Drug-associated agranulocytosis: 20 years of reporting in The Netherlands (1974–1994)

Abstract

In this descriptive study, all 425 reports were included concerning drug-associated agranulocytosis as registered between 1974 and 1994 in the files of the Drug Safety Unit of the Dutch Inspectorate for Health Care. All reports were analysed as to the probability of agranulocytosis or neutropenia according to previously defined criteria. Subsequently , the causal relationship between exposure and outcome was assessed. It concerned 149 men and 271 women. One hundred and twelve reports were unclassifiable because age, gender, or total number of leukocytes at the time of reaction were unknown. In 100 reports agranulocytosis was probable, in 78 possible, in 8 reports neutropenia was probable, in 20 reports neutropenia was possible, and in 107 reports agranulocytosis or neutropenia were unlikely. In the 13 reports of probable agranulocytosis or neutropenia with a certain causal relationship, causative drugs were cimetidine, dipyrone, sulphasala-zine, methyldopa, spironolactone, propylthiouracil (2), thiamazole, sulphamethoxazole with trimethoprim, gentamicin, a combination preparation containing aminophenazone, benzylpenicillin and indomethacin. The individual drugs most often reported to cause agranulocytosis or neutropenia were: dipyrone (19), mianserin (15), sulphasalazine (13), sulphamethoxazole with trimethoprim (11), the group of penicillins (9), cimetidine (8), the thiouracil derivatives (8), phenylbutazone (8), and penicillamine (8). Agranulocytosis is a serious and fairly frequently reported adverse reaction. The reporting system of the Drug Safety Unit can be used very well for signal generation concerning adverse reactions to drugs. Am.

Diagnosis and Management of Idiopathic Drug-Induced Severe Neutropenia and Agranulocytosis

“…Conversely, cases of idiosyncratic agranulocytosis associated with clozapine or antiviral agents were observed only since 2000 and 2005, respectively. These findings are similar to two recent reports that incriminated the same drug families [10,12]. Recently, several new drugs have been listed as causative agents for severe neutropenia, e.g.…”

“…However, for drugs such as antithyroid drugs, ticlopidine, clozapine, phenothiazines, sulfasalazine, trimethoprim-sulfametoxazole (cotrimoxazole), and dipyrone or sulfasalazine, the risk may be higher [10,11]. For antithyroid drugs (propylthiouracil and méthimazole), a risk of 3 per 10,000 users has been reported [1].…”

Indomethacin-associated neutropenia with subsequent Gram-negative sepsis in a preterm infant. Cause or coincidence?

“…1 Neutropenia associated with indomethacin therapy is infrequent in adults. 2,3 This indomethacin-related side effect has not been reported in preterm infants. This report describes a mother who had neutropenia associated with indomethacin therapy.…”

“…The absolute neutrophil count was 3816/mm 3 . At 12 h of life, the infant developed respiratory distress, and a chest radiograph was consistent with the respiratory distress syndrome.…”

“…The absolute neutrophil count was 3408/mm 3 . The day after indomethacin was given, the infant had a white blood cell count of 3.4 Â 10 3 /mm 3 and a differential of 24% mature neutrophils and 2% bands.…”