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Tarar ZI, Zafar MU, Ghous G, Farooq U, Shoukat HMH. Pravastatin-Induced Acute Pancreatitis: A Case Report and Literature Review. J Investig Med High Impact Case Rep 2021; 9:23247096211028386. [PMID: 34180257 PMCID: PMC8243091 DOI: 10.1177/23247096211028386] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Pancreatitis is inflammation of pancreas associated most commonly with chronic
alcoholism and gallstones. Other less common causes of pancreatitis are
hyperlipidemia, infections, surgery, trauma, post endoscopic retrograde
cholangiopancreatography, and drugs. Drugs are now increasingly recognized as a
cause of pancreatitis, and high suspicion and exclusion of other most common
causes is required before considering drug-induced pancreatitis. There are few
case reports of acute pancreatitis in the literature after statin use, but out
of these, only 3 are after starting pravastatin. We are reporting a case of
49-year-old male who presented with nausea, vomiting, and abdominal pain. His
laboratory findings were significant for lipase more than 10 000 on admission,
and computed tomography scan of abdomen was showing peripancreatic fat stranding
and inflammation. After exclusion of most common causes of pancreatitis,
pravastatin was found probable culprit for his symptoms, which he started taking
2 weeks ago. We also reviewed the literature on statins-induced acute
pancreatitis. With increased uses of statins, physician need to be vigilant to
suspect statins as a culprit in cases of pancreatitis with unknown etiology.
Prompt discontinuation of statins is required in these cases.
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Affiliation(s)
- Zahid Ijaz Tarar
- University of Missouri, Columbia, MO,
USA
- Zahid Ijaz Tarar, MD, Department of
Internal Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO 65211,
USA.
| | | | | | - Umer Farooq
- Loyola Medicine, MacNeal Hospital,
Berwyn, IL, USA
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2
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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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Fenofibrate: A Nonlithogenic Means of Recurrent Drug-Induced Pancreatitis. Case Rep Gastrointest Med 2018; 2018:4580860. [PMID: 30271638 PMCID: PMC6151234 DOI: 10.1155/2018/4580860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 08/27/2018] [Indexed: 11/18/2022] Open
Abstract
Medications account for a small portion of the various etiologies of acute pancreatitis. Prompt identification of drugs as the inciting factor decreases disease recurrence and unnecessary invasive diagnostic intervention. This case is a report of fenofibrate-induced acute pancreatitis including a disease recurrence with continuation of fenofibrate which subsequently resolved after drug discontinuation. The patient underwent invasive diagnostic evaluation including endoscopic ultrasound with fine needle aspiration and endoscopic retrograde cholangiopancreatography (ERCP). Based on exclusion of other disease etiologies and a positive drug rechallenge, fenofibrate fits as a class 1A medication in the classification of drug-induced pancreatitis.
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Maghrebi H, Rhaeim R, Haddad A, Makni A, Mohamed J, Montasser K, Zoubeir BS. [Drug-induced acute pancreatitis: about 10 cases]. Pan Afr Med J 2017; 28:80. [PMID: 29255550 PMCID: PMC5724947 DOI: 10.11604/pamj.2017.28.80.12160] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2017] [Accepted: 08/13/2017] [Indexed: 11/11/2022] Open
Abstract
Drug-induced acute pancreatitis (AP) accounts for approximately 2% of acute pancreatitis. Its incidence is increasing, with more than 260 incriminated drugs. However, very few cases have been described in the literature due to accountability problem. We report our experience with 10 cases whose data were collected over a period of 7 years. Clinical presentation of AP was often equivocal. Ranson's score ranged from 0 to 5. We recorded 5 cases of edematous pancreatitis and 5 cases of necro-bleeding pancreatitis. These pancreatitis were often successfully treated without recurrence after discontinuation of the incriminated drug.
