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

Transcript of Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999

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