Risk Factors for Developing Serious Adverse Drug Reactions

N.M. Mirosevic,¹ I.J. Jankovic,² M.L. Lovrek,¹ D.K. Krnic,¹ V.M.S. Macolic,¹ S.T. Tomic,¹ C.D. Duggan,³ I.B. Bates³

1 Agency for Medicinal Products and Medical Devices, Zagreb, Croatia; 2 Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia; 3 The School of Pharmacy, University of London, London, UK

Introduction: Serious adverse drug reactions (ADRs) constitute major concerns in terms of both individual outcomes (e.g. deaths and hospitalizations) and public health expense. Several studies have been conducted to assess the importance and economic consequences of ADRs.[1-4] However, such work has not been previously undertaken in Croatia.
Aim: To identify risk factors associated with developing a serious ADR.
Methods:  We performed a retrospective observational study of the ADRs reported to the Croatian Agency for Medicinal Products and Medical Devices for the period from March 2005 to December 2006. All drugs were classified using the Anatomical Therapeutic Chemical (ATC) classification code system, and subsequently entered into a database. ADRs were considered serious if one of the following criteria were met according to the ICH E2A guidelines: the ADR is life threatening; it led to hospitalization/prolonged stay in hospital; caused congenital malformation; permanent disability; or, medically serious condition. Descriptive statistics and logistic regression using SPSS 14.0 were undertaken.
Results: The results showed that among all the reported ADRs (n = 898), 26.1% referred to serious ADRs (n = 234). The majority of these serious ADRs (59.4%) were caused by drugs belonging to N (25.7%), J (18.5%) and, C (15.2%) ATC groups. From this database of ADRs, polypharmacy was associated with an increased risk of experiencing a serious ADR (B = 1.226; R² = 0.026; p < 0.005). The relationship between serious ADRs, patient demographics and drug interactions were explored as well.
Conclusions: This study has identified factors that contributed to developing serious ADRs reported to Croatian Agency for Medicinal Products and Medical Devices. These data will be used for development of national risk management plans.
References
1. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998; 279: 1200-5
2. Einarson TR. Drug-related hospital admissions. Ann Pharmacother 1993; 27: 832-40
3. Bates DW, Spell N, Cullen DJ, Burdick E, Laird N, Petersen LA, et al. The costs of adverse drug events in hospitalized patients. JAMA 1997; 277: 307-11
4. Moore N, Lecointre D, Noblet C, Mabille M. Frequency and cost of serious adverse drug reactions in a department of general medicine. Br J Clin Pharmacol 1998; 45: 301-8