[Pharmacogenetics of aminoglycoside ototoxicity: State of knowledge and practices - Recommendations of the Francophone Network of Pharmacogenetics (RNPGx)].

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  • Additional Information
    • Transliterated Title:
      Pharmacogénétique de l’ototoxicité des aminosides : état des connaissances et des pratiques – recommandations du Réseau francophone de pharmacogénétique (RNPGx).
    • Source:
      Publisher: Elsevier Masson Country of Publication: France NLM ID: 0420544 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1958-5578 (Electronic) Linking ISSN: 00405957 NLM ISO Abbreviation: Therapie Subsets: MEDLINE
    • Publication Information:
      Publication: 2016- : Paris : Elsevier Masson
      Original Publication: Paris : Doin
    • Subject Terms:
      Aminoglycosides*/adverse effects ; Aminoglycosides*/administration & dosage ; Ototoxicity*/genetics ; RNA, Ribosomal*/genetics ; Pharmacogenetics*/standards; Humans ; Anti-Bacterial Agents/adverse effects ; Anti-Bacterial Agents/pharmacokinetics ; Anti-Bacterial Agents/administration & dosage ; France ; Genetic Predisposition to Disease
    • Abstract:
      The administration of aminoglycosides can induce nephrotoxicity or ototoxicity, which can be monitored through pharmacological therapeutic drug monitoring. However, there are cases of genetic predisposition to ototoxicity related to the MT-RNR1 gene, which may occur from the first administrations. Pharmacogenetic analysis recommendations have recently been proposed by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The Francophone Pharmacogenetics Network (RNPGx) provides a bibliographic synthesis of this genetic predisposition, as well as professional recommendations. The MT-RNR1 gene codes for mitochondrial 12S rRNA, which constitutes the small subunit of the mitochondrial ribosome. Three variants can be identified: the variants m.1555A>G and m.1494C>T of the MT-RNR1 gene have a 'high' level of evidence regarding the risk of ototoxicity. The variant m.1095T>C has a 'moderate' level of evidence. The search for these variants can be performed in the laboratory if the administration of aminoglycosides can be delayed after obtaining the result. However, if the treatment is urgent, there is currently no rapid test available in France (a 'point-of-care' test is authorized in Great Britain). RNPGx considers: (1) the search for the m.1555A>G, m.1494C>T variants as 'highly recommended' and the m.1095T>C variant as 'moderately recommended' before the administration of an aminoglycoside (if compatible with the medical context). It should be noted that the level of heteroplasmy detected does not modify the recommendation; (2) pharmacogenetic analysis is currently not feasible in situations of short-term aminoglycoside administration, in the absence of an available analytical solution (rapid test to be evaluated in France); (3) the retrospective analysis in case of aminoglycoside-induced ototoxicity is 'recommended'; (4) analysis of relatives is 'recommended'. Through this summary, RNPGx proposes an updated review of the MT-RNR1-aminoglycoside gene-drug pair to serve as a basis for adapting practices regarding pharmacogenetic analysis related to aminoglycoside treatment.
      (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
    • Contributed Indexing:
      Keywords: Aminoglycosides; Aminosides; French guidelines; MT-RNR1; Pharmacogenetic; Pharmacogénétique; Recommandations
    • Accession Number:
      0 (Aminoglycosides)
      0 (RNA, ribosomal, 12S)
      0 (RNA, Ribosomal)
      0 (Anti-Bacterial Agents)
    • Publication Date:
      Date Created: 20240614 Date Completed: 20241125 Latest Revision: 20241127
    • Publication Date:
      20241202
    • Accession Number:
      10.1016/j.therap.2024.05.006
    • Accession Number:
      38876950