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Affiliation(s)
- Houcine Maghrebi
- Faculté de Médecine de Tunis, Université Tunis El Manar, Service de Chirurgie Générale A, Hôpital La Rabta, Tunisie
| | - Rami Rhaeim
- Faculté de Médecine de Tunis, Université Tunis El Manar, Service de Chirurgie Générale A, Hôpital La Rabta, Tunisie
| | - Anis Haddad
- Faculté de Médecine de Tunis, Université Tunis El Manar, Service de Chirurgie Générale A, Hôpital La Rabta, Tunisie
| | - Amin Makni
- Faculté de Médecine de Tunis, Université Tunis El Manar, Service de Chirurgie Générale A, Hôpital La Rabta, Tunisie
| | - Jouini Mohamed
- Faculté de Médecine de Tunis, Université Tunis El Manar, Service de Chirurgie Générale A, Hôpital La Rabta, Tunisie
| | - Kacem Montasser
- Faculté de Médecine de Tunis, Université Tunis El Manar, Service de Chirurgie Générale A, Hôpital La Rabta, Tunisie
| | - Ben Safta Zoubeir
- Faculté de Médecine de Tunis, Université Tunis El Manar, Service de Chirurgie Générale A, Hôpital La Rabta, Tunisie
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5
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Abstract
Background: A few cases of statin-associated pancreatitis have been reported in the literature, mostly related to the use of simvastatin. Only 3 cases of pancreatitis associated with lovastatin have been recognized, with 2 of them possibly due to its interaction with gemfibrozil and erythromycin. Case Report: A 49-year-old woman, who had been receiving treatment for hypercholesterolemia with lovastatin 20 mg/d for about a month, was admitted to a hospital with a diagnosis of diarrhea and septic shock. She was later referred to another hospital where surgical diagnosis of necrotizing pancreatitis was made and died after prolonged hospitalization. This patient had no evidence of common risk factors to acute pancreatitis, such as biliary tract disease or alcohol use, but had moderate hyperlipidemia. Assessment of the likelihood of a causal relationship using the Naranjo probability scale suggested that the association between lovastatin and necrotizing pancreatitis in this case was probable or possible, depending on the rejection or acceptance of shock or use of ranitidine and ceftriaxone as alternative causes of pancreatitis. Discussion: There is some evidence that statins are rarely associated with acute edematous and necrotizing pancreatitis, by unknown mechanisms. This case report adds to the evidence that lovastatin is possibly 1 of such statins. Conclusions: Lovastatin is a possible cause of pancreatitis. Prescribers of statins (particularly simvastatin and lovastatin) should take into account the possibility of acute pancreatitis in patients who develop abdominal pain within the first weeks of treatment with these drugs.
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Affiliation(s)
- Sérgio de A Nishioka
- SÉRGIO DE A NISHIOKA MD PhD, Assistant Professor, Medical School and Intensive Care Unit, Hospital de Clínicas, Federal University of Uberlândia, Uberlândia, Brazil
| | - Liliane Q Guedes
- LILIANE Q GUEDES MD, Physician, Faculdade de Medicina, and Unidade de Terapia Intensiva, Hospital de Clínicas, Universidade Federal de Uberlândia
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Wu BU, Pandol SJ, Liu ILA. Simvastatin is associated with reduced risk of acute pancreatitis: findings from a regional integrated healthcare system. Gut 2015; 64:133-8. [PMID: 24742713 PMCID: PMC4877305 DOI: 10.1136/gutjnl-2013-306564] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
OBJECTIVE To characterise the relationship between simvastatin and risk of acute pancreatitis (AP). DESIGN We conducted a retrospective cohort study (2006-2012) on data from an integrated healthcare system in southern California. Exposure to simvastatin was calculated from time of initial dispensation until 60 days following prescription termination. AP cases were defined by ICD-9 CM 577.0 and serum lipase≥3 times normal. Patients were censored at death, last follow-up, and onset of AP or end-of-study. Incidence rate of pancreatitis among simvastatin users was compared with the adult reference population. Robust Poisson regression was used to generate risk ratio (RR) estimates for simvastatin use adjusted for age, gender, race/ethnicity, gallstone-related disorders, hypertriglyceridaemia, smoking and alcohol dependence. Analysis was repeated for atorvastatin. RESULTS Among 3,967,859 adult patients (median duration of follow-up of 3.4 years), 6399 developed an initial episode of AP. A total of 707,236 patients received simvastatin during the study period. Patients that received simvastatin were more likely to have gallstone-related disorders, alcohol dependence or hypertriglyceridaemia compared with the reference population. Nevertheless, risk of AP was significantly reduced with simvastatin use, crude incidence rate ratio 0.626 (95% CL 0.588, 0.668), p<0.0001. In multivariate analysis, simvastatin was independently associated with reduced risk of pancreatitis, adjusted RR 0.29 (95% CL 0.27, 0.31) after adjusting for age, gender, race/ethnicity, gallstone disorders, alcohol dependence, smoking and hypertriglyceridaemia. Similar results were noted with atorvastatin, adjusted RR 0.33(0.29, 0.38). CONCLUSIONS Use of simvastatin was independently associated with reduced risk of AP in this integrated healthcare setting. Similar findings for atorvastatin suggest a possible class effect.
