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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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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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Increased Risk of Acute Pancreatitis with Codeine Use in Patients with a History of Cholecystectomy. Dig Dis Sci 2020; 65:292-300. [PMID: 31468265 DOI: 10.1007/s10620-019-05803-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 08/12/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Codeine has a spasmodic effect on sphincter of Oddi and is suspected to cause acute pancreatitis in patients with a history of cholecystectomy. AIMS To assess the association between codeine use and acute pancreatitis in patients with a previous cholecystectomy. METHODS We conducted a retrospective nested case-control study using the 2005-2015 MarketScan® Commercial Claims and Encounters Database. The cohort included patients aged 18-64; cohort entry began 365 days after cholecystectomy. Odds ratios (ORs) and 95% CIs for acute pancreatitis hospitalization were estimated comparing use of codeine with non-use of codeine. In a secondary analysis, use of codeine was compared with an active comparator: use of non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS Of the 664,083 patients included in the cohort, 1707 patients were hospitalized for acute pancreatitis (incidence 1.1 per 1000 person-years) and were matched to 17,063 controls. Compared with non-use of codeine, use of codeine was associated with an increased risk of acute pancreatitis (OR 2.67; 95% CI 1.63, 4.36), particularly elevated in the first 15 days of codeine use (OR 5.37; 95% CI 2.70, 10.68). Compared with use of NSAIDs, use of codeine was also associated with an increased risk of acute pancreatitis (OR 2.64; 95% CI 1.54, 4.52). CONCLUSION Codeine is associated with an increased risk of acute pancreatitis in patients who have previously undergone cholecystectomy; greater clinician awareness of this association is needed.
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Coté GA. Editorial: the sphincter of Oddi strikes again-eluxadoline illuminates a controversial mechanism for the pathogenesis of acute pancreatitis. Aliment Pharmacol Ther 2018; 47:1324-1325. [PMID: 29644734 DOI: 10.1111/apt.14596] [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: 12/08/2022]
Affiliation(s)
- G A Coté
- Division of Gastroenterology & Hepatology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA
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Turkmen S, Buyukhatipoglu H, Suner A, Apucu HG, Ulas T. Prior cholecystectomy predisposes to acute pancreatitis in codeine-prescribed patients. Int J Crit Illn Inj Sci 2015; 5:114-5. [PMID: 26157656 PMCID: PMC4477388 DOI: 10.4103/2229-5151.158416] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
In this paper, we report a case of drug-induced pancreatitis just after taking a pain pill including a low-dose combination of acetaminophen and codeine. Codeine-induced pancreatitis has been rarely reported, however, well-established. The proposed mechanism for codeine-induced pancreatitis is by increasing Oddi sphincter pressure. However, the clinically important point is that the codeine-induced pancreatitis is seen almost only in the cholecystectomized patients due to lacking of its reservoir capacity. Codeine is commonly used alone or in combination in pain medicine. Therefore, it is fairly important to question whether a patient underwent cholecystectomy when a physician decides to prescribe codeine-included preparations.
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Affiliation(s)
- Serdar Turkmen
- Department of Cardiology, Sanko University School of Medicine, Gaziantep, Turkey
| | - Hakan Buyukhatipoglu
- Department of Internal Medicine, Gaziantep University School of Medicine, Gaziantep, Turkey
| | - Ali Suner
- Department of Internal Medicine, Gaziantep University School of Medicine, Gaziantep, Turkey
| | - Haci Gokhan Apucu
- Department of Internal Medicine, Necip Fazil Metropolitan Hospital, Kahramanmaras, Turkey
| | - Turgay Ulas
- Department of Internal Medicine, Harran University School of Medicine, Sanliurfa, Turkey
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Tabner A, Johnson G. Codeine: An Under-Recognized and Easily Treated Cause of Acute Abdominal Pain. Am J Emerg Med 2015; 33:1847.e1-2. [PMID: 25983269 DOI: 10.1016/j.ajem.2015.04.082] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2015] [Accepted: 04/11/2015] [Indexed: 11/30/2022] Open
Abstract
We present 2 cases of acute abdominal pain secondary to oral codeine that resolved after the administration of intravenous naloxone.
