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BMJ Case Reports Nov 2021Idiosyncratic drug-induced agranulocytosis is a rare life-threatening adverse reaction characterised by an absolute neutrophil count <500 cells/μL of blood....
Idiosyncratic drug-induced agranulocytosis is a rare life-threatening adverse reaction characterised by an absolute neutrophil count <500 cells/μL of blood. Nitrofurantoin has been associated with haematological adverse events, but few agranulocytosis cases worldwide have been reported. We present a case of a 68-year-old woman who presented with fever and agranulocytosis following treatment with nitrofurantoin. Extensive workup for agranulocytosis, including a bone marrow aspirate, was unremarkable. Treatment with nitrofurantoin was discontinued, which led to a complete recovery of the complete blood count. This case stresses the importance of monitoring treatments, given that widely used drugs are not free from severe adverse reactions.
Topics: Aged; Blood Cell Count; Female; Humans; Leukocyte Count; Neutropenia; Neutrophils; Nitrofurantoin
PubMed: 34764131
DOI: 10.1136/bcr-2021-246788 -
Expert Opinion on Drug Metabolism &... Oct 2021Clozapine (CLZ) is the superior drug in treatment of schizophrenia. Serum concentration of CLZ is associated with clinical response and dose-dependents side effects,... (Review)
Review
INTRODUCTION
Clozapine (CLZ) is the superior drug in treatment of schizophrenia. Serum concentration of CLZ is associated with clinical response and dose-dependents side effects, where generalized tonic-clonic seizures are most critical. Thus, therapeutic drug monitoring (TDM) of CLZ may guide individual dosing to reach target exposure and prevent dose-dependent side effects. However, current TDM methods are not capable of predicting the risk of agranulocytosis, which is a dose- side effect restricting use of CLZ to treatment-resistant schizophrenia (TRS).
AREAS COVERED
The article provides an overview of clinical, pharmacological, and toxicological aspects of CLZ, and the role of TDM as a tool for dose titration and follow-up in patients with TRS. Main focus is on current challenges and strategies in CLZ TDM, including future perspectives on potential identification/analysis of CLZ metabolite biomarkers reflecting the risk of granulocyte toxicity.
EXPERT OPINION
The association between CLZ serum concentration, clinical response and risk of seizures is indisputable. TDM should therefore always guide CLZ dose titration. Development of advanced TDM methods, including biomarkers predicting the risk of granulocyte toxicity might extend TDM to be a tool for deciding which patients that can be treated safely with CLZ, potentially increasing its utility beyond TRS.
Topics: Adult; Agranulocytosis; Antipsychotic Agents; Clozapine; Dose-Response Relationship, Drug; Drug Monitoring; Drug Resistance; Humans; Schizophrenia; Seizures
PubMed: 34461790
DOI: 10.1080/17425255.2021.1974400 -
Journal of Oncology Pharmacy Practice :... Jun 2024With the widespread use of anti-programmed death-1 monoclonal antibodies, such as pembrolizumab, rare side effects appear in clinical practice.
INTRODUCTION
With the widespread use of anti-programmed death-1 monoclonal antibodies, such as pembrolizumab, rare side effects appear in clinical practice.
CASE REPORT
We report the case of a man diagnosed with non-keratinizing squamous lung carcinoma stage IVB with programmed death-ligand 1 70% who developed agranulocytosis 10 days after a single dose of pembrolizumab as monotherapy.
MANAGEMENT AND OUTCOME
Pembrolizumab was discontinued immediately. Grade 4 neutrophil decrease is mentioned in the product information sheet as a rare side effect. The patient was admitted in poor physical condition with grade 4 neutropenic fever, mucositis and anemia. Agranulocytosis did not improve despite treatment with granulocyte colony-stimulating factor, intravenous corticosteroids and intravenous immunoglobulins. He experienced a rapid worsening and died 3 weeks after admission. The causal relationship between pembrolizumab and the appearance of agranulocytosis was determined as possible according to Naranjo's modified Karch and Lasagna's imputability algorithm.
DISCUSSION
Hematologic immune-related adverse events are uncommon but important side effects among patients treated with immune checkpoint inhibitors. Agranulocytosis and neutropenia are infrequently reported but can be life-threatening. The main approach for agranulocytosis consists of intravenous corticosteroids, granulocyte colony-stimulating factors and blood products. Depending on bone marrow characteristics, treatments for refractory patients include intravenous immunoglobulins or cyclosporine. After an immune-related adverse event, benefits and risks must be considered before continuation with an immune checkpoint inhibitor. Detection and communication of adverse drug reactions to the Pharmacovigilance Systems have special relevance for rare side effects.
