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O'Connor CE, Dang BQ, Miles B, Mackey J. Statin Therapy and Pancreatitis: A Multi-Institutional Retrospective Analysis. Cureus 2024; 16:e51723. [PMID: 38318563 PMCID: PMC10839132 DOI: 10.7759/cureus.51723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/05/2024] [Indexed: 02/07/2024] Open
Abstract
INTRODUCTION Acute pancreatitis is a serious condition that has numerous etiologies and often requires hospital admission due to its high mortality rates. Statins are used worldwide to reduce the risk of cardiovascular disease. Some studies have shown an association between long-term statin use and acute pancreatitis. However, other studies have shown no effect or even postulated a mild protective effect. Due to conflicting information in the medical literature, the relationship between statins and acute pancreatitis remains unclear. The current study uses the TriNetX global research database to further investigate the impact of statin use on the development of acute pancreatitis over a five-year period. METHODS Two cohorts were created using the TriNetX global research database. One group consisted of patients not taking statins, while the other group included patients taking any statins. Patients in both groups were required to be between the ages of 40 and 75 and had normal low-density lipoprotein cholesterol (LDL) (≤200 mg/dl) and triglyceride (≤150 mg/dl) levels. Patients were matched for age, gender, race, and comorbidities. The statin group was then compared to the no-statin group and measured for the outcome of the incidence of acute pancreatitis and the frequency of episodes within the first five years of statin use. Patients who experienced any acute pancreatitis episode before starting statin therapy or before meeting inclusion criteria were excluded from the study. RESULTS Patients on statin therapy were significantly more likely to develop acute pancreatitis compared to patients not taking statin therapy (risk ratio 1.332, 95% CI: 1.242-1.429, P<0.0001). However, the statin group had a lower mean number of pancreatitis episodes than the no-statin group (4.6 vs. 5.3, P=0.043). CONCLUSION The results from this large global dataset support the previously established idea that prolonged use of statins is associated with an increased risk of pancreatitis. Clinicians should strongly consider statin-induced pancreatitis when other common etiologies have been ruled out.
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Affiliation(s)
| | - Brittany Q Dang
- Internal Medicine, University of Texas Medical Branch, Galveston, USA
| | - Brittany Miles
- Radiology, Baylor University Medical Center, Dallas, USA
| | - James Mackey
- Hematology and Oncology, Baylor University Medical Center, Dallas, USA
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Ahn J, Lee S, Won S. Possible link between statin and iron deficiency anemia: A South Korean nationwide population-based cohort study. SCIENCE ADVANCES 2023; 9:eadg6194. [PMID: 37889968 PMCID: PMC10610901 DOI: 10.1126/sciadv.adg6194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 09/26/2023] [Indexed: 10/29/2023]
Abstract
An extensive evaluation of disease occurrence after statin use based on a "hypothesis-free" approach remains scarce. To examine the effect of statin use on the potential risk of developing diseases, a propensity score-matched cohort study was executed using data from the National Sample Cohort in South Korea. A total of 7847 statin users and 39,235 nonstatin users were included in the final analysis. The period of statin use was defined as our main time-dependent exposure and was divided into three periods: current, recent, and past. The main outcomes were defined as new-onset diseases with ≥100 events based on the International Statistical Classification of Diseases, 10th Revision. We calculated the adjusted hazard ratios and 95% confidence intervals (CIs) using Cox regression. We found that statin use significantly increased the risk of developing iron deficiency anemia up to 5.04 times (95% CI, 2.11 to 12.03). Therefore, the iron levels of patients using statins should be monitored carefully.
