Pancreapedia: Exocrine Pancreas Knowledge Base, DOI: 10.3998/panc.2015.32
Acute pancreatitis (AP) is a heterogeneous disease ranging from a clinically mild form to a more severe forms associated with high morbidity and mortality (78). A correct diagnosis of AP should be made within 48 h of admission. Understanding of the etiology and severity assessment are essential, as they may affect the acute management of the disease (8).
The most common etiology for AP are gallstones and alcohol abuse. Other causes include iatrogenic injury (i.e. post-ERCP), metabolic and autoimmune disorders, inherited disorders, neoplasia (even intraductal papillary mucinous neoplasia- IPMN), anatomical abnormalities, infections, ischaemia, trauma and drugs (87). Additional investigations after recovery from the acute episode are recommended in patients with an episode of AP classified as idiopathic (68).
Drugs may be considered a potential cause of the disease in patients who take medications that have been associated with AP.
Drug-induced pancreatitis (DIP) is assumed to be a relative rare entity, and its incidence is reported between 0.1 and 2% of AP cases (62). However, the true incidence of DIP is still unknown since little evidence has been obtained from clinical trials, and most incidences have been documented as case reports (62) generally limited by the absence or inadequacy of diagnostic criteria for AP, failure to rule out common etiologies of AP, and lack of a re-challenge test.
The main problem in the identification of DIP is the absence of a clear and largely accepted definition of the disease. The diagnosis of DIP is difficult to establish since it is rarely accompanied by clinical or laboratory evidence of a drug reaction and the large proportion of patients admitted for AP are already taking a medication. Therefore, criteria to diagnose DIP should include the evidence for drug intake shortly preceding AP, an increased risk for AP in patients taking the drug, direct correlation between increased risk and dose, presence of a plausible biological mechanism, evidence in clinical trials using the specific drug and a re-challenge test. However, we lack a definition for each of these potential diagnostic criteria for DIP (i.e. elapsed time between drug intake and AP).
Five-hundred and twenty-five different drugs suspected to cause acute pancreatitis are reported in the database of World Health Organization (WHO) (61). The majority of the data are derived from case reports, case series or summaries of them. Furthermore, the causality for many of these drugs remains elusive and for only about thirty of these 525 dugs has a definite causality been established (61). Another methodological problem is the evaluation of other potential cause of AP. Some definitions exclude the presence of other etiologies of AP, primarly biliary lithiasis and alcohol abuse. However, the presence of other causes of AP do not exclude DIP but certainly decrease the probability of DIP.
The re-challenge test under the same conditions as in the first episode of suspected DIP is probably the best diagnostic criterion, but its use in clinical practice is limited particularly in patients with a severe attack of pancreatitis. The consequence is a dramatic decrease in the number of drugs shown to induce pancreatitis using the re-challange test. However, this test cannot be considered as a definitive criterion for the diagnosis since stopping and restarting a drug with a recurrence of pancreatitis may be a coincidence and not a demonstration of a cause and effect. This is probably the reason why Tenner in a recent review raised the question about the real existence of DIP (82).
A consequence of all these problems for the definition of DIP is its classification. Many classifications have been proposed. In the more recent critical review (62, 84), a classification system of the published case reports based on the level of evidence was used. A larger number of case reports and/or a consistent latency among the reports for a particular drug were evaluated. Badalov et al. (7) created a new classification of DIP based on the features of case reports and the presence or absence of a re-challenge test. However, a classification in definite, probable and possible association between drugs and pancreatitis is the most preferred (43, 61) (Table 1), based on the evaluation of the rechallenge/dechallenge test, temporal sequence, exclusion of other causes of pancreatitis. A useful tool to establish the association of a drug with pancreatitis could be the Naranjo Score (58) (Table 2).
A list of drugs classified in definitive and probable is listed on Table 3 (61).