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Affiliation(s)
- Bechien U Wu
- Southern California Permanente Medical Group, Division of Gastroenterology, Center for Pancreatic Care, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA
| | - Stephen J Pandol
- Program in Basic and Translational Pancreatic Research, Cedars Sinai Medical Center, Los Angeles, California, USA
| | - In-Lu Amy Liu
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA
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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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8
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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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Stefanutti C, Bucci A, Di Giacomo S, Fraone N, Pace A, Mareri M, Musca A, Mammarella A. Efficacy, safety and tolerability of combined low-dose simvastatin-fenofibrate treatment in primary mixed hyperlipidaemia. Clin Drug Investig 2012; 24:465-77. [PMID: 17523707 DOI: 10.2165/00044011-200424080-00005] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE In order to assess the long-term (12 months) efficacy and safety of fenofibrate administered with simvastatin in the treatment of primary mixed hyperlipidaemia, we conducted a study that compared increasing dosages of these drugs in subgroups of men and women belonging to a clinical sample of out-patients. DESIGN This was an open study carried out in patients with primary mixed hyperlipidaemia (lipoprotein phenotype IIb) who needed a combined therapeutic approach because of their poor response to a single-drug regimen with an HMG-CoA reductase inhibitor (simvastatin). Thus, a fibrate (fenofibrate) was added to the therapy. The study lasted 12 months. PATIENTS Forty-five patients (mean age: 58.9 +/- 11.3 years) with primary mixed hyperlipidaemia who showed a poor response to the single-drug hypolipidaemic treatment were enrolled. Their average plasma triglyceride level was consistently above 300 mg/dL and low-density lipoprotein cholesterol (LDL-C) was over 160 mg/dL after at least 6 months of a single hypolipidaemic drug (simvastatin) regimen plus antiatherogenic dietary treatment. INTERVENTIONS Five patients received simvastatin 10mg once daily in addition to fenofibrate 200mg; 26 patients received simvastatin 20mg once daily plus fenofibrate 200mg; 11 patients received simvastatin 20mg once daily plus fenofibrate 300mg; and three patients received simvastatin 30mg once daily plus fenofibrate 200mg. The patients were allocated to treatment groups on the basis of their relative response to the therapy. Those making up the progressively higher agent/dose groups were the individuals at higher cardiovascular risk according to the total cholesterol and non-high-density lipoprotein cholesterol (HDL-C) values. RESULTS The double-drug regimen given for 12 months to four different groups, according to the different combined dosages of simvastatin and fenofibrate, resulted in a reduction in total cholesterol of 18% (p </= 0.05) to 39% (p </= 0.05), in LDL-C of 21% (not significant) to 39% (p </= 0.05) and in triglycerides of 35% (p </= 0.05) to 56% (p </= 0.01), and an increase in HDL-C of 8% (p </= 0.05) to 30% (not significant). The cardiovascular risk ratio (total cholesterol/HDL-C) at the end of the study was reduced by 33-60%, whereas the non-HDL-C decreased by 25-38%. No serious adverse effects were reported by the patients. Neither liver biochemistry nor creatine kinase serum concentration were significantly changed. Discontinuation of treatment, if necessary, in case of the occurrence of clinically subjective or objective evidence of adverse effects was assured. CONCLUSION The results confirmed the efficacy of the combination of fenofibrate and simvastatin. The combined therapeutic approach was shown to be safe for the treatment of primary mixed hyperlipidaemia, at least in patients with normal hepatic and renal function.
