Metamizol

Adverse Effects:

Cardiovascular Effects

Cardiovascular finding

1) HYPOTENSION has been reported following intravenous administration of dipyrone [33][34]. Evidence of hypotensive effects has also been described with oral doses [35][36].

Dermatologic Effects

Dermatological finding

1) A variety of cutaneous reactions have been attributed to dipyrone, including nonspecific SKIN RASH, URTICARIA, FIXED DRUG ERUPTION, and TOXIC EPIDERMAL NECROLYSIS [8][26][41][42][37][43]. The overall incidence of skin RASH during dipyrone therapy was 2.4% in 1 epidemiologic study [44].

Diaphoresis

1) Diaphoresis has been reported following oral and parenteral dipyrone [35][36].

Pemphigus vulgaris

1) Pemphigus vulgaris was associated with occasional or short-term use of dipyrone in three patients. A 63-year-old woman who occasionally took dipyrone developed mouth ulcers and a maculopapular eruption on the trunk that lasted for 3 months. The condition responded to treatment with fluocortolone, but was exacerbated on rechallenge with dipyrone. This patient had two mild flare-ups over the ensuing 11 years that were not drug-related. A 25-year-old man developed a bullous eruption and mouth ulcers after taking dipyrone for 10 days. Treatment with concomitant fluocortolone and dipyrone was unsuccessful and the eruption worsened. This patient was found to have an immune sensitization to dipyrone; he improved after treatment withdrawal and experienced no further episodes over a 5-year follow-up period. After occasional dipyrone use, a 69-year- old man suffered from dysphagia and mouth ulcers for 6 weeks. Upon onset of these symptoms, the patient began taking dipyrone daily. At presentation he had diffuse buccolingual and palatal ulcerations, as well as a papulopustular eruption on his back. The condition responded to steroid therapy only after dipyrone was discontinued. All three of these patients had histologic evidence of suprabasal acantholysis and intercellular deposits of immunoglobulin G

Endocrine/Metabolic Effects

Acute intermittent porphyria

Teratogenesis

1) In a case-control study, the odds ratio for maternal ingestion of dipyrone during pregnancy with subsequent development of Wilms’ tumor in the child was 10.9 (95% confidence interval, 2.4 to 49.9). This study included 109 cases with Wilms’ tumor and 218 matched controls. The mean age of the cases at the time of diagnosis of Wilms’ tumor was 41.1 months. Parents (96.6%) or relatives were questioned about the use of medications during pregnancy to determine if a relationship existed to later development of Wilms’ tumor. Dipyrone was ingested often during pregnancy possibly due to easy accessibility from local clinics without charge. Without data from prospective studies, the increased incidence of Wilms’ tumor in children exposed to dipyrone can NOT be attributed definitely to dipyrone; however, based on this study, pregnant women should be discouraged from using this agent

Gastrointestinal Effects

Gastrointestinal tract finding

1) NAUSEA, VOMITING, GASTRIC IRRITATION, and XEROSTOMIA have been described with oral and parenteral dipyrone administration

Hematologic Effects

Agranulocytosis

1) Agranulocytosis has occurred relatively frequently during dipyrone administration, and has been fatal [26][27][28][23][10][8][29][9][30]. Drug-related agranulocytosis was associated most often with dipyrone during a 20-year drug safety period in the Netherlands [31]. The onset of agranulocytosis is unpredictable, and fatal cases have occurred following short-term or intermittent use as well as after long-term administration; a hypersensitivity mechanism is speculated [8].
2) The incidence of dipyrone-induced agranulocytosis has varied geographically (eg, high incidence in Barcelona and Berlin, low incidence in Budapest, Israel and Sofia (Anon, 1986; Arellano & Sacristan, 1990; Anon, 1973; Vlahov & Bacracheva, 1989) and from study to study. Regional differences are most likely related to availability and use patterns in various countries. Overall incidence estimates have ranged from 1.1 per million (during first week of administration) [23] to one case per every 3000 users [29]. Calculations based on available data have suggested that dipyrone use is associated with at least 7000 cases per year of agranulocytosis worldwide [28].
3) Fournier’s gangrene secondary to hemorrhoidectomy and SEVERE AGRANULOCYTOSIS occurred in a 23-year-old male who had received DIPYRONE after the hemorrhoidectomy (1 gram intramuscularly followed by dipyrone tablets) for postoperative analgesia. The patient reported that he also had taken dipyrone (dosage unspecified) for an upper respiratory infection a few days before his hemorrhoid surgery. The authors believe that the dipyrone induced his granulocytopenia, which was a predisposing condition for his Fournier’s gangrene. Examination of the patient’s bone marrow revealed almost total lack of granulopoiesis, with some blast formation and close-to-normal erythropoiesis and megakaryopoiesis. Granulocytopenia resolved after 2 doses of recombinant human granulocyte colony- stimulating factor (5 mcg/kg subcutaneously twice daily) and transfusion of 2 units of packed red blood cells and fresh frozen plasma [32].

Hematology finding

1) HEMOLYTIC ANEMIA and APLASTIC ANEMIA have been reported during dipyrone administration [23][24][25].

Immunologic Effects

Anaphylaxis

1) Anaphylactic shock which has resulted in fatalities has been reported with dipyrone (incidence, 1 in 5000 administrations) [46][26][47].

Neurologic Effects

Central nervous system finding

1) DROWSINESS, tiredness, and HEADACHE have been reported with dipyrone administration [37][36].

Respiratory Effects

Bronchospasm

1) Bronchospasm has been described following administration of dipyrone
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