Azacitidine-Induced Interstitial Pneumonitis

Verrière, Benjamin; Ferreira, Vanessa; Denis, Éric; Zahreddine, Khaled; Deletie, Emmanuelle; Quinsat, D.; Ré, Daniel

doi:10.1097/mjt.0000000000000300

Cited by 7 publications

(9 citation statements)

References 17 publications

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“…Other serious AEs detected included TLS, organizing pneumonia, and cardiac failure signals. These AEs did not differ in frequency from those of the target drug in clinical trials and were reported only on a case-report basis, with only a few reports in Japanese patients [46][47][48][49]. TLS often develops early in the course of treatment and follows a lethal course; this study suggested that it occurs within about 1 week of treatment.…”

Section: Analysis By Route Of Administration Using Pharmacovigilance ...mentioning

confidence: 63%

Adverse Event Profile of Azacitidine: Analysis by Route of Administration Using Japanese Pharmacovigilance Database

Yamaoka¹,

Fujiwara²,

Uchida³

et al. 2023

Oncology

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Introduction: Azacitidine is a useful drug for myelodysplastic syndromes and acute myeloid leukemia. In clinical trials, hematologic toxicity and infection have been observed as adverse events (AEs) of this drug. However, information on the time to onset of high risk AEs and subsequent outcomes, as well as differences in the frequency of AEs due to the route of administration is lacking. In this study, we investigated azacitidine-induced AEs comprehensively using the Japanese Adverse Event Reporting Database (JADER) published by the Pharmaceuticals and Medical Devices Agency, with disproportionate analysis of AE incidence trends, time to onset, and subsequent outcomes. In addition, we analyzed the differences in AEs by route of administration and the number of days until the occurrence of AEs and generated hypotheses. Methods: The study used JADER data reported from April 2004 to June 2022. Risk estimation was conducted using reported odds ratio. A signal was detected when the lower limit of the 95% confidence interval of the calculated ROR was ≥1. Results: A total of 34 signals were detected as AEs due to azacitidine. Among them, 15 were hematologic toxicities and 10 were infections, which demonstrated a particularly high rate of death. Signals of AEs such as tumor lysis syndrome (TLS) and cardiac failure, which have been described in case reports, were also detected, and the rate of death after onset was high. In addition, more AEs generally occurred within the first month of treatment. Conclusion: The results of this study suggest that more attention should be paid to cardiac failure, hematologic toxicity, infection, and TLS. Because many patients in clinical trials have discontinued treatment due to serious AEs before the therapeutic effect became apparent, appropriate supportive care, dose reduction, and drug withdrawal are important for the continuation of treatment.

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Section: Analysis By Route Of Administration Using Pharmacovigilance ...mentioning

confidence: 63%

Adverse Event Profile of Azacitidine: Analysis by Route of Administration Using Japanese Pharmacovigilance Database

Yamaoka¹,

Fujiwara²,

Uchida³

et al. 2023

Oncology

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“…Broad-spectrum antibiotics and antifungal agents 3. IV methylprednisolone (500 mg) + sulfamethoxazole trimethoprim, vancomycin, micafungin Died No Verriere et al 2015; France [ 11 ] AML F 86 Grade III skin reaction, nausea, gastric pain, dry cough, hyperthermia, ear pain, asthenia, anorexia, hyperthermia 2nd day of the 3rd cycle CT scan: diffuse interstitial opacities and ground-glass shadowing (mediastinal and hilar lymph nodes) 1. Piperacillin/tazobactam 2.…”

Section: Discussionmentioning

confidence: 99%

How to Diagnose Early 5-Azacytidine-Induced Pneumonitis: A Case Report

Misra

Gabriël

Nacoulma

et al. 2017

Drug Saf - Case Rep

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Interstitial pneumonitis is a classical complication of many drugs. Pulmonary toxicity due to 5-azacytidine, a deoxyribonucleic acid methyltransferase inhibitor and cytotoxic drug, has rarely been reported. We report a 67-year-old female myelodysplastic syndrome patient treated with 5-azacytidine at the conventional dosage of 75 mg/m2 for 7 days. One week after starting she developed moderate fever along with dry cough and subsequently her temperature rose to 39.5 °C. She was placed under broad-spectrum antibiotics based on the protocol for febrile neutropenia, including ciprofloxacin 750 mg twice daily, ceftazidime 1 g three times daily (tid), and sulfamethoxazole/trimethoprim 400 mg/80 mg tid. High-resolution computed tomography of the chest disclosed diffuse bilateral opacities with ground-glass shadowing and pleural effusion bilaterally. Mediastinal and hilar lymph nodes were moderately enlarged. polymerase chain reaction for Mycobacterium tuberculosis, Pneumocystis jiroveci, and cytomegalovirus were negative. Cultures including viral and fungal were all negative. A diagnosis of drug-induced pneumonitis was considered and, given the negative bronchoalveolar lavage in terms of an infection, corticosteroid therapy was given at a dose of 1 mg/kg body weight. Within 4 weeks, the patient became afebrile and was discharged from hospital. Development of symptoms with respect to drug administration, unexplained fever, negative workup for an infection, and marked response to corticosteroid therapy were found in our case. An explanation could be a delayed type of hypersensitivity (type IV) with activation of CD8 T cell which could possibly explain most of the symptoms. We have developed a decision algorithm in order to anticipate timely diagnosis of 5-azacitidine-induced pneumonitis, and with the aim to limit antibiotics abuse and to set up emergency treatment.

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“…Toxicity from azacitidine is irrelevant to its cumulative dose (46). Most cases occurred after eight weeks of initiation, i.e., the second cycle of azacitidine, but others have been widely inconstant (4,10,37,38,47,48). The severity of lung injury is highly variable, but in most cases, the longer it takes to recognize it and start steroids, the higher the risk of serious complications, including mortality (49).…”

Section: Azacitidine-induced Lung Toxicitymentioning

confidence: 99%

“…Abdominal pain, constipation, diarrhea, nausea, vomiting and mucositis (3,10,23,(37)(38)(39)(40)(41).…”

Section: Gastrointestinal and Hepatobiliary Systems*mentioning

confidence: 99%

Azacitidine induced lung injury: report and contemporary discussion on diagnosis and management

Alyamany,

Alnughmush,

Almutlaq

et al. 2024

Front. Oncol.

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Azacitidine, a hypomethylating agent, has caused a paradigm shift in the outcomes of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) who are not eligible for stem cell transplantation, particularly in combination with BCL2 and IDH inhibitors. Azacitidine and Azacitidine-based combinations have been widely considered a safe low-intensity therapy when compared to traditional conventional treatments. The development of lung toxicity from azacitidine is not a well-characterized adverse event. However, if it happens, it can be fatal, especially if not recognized and treated promptly. In this review, we aim to familiarize the reader with the presentation of azacitidine-induced lung injury, provide our suggested approach to management based on our experience and the current understanding of its mechanism, and review the literature of 20 case reports available on this topic.

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Azacitidine-Induced Interstitial Pneumonitis

Cited by 7 publications

References 17 publications

Adverse Event Profile of Azacitidine: Analysis by Route of Administration Using Japanese Pharmacovigilance Database

Adverse Event Profile of Azacitidine: Analysis by Route of Administration Using Japanese Pharmacovigilance Database

How to Diagnose Early 5-Azacytidine-Induced Pneumonitis: A Case Report

Azacitidine induced lung injury: report and contemporary discussion on diagnosis and management

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