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Affiliation(s)
- Andrew Tabner
- Emergency Department, Royal Derby Hospital, Derby DE22 3NE, United Kingdom.
| | - Graham Johnson
- Emergency Department, Royal Derby Hospital, Derby DE22 3NE, United Kingdom
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Ksiądzyna D. Drug-induced acute pancreatitis related to medications commonly used in gastroenterology. Eur J Intern Med 2011; 22:20-5. [PMID: 21238888 DOI: 10.1016/j.ejim.2010.09.004] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2010] [Revised: 08/18/2010] [Accepted: 09/07/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND With the growing number of pharmacological agents available nowadays, the gastrointestinal drug-induced side effects become more common than ever. However, drug-induced pancreatitis belongs to rather seldom reported adverse drug reactions, probably because of the difficulty in proving the relationship between an inflammation of the pancreas and the pharmacotherapy with a certain drug. AIM The aim of this review is to draw attention to an infrequent but real problem of drug-induced acute pancreatitis associated with medications commonly used in the treatment of gastrointestinal disorders. METHODOLOGY For the purpose of that the PubMed database was searched using the keywords "drug-induced pancreatitis", "drug-associated pancreatitis", "acute pancreatitis", "pancreatitis" in various combinations and relevant literature was reviewed. RESULTS A substantial number of drugs commonly prescribed for gastrointestinal disorders are known to cause acute pancreatitis. Case reports and review articles published so far draw attention to medications already known to cause drug-induced pancreatic damage as well as implicate new drugs. Generally, the etiopathological mechanisms involved in drug-induced pancreatitis remain unclear. It is difficult to establish or rule out definitely such unwanted event, especially in patients taking numerous medications prescribed for multiple comorbidities. CONCLUSION Pharmacological agents are among etiologic factors that should be considered in all patients presenting with signs and symptoms consistent with acute pancreatitis. The diagnosis of drug-induced AP is often difficult to established. Therefore a high index of suspicion and thorough drug history are crucial for making the final diagnosis.
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Affiliation(s)
- Dorota Ksiądzyna
- Silesian Piasts Medical University, Department of Pharmacology, Wrocław, Poland.
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Zardi EM, Di Matteo F, Santini D, Uwechie V, Crucitti P, Carassiti M, Picardi A, Perrella E, Caricato M, Tonini G, Coppola R, Afeltra A. Pancreatitis after percutaneous ethanol injection into HCC: a minireview of the literature. J Exp Clin Cancer Res 2008; 27:28. [PMID: 18702805 PMCID: PMC2531081 DOI: 10.1186/1756-9966-27-28] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2008] [Accepted: 08/14/2008] [Indexed: 12/18/2022] Open
Abstract
Deaths after percutaneous ethanol injection (PEI) into hepatocellular carcinoma (HCC) may occur within a few hours to a few days following the procedure because of hemoperitoneum and haemorrhage from oesophageal varices or hepatic insufficiency. Pancreatitis has been recently reported as a rare lethal complication of intra-arterial PEI, another modality for treating HCCs. In this minireview, we analyze the literature concerning the development of acute pancreatitis after PEI. Pathogenesis of pancreatitis from opioids and ethanol is also addressed. Treatment with opioids to reduce the patient's abdominal pain after PEI in combination with the PEI itself may lead to direct toxic effects, thus favouring the development of pancreatitis.
