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      Quinolones-Induced Musculoskeletal, Neurological, and Psychiatric ADRs: A Pharmacovigilance Study Based on Data From the Italian Spontaneous Reporting System

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          Abstract

          Background

          The use of quinolones has been associated with the development of serious and persistent adverse drug reaction (ADR) mainly affecting muscles, joints and the nervous system. This risk has led the European Medicines Agency (EMA) to endorse some restrictions on the use of this class of antibiotic. Therefore, we performed a study to primary estimate the reporting probability of musculoskeletal, neurological, and psychiatric ADRs among quinolone generations using national data.

          Methods

          We retrieved Individual Case Safety Reports (ICSRs) with a quinolone as suspected drug among those reported through the Campania spontaneous reporting system from January 1 st, 2001 to April 30 th 2019. Moreover, we retrieved national aggregated safety data from the online public report system (RAM system) for the period from January 1 st, 2002 to March 31 st, 2019. Risk factors were classified as “age greater than 60 years,” “therapeutic indication,” “renal failure,” “organ transplantation,” “use of corticosteroid,” and “history of side effects”. Reporting odds ratio (ROR) was computed to evaluate the reporting probability of musculoskeletal, neurological, or psychiatric events among quinolones generations.

          Results

          A total of 87 ICSRs with a quinolone as suspected drug that reported at least one musculoskeletal, neurological, and psychiatric adverse event were identified in the Campania spontaneous reporting system. Forty-nine (56.3%) ICSRs reported risk factors (total risk factors 59). The most reported risk factor was “age greater than 60 years” (69.5%), followed by “therapeutic indication” (16.9%), “renal failure” (5.1%), “organ transplantation” (3.4%), “use of corticosteroid” (3.4%), and “history of side effects” (1.7%). Second-generation quinolones were associated with a lower reporting probability of musculoskeletal (ROR 0.70; 95% CI 0.63–0.79), neurological (ROR 0.81; 95% CI 0.73–0.90), and psychiatric (ROR 0.55; 95% CI 0.44–0.63) ADRs compared to the third generation of quinolones.

          Conclusions

          Our findings showed that third-generation quinolones were always associated with a higher reporting probability of musculoskeletal, neurological, and psychiatric ADRs compared to the second generation ones. Moreover, we described risk factors in more than half of our cases suggesting that the inappropriate use of quinolones is a phenomenon that may frequently predispose patients to the occurrence of these ADRs.

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          Most cited references51

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          Inappropriate antibiotic prescription for respiratory tract indications: most prominent in adult patients.

          Numerous studies suggest overprescribing of antibiotics for respiratory tract indications (RTIs), without really authenticating inappropriate prescription; the strict criteria of guideline recommendations were not taken into account as information on specific diagnoses, patient characteristics and disease severity was not available.
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            Fluoroquinolone-associated tendinopathy: a critical review of the literature.

            With the expanded use of fluoroquinolones for the treatment of community-acquired respiratory infections and reports of tendon injury linked to the use of these agents, we reviewed the literature to investigate the frequency and strength of this association. Ninety-eight case reports were available for review. The incidence of tendon injury associated with fluoroquinolone use is low in a healthy population but increases in patients who have renal dysfunction, who are undergoing hemodialysis, or who have received renal transplants. Pefloxacin and ciprofloxacin were most frequently implicated, but tendon injury was reported with most fluoroquinolones. The median duration of fluoroquinolone treatment before the onset of tendon injury was 8 days, although symptoms occurred as early as 2 hours after the first dose and as late as 6 months after treatment was stopped. Up to one-half of patients experienced tendon rupture, and almost one-third received long-term corticosteroid therapy. Tendon injury associated with fluoroquinolone use is significant, and risk factors such as renal disease or concurrent corticosteroid use must be considered when these agents are prescribed.
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              • Article: not found

              Do Women Have More Adverse Drug Reactions?

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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                15 April 2020
                2020
                : 11
                : 428
                Affiliations
                [1] 1 Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology , Naples, Italy
                [2] 2 Department of Experimental Medicine, Section of Pharmacology “L. Donatelli”, University of Campania “Luigi Vanvitelli” , Naples, Italy
                Author notes

                Edited by: Roberto Paganelli, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy

                Reviewed by: Genevieve Durrieu, Centre Hospitalier Universitaire de Toulouse, France; Mele Antonietta, University of Bari Aldo Moro, Italy

                *Correspondence: Annamaria Mascolo, annamaria.mascolo@ 123456unicampania.it

                This article was submitted to Translational Pharmacology, a section of the journal Frontiers in Pharmacology

                †These authors have contributed equally to this work and share first authorship

                ‡These authors have contributed equally to this work and share senior authorship

                Article
                10.3389/fphar.2020.00428
                7174713
                32351386
                7f6b3975-76af-487a-bc35-f82abea143ea
                Copyright © 2020 Scavone, Mascolo, Ruggiero, Sportiello, Rafaniello, Berrino and Capuano

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 December 2019
                : 19 March 2020
                Page count
                Figures: 2, Tables: 5, Equations: 0, References: 70, Pages: 14, Words: 7703
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                quinolones,safety,pharmacovigilance,spontaneous reporting system,musculoskeletal,neurological and psychiatric events,adverse drug reaction,italy

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