2. Drugs More Commonly Associated with AP
Azathioprine and 6-Mercaptopurine
Since 1980, azathioprine (AZA) and its metabolite 6-mercaptopurine (6-MP) were reported to be able to induce pancreatitis (33). The incidence is reported between 1% and 6% of exposed individuals. A Danish study (24)demonstrate a 7 to 8 fold increase in the risk to develop AP comparing ever- with never-takers. Despite the large size of the sample of study, the uniformly organized health care system and the use of appropriate population controls, the limit of the study was the incomplete registration of confounders (risk factors i.e. alcohol or gallstones), included potential association between inflammatory bowel disease (IBD) and autoimmune pancreatitis (25). Indeed, previous case reports have suggested that IBD is associated with a liability to develop pancreatitis, especially for Crohn's disease, because of common pathogenic mechanisms, diminished entero-hepatic circulation of bile acids in patients with ileal involvement or who underwent surgical ileal resection) (25), mechanic factors in duodenal localizations of disease (papilla of Oddi’s disfunctionand coexistence of therapy with other drugs involved in DIP like mesalamine, glucocorticoids or metronidazole (35).
The mechanism of how azathioprine causes pancreatitis is not well elucidated and the development of pancreatitis did not appear to be dose related(36). Therefore, it may be better classified as allergic or idiosyncratic. Although some authors have suggested the utility of thiopurine methyltransferase (TPMT) heterozygosity and enzyme activity as predictive tests for the development of azathioprine-related adverse events, the role in predicting acute pancreatitis has not been studied yet (34). Even if some authors have communicated that MP could safely be used after an AZA-induced episode of AP (1),most authors agree that a cross reaction after re- exposure of the related drug is probable.
ACE inhibitors are one of the most commonly prescribed classes of medications, as they are used in hypertension, heart failure and proteinuria (32). The first reported case of ACE inhibitor-induced pancreatitis was seen with enalapril (15, 31, 54). Other case reports about pancreatitis induced by lisinopril (13, 28, 42, 53), captopril (38), ramipril (41)and perindopril (27) have been also published.
In one case-control study, the use of ACE inhibitor was associated with an increased risk of acute pancreatitis, with an odds ratio of 1.5. The risk increased with higher daily doses and was highest during the first 6 months of therapy (22).
Pancreatitis associated with ACE inhibitors is thought to reflect localized angioedema of the gland, linked probably to an increase of bradykinin secondary to its decreased degradation. Angiotensin II receptors regulate pancreatic secretion and microcirculation, and these effects may be contribute to the pathogenesis of ACE inhibitors induced pancreatitis (73).However, ACE inhibitors, in particular captopril, showed an important role in attenuating vascular permeability in experimental severe acute pancreatitis in rats, reducing expression of matrix metalloproteinase 9. No human studies are available yet to confirm this experimental evidence and to develop a target therapy. In summary, there are controversies on the role of ACE inhibitors in DIP, since they may induce mild pancreatitis in humans, but may reduce the severity of experimental AP in animals.
Metformin, a biguanide commonly used in type 2 diabetes, is considered to be a safe drug with minimal side effects and only few papers (case report) data suggest metformin as associated with DIP. Among these published case reports, the mechanisms postulated are drug overdose, drug accumulation, and acute renal failure triggered by vomiting (12, 23, 52). Therefore, metformin has been classified as possible DIP.
Incretin-based therapies such as glucagon-like peptide-1 agonists (GLP-1) and di-peptidyl peptidase-4 (DPP-4) inhibitors have become important therapeutic options for treatment of type 2 diabetes. Proposed mechanisms of action include enhanced glucose-dependent insulin secretion from pancreatic-cells, restoration of first phase insulin response, suppression of glucagon secretion, and delay of gastric emptying. Acute pancreatitis has been reported with both GLP-1 agonist (5, 44, 48, 75, 83) and DPP-4 inhibitor (30, 46).Over the last several years post-marketing reporting of this adverse events to FDA resulted in manufacturers emphasizing for acute pancreatitis and, later, in controindications for incretin-based therapies in patients with a history of pancreatitis (37).
Recently, several metanalysis and cohort studies demonstrated that the incidence of pancreatitis in patients taking incretins is low and that these drugs do not increase the risk of pancreatitis (3, 20, 21, 26, 29, 39, 50, 56). Li et al. found no association between the use of GLP-1-based therapies and pancreatitis in a self-controlled case series analysis in a large observational database from dispensing data on 1.2 million patients (50). Even animal research demonstrated no evidence of acute pancreatitis in GLP-1 agonist/DPP-4 inhibitors (6, 45, 80, 81, 86).A recent meta-analysis of randomised and non randomised studies confirmed that the risk of AP under incretin-based therapy is not increased (49).
