Fatal adverse drug reactions reported in Denmark 1968–1988

Abstract

During the period 1968–88 a total of 27,938 reports on adverse drug reactions (ADR) were received through the voluntary reporting system in Denmark, of which 713 concerned fatal reactions. Excluding cases of overdosage, congenital malformations and unclassifiable reactions, 590 reports were selected for analysis. Of 215 drugs involved, 41% were marketed before 1968. When corrected for drug consumption figures no significant differences in incidence were found with age and gender. The most frequently reported drug groups were antirheumatics (92), cytostatics (54), antibiotics (53) and oral contraceptives (50). Over-the-counter drugs were involved in 13 reports. Fatal drug interactions were reported in 17 cases. In general the duration of treatment was longer in cases of fatal ADR than the average for ADR as a whole. The diagnoses most frequently reported were bone marrow depression (105), “sudden unexpected death” (57), anaphylactic shock (30) and malignant disease (23). The incidence of fatal thromboembolism involving oral contraceptives was halved following the withdrawal of high-estrogen preparations resulting in an incidence over the period 1983–88 of 1 per 141, 000 user years. The corresponding figure concerning non-steroidal antiinflammatory agents was 1 fatal ADR per 26,000 treatment years. Halothane-induced hepatic damage was reported in 33 cases during 1968–83, but only in 2 cases over the period 1983–88. The number of fatal ADR following use of inhaled adrenergic antiasthmatics was 19 during 1968–83, but 0 during 1983–88 despite a sale corresponding to 360,000 treatment years. Lactate acidosis following oral antidiabetics was reported in 18 cases during 1968–78, but only in 1 during 1978–88 following the withdrawal of phenformin. The annual number of reported fatal ADR remained fairly constant throughout the period despite the introduction of numerous potent drugs. Subject to reservations reflecting the shortcomings inherent in a retrospective analysis of data from a voluntary ADR reporting system, the risk of a fatal ADR is considered extremely low, being estimated at 6 per million inhabitants per year and 1 per 180,000 treatment years.