| アブストラクト | OBJECTIVES: Despite the widespread use of fluorinated medicines - with approximately 20% of the drugs marketed in 2020 containing fluoride compounds - the association between these medications and fluorosis remains under-recognized. This study aimed to identify medications most likely to induce fluorosis in real-world clinical settings using pharmacovigilance databases. METHODS: A descriptive and disproportionality study was conducted using French national (FPVB) and international pharmacovigilance databases (VigiBase(R)). Cases of fluorosis were extracted from Vigibase(R) up to July 8, 2024, using the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "fluorosis", "fluoride increased" and "fluorosis dental". French cases were subsequently extracted from the FPVB. Disproportionality signals were evaluated by calculating the reporting odds ratio (ROR) and corresponding 95% confidence interval (CI). RESULTS: A total of 72 cases of suspected drug-induced fluorosis were identified in VigiBase(R). The most frequently reported adverse effects were musculoskeletal disorders (n=39, 54.2%), dental disorders (n=11, 15.3%), and eyes and visual disorders (n=8, 11.1%). Two-third of the cases (n=52) were classified as serious. In 40% of cases (n=29), the outcome was favorable. Voriconazole, sodium fluoride, fluconazole and ciprofloxacin were identified as single suspects. Disproportionality signals were detected for sodium fluoride (ROR=2305.7; 95% CI [1143.9; 4647.3]), voriconazole (ROR=1415.4; 95% CI [891.5; 2247.3]), fluconazole (ROR=110.4; 95% CI [52.9; 230.3]), fludarabine (ROR=87.3; 95% CI [31.8; 239.3]) and ciprofloxacin (ROR=7.1; 95% CI [2.2; 22.4]). The 16 cases from the FPVB provided more detailed information, including the clinical context - mainly hematological malignancies (37.5%) and organ transplants (12.5%) - the median time to onset (361 days), mean plasma fluoride concentration (1.33mg/L; range 0.006-7.2mg/L), and results imaging explorations. CONCLUSION: This study highlights pharmacovigilance signals suggesting a potential association between fluorosis and certain fluorinated compounds, particularly sodium fluoride, voriconazole, fluconazole, fludarabine and ciprofloxacin. Among these, only sodium fluoride and voriconazole include fluorosis in the summary of product characteristics. Clinicians should remain vigilant regarding this potential adverse drug reaction, especially with long-term use of these medications. |
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| ジャーナル名 | Therapie |
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| Pubmed追加日 | 2025/7/21 |
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| 投稿者 | Mellou, Myriam; Lelievre, Benedicte; Bourneau-Martin, Delphine; Le Beller, Christine; Pizzoglio, Veronique; Veyrac, Gwenaelle; Michot, Joelle; Parant, Francois; Briet, Marie |
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| 組織名 | Department of Pharmacology-Toxicology and Pharmacovigilance, University Hospital;of Angers, 49100 Angers, France.;Inserm, Innovative Therapies in Haemostasis, Department of Pharmacovigilance,;Hopital Europeen Georges-Pompidou, Centre - Universite Paris-Cite, AP-HP, 75000;Paris, France.;Regional Pharmacovigilance Centre, Lyon University Hospital, 69000 Lyon, France.;Regional Pharmacovigilance Centre, Nantes University Hospital, 44000 Nantes,;France.;Regional Pharmacovigilance Centre, Saint-Antoine University Hospital, Assistance;Publique-Hopitaux de Paris (AH-HP), 75000 Paris, France.;Service de Biochimie et Biologie Moleculaire, Laboratoire de Biologie Medicale;Multi-Sites (LBMMS), Hopital Lyon-Sud - Hospices Civils de Lyon, 69310;Pierre-Benite, France.;of Angers, 49100 Angers, France; Universite d'Angers, 49035 Angers, France; UMR;CNRS 6214 Inserm 1083, Research Institute MitoVasc, 49100 Angers, France.;Electronic address: marie.briet@chu-angers.fr. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/40685290/ |
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