Recognition and management of drug-induced blood cytopenias: the example of drug-induced acute neutropenia and agranulocytosis

Andrès, Emmanuel; Fédérici, Laure; Weitten, Thierry; Vogel, Thomas; Alt, M.

doi:10.1517/14740338.7.4.481

Cited by 37 publications

(42 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Despite appropriate management, the mortality rate of agranulocytosis induced by nonchemotherapy drugs is 4-5% [15]. Recently, an association between ATD-induced agranulocytosis and HLAs has been reported in various ethnic groups [1,6,16].…”

Section: Discussionmentioning

confidence: 99%

Novel Association between Flavin-Containing Monooxygenase 3 Gene Polymorphism and Antithyroid Drug-Induced Agranulocytosis in the Han Population

Hasan

Zhang

et al. 2019

Ann Nutr Metab

View full text Add to dashboard Cite

Some effective antithyroid drugs (ATDs) have been widely used for patients with Graves’ disease (GD) but are associated with ATD-induced agranulocytosis. We selected 29 ATD-induced agranulocytosis patients, 44 ATD-induced neutropenia patients, and 140 GD controls among the Chinese Han population who were recruited at the First Affiliated Hospital of Xi’an Jiao Tong University. We assessed their response to ATDs treatment by performing genotyping for a candidate gene association study of samples from patients receiving treatment. Human flavin-containing monooxygenase 3 (FMO3), which is the major hepatic enzyme involved in the production of N-oxide of trimethylamine, catalyzes the oxygenation of a variety of drug compounds. Six single SNP, genotype, haplotype (HAP), and association analyses of the FMO3 gene with ATD-induced agranulocytosis/neutropenia under different models (i.e., additive, dominant, and recessive models) were performed. Rs1736557, which caused an amino acid variation V257M, showed a strong association between ATD-induced agranulocytosis and GD controls after Bonferroni correction (p = 0.011, OR 2.301, 95% CI 1.201–4.409). The presence of HAP 3 (HAP3) in the FMO3 gene HAP was statistically associated with ATD-induced agranulocytosis (p = 0.038, permutation p value). Our findings indicate that genetic variations in the FMO3 gene are associated with the response to ATDs maintenance treatment in ATD-induced agranulocytosis patients of Chinese Han population.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel Association between Flavin-Containing Monooxygenase 3 Gene Polymorphism and Antithyroid Drug-Induced Agranulocytosis in the Han Population

Hasan

Zhang

et al. 2019

Ann Nutr Metab

View full text Add to dashboard Cite

show abstract

“…1 Drug-induced agranulocytosis (DIA) is idiosyncratic in nature and has a reported mortality rate of approximately 5%. 3,4 This rate has declined from 10% to 16% twenty years ago due to the early recognition of DIA by practitioners and the early initiation of aggressive therapy. 1,3,4 Drug-induced agranulocytosis appears to be rare with an annual incidence rate of 3 to 16 cases per million population.…”

Section: Introductionmentioning

confidence: 99%

Nonchemotherapy Drug-Induced Neutropenia and Agranulocytosis

Pick

Nystrom

2014

Journal of Pharmacy Practice

View full text Add to dashboard Cite

Drug-induced agranulocytosis is a severe complication that has been implicated with most classes of medications. Medications such as clozapine, trimethoprim-sulfamethoxazole and methimazole have been more commonly associated with agranulocytosis than other agents. Although the pathogenesis isn't fully elucidated, it appears to be two-fold with a direct toxicity to the myeloid cell line and immune-mediated destruction. Patients may be asymptomatic at the time neutropenia is discovered or may present with more severe complications such as sepsis. In approximately 5% of cases drug-induced agranulocytosis may be fatal. Management of drug-induced agranulocytosis includes the immediate discontinuation of the offending medication, initiation of broad-spectrum antibiotics and consideration of the use of granulocyte colony-stimulating factors in high-risk patients.

show abstract

“…Idiosyncratic adverse drug reactions can affect any organ, including the liver (Srivastava et al, 2010), skin (Wolf et al, 2005;Sevketoglu et al, 2009;Svensson, 2009), and bone marrow (Handoko et al, 2006;Andrès et al, 2008), and these organs have been considered as the most common targets. Among these, drug-induced liver injury (DILI) is the most frequent reason for drug withdrawal and is also a major cause of attrition in drug development (Kaplowitz, 2004).…”

Section: Introductionmentioning

confidence: 99%

Role of cytochrome P450-mediated metabolism and involvement of reactive metabolite formations on antiepileptic drug-induced liver injuries

Sasaki

Yokoi

2018

J. Toxicol. Sci.

View full text Add to dashboard Cite

-Several drugs have been withdrawn from the market or restricted to avoid unexpected adverse outcomes. Drug-induced liver injury (DILI) is a serious issue for drug development. Among DILIs, idiosyncratic DILIs have been a serious problem in drug development and clinical uses. Idiosyncratic DILI is most often unrelated to pharmacological effects or the dosing amount of a drug. The number of drugs that cause idiosyncratic DILI continue to grow in part because no practical preclinical tests have emerged that can identify drug candidates with the potential for developing idiosyncratic DILIs. Nevertheless, the implications of drug metabolism-related factors and immune-related factors on idiosyncratic DILIs has not been fully clarified because this toxicity can not be reproduced in animals. Therefore, accumulated evidence for the mechanisms of the idiosyncratic toxicity has been limited to only in vitro studies. This review describes current knowledge of the effects of cytochrome P450 (CYP)-mediated metabolism and its detoxification abilities based on studies of idiosyncratic DILI animal models developed recently. This review also focused on antiepileptic drugs, phenytoin (diphenyl hydantoin, DPH) and carbamazepine (CBZ), which have rarely caused severe adverse reactions, such as fulminant hepatitis, and have been recognized as sources of idiosyncratic DILI. The studies of animal models of idiosyncratic DILIs have produced new knowledge of chronic administration, CYP inductions/inhibitions, glutathione contents, and immune-related factors for the initiation of idiosyncratic DILIs. Considering changes in the drug metabolic profile and detoxification abilities, idiosyncratic DILIs caused by antiepileptic drugs will lead to understanding the mechanisms of these DILIs.

show abstract

Recognition and management of drug-induced blood cytopenias: the example of drug-induced acute neutropenia and agranulocytosis

Cited by 37 publications

References 28 publications

Novel Association between <b><i>Flavin-Containing Monooxygenase 3</i></b> Gene Polymorphism and Antithyroid Drug-Induced Agranulocytosis in the Han Population

Novel Association between <b><i>Flavin-Containing Monooxygenase 3</i></b> Gene Polymorphism and Antithyroid Drug-Induced Agranulocytosis in the Han Population

Nonchemotherapy Drug-Induced Neutropenia and Agranulocytosis

Role of cytochrome P450-mediated metabolism and involvement of reactive metabolite formations on antiepileptic drug-induced liver injuries

Contact Info

Product

Resources

About