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Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
2002 (English)In: European Journal of Clinical Pharmacology, ISSN 0031-6970, Vol. 58, no 4, 265-274 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Agranulocytosis is a potentially lethal adverse drug reaction of dipyrone (metamizole). According to case-control studies, the frequency is low, approximately one per million users. The aim of the study was to describe the pattern of blood dyscrasias associated with dipyrone, identify possible risk factors and calculate the incidence of agranulocytosis associated with dipyrone. METHODS: All spontaneous reports of serious blood dyscrasias associated with dipyrone in Sweden were reviewed. The reports were scrutinised for additional information, including bone marrow findings. The reported incidence of agranulocytosis was estimated from total prescription sales of dipyrone. RESULTS: The reported incidence of agranulocytosis with dipyrone in Sweden was estimated to be at least 1:1439 (95% confidence interval 1:850, 1:4684) prescriptions. Ninety-two percent of the cases of blood dyscrasias occurred during the first 2 months of treatment. Additional risk factors were identified in 36% of the patients. In a total of five cases of which four were fatal, all three haematopoieses were affected according to bone marrow sample findings. Among the fatal cases, a higher proportion had bi- or tricytopenia than among the non-fatal cases ( P<0.005). CONCLUSION: Based on sales data and spontaneous reporting of adverse drug reactions in Sweden, the risk of agranulocytosis with dipyrone seems to be considerably higher than the previously estimated risks. Dipyrone is also associated with other blood dyscrasias, and the prognosis for combined dyscrasias seems to be poorer than for isolated agranulocytosis.

Place, publisher, year, edition, pages
2002. Vol. 58, no 4, 265-274 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-93242DOI: 10.1007/s00228-002-0465-2PubMedID: 12136373OAI: oai:DiVA.org:uu-93242DiVA: diva2:166667
Available from: 2005-06-02 Created: 2005-06-02 Last updated: 2010-03-04Bibliographically approved
In thesis
1. Hazards of Drug Therapy: On the Management of Adverse Drug Reactions: From Signal Detection and Evaluation to Risk Minimization
Open this publication in new window or tab >>Hazards of Drug Therapy: On the Management of Adverse Drug Reactions: From Signal Detection and Evaluation to Risk Minimization
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Spontaneous reporting systems (SRSs) for adverse drug reactions (ADRs) have been developed as a result of the thalidomide disaster, whereby thousands of children world-wide were born with birth defects. The Swedish Adverse Drug Reactions Advisory Committee was established in 1965. Since 1975, reporting has been compulsory for all suspected serious or new ADRs. International collaboration started in 1968 with countries contributing their ADR reports to an international database set up by the World Health Organization.

ADRs represent the negative side of the benefit-to-risk balance that in theory needs to be counteracted by perceived or established positive drug effects. All drugs are subject to preclinical and clinical testing prior to marketing authorization. However, these studies are insufficient to detect rare ADRs, ADRs that occur after long-term administration or with latency, ADRs that occur in special patient groups such as children, the elderly, patients with renal or hepatic insufficiency or patients on concomitant drug treatment, and ADRs that represent a modest increase in the risk of diseases (including mortality) that are prevalent in the study population. Postmarketing surveillance of drugs is therefore essential, and regulatory action may be needed on the basis of new ADR information.

SRSs are important sources of ADR information as exemplified here by the evaluation of peripheral sensory disturbances with fluoroquinolones, hyponatremia with antidepressants, blood dyscrasias with dipyrone, glucose intolerance with atypical antipsychotics, pulmonary embolism with combined oral contraceptives and extrapyramidal symptoms with selective serotonin reuptake inhibitors. SRSs can be used to study clinical manifestations of ADRs (that can give insights into potential ADR mechanisms), risk factors for the ADR or for specific outcomes of the ADR, and ADR reporting incidences when combined with sales data. Signals from SRSs may need to be studied further e.g., by use of large-scale epidemiologic studies based on record linkage between drug prescription databases and health databases. Owing to the rapid availability of information, however, SRSs are likely to remain of major importance for the post-marketing surveillance of drugs.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 86 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 54
Pharmacology, adverse drug reactions, spontaneous reporting systems, drug regulation, pharmacovigilance, incidence, Farmakologi
National Category
Pharmacology and Toxicology
urn:nbn:se:uu:diva-5866 (URN)91-554-6291-X (ISBN)
Public defence
2005-09-16, Enghoffsalen, Ingång 50, Akademiska sjukhuset, Uppsala, 09:15
Available from: 2005-06-02 Created: 2005-06-02Bibliographically approved

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