While statins are generally well tolerated they have been known to be associated with pancreatitis.
DIP is a rare adverse effect of statin therapy, but it has been documented mainly in case reports involving atorvastatin (11, 77), fluvastatin (85), rosuvastatin (17, 47), simvastatin (40, 67, 69),and pravastatin (4, 10), leading to the conclusion that statins induced pancreatitis may be a class-effect (74). An immune-mediated inflammatory response, direct cellular toxicity and metabolic effect have all been postulated, even though the mechanism of action remains ill-defined. Statin-induced pancreatitis can occur at any time but seems to be very uncommon early in treatment and more likely to occur after months of therapy. Singh and Loke have postulated that differences exist in the safety profiles of the various statins that may correlate with the degree to which they inhibit cytochrome P450 CYPA4 as well as the degree of their lipophilicity (76).
Recently, larger studies have challenged the correlations made by earlier case reports, and demonstrate instead a mild protective effect in statin users, as previously shown in animal models of acute pancreatitis (18), where statins appear to reduce inflammatory cytokines and pulmonary neutrophilic activation in a severe acute pancreatitis model (2).
5-ASA and Derivatives
Since 1989 mesalamine induced pancreatitis has been described (71). Several mesalamine preparations have been implicated in causing pancreatitis, both orally and via enema, and sulfasalazine. A hypersensitivity mechanism seems to be involved and pancreatitis occurs usually after few days or weeks (short latency).
A higher frequency of pancreatitis has been proposed for new mesalamine formulations, included MMX. However, a recent pharmaco-epidemiological study showed a similar incidence compared to delayed or controlled release, warranting a formal postmarketing safety assessment. It has been well established that newer drugs are monitored more closely for adverse effects (AEs) and that those AEs are more likely to be reported than for medications that have been in long-term use (70).
Metronidazole has been reported as having a probable association with acute pancreatitis(16, 19, 60, 63, 64, 79), although the mechanism of DIP is still unknown. Speculative mechanism may be free radical production, immune-mediated inflammatory response, and metabolic effects (79). The association is based on case reports, 3 of them with positive rechallenge test (latency time 1-7 days) (16, 19, 64).In a population-based case-control study, Nørgaard et al. showed that metronidazole was associated to a threefold increased risk of acute pancreatitis (63). Furthermore, the use of metronidazole in combination with other drugs used for H. pylori (PPI, antibiotics) within 30 days before admission was associated with an eightfold increased risk of acute pancreatitis.
Tetracyclines have been implicated as a causative agent for acute pancreatitis. Early reports of acute pancreatitis after tetracycline administration were associated with liver dysfunction attributed to the drug's ability to induce fatty degeneration of this organ (59). In the following years, case reports about tetracycline induced pancreatitis even in patients without evidence of liver abnormalities have been described. A large Swedish pharmaco-epidemiological study reported a 1.6 odds ratio among current users of tetracycline after adjustment for potential confounders (51).
Regards the new drug tygecicline, an analogue of the semi-synthetic tetracycline minocycline, in Phase 3 and 4 clinical studies McGovern et al. defined the pancreatitis as uncommon in treated patients, with an occurrence of <1%. Caution should be exercised with close monitoring in patients with past acute or chronic pancreatitis, although there is documented safety even in these patients (55).
Valproic acid (VPA)
Since the introduction of VPA in 1979, a drug commonly prescribed for generalized and focal epilepsy, migraine, neuropathic pain, and bipolar disorder, cases of coincident pancreatitis have been reported (9, 14, 57, 65, 72), often involving children. Acute pancreatitis is rarely seen in children, and, in contrast to cases in adults, it is more commonly associated with drugs. The common side effects associated with VPA are typically benign, but more serious adverse effects may occur. These include hepatotoxicity, hyperammonemic encephalopathy, coagulation disorders, and pancreatitis. The possible association between VPA and pancreatitis led the US Food and Drug Association to issue a box warning for all VPA products in 2000. In a recent systematic review Pellock et al.(66) reported that there were several confounding elements and possible alternative etiologies in many of the trials and case reports, leading to the conclusion that VPA-coincident acute pancreatitis is an uncommon but definite and idiosyncratic event. It is most common during the first year of therapy and during dosage increases.
