Spontaneous reporting of adverse reactions to carbimazole and propylthiouracil in the UK

Abstract

To determine the frequency and spectrum of serious adverse drug reactions (ADRs) to thionamide antithyroid drugs. Data spontaneously reported to the UK-wide pharmacovigilance agency, The Committee on Safety of Medicines (Yellow Card Scheme), between 1963 and 2003 were analysed to determine the spectrum and relative frequency of ADRs to carbimazole and propylthiouracil. Representative data on the number of dispensed prescriptions were available from 1981, and were used as a denominator to estimate relative reporting rates of ADRs attributed to the drugs. Between 1981 and 2003 there were 5.23 million prescriptions for thionamide drugs in England and Scotland, 94% of which were for carbimazole. Neutrophil dyscrasia (agranulocytosis and neutropenia) accounted for 49% of all fatalities attributed to these medications. The median time reported for the appearance of neutrophil dyscrasia was 30 days of treatment, but there was a wide range (7-875 days). Neutrophil dyscrasia was more frequently fatal in subjects over 65 years of age; 13.8%vs. 1.2% of fatal reports in younger subjects [odds ratio (OR) 12.90; 5-95% confidence intervals (CI) 1.45-114.92]. Since 1981, reports of most ADRs, including neutrophil dyscrasia, were made significantly more frequently per propylthiouracil prescription dispensed than per carbimazole prescription. Detailed data about ADRs to these compounds, and their patient demography, based on a large number of reports are described. Neutrophil dyscrasia is the commonest life-threatening ADR to thionamides. The excess of ADR reports for propylthiouracil compared to carbimazole could reflect genuine differences in toxicity between the compounds, the relative unfamiliarity of UK physicians with propylthiouracil, or the higher use of propylthiouracil in certain patient groups.