spontaneous reports on drug-induced pancreatitis in denmark from 1968 to 1999

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PHARMACOEPIDEMIOLOGY AND PRESCRIPTION Vibeke Andersen á Jesper Sonne á Morten Andersen Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999 Received: 16 February 2001 / Accepted in revised form: 26 June 2001 / Published online: 16 August 2001 Ó Springer-Verlag 2001 Abstract Objectives: To present an update on drug-in- duced pancreatitis reported to the Danish Committee on Adverse Drug Reactions. Design: Retrospective study of spontaneous case reports to the Danish reporting system on adverse drug reac- tions. Methods: All cases of suspected drug-induced pancrea- titis reported to the Danish Committee on Adverse Drug Reactions from 1968 to 1999 were analysed. Three cases were excluded leaving 47 cases for analysis. Results: Drug-induced pancreatitis made up 0.1% of all the reports to the committee from 1968 to 1999. The proportion seemed to increase and was 0.3% during the last 8 years. The 47 cases corresponded to 0.1% of the number of patients discharged due to pancreatic disease without cancers) per year in Denmark. Serious courses were frequent as indicated by death and hospitalisation being reported in 4 9%) and 32 68%) cases, respec- tively. Death occurred after valproate two cases), clo- mipramine one case) and azathioprine one case). De®nite relationship was stated for mesalazine three cases), azathioprine two cases) and simvastatin one case) on the basis of re-challenge. A possible or probable causality was considered for a further 30 drugs including 5-acetylsalicylic acid agents, angiotensin-converting enzyme inhibitors, estrogen preparations, didanosine, valproate, codeine, antiviral agents used in acquired immunode®ciency syndrome therapy, various lipid- reducing agents, interferon, paracetamol, griseofulvin, ticlopine, allopurinol, lithium and the MMR measles/ mumps/rubella) vaccination. Conclusion: Drug-induced pancreatitis is rarely reported. The incidence may be increasing and the course is often serious. This is the ®rst report on de®nite simvastatin- induced pancreatitis. Further studies on the pancreo- toxic potential of drugs are warranted. Keywords Adverse drug reaction reporting systems á Drug monitoring á Drugs/adverse reactions Introduction Knowledge on potential adverse drug eects is impor- tant in clinical decision making. Drug-induced pancre- atitis is considered to be rare [1, 2], although the incidence may be higher among subgroups [3, 4, 5]. The diagnosis of drug-induced pancreatitis may be dicult and depends on a high level of awareness. Drug- induced pancreatitis presents as clinically like pancrea- titis due to any other cause. The diagnosis of acute pancreatitis is based on abdominal pain, blood tests showing signi®cantly elevated amylase, leucocytosis and hyperglycaemia together with relevant changes in diag- nostic imaging, none of these being pathognomonic. The strongest evidence for a causal relationship is obtained by: 1. A temporal relationship between ingestion of the drug and the adverse outcome 2. Relief upon discontinuation of the drug 3. A positive re-challenge, i.e. reoccurrence of the symptoms with re-exposition to the drug in question 4. The exclusion of other causes [3, 4, 5] However, due to ethical reasons, re-exposure may not be justi®ed. Data from spontaneous reporting systems may form a basis of drug surveillance. The Danish reporting sys- tem has proven to be a valuable tool for analysis of adverse drug eects [6, 7]. The aim of this study was to Eur J Clin Pharmacol 2001) 57: 517±521 DOI 10.1007/s002280100346 V. Andersen &) Medical Department, Viborg County Hospital, 8800 Viborg, Denmark E-mail: [email protected] Tel.: +45-89272727 J. Sonne Clinical Pharmacological Unit, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark M. Andersen Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense, Denmark

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