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Affiliation(s)
- Juhee Ahn
- Department of Public Health Science, Seoul National University, Seoul, Republic of Korea
| | - Sanghun Lee
- Department of Bioconvergence Engineering, Dankook University, Gyeonggi-do, Republic of Korea
- NH Institute for Natural Product Research, Myungji Hospital, Ilsan, Republic of Korea
| | - Sungho Won
- Department of Public Health Science, Seoul National University, Seoul, Republic of Korea
- Interdisciplinary Program of Bioinformatics, Seoul National University, Seoul, Republic of Korea
- Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea
- RexSoft Inc, Seoul, Republic of Korea
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Twohig PA, de-Madaria E, Thakkar S, Dulai P, Gardner TB, Kochhar G, Sandhu DS. Quantifying the Risk of Drug-Induced Pancreatitis With Angiotensin-Converting Enzyme Inhibitors and Statins Using a Large Electronic Medical Record Database. Pancreas 2021; 50:1212-1217. [PMID: 34714286 DOI: 10.1097/mpa.0000000000001895] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Quantify the risk of drug-induced pancreatitis (DIP) from angiotensin-converting enzyme inhibitors (ACEis) and 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins). METHODS Retrospective cohort analysis using IBM Explorys (1999-2019), a pooled, deidentified clinical database of more than 63 million patients across the United States. Odds ratios were calculated to determine the risk of DIP from ACEi, statins, and both medications together. χ2 testing assessed the relationship between age, sex, ethnicity, insurance status, and mortality among patients with DIP from ACEi, statins, or both combined. RESULTS Acute pancreatitis (AP) was found in 280,740 patients. Odds ratios for ACEi, statins, and both combined were 6.12, 4.97, and 5.72, respectively. Thirty-eight percent of all-cause AP occurs in adults older than 65 years. Acute pancreatitis from ACEi and statins occurs in 49% and 56% of patients older than 65 years, respectively. Men and patients older than 65 years are at higher risk of DIP from ACEi and statins. Patients on Medicaid are at higher risk of DIP from statins, and Asian patients are at highest risk of DIP from ACEi. CONCLUSIONS We found that ACEi and statins increase the odds of DIP. Although ACEis and statins are critical medications for many patients, clinicians should consider using alternatives in patients with AP of unclear etiology.
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Affiliation(s)
| | - Enrique de-Madaria
- Gastroenterology Department, Alicante University General Hospital, Alicante Institute for Health and Biomedical Research (ISABIAL), Alicante, Spain
| | - Shyam Thakkar
- Department of Medicine, Section of Gastroenterology & Hepatology, West Virginia University, Morgantown, WV
| | - Parambir Dulai
- Department of Gastroenterology, University of California San Diego, San Diego, CA
| | - Timothy B Gardner
- Department of Gastroenterology, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - Gursimran Kochhar
- Department of Gastroenterology & Hepatology, Allegheny Health Network, Pittsburgh, PA
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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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Abstract
Drug-induced acute pancreatitis (DIAP) is a rare entity that is often challenging for clinicians. The aim of our study was to provide updated DIAP classes considering the updated definition of acute pancreatitis (AP) and in light of new medications and new case reports. A MEDLINE search (1950-2018) of the English language literature was performed looking for all adult (≥17 years old) human case reports with medication/drug induced as the cause of AP. The included case reports were required to provide the name of the drug, and diagnosis of AP must have been strictly established based on the revised Atlanta Classification criteria. A total of 183 medications were found to be implicated in 577 DIAP cases. A total of 78 cases were excluded because of minimal details or lack of definite diagnosis of AP. Drug-induced AP is rare, and most drugs cause mild DIAP. Only 2 drugs are well described in the literature to explain causation rather than association (azathioprine and didanosine). Larger case-control studies and a formal standardized DIAP reporting system are essential to study the true potential of the DIAP-implicated drugs described in this review.