Drug-induced pancreatitis is a rare entity and difficult to diagnose. Only a minority of cases associated with acute pancreatitis are linked to drugs and clinical presentation and mechanisms of injury to the pancreas are not well understood or controversial. The diagnosis of DIP remains possible or probable in many patients. Several of these drugs are used for diseases associated with pancreatitis (i.e. inflammatory bowel diseases, dyslipidemia). The resolution of pancreatitis after drug discontinuation (de-challange test), could improve the diagnosis of DIP. However, it is difficult to establish the direct correlation between resolution of symptoms and drug withdrawal. Re-challenge tests may be performed in some cases, but it is strictly dependant on the severity of the index pancreatitis.
Clinically, it is important to exclude any alternative possible etiology to avoid unnecessary drug withdrawal. However, drugs suspected to induce pancreatitis should be discontinued or exchanged with an alternative drug, when possible. Drugs even probably associated to pancreatitis should be avoided in patients with previous episode(s) of pancreatitis. The knowledge of drugs commonly linked to acute pancreatitis (Table 3) may lead to earlier suspicion of the diagnosis of DIP and to more quickly discontinue drug administration in patients where a cause of AP cannot be found.
- Alexander S and Dowling D. Azathioprine pancreatitis in inflammatory bowel disease and successful subsequent treatment with mercaptopurine. Intern Med J 35(9): 570-571, 2005. PMID: 16105163.
- Almeida JL, Sampietre SN, Mendonca Coelho AM, Trindade Molan NA, Machado MC, Monteiro da Cunha JE, et al. Statin pretreatment in experimental acute pancreatitis. JOP 9(4): 431-439, 2008. PMID: 18648134.
- Alves C, Batel-Marques F and Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract 98(2): 271-284, 2012. PMID: 23010561.
- Anagnostopoulos GK, Tsiakos S, Margantinis G, Kostopoulos P and Arvanitidis D. Acute pancreatitis due to pravastatin therapy. JOP 4(3): 129-132, 2003. PMID: 12743419.
- Anderson SL and Trujillo JM. Association of pancreatitis with glucagon-like peptide-1 agonist use. Ann Pharmacother 44(5): 904-909, 2010. PMID: 20371755.
- Aston-Mourney K, Subramanian SL, Zraika S, Samarasekera T, Meier DT, Goldstein LC, et al. One year of sitagliptin treatment protects against islet amyloid-associated beta-cell loss and does not induce pancreatitis or pancreatic neoplasia in mice. Am J Physiol Endocrinol Metab 305(4): E475-484, 2013. PMID: 23736544.
- Badalov N, Baradarian R, Iswara K, Li J, Steinberg W and Tenner S. Drug-induced acute pancreatitis: an evidence-based review. Clin Gastroenterol Hepatol 5(6): 648-661; quiz 644, 2007. PMID: 17395548.
- Banks PA, Freeman ML and Practice Parameters Committee of the American College of G. Practice guidelines in acute pancreatitis. Am J Gastroenterol 101(10): 2379-2400, 2006. PMID: 17032204.
- Batalden PB, Van Dyne BJ and Cloyd J. Pancreatitis associated with valproic acid therapy. Pediatrics 64(4): 520-522, 1979. PMID: 114966.
- Becker C, Hvalic C, Delmore G, Krahenbuhl S and Schlienger R. [Recurrent acute pancreatitis during pravastatin-therapy]. Praxis (Bern 1994) 95(4): 111-116, 2006. PMID: 16485606.
- Belaiche G, Ley G and Slama JL. [Acute pancreatitis associated with atorvastatine therapy]. Gastroenterol Clin Biol 24(4): 471-472, 2000. PMID: 10844297.
- Ben MH, Thabet H, Zaghdoudi I and Amamou M. Metformin associated acute pancreatitis. Vet Hum Toxicol 44(1): 47-48, 2002. PMID: 11824780.
