Case series: Heinz body formation in 13 multimorbid dogs following metamizole administration

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. 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. 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). 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. Show more

Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in human and veterinary medicine. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro-drug, which spontaneously breaks down after oral administration to structurally related pyrazolone compounds. Apart from its analgesic effect, the medication is an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic effect is a complex one, and most probably rests on the inhibition of a central cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system. Metamizole can block both PG-dependent and PG-independent pathways of fever induced by LPS, which suggests that this drug has a profile of antipyretic action distinctly different from that of NSAIDs. The mechanism responsible for the spasmolytic effect of metamizole is associated with the inhibited release of intracellular Ca2+ as a result of the reduced synthesis of inositol phosphate. Metamizole is predominantly applied in the therapy of pain of different etiology, of spastic conditions, especially affecting the digestive tract, and of fever refractory to other treatments. Co-administration of morphine and metamizole produces superadditive, antinociceptive effects. Metamizole is a relatively safe pharmaceutical preparation although it is not completely free from undesirable effects. Among these side-effects, the most serious one that raises most controversy is the myelotoxic effect. It seems that in the past the risk of metamizole-induced agranulocytosis was exaggerated. Despite the evidence showing no risk of teratogenic and embryotoxic effects, the drug must not be administered to pregnant women, although it is allowed to be given to pregnant and lactating animals. This paper seeks to describe the characteristics of metamizole in the light of current knowledge. Show more