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Affiliation(s)
- C Roberto Simons-Linares
- From the Digestive Disease Institute, Gastroenterology and Hepatology Department, Cleveland Clinic, Cleveland, OH
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Lin CM, Liao KF, Lin CL, Lai SW. Use of Simvastatin and Risk of Acute Pancreatitis: A Nationwide Case-Control Study in Taiwan. J Clin Pharmacol 2017; 57:918-923. [PMID: 28301063 DOI: 10.1002/jcph.881] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2016] [Accepted: 01/19/2017] [Indexed: 12/24/2022]
Abstract
The correlation between simvastatin use and acute pancreatitis is explored. A case-control study was conducted to analyze claim data from the Taiwan National Health Insurance Program. The case group comprising a total of 3882 subjects aged 20 to 84 years with their first acute pancreatitis episode occurring between 1998 and 2011 formed the case group, against 3790 randomly selected controls matched for sex, age, comorbidities, and index year of acute pancreatitis diagnosis. Recent use of simvastatin was defined as subjects whose last remaining simvastatin tablet was noted ≤7 days before the date of acute pancreatitis diagnosis. Remote use of simvastatin was defined as subjects whose last remaining 1 tablet for simvastatin was noted >7 days before the date of acute pancreatitis diagnosis. Never use of simvastatin was defined as subjects who had never been prescribed simvastatin. A multivariable unconditional logistic regression model was used to estimate the odds ratio and 95%CI to explore the correlation between simvastatin use and acute pancreatitis. After adjustment for confounders, multivariable logistic regression analysis revealed that the adjusted odds ratio of acute pancreatitis was 1.3 for subjects with recent use of simvastatin (95%CI 1.02, 1.73), when compared with those with never use of simvastatin. The crude odds ratio decreased to 1.1 for those with remote use of simvastatin (95%CI 0.93, 1.34) but without statistical significance. Recent use of simvastatin is associated with acute pancreatitis. Clinicians should consider the possibility of simvastatin-associated acute pancreatitis for patients presenting for acute pancreatitis without known cause.
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Affiliation(s)
- Chih-Ming Lin
- Department of Internal Medicine, Taichung Tzu Chi General Hospital, Taichung, Taiwan
| | - Kuan-Fu Liao
- Department of Internal Medicine, Taichung Tzu Chi General Hospital, Taichung, Taiwan.,College of Medicine, Tzu Chi University, Hualien, Taiwan.,Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
| | - Cheng-Li Lin
- College of Medicine, China Medical University, Taichung, Taiwan.,Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
| | - Shih-Wei Lai
- College of Medicine, China Medical University, Taichung, Taiwan.,Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
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Kovacic S, Roginic S, Nemrava J, Gospocic K, Seferovic Saric M, Luetic K. Acute pancreatitis in two patients with Parkinson’s disease. COGENT MEDICINE 2017. [DOI: 10.1080/2331205x.2017.1312802] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Affiliation(s)
- Sanja Kovacic
- Department of Neurology, General Hospital Zabok and Hospital of Croatian Veterans, Bracak 8, 49210 Zabok, Croatia
- Faculty of Medicine, University of Osijek, Josip Juraj Strosmayer, 31000 Osijek, Croatia
| | - Sinisa Roginic
- Department of Internal Medicine, General Hospital Zabok and Hospital of Croatian, Veterans, Bracak 8, 49210 Zabok, Croatia
| | - Johann Nemrava
- Department of Surgery, General Hospital Zabok and Hospital of Croatian Veterans, Bracak 8, 49210 Zabok, Croatia
| | - Ksenija Gospocic
- Department of Radiology, General Hospital Zabok and Hospital of Croatian Veterans, Bracak 8, 49210 Zabok, Croatia
| | - Maida Seferovic Saric
- Department of Neurology, General Hospital Zabok and Hospital of Croatian Veterans, Bracak 8, 49210 Zabok, Croatia
| | - Kresimir Luetic
- Clinic for Internal Medicine, University Hospital Sv. Duh, Sv. Duh 64, 10000 Zagreb, Croatia
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Shiu SI, Su PF, Jang LH, Lee BJ, Wang CY. Prior statin use and the outcomes in patients with first-attack acute pancreatitis: A retrospective cohort study. Eur J Intern Med 2015; 26:425-8. [PMID: 25997756 DOI: 10.1016/j.ejim.2015.05.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 04/30/2015] [Accepted: 05/02/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND We investigated whether prior stain use before admission for a first-attack AP would reduce the severity and mortality rate of a first-attack of AP with a dose-response relationship. METHODS We conducted a retrospective cohort study from a tertiary medical center's database in Taiwan. We evaluated the dose-response relationship between statin use and the first-attack of AP by defining the daily dose (DDD). The cumulative DDD (cDDD) was calculated as the sum of the dispensed DDD of any specific statin. The outcome measures in our study included the hospital mortality rate, duration of hospitalization, Ranson's score, computed tomography severity index (CTSI), and C-reactive protein (CRP) level. RESULTS In our study, we enrolled 31 patients in statin group and 63 matched patients in control group. In the univariate analysis there was no significant difference between them with regard to the outcomes except the CTSI and serum calcium concentration. According to multivariate analysis the serum calcium concentration was significantly higher in the statin group, and the CTSI was lower in the statin group. In subgroup analysis we divided the statin group into two groups according to the cDDDs (<365days and >365days) and the results showed no significance in the demographic data, overall mortality rate, hospitalization days, CRP level, Ranson's score, or CTSI. CONCLUSION Our study rejected the hypothesis that statins have beneficial effects on the clinical outcomes of patients with a first-attack of AP. However we demonstrated that statins have a positive effect on the CTSI.