- Brown KV, Khan AZ and Paterson IM. Lisinopril-induced acute pancreatitis. J R Army Med Corps 153(3): 191-192, 2007. PMID: 18200917.
- Camfield PR, Bagnell P, Camfield CS and Tibbles JA. Pancreatitis due to valproic acid. Lancet 1(8127): 1198-1199, 1979. PMID: 86928.
- Carnovale A, Esposito P, Bassano P, Russo L and Uomo G. Enalapril-induced acute recurrent pancreatitis. Dig Liver Dis 35(1): 55-57, 2003. PMID: 12725609.
- Celifarco A, Warschauer C and Burakoff R. Metronidazole-induced pancreatitis. Am J Gastroenterol 84(8): 958-960, 1989. PMID: 2756988.
- Chintanaboina J and Gopavaram D. Recurrent acute pancreatitis probably induced by rosuvastatin therapy: a case report. Case Rep Med 2012: 973279, 2012. PMID: 22536267.
- Choi OS, Park SJ, Seo SW, Park CS, Cho JJ and Ahn HJ. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, lovastatin (statin) ameliorates CCK-induced acute pancreatitis in rats. Biol Pharm Bull 28(8): 1394-1397, 2005. PMID: 16079481.
- de Jongh FE, Ottervanger JP and Stuiver PC. [Acute pancreatitis caused by metronidazole]. Ned Tijdschr Geneeskd 140(1): 37-38, 1996. PMID: 8569910.
- Dore DD, Bloomgren GL, Wenten M, Hoffman C, Clifford CR, Quinn SG, et al. A cohort study of acute pancreatitis in relation to exenatide use. Diabetes Obes Metab 13(6): 559-566, 2011. PMID: 21320263.
- Dore DD, Hussein M, Hoffman C, Pelletier EM, Smith DB and Seeger JD. A pooled analysis of exenatide use and risk of acute pancreatitis. Curr Med Res Opin 29(12): 1577-1586, 2013. PMID: 23981106.
- Eland IA, van Puijenbroek EP, Sturkenboom MJ, Wilson JH and Stricker BH. Drug-associated acute pancreatitis: twenty-one years of spontaneous reporting in The Netherlands. Am J Gastroenterol 94(9): 2417-2422, 1999. PMID: 10484002.
- Fimognari FL, Corsonello A, Pastorell R and Antonelli-Incalzi R. Metformin-induced pancreatitis: A possible adverse drug effect during acute renal failure. Diabetes Care 29(5): 1183, 2006. PMID: 16644670.
- Floyd A, Pedersen L, Nielsen GL, Thorlacius-Ussing O and Sorensen HT. Risk of acute pancreatitis in users of azathioprine: a population-based case-control study. Am J Gastroenterol 98(6): 1305-1308, 2003. PMID: 12818274.
- Fraquelli M, Losco A, Visentin S, Cesana BM, Pometta R, Colli A, et al. Gallstone disease and related risk factors in patients with Crohn disease: analysis of 330 consecutive cases. Arch Intern Med 161(18): 2201-2204, 2001. PMID: 11575976.
- Funch D, Gydesen H, Tornoe K, Major-Pedersen A and Chan KA. A prospective, claims-based assessment of the risk of pancreatitis and pancreatic cancer with liraglutide compared to other antidiabetic drugs. Diabetes Obes Metab 16(3): 273-275, 2014. PMID: 24199745.
- Gallego-Rojo FJ, Gonzalez-Calvin JL, Guilarte J, Casado-Caballero FJ and Bellot V. Perindopril-induced acute pancreatitis. Dig Dis Sci 42(8): 1789-1791, 1997. PMID: 9286249.
- Gershon T and Olshaker JS. Acute pancreatitis following lisinopril rechallenge. Am J Emerg Med 16(5): 523-524, 1998. PMID: 9725973.
- Giorda CB, Picariello R, Nada E, Tartaglino B, Marafetti L, Costa G, et al. Incretin therapies and risk of hospital admission for acute pancreatitis in an unselected population of European patients with type 2 diabetes: a case-control study. Lancet Diabetes Endocrinol 2(2): 111-115, 2014. PMID: 24622714.
