Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole).
OBJECTIVE
Agranulocytosis is a potentially lethal adverse drug reaction of dipyrone (metamizole). According to case-control studies, the frequency is low, approximately one per million users. The aim of the study was to describe the pattern of blood dyscrasias associated with dipyrone, identify possible risk factors and calculate the incidence of agranulocytosis associated with dipyrone.


METHODS
All spontaneous reports of serious blood dyscrasias associated with dipyrone in Sweden were reviewed. The reports were scrutinised for additional information, including bone marrow findings. The reported incidence of agranulocytosis was estimated from total prescription sales of dipyrone.


RESULTS
The reported incidence of agranulocytosis with dipyrone in Sweden was estimated to be at least 1:1439 (95% confidence interval 1:850, 1:4684) prescriptions. Ninety-two percent of the cases of blood dyscrasias occurred during the first 2 months of treatment. Additional risk factors were identified in 36% of the patients. In a total of five cases of which four were fatal, all three haematopoieses were affected according to bone marrow sample findings. Among the fatal cases, a higher proportion had bi- or tricytopenia than among the non-fatal cases ( P<0.005).


CONCLUSIONS
Based on sales data and spontaneous reporting of adverse drug reactions in Sweden, the risk of agranulocytosis with dipyrone seems to be considerably higher than the previously estimated risks. Dipyrone is also associated with other blood dyscrasias, and the prognosis for combined dyscrasias seems to be poorer than for isolated agranulocytosis.
Drug Epidemiology Unit, Medical Products Agency, Box 26, 751 02 Uppsala, Sweden. karin.hedenmalm@mpa.se
Karin
K
Hedenmalm
Olav
O
Spigset
D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D004177:Dipyrone / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013548:Sweden
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004177:Dipyrone