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Affiliation(s)
- Enrico M Zardi
- Department of Clinical Medicine, "Campus Bio-Medico" University, Rome, Italy
| | - Francesco Di Matteo
- Department of Digestive Diseases, GI Endoscopy Unit, " Campus Bio-Medico" University, Rome, Italy
| | - Daniele Santini
- Medical Oncology, "Campus Bio-Medico" University, Rome, Italy
| | - Valentina Uwechie
- Department of Infectious and Tropical Diseases, University "La Sapienza", Rome, Italy
| | | | | | - Antonio Picardi
- Department of Clinical Medicine, "Campus Bio-Medico" University, Rome, Italy
| | - Eleonora Perrella
- Department of Pathology, "Campus Bio-Medico" University, Rome, Italy
| | - Marco Caricato
- Department of General Surgery, "Campus Bio-Medico" University, Rome, Italy
| | - Giuseppe Tonini
- Medical Oncology, "Campus Bio-Medico" University, Rome, Italy
| | - Roberto Coppola
- Department of General Surgery, "Campus Bio-Medico" University, Rome, Italy
| | - Antonella Afeltra
- Department of Clinical Medicine, "Campus Bio-Medico" University, Rome, Italy
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Sule AA, Tai DYH, Tze CC, Deepa B, Leow M. Potentially Fatal Paracetamol Overdose and Successful Treatment with 3 Days of Intravenous N-acetylcysteine Regime – A Case Report. ANNALS OF THE ACADEMY OF MEDICINE, SINGAPORE 2006. [DOI: 10.47102/annals-acadmedsg.v35n2p108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
Introduction: Paracetamol overdose is the most common drug overdose worldwide. To our knowledge, the maximum number of paracetamol tablets ingested reported in the literature is 45 g.
Clinical Picture: We describe a 21-year-old patient who acutely ingested 120 tablets, each 500 mg paracetamol (i.e., 60 g equivalent to 1200 mg/kg body weight) in a suicidal attempt. Our patient also drank 2 bottles of codeine-based cough syrup equivalent to 360 mg of codeine. At 6 hours post ingestion, her serum paracetamol level was 207 mg/L. The poor prognostic factors for paracetamol overdose in our patient included massive paracetamol ingestion (confirmed by blood levels), codeine co-ingestion and elevated serum amylase (189 U/L).
Treatment: She was treated with a 3-day modified regimen of intravenous N-acetylcysteine.
Outcome: The liver function tests and the prothrombin time remained normal over the second and third day of admission and the patient was discharged without complications on the fifth day.
Conclusion: From this experience we feel that in very severe paracetamol poisoning, a modified regime of intravenous N- acetylcysteine for 3 days is safe and efficacious.
Key words: Codeine, Hyperamylasaemia, Ingestion, Suicidal
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Abstract
BACKGROUND AND AIMS Many frequently prescribed drugs are suspected to cause acute pancreatitis (AP). The goal of this paper is to bring to light the often occult but real problem of drug-induced pancreatitis (DIP). METHODS We searched the National Library of Medicine/Pubmed for reported cases of DIP from 1966 to April 30, 2004. Medications implicated in AP are classified based on the strength of evidence into one of three classes of drugs associated with pancreatitis. We reviewed the top 100 prescription medications in the United States for their association with AP. RESULTS Class I medications (medications implicated in greater than 20 reported cases of acute pancreatitis with at least one documented case following reexposure): didanosine, asparaginase, azathioprine, valproic acid, pentavalent antimonials, pentamidine, mercaptopurine, mesalamine, estrogen preparations, opiates, tetracycline, cytarabine, steroids, trimethoprim/sulfamethoxazole, sulfasalazine, furosemide, and sulindac. Class II medications (medications implicated in more than 10 cases of acute pancreatitis): rifampin, lamivudine, octreotide, carbamazepine, acetaminophen, phenformin, interferon alfa-2b, enalapril, hydrochlorothiazide, cisplatin, erythromycin, and cyclopenthiazide. Class III medications (all medications reported to be associated with pancreatitis). Of the top 100 most frequently prescribed medications in the United States, 44 have been implicated in AP, 14 of them fall into either Class I or II of medications associated with AP. CONCLUSIONS Among adverse drug reactions, pancreatitis is often-ignored because of the difficulty in implicating a drug as its cause. The physician should have a high index of suspicion for DIP, especially in specific subpopulations such as geriatric patients who may be on multiple medications, HIV+ patients, cancer patients, and patients receiving immunomodulating agents.