- Girgis CM and Champion BL. Vildagliptin-induced acute pancreatitis. Endocr Pract 17(3): e48-50, 2011. PMID: 21324812.
- Gonzalez Ramallo VJ, Muino Miguez A and Torres Segovia FJ. Necrotizing pancreatitis and enalapril. Eur J Med 1(2): 123, 1992. PMID: 1342370.
- Grendell JH. Editorial: drug-induced acute pancreatitis: uncommon or commonplace? Am J Gastroenterol 106(12): 2189-2191, 2011. PMID: 22138943.
- Guillaume P, Grandjean E and Male PJ. Azathioprine-associated acute pancreatitis in the course of chronic active hepatitis. Dig Dis Sci 29(1): 78-79, 1984. PMID: 6692736.
- Heckmann JM, Lambson EM, Little F and Owen EP. Thiopurine methyltransferase (TPMT) heterozygosity and enzyme activity as predictive tests for the development of azathioprine-related adverse events. J Neurol Sci 231(1-2): 71-80, 2005. PMID: 15792824.
- Hegnhoj J, Hansen CP, Rannem T, Sobirk H, Andersen LB and Andersen JR. Pancreatic function in Crohn's disease. Gut 31(9): 1076-1079, 1990. PMID: 1698692.
- Inoue H, Shiraki K, Okano H, Deguchi M, Yamanaka T, Sakai T, et al. Acute pancreatitis in patients with ulcerative colitis. Dig Dis Sci 50(6): 1064-1067, 2005. PMID: 15986855.
- Iyer SN, Tanenberg RJ, Mendez CE, West RL and Drake AJ, 3rd. Pancreatitis associated with incretin-based therapies. Diabetes Care 36(4): e49, 2013. PMID: 23520376.
- Jeandidier N, Klewansky M and Pinget M. Captopril-induced acute pancreatitis. Diabetes Care 18(3): 410-411, 1995. PMID: 7555489.
- Jespersen MJ, Knop FK and Christensen M. GLP-1 agonists for type 2 diabetes: pharmacokinetic and toxicological considerations. Expert Opin Drug Metab Toxicol 9(1): 17-29, 2013. PMID: 23094590.
- Johnson JL and Loomis IB. A case of simvastatin-associated pancreatitis and review of statin-associated pancreatitis. Pharmacotherapy 26(3): 414-422, 2006. PMID: 16503723.
- Kanbay M, Korkmaz M, Yilmaz U, Gur G and Boyacioglu S. Acute pancreatitis due to ramipril therapy. Postgrad Med J 80(948): 617-618, 2004. PMID: 15467001.
- Kanbay M, Selcuk H, Yilmaz U and Boyacioglu S. Recurrent acute pancreatitis probably secondary to lisinopril. South Med J 99(12): 1388-1389, 2006. PMID: 17233197.
- Karch FE and Lasagna L. Adverse drug reactions. A critical review. JAMA 234(12): 1236-1241, 1975. PMID: 1242749.
- Knezevich E, Crnic T, Kershaw S and Drincic A. Liraglutide-associated acute pancreatitis. Am J Health Syst Pharm 69(5): 386-389, 2012. PMID: 22345417.
- Koehler JA, Baggio LL, Lamont BJ, Ali S and Drucker DJ. Glucagon-like peptide-1 receptor activation modulates pancreatitis-associated gene expression but does not modify the susceptibility to experimental pancreatitis in mice. Diabetes 58(9): 2148-2161, 2009. PMID: 19509017.
- Kunjathaya P, Ramaswami PK, Krishnamurthy AN and Bhat N. Acute necrotizing pancreatitis associated with vildagliptin. JOP 14(1): 81-84, 2013. PMID: 23306341.
- Lai SW, Lin CL and Liao KF. Rosuvastatin and risk of acute pancreatitis in a population-based case-control study. Int J Cardiol 187: 417-420, 2015. PMID: 25841139.
- Lee PH, Stockton MD and Franks AS. Acute pancreatitis associated with liraglutide. Ann Pharmacother 45(4): e22, 2011. PMID: 21487080.
- Li L, Shen J, Bala MM, Busse JW, Ebrahim S, Vandvik PO, et al. Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: systematic review and meta-analysis of randomised and non-randomised studies. BMJ 348: g2366, 2014. PMID: 24736555.