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Affiliation(s)
- C Stefanutti
- Dipartimento di Clinica e Terapia Medica Applicata, University "La Sapienza" of Rome, Policlinico Umberto I, Rome, Italy
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10
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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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Affiliation(s)
- Anil R Balani
- Division of Gastroenterology, Hepatology and Nutrition, Winthrop University Hospital, Mineola, New York 11501, USA
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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: 357] [Impact Index Per Article: 19.8] [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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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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14
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Abstract
Acute pancreatitis (AP) secondary to drugs is un-common, with an incidence ranging from 0.3% to 2.0% of AP cases. Drug-induced AP due to statins is rare, and only 12 cases have thus far been reported. In this case report, we report a case of a 50-year-old female on pravastatin therapy for 3 d prior to developing symptoms of AP. The common etiological factors for AP were all excluded. The patient was admitted to the intensive care unit secondary to respiratory distress, though she subsequently improved and was discharged 14 d after admission. Although the incidence of drug-induced AP is low, clinicians should have a high index of suspicion for it in patients with AP due to an unknown etiology. Clinicians should be aware of the association of statins with AP. If a patient taking a statin develops abdominal pain, clinicians should consider the diagnosis of AP and conduct the appropriate laboratory and diagnostic evaluation if indicated.
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Affiliation(s)
- Constantine Tsigrelis
- Department of Internal Medicine, Saint Peter's University Hospital, Robert Wood Johnson Medical School New Brunswick, NJ, USA
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15
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Johnson JL, Loomis IB. A case of simvastatin-associated pancreatitis and review of statin-associated pancreatitis. Pharmacotherapy 2006; 26:414-22. [PMID: 16503723 DOI: 10.1592/phco.26.3.414] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Reduction of low-density lipoprotein cholesterol (LDL) concentration has become the primary goal and a standard of care in the practice of cholesterol management. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, are the most frequently prescribed lipid lowering agents on the market. As more information is learned through the results of clinical trials, LDL goals become more stringent and difficult to attain. Large doses of high-potency statins, sometimes given in combination with other lipid-lowering agents, are frequently necessary to achieve these goals. As a result, the frequency of adverse effects from statin therapy may be expected to increase, and less common adverse effects may occur more often. As statins are used more aggressively, rare and possibly dangerous adverse effects must be identified, especially those that are becoming more frequently encountered. Increased awareness may lead to earlier diagnosis and management of diseases that may be caused by the statins. We describe a 58-year-old man who was hospitalized with idiopathic pancreatitis 4 months after starting simvastatin therapy. His oral drug therapy was withheld, and he was treated with bowel rest. The patient was discharged on hospital day 5, and his oral drug regimen, including simvastatin, was resumed. He was admitted again 16 months later with a second diagnosis of acute pancreatitis and was discharged after 3 days of bowel rest with no oral drug therapy. Simvastatin was restarted on discharge, but the patient stopped taking it after experiencing muscle soreness and weakness in his arms. He recalled having similar arm pain that preceded the previous episode of acute pancreatitis. All other causes of the pancreatitis had been ruled out; thus, the correlation between simvastatin-induced myalgia and onset of acute pancreatitis on two separate occasions made simvastatin the suspected instigating agent. Pancreatitis is a rare adverse effect of statin therapy, but it has been documented in several case reports involving most of the statins. Continued reporting is necessary to increase awareness of this rare adverse effect of simvastatin so that it may be promptly managed or avoided in the future.
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Affiliation(s)
- Jeremy L Johnson
- Department of Pharmacy: Clinical and Administrative Sciences, College of Pharmacy, University of Oklahoma Schusterman Center, Tulsa, Oklahoma 74135, USA.
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16
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Thisted H, Jacobsen J, Munk EM, Nørgaard B, Friis S, McLaughlin JK, Sørensen HT, Johnsen SP. Statins and the risk of acute pancreatitis: a population-based case-control study. Aliment Pharmacol Ther 2006; 23:185-90. [PMID: 16393296 DOI: 10.1111/j.1365-2036.2006.02728.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
BACKGROUND Case reports have suggested that statins may cause acute pancreatitis. AIM To examine if statins are associated with risk of acute pancreatitis. METHODS We identified 2576 first-time admitted cases of acute pancreatitis from hospital discharge registers in three Danish counties, and 25 817 age- and gender-matched controls from the general population. Prescriptions for statins prior to admission with acute pancreatitis or index date among controls were retrieved from prescription databases. We used conditional logistic regression analysis to estimate odds ratios for acute pancreatitis among ever (ever before), current (0-90 days before), new (first prescription in 0-90 days before) and former (>90 days, but not 0-90 days before) users of statins. RESULTS Adjusted odds ratios for acute pancreatitis among ever, current, new and former users of statins were 1.44 (95% confidence interval: 1.115-1.80), 1.26 (95% confidence interval: 0.96-1.64), 1.01 (95% confidence interval: 0.43-2.37) and 2.02 (95% confidence interval: 1.37-2.97), respectively. There was an indication of an inverse association between the number of filled prescriptions and risk of acute pancreatitis. CONCLUSIONS Our findings speak against a strong causative effect of statins on the risk of acute pancreatitis, and may even indicate a mild protective effect.
