David J Graham1, Carol R Drinkard, Deborah Shatin. 1. Office of Drug Safety, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20857, USA.
Abstract
OBJECTIVE: Troglitazone, a thiazolidinedione antidiabetic agent, was withdrawn from the U.S. market in March, 2000, after 94 cases of acute liver failure (ALF) were reported with its use. Based on a literature review, the estimated background rate of hospitalization for idiopathic acute liver injury is 22 per million person-years and for idiopathic ALF, less than 1 per million person-years. This study was conducted to estimate the incidence rates of hospitalized idiopathic acute liver injury and ALF among troglitazone-treated patients. METHODS: An observational retrospective inception cohort of patients treated with troglitazone was assembled using claims data from a large multistate health care organization. Patients with at least 90 days of health plan enrollment before their first troglitazone prescription between April, 1997 and December, 1998 were enrolled. Hospitalized cases of potential troglitazone-induced acute liver injury or ALF were identified from claims data based on International Classification of Diseases, 9th Revision, coding. Primary medical records were reviewed for case validation, and incidence rates of acute liver injury were calculated using person-years of troglitazone exposure as the denominator. RESULTS: A total of 7568 patients contributed 4020 person-years of troglitazone exposure. Of these, five were hospitalized with acute liver injury attributed to the drug and not explained by other causes. Incidence rates (95% CI) per million person-years of acute idiopathic liver injury were as follows: hospitalization (n = 5), 1244 (404, 2900); hospitalized jaundice (n = 4), 995 (271, 2546); and ALF (n = 1), 240 (6.3, 1385). CONCLUSIONS: Troglitazone use was associated with a marked increase in risk of hospitalized acute idiopathic liver injury and ALF.
OBJECTIVE:Troglitazone, a thiazolidinedione antidiabetic agent, was withdrawn from the U.S. market in March, 2000, after 94 cases of acute liver failure (ALF) were reported with its use. Based on a literature review, the estimated background rate of hospitalization for idiopathic acute liver injury is 22 per million person-years and for idiopathic ALF, less than 1 per million person-years. This study was conducted to estimate the incidence rates of hospitalized idiopathic acute liver injury and ALF among troglitazone-treated patients. METHODS: An observational retrospective inception cohort of patients treated with troglitazone was assembled using claims data from a large multistate health care organization. Patients with at least 90 days of health plan enrollment before their first troglitazone prescription between April, 1997 and December, 1998 were enrolled. Hospitalized cases of potential troglitazone-induced acute liver injury or ALF were identified from claims data based on International Classification of Diseases, 9th Revision, coding. Primary medical records were reviewed for case validation, and incidence rates of acute liver injury were calculated using person-years of troglitazone exposure as the denominator. RESULTS: A total of 7568 patients contributed 4020 person-years of troglitazone exposure. Of these, five were hospitalized with acute liver injury attributed to the drug and not explained by other causes. Incidence rates (95% CI) per million person-years of acute idiopathic liver injury were as follows: hospitalization (n = 5), 1244 (404, 2900); hospitalized jaundice (n = 4), 995 (271, 2546); and ALF (n = 1), 240 (6.3, 1385). CONCLUSIONS:Troglitazone use was associated with a marked increase in risk of hospitalized acute idiopathic liver injury and ALF.
Authors: A Ruigómez; R Brauer; L A García Rodríguez; C Huerta; G Requena; M Gil; Francisco de Abajo; G Downey; A Bate; M Feudjo Tepie; M de Groot; R Schlienger; R Reynolds; O Klungel Journal: Eur J Clin Pharmacol Date: 2014-07-29 Impact factor: 2.953
Authors: Krista F Huybrechts; Rishi J Desai; Moa Park; Joshua J Gagne; Mehdi Najafzadeh; Jerry Avorn Journal: Med Care Date: 2017-06 Impact factor: 2.983