- Li X, Zhang Z and Duke J. Glucagon-like peptide 1-based therapies and risk of pancreatitis: a self-controlled case series analysis. Pharmacoepidemiol Drug Saf 23(3): 234-239, 2014. PMID: 24741695.
- Ljung R, Lagergren J, Bexelius TS, Mattsson F and Lindblad M. Increased risk of acute pancreatitis among tetracycline users in a Swedish population-based case-control study. Gut 61(6): 873-876, 2012. PMID: 21957155.
- Mallick S. Metformin induced acute pancreatitis precipitated by renal failure. Postgrad Med J 80(942): 239-240, 2004. PMID: 15082849.
- Marinella MA and Billi JE. Lisinopril therapy associated with acute pancreatitis. West J Med 163(1): 77-78, 1995. PMID: 7667995.
- Maringhini A, Termini A, Patti R, Ciambra M, Biffarella P and Pagliaro L. Enalapril-associated acute pancreatitis: recurrence after rechallenge. Am J Gastroenterol 92(1): 166-167, 1997. PMID: 8995963.
- McGovern PC, Wible M, Korth-Bradley JM and Quintana A. Pancreatitis in tigecycline Phase 3 and 4 clinical studies. J Antimicrob Chemother 69(3): 773-778, 2014. PMID: 24216769.
- Monami M, Dicembrini I, Nardini C, Fiordelli I and Mannucci E. Glucagon-like peptide-1 receptor agonists and pancreatitis: a meta-analysis of randomized clinical trials. Diabetes Res Clin Pract 103(2): 269-275, 2014. PMID: 24485345.
- Murphy MJ, Lyon IW, Taylor JW and Mitts G. Valproic acid associated pancreatitis in an adult. Lancet 1(8210): 41-42, 1981. PMID: 6109073.
- Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30(2): 239-245, 1981. PMID: 7249508.
- Nicolau DP, Mengedoht DE and Kline JJ. Tetracycline-induced pancreatitis. Am J Gastroenterol 86(11): 1669-1671, 1991. PMID: 1951248.
- Nigwekar SU and Casey KJ. Metronidazole-induced pancreatitis. A case report and review of literature. JOP 5(6): 516-519, 2004. PMID: 15536294.
- Nitsche C, Maertin S, Scheiber J, Ritter CA, Lerch MM and Mayerle J. Drug-induced pancreatitis. Curr Gastroenterol Rep 14(2): 131-138, 2012. PMID: 22314811.
- Nitsche CJ, Jamieson N, Lerch MM and Mayerle JV. Drug induced pancreatitis. Best Pract Res Clin Gastroenterol 24(2): 143-155, 2010. PMID: 20227028.
- Norgaard M, Ratanajamit C, Jacobsen J, Skriver MV, Pedersen L and Sorensen HT. Metronidazole and risk of acute pancreatitis: a population-based case-control study. Aliment Pharmacol Ther 21(4): 415-420, 2005. PMID: 15709992.
- O'Halloran E, Hogan A and Mealy K. Metronidazole-induced pancreatitis. HPB Surg 2010: 523468, 2010. PMID: 20862338.
- Parker PH, Helinek GL, Ghishan FK and Greene HL. Recurrent pancreatitis induced by valproic acid. A case report and review of the literature. Gastroenterology 80(4): 826-828, 1981. PMID: 6162706.
- Pellock JM, Wilder BJ, Deaton R and Sommerville KW. Acute pancreatitis coincident with valproate use: a critical review. Epilepsia 43(11): 1421-1424, 2002. PMID: 12423394.
- Pezzilli R, Ceciliato R, Corinaldesi R and Barakat B. Acute pancreatitis due to simvastatin therapy: increased severity after rechallenge. Dig Liver Dis 36(9): 639-640, 2004. PMID: 15460851.
- Pezzilli R, Zerbi A, Di Carlo V, Bassi C, Delle Fave GF and Working Group of the Italian Association for the Study of the Pancreas on Acute P. Practical guidelines for acute pancreatitis. Pancreatology 10(5): 523-535, 2010. PMID: 20975316.
