Comedications alter drug-induced liver injury reporting frequency: Data mining in the WHO VigiBase

• Published in: Regulatory toxicology and pharmacology Vol. 72; no. 3; pp. 481 - 490
• Main Authors: Suzuki, Ayako, Yuen, Nancy A., Ilic, Katarina, Miller, Richard T., Reese, Melinda J., Brown, H. Roger, Ambroso, Jeffrey I., Falls, J. Gregory, Hunt, Christine M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.08.2015
• Subjects: Acetaminophen - adverse effects; Adverse Drug Reaction Reporting Systems - statistics & numerical data; Amoxicillin-Potassium Clavulanate Combination - adverse effects; Chemical and Drug Induced Liver Injury - etiology; Concomitant medications; Data Mining; Databases, Factual; Drug Interactions; Drug-induced liver injury; Hepatotoxicity; Isoniazid - adverse effects; Quantitative signal detection methods; Spontaneous adverse event reporting system; Valproic Acid - adverse effects; World Health Organization; APAP; ADE; FDA; INTSS; NSAID; TNF; 2D; ACEI; ICSR; Hepatotoxicity; Quantitative signal detection methods; Concomitant medications; WHO; DILI; Spontaneous adverse event reporting system; BSEP; EBGM; MedDRA; COX; SSRI; 3D; ATIIA; Drug-induced liver injury; AERS; ATC classification; OTC
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2015.05.004

•Adverse drug reactions are increasingly recognized in medical practice.•Polypharmacy is common in the elderly; complementary medication use is increasing.•Limited data is available on how comedications affect drug-induced liver injury.•Comedications altered the liver event reporting frequency of four key drugs.•Comedications may affect drug hepatic safety. 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.