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Affiliation(s)
- Sz-Iuan Shiu
- Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
| | - Pei-Fang Su
- Department of Statistics, National Cheng-kung University, Tainan, Taiwan, ROC
| | - Li-Ho Jang
- Intensive Care Unit, Dachien Hospital, Miaoli, Taiwan, ROC
| | - Bor-Jen Lee
- Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
| | - Chen-Yu Wang
- Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
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9
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Etienne D, Reda Y. Statins and their role in acute pancreatitis: Case report and literature review. World J Gastrointest Pharmacol Ther 2014; 5:191-195. [PMID: 25133048 PMCID: PMC4133445 DOI: 10.4292/wjgpt.v5.i3.191] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 06/20/2014] [Accepted: 06/27/2014] [Indexed: 02/06/2023] Open
Abstract
Statin induced pancreatitis has historically been considered a diagnosis of exclusion, with literature references typically in the form of case reports and observational studies. Recently, larger studies have challenged the correlations made by earlier case reports, and instead demonstrate a mild protective effect in statin users. We present a case report of likely statin induced pancreatitis in a 58-year-old male (which we have attributed to drug-drug interaction with resulting inhibition of hepatic cytochrome P450 enzymes) and have reviewed the apparent dichotomy in the available literature.
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10
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Abstract
OBJECTIVE The long-term use of statins may be associated with a decreased risk for gallstones and biliary-induced acute pancreatitis (AP). Our aim was to study the relationship of statin use and outcome of AP. METHODS We investigated the records of 461 consecutive patients with AP and 1140 patients with symptomatic gallstones during 2008 to 2010. The use of lipid-lowering drugs, patient's characteristics, and outcome of patients were recorded. All known risk factors for AP and particularly statin use in idiopathic AP were analyzed. RESULTS Statin use was comparable between the patients with AP (22%) and patients with cholelithiasis (24%). The frequencies of surgical treatment, duration of hospital stay, or mortality were not different between the statin users compared with the nonusers. Idiopathic AP was more often associated with the use of statins than alcohol- or gallstone-induced AP (44% vs 30% vs 13%, P < 0.002). The etiology of AP was alcohol in 56% of the patients, gallstones in 28% of the patients, and unknown (idiopathic) or miscellaneous in 16% of the patients. CONCLUSIONS No beneficial effect of statins was observed in mortality or other outcome parameters of patients with AP. Statin use was more frequent in patients with idiopathic AP than in patients with biliary- or alcohol-induced AP.
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Recurrent acute pancreatitis probably induced by rosuvastatin therapy: a case report. Case Rep Med 2012; 2012:973279. [PMID: 22536267 PMCID: PMC3318890 DOI: 10.1155/2012/973279] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Accepted: 02/13/2012] [Indexed: 01/05/2023] Open
Abstract
Context. Approximately 1.4–2% of all cases of acute pancreatitis are drug related in general population. The literature on statin-induced pancreatitis consists primarily of anecdotal case reports. We report a case of possible rosuvastatin-induced pancreatitis. Case Report. A 67-year-old female presented with progressively worsening abdominal pain and vomiting for 7 days. Home medications included rosuvastatin and clonidine. CT scan of abdomen, with intravenous contrast, showed findings consistent with acute pancreatitis. She responded to conservative management. Rosuvastatin was resumed at the time of discharge from the hospital, and she presented two months later with recurrence of acute pancreatitis. Further workup ruled out all likely causes of acute pancreatitis. Rosuvastatin was stopped completely when she was discharged the second time, and she did not have any further episodes of acute pancreatitis. She was completely asymptomatic throughout the 18-month follow-up period. Conclusion. This paper reinforces the possible association of rosuvastatin, a novel statin, with acute pancreatitis, even though the exact underlying mechanism of statin-induced pancreatitis remains unknown.
