Comedications alter drug-induced liver injury reporting frequency: Data mining in the WHO VigiBase™.
Polypharmacy is common, and may modify mechanisms of drug-induced liver injury. We examined the effect of these drug-drug interactions on liver safety reports of four drugs highly associated with hepatotoxicity. In the WHO VigiBase™, liver event reports were examined for acetaminophen, isoniazid, valproic acid, and amoxicillin/clavulanic acid. Then, we evaluated the liver event reporting frequency of these 4 drugs in the presence of co-reported medications. Each of the 4 primary drugs was reported as having more than 2000 liver events, and co-reported with more than 600 different medications. Overall, the effect of 2275 co-reported drugs (316 drug classes) on the reporting frequency was analyzed. Decreased liver event reporting frequency was associated with 245 drugs/122 drug classes, including anti-TNFα, opioids, and folic acid. Increased liver event reporting frequency was associated with 170 drugs/82 drug classes; in particular, halogenated hydrocarbons, carboxamides, and bile acid sequestrants. After adjusting for age, gender, and other co-reported drug classes, multiple co-reported drug classes were significantly associated with decreased/increased liver event reporting frequency in a drug-specific/unspecific manner. In conclusion, co-reported medications were associated with changes in the liver event reporting frequency of drugs commonly associated with hepatotoxicity, suggesting that comedications may modify drug hepatic safety.
Duke Scholars
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Related Subject Headings
- World Health Organization
- Valproic Acid
- Toxicology
- Isoniazid
- Drug Interactions
- Databases, Factual
- Data Mining
- Chemical and Drug Induced Liver Injury
- Amoxicillin-Potassium Clavulanate Combination
- Adverse Drug Reaction Reporting Systems
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- World Health Organization
- Valproic Acid
- Toxicology
- Isoniazid
- Drug Interactions
- Databases, Factual
- Data Mining
- Chemical and Drug Induced Liver Injury
- Amoxicillin-Potassium Clavulanate Combination
- Adverse Drug Reaction Reporting Systems