Relationship Between Trimethoprim‐Sulfamethoxazole‐Induced Hepatotoxicity and Cytochrome Protein 450 2C9 Using Food and Drug Administration Adverse Event Reporting System Database.
Background: Trimethoprim‐sulfamethoxazole (TMP‐SMX) is the second most frequently implicated drug for liver injury. A previous study reported that its onset may be due to the activation of cytochrome protein 450 (CYP) 2C9. However, few studies have measured the expression levels of CYP2C9 in clinica...
| Publicado en: | Journal of Clinical Pharmacy & Therapeutics Vol. 2026; pp. 1 - 8 |
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| Autores principales: | , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
3/3/2026
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=192000741&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 192000741 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: 3/3/2026 vid: 2026 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 192000741 192000741 192000741 10.1155/jcpt/8891620 192000741 ppf: 1 ppct: 7 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: Relationship Between Trimethoprim‐Sulfamethoxazole‐Induced Hepatotoxicity and Cytochrome Protein 450 2C9 Using Food and Drug Administration Adverse Event Reporting System Database. aug: au: Kato, Hideo Shiraishi, Chihiro Hagihara, Mao Mikamo, Hiroshige Iwamoto, Takuya Imran, Ali affil: Department of Pharmacy,, Mie University Hospital,, Tsu, Mie, Japan, mie-u.ac.jp sug: subj: Hepatotoxicity Trimethoprim-Sulfamethoxazole Combination Adverse Effects Cytochrome P-450 Enzyme System Adverse Drug Event United States Food and Drug Administration Voluntary Reporting Human Female Male Pharmacovigilance Hypothesis Drug Interactions Fluconazole Metronidazole Voriconazole Relative Risk Data Analysis Software Descriptive Statistics Confidence Intervals Odds Ratio Statistical Significance Female Male ab: Background: Trimethoprim‐sulfamethoxazole (TMP‐SMX) is the second most frequently implicated drug for liver injury. A previous study reported that its onset may be due to the activation of cytochrome protein 450 (CYP) 2C9. However, few studies have measured the expression levels of CYP2C9 in clinical settings; thus, the association between TMP‐SMX–induced liver injury and CYP2C9 has not yet been revealed. This study investigated the reporting frequency of liver injury associated with TMP‐SMX alone and in combination with a CYP2C9 inducer or inhibitor. Methods: Disproportionality analyses using the Food and Drug Administration adverse event reporting system database were performed to compare the reporting frequency (reporting odds ratio [ROR]; 95% confidence interval [CI]) of drug‐induced liver injuries. The reference group consisted of patients administered TMP‐SMX alone. Rifampicin was used as the CYP inducer, and fluconazole, metronidazole, and voriconazole as the inhibitors. Drug–drug interaction (DDI) signals were calculated based on the Ω shrinkage measure. Results: The reporting frequency of liver injury increased when used in combination with rifampicin (ROR = 16.90, 95% CI = 13.50–21.15). The concomitant use of inhibitors did not increase the reporting frequency of liver injury (fluconazole, ROR = 0.675, 95% CI = 0.583–0.782; metronidazole, ROR = 0.672, 95% CI = 0.585–0.772; voriconazole, ROR = 1.435, 95% CI = 1.237–1.665). TMP‐SMX plus rifampicin only demonstrated DDI signals of liver injury in the Ω shrinkage measure (Ω = 2.878, 95% CI = 2.607–3.148). Conclusions: The present study provides insight into the reporting patterns of TMP‐SMX–associated liver injury with the concomitant use of CYP inducers and inhibitors and suggests a potential safety signal involving increased CYP2C9 activity. These findings should be interpreted with caution because disproportionality analyses cannot establish causality, and further clinical and mechanistic studies are warranted. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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