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Affiliation(s)
- H Thisted
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
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17
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Grahit Vidosa V, Avilés Cigüela S, Ribas Batllori A, Juncadella García E. [Acute pancreatitis due to lipid-lowering drugs]. Aten Primaria 2005; 35:437-8. [PMID: 15882504 PMCID: PMC7668674 DOI: 10.1157/13074803] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
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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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Gotto AM. Should patients with combined hyperlipidemia receive statin-fibrate combination therapy? NATURE CLINICAL PRACTICE. CARDIOVASCULAR MEDICINE 2005; 2:284-5. [PMID: 16265530 DOI: 10.1038/ncpcardio0217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2005] [Accepted: 04/18/2005] [Indexed: 05/05/2023]
Affiliation(s)
- Antonio M Gotto
- Weill Medical College, Cornell University, New York, NY, USA.
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Kanbay M, Sekuk H, Yilmaz U, Gur G, Boyacioglu S. Acute pancreatitis associated with combined lisinopril and atorvastatin therapy. Dig Dis 2005; 23:92-4. [PMID: 15920330 DOI: 10.1159/000084729] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Few data exist about the incidence of drug-induced pancreatitis in the general population. Drugs are related to the etiology of pancreatitis in about 1.4-2% of cases. Although statins are generally well tolerated, acute pancreatitis has been reported in a few cases treated with atorvastatin, fluvastatin and simvastatin. A 86-year-old man with long-standing history of hypertension and hyperlipidemia, who was treated with lisinopril 10 mg and atorvastatin 20 mg once daily presented with acute pancreatitis. Other causes of the disease were ruled out. After cessation of the drugs, his physical condition improved and the amylase level decreased. To our knowledge, pancreatitis induced by a combination of atorvastatin together with lisinopril has never been reported in the literature.
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Affiliation(s)
- Mehmet Kanbay
- Department of Internal Medicine, Baskent University Faculty of Medicine, Fevzi Cakmak Caddesi, Bahcelievler, Ankara, Turkey.
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Pezzilli R, Ceciliato R, Corinaldesi R, Barakat B. Acute pancreatitis due to simvastatin therapy: increased severity after rechallenge. Dig Liver Dis 2004; 36:639-40. [PMID: 15460851 DOI: 10.1016/j.dld.2004.05.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Abstract
Fenofibrate is a fibric acid derivative that has been marketed since the mid-1970's (1998 in the United States). Its active metabolite, fenofibric acid, is responsible for the primary pharmacodynamic effects of the drug: reductions in total plasma cholesterol, low density lipoprotein cholesterol, triglycerides, and very low-density lipoprotein concentrations and increases in high-density lipoprotein cholesterol and apolipoproteins AI and AII concentrations. These effects are mediated by activation of peroxisome proliferator-activated receptor-alpha (PPAR(alpha)). The drug has broad spectrum utility, with documented efficacy in Fredrickson types IIa, IIb, III, IV, and V hyperlipidemias. Fenofibrate is well tolerated, with digestive and musculoskeletal side effects similar to those of other fibrates. Results of the initial cardiovascular morbidity/mortality outcomes study with fenofibrate (known as DAIS [Diabetes Atherosclerosis Intervention Study]) were encouraging vis-à-vis slowing of atherosclerotic progression in the coronary vasculature of type II diabetics. The results of other ongoing outcome trials are eagerly awaited. These results will help to establish the overall place of fenofibrate in the hypolipidemic armamentarium.
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Affiliation(s)
- David R P Guay
- University of Minnesota, College of Pharmacy, Weaver-Densford Hall 7 - 115C, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
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23
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Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2002; 11:421-36. [PMID: 12271887 DOI: 10.1002/pds.661] [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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