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12
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Affiliation(s)
- Tracie Kaurich
- Department of Pharmacy Services, Baylor University Medical Center, Dallas, Texas, USA.
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13
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Deshpande PR, Khera K, Thunga G, Hande M, Gouda STG, Nagappa AN. Atorvastatin-induced acute pancreatitis. J Pharmacol Pharmacother 2011; 2:40-2. [PMID: 21701646 PMCID: PMC3117569 DOI: 10.4103/0976-500x.77114] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Atorvastatin-induced acute pancreatitis (AP) is one of the rare adverse effects available in the literature. We report a case of 53-year-old patient developed AP after treatment with atorvastatin monotherapy which resolved after drug withdrawal. Extensive workup on AP failed to reveal any other etiology for it. To our knowledge, this is one of the rare case reports of AP caused due to atorvastatin monotherapy and it further strengthens the fact that statins may cause AP. There is need of continued reporting of such a rare adverse effect of atorvastatin for increasing awareness and to manage and avoid the same.
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Affiliation(s)
- Prasanna R Deshpande
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, India
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14
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Van Woerkom RC, Adler DG. Letter to the Editor. J Clin Lipidol 2010; 4:314-5. [DOI: 10.1016/j.jacl.2010.03.075] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2010] [Revised: 03/24/2010] [Accepted: 03/25/2010] [Indexed: 10/19/2022]
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Molecular mechanisms of toxicity of simvastatin, widely used cholesterol-lowering drug. A review. Open Med (Wars) 2010. [DOI: 10.2478/s11536-009-0123-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
AbstractStatins are widely used and well tolerated cholesterol-lowering drugs, and when used for therapy purposes reduce morbidity and mortality from coronary heart disease. Simvastatin is one of nine known statins, specific inhibitors of hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting step of cholesterol biosynthesis, and is believed to reduce plasma cholesterol levels by decreasing the activity of this enzyme. Statin drugs represent the major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Although statins are generally safe, minor and severe adverse reactions are well known complications of statin use. Adverse events associated with simvastatin therapy are uncommon, but potentially serious. In this review some details about statins including their adverse effects in humans and animals, the effects of simvastatin on various intracellular and mitochondrial processes, and molecular mechanisms underlying simvastatin cytotoxicity are discussed.
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Audia P, Feinfeld DA, Dubrow A, Winchester JF. Metformin-induced lactic acidosis and acute pancreatitis precipitated by diuretic, celecoxib, and candesartan-associated acute kidney dysfunction. Clin Toxicol (Phila) 2008; 46:164-6. [PMID: 18259965 DOI: 10.1080/15563650701355314] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Polypharmacy may lead to synergistic complications from the different medications. We report the case of a 50-year-old woman who was prescribed 11 drugs, including a diuretic, celecoxib, metformin, and candesartan, and who developed acute kidney dysfunction while on these drugs, manifesting as severe proteinuria, acute azotemia, hyperkalemia. The kidney injury caused the accumulation of metformin, leading to lactic acidosis and acute pancreatitis. Sodium bicarbonate hemodialysis not only improved the metabolic abnormalities but also hastened the removal of metformin.
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Affiliation(s)
- Pat Audia
- Beth Israel Medical Center, Nephrology and Hypertension, New York, New York 10003, USA
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17
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Abstract
Acute pancreatitis is an inflammatory disease of the pancreas. Acute abdominal pain is the most common symptom, and increased concentrations of serum amylase and lipase confirm the diagnosis. Pancreatic injury is mild in 80% of patients, who recover without complications. The remaining patients have a severe disease with local and systemic complications. Gallstone migration into the common bile duct and alcohol abuse are the most frequent causes of pancreatitis in adults. About 15-25% of pancreatitis episodes are of unknown origin. Treatment of mild disease is supportive, but severe episodes need management by a multidisciplinary team including gastroenterologists, interventional radiologists, intensivists, and surgeons. Improved understanding of pathophysiology and better assessments of disease severity should ameliorate the management and outcome of this complex disease.
