Genetic factors and risk of agranulocytosis from metamizol

Vlahov, V.; Bacracheva, N; Tontcheva, D; Naumova, E.; Mavrudieva, M; Ilieva, P.; Michailova, A.

doi:10.1097/00008571-199602000-00005

Cited by 46 publications

(21 citation statements)

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“…7 For example, data from a Bulgarian study have suggested that the histocompatibility antigen (human lymphocyte antigen [HLA]) A24 is involved in the predisposition to metamizole-induced agranulocytosis. 12 An association between HLA-B27 and HLA-B38 and increased risk of agranulocytosis with clozapine has also been reported. 13 Patients who receive clozapine need to have their full blood counts monitored regularly and, if the total white cell and/or neutrophil counts indicate agranulocytosis, clozapine must be terminated.…”

Section: Discussionmentioning

confidence: 95%

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Update on the Incidence of Metamizole Sodium-Induced Blood Dyscrasias in Poland

2010

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Metamizole sodium (metamizole) is a popular non-opioid analgesic and a common non-prescription product in Poland. Controversy exists regarding the level of risk of agranulocytosis or aplastic anaemia associated with its use. Two previous pharmacovigilance studies conducted in Poland found the risk was low. Twenty-four of the 25 haematology centres that provide specialist care for the 30 million adults in Poland participated in this prospective 12-month study. Twentyone cases of agranulocytosis, 48 of aplastic anaemia, 15 of neutropenia and 11 of pancytopenia were reported. Of these cases, three (two agranulocytosis; one aplastic anaemia) were judged as being possibly related to metamizole. Crude estimates of the rate of agranulocytosis and aplastic anaemia associated with metamizole were 0.16 and 0.08 cases/million person-days of use, respectively. Ongoing national safety surveillance in Poland shows that, despite the possibility of drug-induced blood dyscrasias with metamizole, the risk is very low.

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Section: Discussionmentioning

confidence: 95%

“…Investigations led to a diagnosis of coeliac disease. After administration of folic acid and vitamin B 12 , her blood count returned to within normal values. Pancytopenia was judged to be unrelated to metamizole in this patient.…”

Section: Case 5: Pancytopeniamentioning

confidence: 87%

Update on the Incidence of Metamizole Sodium-Induced Blood Dyscrasias in Poland

2010

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“…Recently, a case-control study has shown that acetaminophen was the most common analgesic used by patients with cirrhosis, and this use at therapeutic doses was not associated with an increased risk of being hospitalized for liver-associated events [9]. Dipyrone is among the most used non-prescribed analgesic and antipyretic drugs in countries like Brazil, Israel, Mexico, Russia and Spain [10,11], while it has been banned in some countries because to its capacity to induce agranulocytosis and aplastic anaemia [12], an adverse effect that has been related to genetic factors and is more frequent in specific populations [13,14]. Acetaminophen and dipyrone differ from the classic NSAIDs in that both are, relative to their antipyretic and analgesic Author for correspondence: Pedro Zapater, CIBERehd -Hospital General Universitario de Alicante, Avda.…”

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confidence: 99%

Acute Effects of Dipyrone on Renal Function in Patients with Cirrhosis: A Randomized Controlled Trial

Zapater

Llanos

Barquero

et al. 2014

Basic Clin Pharma Tox

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Use of non-steroidal anti-inflammatory drugs in cirrhosis has been associated with impairment of renal function based on its ability to inhibit the renal production of prostaglandins. Renal effects of dipyrone in patients with cirrhosis have not been evaluated. We aimed to assess the renal effect of therapeutic doses of dipyrone used for short periods of time in patients with cirrhosis. Twenty-nine patients with cirrhosis were included in an observer-blind clinical trial. Patients were randomized to receive three times a day oral acetaminophen (500 mg; N = 15) or dipyrone (575 mg; N = 14) for 72 hr. Serum and urine samples were obtained at baseline, 48 and 72 hr, and cystatin C, creatinine, aldosterone, 6-keto-Prostaglandin-F1 alpha and prostaglandin E2 were measured. Cystatin C and creatinine levels remained comparable in patients treated with acetaminophen and dipyrone. Urine and serum prostaglandins concentrations were significantly decreased at 72 hr in patients treated with dipyrone regardless of the status of ascites. One patient with ascites treated with dipyrone required a paracentesis and developed renal insufficiency. We conclude that dipyrone and acetaminophen did not reduce renal function when used for short periods of time (up to 72 hr) in patients with cirrhosis. However, considering that dipyrone lowered renal vasodilator prostaglandins synthesis, acetaminophen appears as the safest choice with respect to kidney function in cirrhosis.Patients with advanced cirrhosis show a hyperdynamic circulation, characterized by an enhanced splanchnic blood flow, arterial vasodilatation and hypervolaemia, together with an increased reabsorption of sodium and water related with a marked activation of neurohormonal vasoconstrictor systems such as the sympathetic nervous and renin-angiotensin systems [1,2]. In fact, angiotensin II reduces renal blood flow and renal excretory function by directly constricting the renal vascular smooth muscle and by facilitating renal sympathetic tone. This detrimental effect can partly be counteracted by renal prostaglandin production through their local vasodilating effects [2,3].Patients with cirrhosis show an increased production of prostaglandin E2 (PGE2) in the medullary and juxtamedullary vessels of kidney that has been associated with relative

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“…8 A genetic predisposition to metamizole-induced agranulocytosis has been described. 18 Metamizole has been linked with other serious side effects, including anaphylaxis. 1,19 When used during pregnancy, it has been associated with increased risk of Wilms' tumor 20 and infant leukemia.…”

Section: Discussionmentioning

confidence: 99%

Metamizole Use by Latino Immigrants: A Common and Potentially Harmful Home Remedy

Bonkowsky¹,

Frazer²,

Buchi³

et al. 2002

Pediatrics

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ABSTRACT. A 4-year-old boy presented with fever, septic arthritis, and persistent neutropenia. Bone marrow biopsy revealed no evidence of neoplasia. Additional history disclosed that the patient had been given metamizole for pain before onset of his illness. Metamizole, a nonsteroidal antiinflammatory agent, is prohibited in the United States because of the risk of agranulocytosis but is widely used in Mexico and other countries. The increasing number of Latinos in the United States and the extensive cross-border transfer of medicines raise concerns that metamizole use and associated complications may become more frequent. After identification of the index patient, additional inquiry revealed that the patient's mother was hospitalized previously for overwhelming sepsis associated with metamizole use. These cases prompted an investigation of metamizole use in an urban pediatric clinic, which revealed that 35% of Spanish-speaking Latino families had used metamizole; 25% of these families had purchased the medication in the United States. We conclude that metamizole use is common and may be underrecognized in immigrant Latino patients. Physicians in the United States, especially those who practice primary care, hematology/oncology, and infectious diseases, must be aware of the availability and use of metamizole in specific patient populations and its potential for harmful side effects. Pediatrics 2002;109(6). URL: http://www.pediatrics.org/cgi/content/full/109/6/ e98; metamizole, neutropenia, home remedy.

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Genetic factors and risk of agranulocytosis from metamizol

Cited by 46 publications

References 0 publications

Update on the Incidence of Metamizole Sodium-Induced Blood Dyscrasias in Poland

Update on the Incidence of Metamizole Sodium-Induced Blood Dyscrasias in Poland

Acute Effects of Dipyrone on Renal Function in Patients with Cirrhosis: A Randomized Controlled Trial

Metamizole Use by Latino Immigrants: A Common and Potentially Harmful Home Remedy

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