-negative distribution of the ADR signal for drug classes, the drug class with the greatest number of positive drugs was antineoplastic agents. In this study, we provided the current comprehensive landscape of AP culprit-drugs from the pharmacovigilance perspective, which can provide reference information for clinical practice.
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Affiliation(s)
- Dongxuan Li
- Department of Pharmacy, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hongli Wang
- Department of Pharmacy, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, China
| | - Chunmeng Qin
- Department of Pharmacy, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
- College of Pharmacy, Chongqing Medical University, Chongqing, China
| | - Dan Du
- Department of Pharmacy, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yalan Wang
- Department of Pharmacy, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
- College of Pharmacy, Chongqing Medical University, Chongqing, China
| | - Qian Du
- Department of Pharmacy, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Songqing Liu
- Department of Pharmacy, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Aslam H, Ahmed K, Iskander PA, Aloysius MM, Khurana V, Nasr S, Amjad MA. A Case of Mirtazapine-Induced Pancreatitis. Cureus 2023; 15:e37129. [PMID: 37153315 PMCID: PMC10159629 DOI: 10.7759/cureus.37129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2023] [Indexed: 04/07/2023] Open
Abstract
Acute pancreatitis is a concerning cause of hospitalization in the United States, with the most common etiologies being secondary to alcohol abuse and gallstones. Rarely, medications can trigger this inflammatory response, whether via direct toxic effects or other metabolic derangements. Mirtazapine is an antidepressant that has been associated with elevations in triglyceride levels on initiation. Relatedly, high triglyceride levels and autoimmune disorders are other causes of pancreatitis exacerbations. Here, we present the case of a female who was started on mirtazapine therapy and found to have elevated triglyceride levels. The course was complicated by acute pancreatitis requiring plasmapheresis, despite medication discontinuation, to which she responded well.
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Szatmary P, Grammatikopoulos T, Cai W, Huang W, Mukherjee R, Halloran C, Beyer G, Sutton R. Acute Pancreatitis: Diagnosis and Treatment. Drugs 2022; 82:1251-1276. [PMID: 36074322 PMCID: PMC9454414 DOI: 10.1007/s40265-022-01766-4] [Citation(s) in RCA: 228] [Impact Index Per Article: 76.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/04/2022] [Indexed: 11/11/2022]
Abstract
Acute pancreatitis is a common indication for hospital admission, increasing in incidence, including in children, pregnancy and the elderly. Moderately severe acute pancreatitis with fluid and/or necrotic collections causes substantial morbidity, and severe disease with persistent organ failure causes significant mortality. The diagnosis requires two of upper abdominal pain, amylase/lipase ≥ 3 ×upper limit of normal, and/or cross-sectional imaging findings. Gallstones and ethanol predominate while hypertriglyceridaemia and drugs are notable among many causes. Serum triglycerides, full blood count, renal and liver function tests, glucose, calcium, transabdominal ultrasound, and chest imaging are indicated, with abdominal cross-sectional imaging if there is diagnostic uncertainty. Subsequent imaging is undertaken to detect complications, for example, if C-reactive protein exceeds 150 mg/L, or rarer aetiologies. Pancreatic intracellular calcium overload, mitochondrial impairment, and inflammatory responses are critical in pathogenesis, targeted in current treatment trials, which are crucially important as there is no internationally licenced drug to treat acute pancreatitis and prevent complications. Initial priorities are intravenous fluid resuscitation, analgesia, and enteral nutrition, and when necessary, critical care and organ support, parenteral nutrition, antibiotics, pancreatic exocrine and endocrine replacement therapy; all may have adverse effects. Patients with local complications should be referred to specialist tertiary centres to guide further management, which may include drainage and/or necrosectomy. The impact of acute pancreatitis can be devastating, so prevention or reduction of the risk of recurrence and progression to chronic pancreatitis with an increased risk of pancreas cancer requires proactive management that should be long term for some patients.
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Affiliation(s)
- Peter Szatmary
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Tassos Grammatikopoulos
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital NHS Foundation Trust, London, UK
| | - Wenhao Cai
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,West China Centre of Excellence for Pancreatitis and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Wei Huang
- West China Centre of Excellence for Pancreatitis and West China-Liverpool Biomedical Research Centre, West China Hospital, Sichuan University, Chengdu, China
| | - Rajarshi Mukherjee
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.,Department of Molecular Physiology and Cell Signalling, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool , UK
| | - Chris Halloran
- Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Georg Beyer
- Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
| | - Robert Sutton
- Liverpool Pancreatitis Research Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. .,Department of Molecular and Clinical Cancer Medicine, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK. .,Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
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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.
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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
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