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Saini J, Marino D, Badalov N, Vugelman M, Tenner S. Drug-Induced Acute Pancreatitis: An Evidence-Based Classification (Revised). Clin Transl Gastroenterol 2023; 14:e00621. [PMID: 37440319 PMCID: PMC10461957 DOI: 10.14309/ctg.0000000000000621] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 07/06/2023] [Indexed: 07/15/2023] Open
Abstract
INTRODUCTION Drug induced acute pancreatitis is a difficult diagnosis for clinicians. We previously published an "Evidence-Based Classification System" on Drug-Induced Acute Pancreatitis widely used by clinicians to assist in the identification of drugs. Unfortunately, this prior analysis based only on published case reports has been misunderstood. The prior review did not include studies with higher evidentiary value, such as randomized trials, case-control studies, and/or pharmacoepidemiologic studies. The use of the prior classification system has led to many patients being inappropriately labeled as having drug-induced acute pancreatitis. We now propose a "Revised" Evidence- Based Classification System for the purpose of determining which drugs cause acute pancreatitis based on the Grading of Recommendations, Development, and Evaluation criteria. METHODS A search of the English Language literature was performed to identify all case reports with medication and/or drug induced acute pancreatitis. We divided the drugs implicated as causing acute pancreatitis into four groups based on the quality of evidence as defined by GRADE quality parameters. RESULTS Although 141 drugs were identified in the literature as causing acute pancreatitis, only 106 drugs published in the literature as causing acute pancreatitis were high quality case reports. Only 3 drugs had evidence as causing acute pancreatitis from randomized controlled clinical trials, including 6-mercaptopurine and azathioprine. DISCUSSION The vast majority of drugs implicated as causing acute pancreatitis in the literature have low or very low quality of evidence supporting those claims.
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Affiliation(s)
- Jasmine Saini
- Maimonides Medical Center, State University of New York–Downstate Medical Center, Brooklyn, New York, USA
| | - Daniel Marino
- Maimonides Medical Center, State University of New York–Downstate Medical Center, Brooklyn, New York, USA
| | - Nison Badalov
- Maimonides Medical Center, State University of New York–Downstate Medical Center, Brooklyn, New York, USA
| | - Melanie Vugelman
- Maimonides Medical Center, State University of New York–Downstate Medical Center, Brooklyn, New York, USA
| | - Scott Tenner
- Maimonides Medical Center, State University of New York–Downstate Medical Center, Brooklyn, New York, USA
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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.
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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.
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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
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4
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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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Wolfe D, Kanji S, Yazdi F, Barbeau P, Rice D, Beck A, Butler C, Esmaeilisaraji L, Skidmore B, Moher D, Hutton B. Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations. PLoS One 2020; 15:e0231883. [PMID: 32302358 PMCID: PMC7164626 DOI: 10.1371/journal.pone.0231883] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 04/02/2020] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations. METHODS A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency. RESULTS Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis. DISCUSSION Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations. REGISTRATION CRD42017060473.
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Affiliation(s)
- Dianna Wolfe
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Salmaan Kanji
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Department of Pharmacy, The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Fatemeh Yazdi
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Pauline Barbeau
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Danielle Rice
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Andrew Beck
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Claire Butler
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Leila Esmaeilisaraji
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Becky Skidmore
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - David Moher
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Brian Hutton
- Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Ontario, Canada
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Navarro Dávila MA, Shihadeh LA, Plasencia García I. Mirtazapine-associated pancreatitis. Med Clin (Barc) 2018; 150:206. [PMID: 28923677 DOI: 10.1016/j.medcli.2017.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 08/03/2017] [Accepted: 08/06/2017] [Indexed: 10/18/2022]
Affiliation(s)
| | - Leydimar Anmad Shihadeh
- Servicio de Cardiología, Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, España
| | - Inmaculada Plasencia García
- Servicio de Farmacia, Hospital Universitario Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, España
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Abstract
Acute pancreatitis has numerous etiologies, with the most common including gallstones, alcohol abuse, and medications such as angiotensin-converting enzyme (ACE) inhibitors, statins, and diuretics. Mirtazapine has been associated with increased serum cholesterol and serum triglyceride levels. However, few studies have reported dangerously elevated triglyceride levels resulting in acute pancreatitis. This report discusses a case of mirtazapine-induced pancreatitis in a 46-year-old African American female. The patient presented to the emergency department with pancreatitis, presumably alcohol-induced as with a prior admission, but she denied any recent alcohol use. Mirtazapine then became the suspected cause of her hypertriglyceridemia-induced pancreatitis and was discontinued. After discontinuing mirtazapine, and utilizing an insulin infusion, her triglyceride levels normalized and symptoms of pancreatitis resolved. Using the Naranjo Adverse Drug Reaction Probability Scale, a total score of 5 was calculated indicating a probable adverse drug reaction of acute pancreatitis from mirtazapine.
