Allopurinol and Agranulocytosis

Wilkinson, Doris

doi:10.1016/s0140-6736(77)92683-6

Cited by 13 publications

(5 citation statements)

References 12 publications

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“…Hematologic side effects include bone marrow suppression resulting in severe anemia, thrombocytopenia, and leukopenia, which have been reported in 0.2-0.6% of patients. Studies have also described cases of aplastic anemia, agranulocytosis, eosinophilic fibrohistiocytic bone marrow lesions, pancytopenia, prothrombin decreases, anemia, hemolytic anemia, reticulocytosis, lymphadenopathy, and lymphocytosis [4][5][6][7][8][9][10].…”

Section: Discussionmentioning

confidence: 99%

“…In clinical trials, eosinophilia and leukocytosis have been reported in fewer than 1% of patients treated with allopurinol [4,5,[7][8][9][10]. A macular skin rash appears to precede this hematologic adverse effect [6,[17][18][19][20] and occurs in patients with underlying cirrhosis [17], diabetes mellitus [6], or concomitantly using a statin [21], azathioprine or mercaptopurine.…”

Section: [ ( ) T D $ F I G ]mentioning

confidence: 99%

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Agranulocytosis: an adverse effect of allopurinol treatment

Mari¹,

Ricci²,

Imberti³

et al. 2013

Ital J Med

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Introduction: Allopurinol is a xanthine oxidase inhibitor that is primarily used to treat hyperuricemia and its complications. The drug is rarely associated with adverse effects, but those that occur can be significant. Hematologic side effects, including bone marrow suppression, severe anemia, thrombocytopenia, and leukopenia, have been reported in 0.2-0.6% of treated patients. Materials and methods: We report a case of agranulocytosis associated with allopurinol therapy in a patient admitted for fever.

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Section: Discussionmentioning

confidence: 99%

Section: [ ( ) T D $ F I G ]mentioning

confidence: 99%

Agranulocytosis: an adverse effect of allopurinol treatment

Mari¹,

Ricci²,

Imberti³

et al. 2013

Ital J Med

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“…In this case, the patient’s colchicine dose was unchanged from previous, his renal function was only mildly reduced from baseline and the cardinal colchicine toxicity symptom of diarrhoea was absent. Rare cases of neutropaenia associated with allopurinol have also been reported,13 but in our experience, this is extremely uncommon in patients on long-term stable doses of this drug. Ceftriaxone has been associated with agranulocytosis in three prior case reports; however, the patient in this case had significant neutropaenia on initial presentation prior to the administration of ceftriaxone 14…”

Section: Discussionmentioning

confidence: 55%

Transient immune-mediated agranulocytosis followingMycoplasma pneumoniaeinfection

Barge¹,

Pahn

Weber

2018

BMJ Case Reports

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is a common respiratory pathogen which may cause haematological manifestations including haemolytic anaemia and thrombocytopaenia. Severe neutropaenia is rare with very few cases reported in the literature. An 85-year-old man was transferred to our facility with agranulocytosis in the context of an infective exacerbation of chronic obstructive pulmonary disease with positive serological testing for No alternative infective, autoimmune or lymphoproliferative cause of the neutropaenia was identified. Granulocyte autoantibody testing was performed with a positive result for neutrophil-bound IgG and IgM autoantibodies and significant agglutination reactions. The patient was treated with azithromycin and granulocyte colony-stimulating factor which resulted in a sustained resolution of his neutropaenia.

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“…Although rare, allopurinol may cause neutropenia; therefore, the pharmacodynamic additive effect of MTX and allopurinol may increase the risk of hematologic events. 20 Further studies are needed to investigate the possible clinical effects of this interaction in MTX users.…”

Section: Discussionmentioning

confidence: 99%

Risk of Hematologic Events With Coadministration of Methotrexate and the Breast Cancer Resistance Protein Inhibitor Febuxostat

et al. 2021

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Background: The breast cancer resistance protein (BCRP) is a key drug transporter found in the liver, kidney, central nervous system, and gastrointestinal tract. Due to the wide expression of BCRP, interactions of other drugs with methotrexate (MTX) may differ in oral and intravenous MTX users, and understanding of these interactions may be useful in preventing severe adverse events. Febuxostat, a urate-lowering drug, inhibits BCRP. Objective: The objective of this study was to clarify the differences in the drug-drug interaction profiles of oral and intravenous methotrexate, associated with BCRP. Methods: We analyzed the Japanese Adverse Drug Event Report database and compared the frequency of hematologic events in patients taking oral and intravenous MTX, with or without the concomitant use of febuxostat or allopurinol. Hematologic events were defined as pancytopenia and neutropenia. Multiple logistic regression analysis was then used to identify the risk factors for hematologic events in oral and intravenous MTX users. Results: We identified 8 453 oral and 810 intravenous MTX users with 546 and 126 cases of hematologic events, respectively. Compared with those not using febuxostat, a disproportionate number of hematologic events was observed in intravenous MTX users concomitantly using febuxostat ( P < 0.01). The multivariate logistic analysis of intravenous MTX users showed that hematologic events were significantly associated with febuxostat use ( P < 0.01) and age ≥ 60 years ( P < 0.01). Conclusion and Relevance: Our findings suggest that patients being treated with intravenous MTX who concomitantly use febuxostat may be at an increased risk of hematologic events, presumably due to BCRP-mediated drug-drug interaction.

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Allopurinol and Agranulocytosis

Cited by 13 publications

References 12 publications

Agranulocytosis: an adverse effect of allopurinol treatment

Agranulocytosis: an adverse effect of allopurinol treatment

Transient immune-mediated agranulocytosis followingMycoplasma pneumoniaeinfection

Risk of Hematologic Events With Coadministration of Methotrexate and the Breast Cancer Resistance Protein Inhibitor Febuxostat

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