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Affiliation(s)
- Jean-Louis Frossard
- Division de Gastroentérologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
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18
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Affiliation(s)
- Anil R Balani
- Division of Gastroenterology, Hepatology and Nutrition, Winthrop University Hospital, Mineola, New York 11501, USA
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19
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Singh S, Loke YK. Statins and pancreatitis: a systematic review of observational studies and spontaneous case reports. Drug Saf 2007; 29:1123-32. [PMID: 17147459 DOI: 10.2165/00002018-200629120-00004] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Many anecdotal reports have suggested that therapy with HMG-CoA reductase inhibitors ('statins') can cause acute pancreatitis. We aimed to quantify the association between statins and pancreatitis and to classify the adverse effect under the dose, time, susceptibility (DoTS) system. We searched for controlled observational studies that assessed the risk of pancreatitis in patients receiving statins. In order to identify case reports of statin-induced pancreatitis, we looked for reports published in scientific journals and manually reviewed reports within the Canadian Adverse Drug Event Monitoring System (CADRMP) database. Two observational studies were identified and the data pooled together in a meta-analysis. This yielded an odds ratio of 1.41 (95% CI 1.15, 1.74) for the risk of acute pancreatitis in patients with a past history of exposure to statins. We also identified 20 published case reports and 33 spontaneous reports from the CADRMP database. These data showed that pancreatitis can occur at both high and low doses, with 12 cases developing pancreatitis at less than the dose equivalent of simvastatin 20 mg daily. Statin-induced pancreatitis can occur at any time but seems to be very uncommon early on and more likely to occur after many months of therapy. There does not appear to be a cumulative dose effect and increasing age does not appear to be a major susceptibility factor. These finding should help clinicians to better manage and diagnose patients who are at risk of statin-induced pancreatitis.
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Affiliation(s)
- Sonal Singh
- Department of Internal Medicine, Section on General Internal Medicine, Wake Forest University Health Sciences, Winston Salem, North Carolina, USA.
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Kiortsis DN, Filippatos TD, Mikhailidis DP, Elisaf MS, Liberopoulos EN. Statin-associated adverse effects beyond muscle and liver toxicity. Atherosclerosis 2006; 195:7-16. [PMID: 17094994 DOI: 10.1016/j.atherosclerosis.2006.10.001] [Citation(s) in RCA: 73] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2006] [Revised: 09/17/2006] [Accepted: 10/02/2006] [Indexed: 01/02/2023]
Abstract
Randomized controlled trials with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have consistently demonstrated significant reductions in cardiovascular morbidity and mortality. Statins are currently the most widely used drugs in many countries. The most important adverse effects are associated with muscle and liver toxicity. However, with increased use and dose of statins and their over-the-counter availability in some countries more cases of other rare side effects may be seen in clinical practice. In the present article we review the literature concerning the statin-related adverse effects other than muscle and liver injury and we provide insight into their clinical relevance and possible underlying mechanisms.
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Affiliation(s)
- D N Kiortsis
- Laboratory of Physiology, Medical School, University of Ioannina, Ioannina, Greece
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Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2006. [DOI: 10.1002/pds.1182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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Shuster J. Myopathy with Ezetimibe Monotherapy; Statin-Associated Pancreatitis; Linezolid Associated Toxic Optic Neuropathy; Hiccups and Dopamine Agonists; SIADH and Seizures in a Patient Treated with Duloxetine; Prevention of a Well-Known Adverse Drug Reaction. Hosp Pharm 2006. [DOI: 10.1310/hpj4105-408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the FDA's medWatch program (800-FDA-1088). If you have reported an interesting preventable ADR to medWatch, please consider sharing the account with our readers.
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Affiliation(s)
- Joel Shuster
- ISMP, 1800 Byberry Road, Suite 810, Huntingdon Valley, PA 19006
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