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Affiliation(s)
- Chirag D Trivedi
- Department of Medicine, Robert Wood Johnson Medical School, and Division of Gastroenterology, Hepatology and Clinical Nutrition, St. Peter's University Hospital, New Brunswick, NJ 08901, USA
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Perney P, Berthier E, Pageaux GP, Hillaire-Buys D, Roques V, Fabbro-Peray P, Melki M, Hanslik B, Bauret P, Larrey D, Blayac JP, Blanc F. Are drugs a risk factor of post-ERCP pancreatitis? Gastrointest Endosc 2003; 58:696-700. [PMID: 14595303 DOI: 10.1016/s0016-5107(03)02019-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatitis is the most severe complication of ERCP. The aim of this study was to assess whether the use of potentially pancreatotoxic drugs is a risk factor for post-ERCP pancreatitis. METHODS Risk factors for post-ERCP pancreatitis and all drugs taken during the month before ERCP were recorded retrospectively in a database. Patients with other causes of acute pancreatitis or chronic pancreatitis were excluded from the analysis. Post-ERCP pancreatitis was defined as abdominal pain and/or vomiting associated with amylase/lipase plasma levels equal to or greater than twice the upper normal value. RESULTS A total of 173 patients (95 men, 78 women; mean age, 68 [16] years) were included. Post-ERCP pancreatitis occurred in 31 patients (18%). Several risk factors were identified in a multivariate analysis: difficulty in cannulation (p<0.001), endoscopic sphincterotomy (p<0.005), and female gender (p=0.02). Having taken potent pancreatotoxic drugs increased the occurrence of post-ERCP pancreatitis: odds ratio 3.7: 95% confidence intervals [1.1,12.4], p=0.04. CONCLUSIONS Use of pancreatotoxic drugs before or during ERCP significantly increased the risk of post-ERCP pancreatitis. Thus, discontinuation of the use of such drugs before ERCP seems justified whenever possible.
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Affiliation(s)
- Pascal Perney
- Service de Médecine Interne E, Service d'Hépato-Gastroentérologie, Hôpital Saint Eloi, Montpellier Cedex 5, Montpellier, France
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Sobrino JF, Campo R, Brullet E, Montserrat A, Vergara M, Gil M, Dalmau B, Calvet X. [Paracetamol-codeine induced hepatic colic]. GASTROENTEROLOGIA Y HEPATOLOGIA 2001; 24:365-6. [PMID: 11481075 DOI: 10.1016/s0210-5705(01)70196-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Hastier P, Buckley MJ, Peten EP, Demuth N, Dumas R, Demarquay JF, Caroli-Bosc FX, Delmont JP. A new source of drug-induced acute pancreatitis: codeine. Am J Gastroenterol 2000; 95:3295-8. [PMID: 11095359 DOI: 10.1111/j.1572-0241.2000.03213.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
A variety of drugs have been reported to cause acute pancreatitis during the past 40 years. We report the first series of four cases of acute pancreatitis related to codeine ingestion. Four patients (three female, mean age 50.2 yr) presented with clinical, biochemical, and radiological evidence of acute pancreatitis. All four had ingested a therapeutic dose of codeine 1-3 h before the onset of abdominal symptoms. Unintentional rechallenge occurred in three cases and was followed by recurrence of acute pancreatitis in all three. All patients made a full recovery. All four patients had had a previous cholecystectomy. The likely underlying pathophysiological mechanism is codeine-induced spasm of the sphincter of Oddi combined with sphincter of Oddi dysfunction related to a previous cholecystectomy. Codeine ingestion leads to acute pancreatitis in some individuals. Previous cholecystectomy seems to predispose to codeine-induced pancreatitis.
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Affiliation(s)
- P Hastier
- Department of Hepato-Gastroenterology, Archet II University Hospital, Nice, France
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