Topics: Humans; Agranulocytosis; Male; Antibodies, Monoclonal, Humanized; Lung Neoplasms; Fatal Outcome; Antineoplastic Agents, Immunological; Aged; Carcinoma, Squamous Cell; Carcinoma, Non-Small-Cell Lung; Middle Aged
PubMed: 38291678
DOI: 10.1177/10781552241228774 -
Cancer Treatment Reviews Sep 2022
Review
Topics: Antineoplastic Agents; Granulocyte Colony-Stimulating Factor; Humans; Neutropenia
PubMed: 35785754
DOI: 10.1016/j.ctrv.2022.102427 -
CMAJ : Canadian Medical Association... Dec 2022
Topics: Humans; Neutropenia
PubMed: 36535676
DOI: 10.1503/cmaj.220499 -
La Tunisie Medicale Jul 2023In the era of genomics, orientation in the face of hereditary neutropenia still requires, first and foremost, a good clinical and cytological analysis. The thirty... (Review)
Review
In the era of genomics, orientation in the face of hereditary neutropenia still requires, first and foremost, a good clinical and cytological analysis. The thirty responsible genes now explain 60% of congenital neutropenia. These are rare since they are only found in 1‰ of all congenital neutropenia, estimated at 1% of the population. The clinical examination looks for phenotypes associated with syndromic hereditary neutropenia and cytology will guide this etiological research thanks to the data collected from blood count and bone marrow analysis. The objective of this narrative literature review is to provide an overview of the most recent literature regarding acquired and congenital chronic neutropenia and will provide a decision tree to guide towards aetiology. This will allow a better discussion with geneticists even if the genotype-phenotype correlation is not very strong.
Topics: Child; Humans; Neutropenia; Congenital Bone Marrow Failure Syndromes; Phenotype; Physical Examination
PubMed: 38445418
DOI: No ID Found -
Enfermedades Infecciosas Y... Apr 2020Febrile neutropenia is a very common complication in patients with hematological malignancies receiving chemotherapy, and is associated with high morbidity and...
Executive summary of the consensus document of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Network for Research in Infectious Diseases (REIPI) and the Spanish Society of Haematology and Haemotherapy (SEHH) on the management of febrile neutropenia in...
Febrile neutropenia is a very common complication in patients with hematological malignancies receiving chemotherapy, and is associated with high morbidity and mortality. Infections caused by multidrug-resistant bacteria have become a therapeutic challenge in this high-risk patient population, since inadequate initial empirical treatment can seriously compromise prognosis. However, reducing antimicrobial exposure is one of the most significant cornerstones in the fight against resistance. The objective of these new guidelines is to update recommendations for the initial management of hematological patients who develop febrile neutropenia in this scenario of multidrug resistance. The two participating Societies (the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica [Spanish Society of Infectious Diseases and Clinical Microbiology] and the Sociedad Española de Hematología y Hemoterapia [Spanish Society of Haematology and Haemotherapy]), designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on bacterial infections. Other aspects related to opportunistic infections, such as those caused by fungi or other microorganisms, especially in hematopoietic stem cell transplantation, are also touched upon.
Topics: Bacterial Infections; Communicable Diseases; Consensus; Drug Resistance, Multiple, Bacterial; Febrile Neutropenia; Hematologic Neoplasms; Hematology; Humans; Opportunistic Infections; Societies, Medical; Spain
PubMed: 30926172
DOI: 10.1016/j.eimc.2019.01.013 -
BMJ Supportive & Palliative Care Dec 2019Multiple studies have questioned the benefit of neutropenic diets in decreasing infections in patients with cancer, but recent surveys showed that such diets are still... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Multiple studies have questioned the benefit of neutropenic diets in decreasing infections in patients with cancer, but recent surveys showed that such diets are still prescribed. In this study, we sought to evaluate the effectiveness of neutropenic diet in decreasing infection and mortality in neutropenic patients with cancer with neutropenia. This review is an update of a previously published systematic review.
MATERIALS AND METHODS
We searched different databases to identify comparative studies that investigated the effect of neutropenic diet compared with regular diet in neutropenic adults and children with cancer. We conducted random-effects meta-analyses using the Der-Simonian and Laird method to pool treatment effects from included studies. Outcomes of interest were mortality, bacteremia/fungemia, major infections, quality of life, and the composite outcome for neutropenic fever and/or infection.
RESULTS
We included six studies (five randomised) with 1116 patients, with 772 (69.1%) having underwent haematopoietic cell transplant. There was no statistically significant difference between neutropenic diet and regular diet in the rates of major infections (relative risk [RR] 1.16; 95% CI 0.94 to 1.42) or bacteremia/fungemia (RR 0.96; 95% CI 0.60 to 1.53). In haematopoietic cell transplant patients, neutropenic diet was associated with a slightly higher risk of infections (RR 1.25; 95% CI 1.02 to 1.54). No difference in mortality was seen between neutropenic diet and regular diet (RR 1.08, 95% CI 0.78 to 1.50).
CONCLUSION
There is currently no evidence to support the use of neutropenic diet or other food restrictions in neutropenic patients with cancer. Patients and clinicians should continue to follow the safe food-handling guidelines as recommended by the U.S. Food and Drug Administration.
Topics: Adult; Bacterial Infections; Child; Diet; Humans; Neoplasms; Neutropenia
PubMed: 30948447
DOI: 10.1136/bmjspcare-2018-001742 -
CMAJ : Canadian Medical Association... Apr 2023
Topics: Humans; Neutropenia
PubMed: 37094869
DOI: 10.1503/cmaj.220499-f -
Drug and Therapeutics Bulletin May 2023
Topics: Humans; Nitrofurantoin; Agranulocytosis
PubMed: 36585225
DOI: 10.1136/dtb.2022.246788.rep