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Affiliation(s)
- Riley D Bowers
- Department of Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA.,Duke Regional Hospital, Durham, NC, USA.,Cape Fear Valley Medical Center, Fayetteville, NC, USA
| | - Sara M Valanejad
- Department of Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA
| | - Ashley A Holombo
- Department of Pharmacy Practice, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA
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Abstract
Pancreatitis can be a rare but serious side-effect of Mirtazapine. There are very few case reports worldwide that highlight this. We present a case of recurrent pancreatitis which demonstrates this potential clinical association.
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Affiliation(s)
- Abrar Hussain
- Community Mental Health Team, Northamptonshire Healthcare NHS Trust, Clarendon House, Kettering, Northants, NN15 7HH, UK.
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Badalov N, Baradarian R, Iswara K, Li J, Steinberg W, Tenner S. Drug-induced acute pancreatitis: an evidence-based review. Clin Gastroenterol Hepatol 2007; 5:648-61; quiz 644. [PMID: 17395548 DOI: 10.1016/j.cgh.2006.11.023] [Citation(s) in RCA: 364] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The diagnosis of drug-induced acute pancreatitis often is difficult to establish. Although some medications have been shown to cause acute pancreatitis with a large body of evidence, including rechallenge, some medications have been attributed as a cause of acute pancreatitis merely by a single published case report in which the investigators found no other cause. In addition, some medications reported to have caused acute pancreatitis have obvious patterns of presentation, including the time from initiation to the development of disease (latency). There also appear to be patterns in the severity of disease. After reviewing the literature, we have classified drugs that have been reported to cause acute pancreatitis based on the published weight of evidence for each agent and the pattern of clinical presentation. Based on our analysis of the level of evidence, 4 classes of drugs could be identified. Class I drugs include medications in which at least 1 case report described a recurrence of acute pancreatitis with a rechallenge with the drug. Class II drugs include drugs in which there is a consistent latency in 75% or more of the reported cases. Class III drugs include drugs that had 2 or more case reports published, but neither a rechallenge nor a consistent latency period. Class IV drugs were similar to class III drugs, but only 1 case report had been published. Our analysis allows an evidence-based approach when suspecting a drug as causing acute pancreatitis.
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Affiliation(s)
- Nison Badalov
- Division of Gastroenterology, Maimonides Medical Center, Mount Sinai School of Medicine, Brooklyn, New York 11235, USA
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Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2003; 12:523-38. [PMID: 14513666 DOI: 10.1002/pds.792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Chen JL, Spinowitz N, Karwa M. Hypertriglyceridemia, acute pancreatitis, and diabetic ketoacidosis possibly associated with mirtazapine therapy: a case report. Pharmacotherapy 2003; 23:940-4. [PMID: 12885107 DOI: 10.1592/phco.23.7.940.32725] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
A 44-year-old woman with a history of major depression and obsessive-compulsive disorder was prescribed mirtazapine. She came to the emergency department approximately 2 months after starting therapy; severe hypertriglyceridemia, acute pancreatitis, and diabetic ketoacidosis were diagnosed. Although these adverse effects have been reported in early clinical trials, we found only three published cases of subclinical pancreatitis possibly associated with mirtazapine therapy. We suspect that mirtazapine-associated hypertriglyceridemia had contributed to the development of acute pancreatitis and diabetic ketoacidosis in our patient. All these problems resolved with supportive care and discontinuation of mirtazapine. Her serum amylase, lipase, and lipid levels were normal 2 months after the acute event occurred. Health care providers should be aware of these possible adverse effects. Serum glucose and triglyceride levels should be measured at baseline and monitored regularly thereafter in all patients receiving mirtazapine therapy.
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Affiliation(s)
- Julie L Chen
- Department of Pharmacy, Montefiore Medical Center, The University Hospital for the Albert Einstein College of Medicine, Bronx, New York 10467-2400, USA
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