Collagen-associated side effects of fluoroquinolones: aneurysm and aortic dissection (systematic review)

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Abstract

Well known for fluoroquinolones cause the development of collagen-associated side effects – tendopathies – with the risk of tendon rupture and retinal detachment, which is associated with the damaging effect and degradation of type I and type III collagen. The aorta is also rich in collagen type I and type III up to 80–90%, which has the potential to play a role in the development of aortopathies in cases of fluoroquinolone use. Since 2015, the first publications of research results on the collagen-associated effect of fluoroquinolones on the development of aneurysm and aortic dissection, often called aortopathy, began to appear. A systematic review of observational studies and 5 meta-analyzes of the development of a novel side effect of fluoroquinolones is presented. An absolute incidence of this side effect of 1.1% and a twofold increased relative risk of developing aneurysm/aortic dissection (RR 2.04–2.23), aortic aneurysm (RR 1.74–2.83), and aortic dissection (RR 1.88–2.79). When analyzing age subgroups, an increase in the risk of aneurysm/aortic dissection was noted already from the age of 35 years and was more significant in elderly patients (over 65 years). Analisys of the course duration of fluoroquinolone use (3–14 days or >14 days) was carried out in two studies and showed an increase in the risk of aneurysm/aortic dissection with increasing duration of fluoroquinolone therapy (RR 1.72 versus RR 1.92). The risk of developing a fluoroquinolone-associated aortopathy was highest during the first 30 days after the course use of fluoroquinolones, with a slight decrease within 60–90 days after the course. The signal was confirmed by the FDA pharmacovigilance system (USA) during the analysis of cases of aneurysm/aortic dissection against the background of fluoroquinolones use. International regulatory authorities (FDA and EMA) have announced official documents warning of an increased incidence of rare but serious cases of aortic dissection or ruptured aortic aneurysm with oral fluoroquinolones. Fluoroquinolones should not be given to patients at increased risk unless other treatment options are available. The increased risk category includes patients with a history of aortic or other blood vessel aneurysm, high blood pressure, and the elderly.

About the authors

Marina V. Leonova

Clinical Pharmacology – branch of the Scientific Center of Biomedical Technologies; Association of Clinical Pharmacologists

Author for correspondence.
Email: anti23@mail.ru
ORCID iD: 0000-0001-8228-1114
Scopus Author ID: 7004151126

D. Sci. (Med.), Prof., Corr. Memb. RANS, Clinical Pharmacology – branch of the Scientific Center of Biomedical Technologies, Association of Clinical Pharmacologists

Russian Federation, Moscow; Moscow

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