DRUG-ASSOCIATED AGRANULOCYTOSIS - 20 YEARS OF REPORTING IN THE NETHERLANDS (1974-1994)

In this descriptive study, all 425 reports were included concerning dr ug-associated agranulocytosis as registered between 1974 and 1994 in t he files of the Drug Safety Unit of the Dutch Inspectorate for Health Care. All reports were analysed as to the probability of agranulocytos is or neutropenia according to previously defined criteria. Subsequent ly, the causal relationship between exposure and outcome was assessed. It concerned 149 men and 271 women. One hundred and twelve reports we re unclassifiable because age, gender, or total number of leukocytes a t the time of reaction were unknown. In 100 reports agranulocytosis wa s probable, in 78 possible, in 8 reports neutropenia was probable, in 20 reports neutropenia was possible, and in 107 reports agranulocytosi s or neutropenia were unlikely. In the 13 reports of probable agranulo cytosis or neutropenia with a certain causal relationship, causative d rugs were cimetidine, dipyrone, sulphasalazine, methyldopa, spironolac tone, propylthiouracil (2), thiamazole, sulphamethoxazole with trimeth oprim, gentamicin, a combination preparation containing aminophenazone , benzylpenicillin and indomethacin. The individual drugs most often r eported to cause agranulocytosis or neutropenia were: dipyrone (19), m ianserin (15), sulphasalazine (13), sulphamethoxazole with trimethopri m (11), the group of penicillins (9), cimetidine (8), the thiouracil d erivatives (8), phenylbutazone (8), and penicillamine (8). Agranulocyt osis is a serious and fairly frequently reported adverse reaction. The reporting system of the Drug Safety Unit can he used very well for si gnal generation concerning adverse reactions to drugs. (C) 1998 Wiley- Liss, Inc.