- Ramdani M, Schmitt AM, Liautard J, Duhamel O, Legroux P, Gislon J, et al. [Simvastatin-induced acute pancreatitis: two cases]. Gastroenterol Clin Biol 15(12): 986, 1991. PMID: 1783260.
- Russo L, Schneider G, Gardiner MH, Lanes S, Streck P and Rosen S. Role of pharmacoepidemiology studies in addressing pharmacovigilance questions: a case example of pancreatitis risk among ulcerative colitis patients using mesalazine. Eur J Clin Pharmacol 70(6): 709-717, 2014. PMID: 24609467.
- Sachedina B, Saibil F, Cohen LB and Whittey J. Acute pancreatitis due to 5-aminosalicylate. Ann Intern Med 110(6): 490-492, 1989. PMID: 2465715.
- Sasaki M, Tonoda S, Aoki Y and Katsumi M. Pancreatitis due to valproic acid. Lancet 1(8179): 1196, 1980. PMID: 6104020.
- Singh S. Angiotensin-converting enzyme (ACE) inhibitor-induced acute pancreatitis: in search of the evidence. South Med J 99(12): 1327-1328, 2006. PMID: 17233187.
- Singh S. Drug induced pancreatitis might be a class effect of statin drugs. JOP 6(4): 380; author reply 380-381, 2005. PMID: 16006693.
- Singh S, Chang HY, Richards TM, Weiner JP, Clark JM and Segal JB. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med 173(7): 534-539, 2013. PMID: 23440284.
- Singh S and Loke YK. Statins and pancreatitis: a systematic review of observational studies and spontaneous case reports. Drug Saf 29(12): 1123-1132, 2006. PMID: 17147459.
- Singh S, Nautiyal A and Dolan JG. Recurrent acute pancreatitis possibly induced by atorvastatin and rosuvastatin. Is statin induced pancreatitis a class effect? JOP 5(6): 502-504, 2004. PMID: 15536291.
- Steinberg W and Tenner S. Acute pancreatitis. N Engl J Med 330(17): 1198-1210, 1994. PMID: 7811319.
- Sura ME, Heinrich KA and Suseno M. Metronidazole-associated pancreatitis. Ann Pharmacother 34(10): 1152-1155, 2000. PMID: 11054984.
- Tatarkiewicz K, Belanger P, Gu G, Parkes D and Roy D. No evidence of drug-induced pancreatitis in rats treated with exenatide for 13 weeks. Diabetes Obes Metab 15(5): 417-426, 2013. PMID: 23163898.
- Tatarkiewicz K, Smith PA, Sablan EJ, Polizzi CJ, Aumann DE, Villescaz C, et al. Exenatide does not evoke pancreatitis and attenuates chemically induced pancreatitis in normal and diabetic rodents. Am J Physiol Endocrinol Metab 299(6): E1076-1086, 2010. PMID: 20923958.
- Tenner S. Drug induced acute pancreatitis: does it exist? World J Gastroenterol 20(44): 16529-16534, 2014. PMID: 25469020.
- Tripathy NR, Basha S, Jain R, Shetty S and Ramachandran A. Exenatide and acute pancreatitis. J Assoc Physicians India 56: 987-988, 2008. PMID: 19322980.
- Trivedi CD and Pitchumoni CS. Drug-induced pancreatitis: an update. J Clin Gastroenterol 39(8): 709-716, 2005. PMID: 16082282.
- Tysk C, Al-Eryani AY and Shawabkeh AA. Acute pancreatitis induced by fluvastatin therapy. J Clin Gastroenterol 35(5): 406-408, 2002. PMID: 12394230.
- Vrang N, Jelsing J, Simonsen L, Jensen AE, Thorup I, Soeborg H, et al. The effects of 13 wk of liraglutide treatment on endocrine and exocrine pancreas in male and female ZDF rats: a quantitative and qualitative analysis revealing no evidence of drug-induced pancreatitis. Am J Physiol Endocrinol Metab 303(2): E253-264, 2012. PMID: 22589391.
- Wang GJ, Gao CF, Wei D, Wang C and Ding SQ. Acute pancreatitis: etiology and common pathogenesis. World J Gastroenterol 15(12): 1427-1430, 2009. PMID: 19322914.