TY - JOUR
T1 - Risk of oral antifungal agent-induced liver injury in Taiwanese
AU - Kao, Wei Yu
AU - Su, Chien Wei
AU - Huang, Yi Shin
AU - Chou, Yueh Ching
AU - Chen, Yi Chih
AU - Chung, Wen Hung
AU - Hou, Ming Chih
AU - Lin, Han Chieh
AU - Lee, Fa Yauh
AU - Wu, Jaw Ching
PY - 2014/1
Y1 - 2014/1
N2 - Aim Oral antifungal agent-induced liver injury is a common safety concern that may lead to patients' hesitation in treating fungal infections such as onychomycosis. This study evaluated risk of drug-induced liver injury (DILI) caused by oral antifungal agents in Taiwanese populations. Methods A population-based study was conducted by analyzing who used oral antifungal agents from 2002 to 2008 from the Taiwan National Health Insurance Database. A comparison control group was randomly extracted from the remainder of the original cohort. Results Of the 90 847 oral antifungal agents users, 52 patients had DILI. Twenty-eight DILI cases used ketoconazole, 12 fluconazole, eight griseofulvin, three itraconazole and two terbinafine. The incidence rates (IR) of DILI per 10 000 persons were 31.6, 4.9, 4.3, 3.6 and 1.6 for fluconazole, ketoconazole, griseofulvin, itraconazole and terbinafine, respectively. Longer exposure duration increased the risk of DILI, with IR for exposure duration ≥ 60 defined daily dose (DDD) of 170.9, 62.5, and 36.1 per 10 000 persons for ketoconazole, itraconazole and terbinafine, respectively. Patients taking antifungal agents had higher incidences of developing DILI compared with those in the control group after adjusting for age, gender and co-morbidities (relative risk 2.38, P < 0.001). All of the six patients with fatal DILI used fluconazole. Old age and fluconazole increased the risk of oral antifungal-induced fatal DILI. Conclusions Oral antifungal agents are associated with low incidence of acute liver injury, but which may be fatal, especially for the elderly. Longer treatment duration may increase the risk of antifungal agent-induced liver injury, especially ketoconazole.
AB - Aim Oral antifungal agent-induced liver injury is a common safety concern that may lead to patients' hesitation in treating fungal infections such as onychomycosis. This study evaluated risk of drug-induced liver injury (DILI) caused by oral antifungal agents in Taiwanese populations. Methods A population-based study was conducted by analyzing who used oral antifungal agents from 2002 to 2008 from the Taiwan National Health Insurance Database. A comparison control group was randomly extracted from the remainder of the original cohort. Results Of the 90 847 oral antifungal agents users, 52 patients had DILI. Twenty-eight DILI cases used ketoconazole, 12 fluconazole, eight griseofulvin, three itraconazole and two terbinafine. The incidence rates (IR) of DILI per 10 000 persons were 31.6, 4.9, 4.3, 3.6 and 1.6 for fluconazole, ketoconazole, griseofulvin, itraconazole and terbinafine, respectively. Longer exposure duration increased the risk of DILI, with IR for exposure duration ≥ 60 defined daily dose (DDD) of 170.9, 62.5, and 36.1 per 10 000 persons for ketoconazole, itraconazole and terbinafine, respectively. Patients taking antifungal agents had higher incidences of developing DILI compared with those in the control group after adjusting for age, gender and co-morbidities (relative risk 2.38, P < 0.001). All of the six patients with fatal DILI used fluconazole. Old age and fluconazole increased the risk of oral antifungal-induced fatal DILI. Conclusions Oral antifungal agents are associated with low incidence of acute liver injury, but which may be fatal, especially for the elderly. Longer treatment duration may increase the risk of antifungal agent-induced liver injury, especially ketoconazole.
KW - Taiwanese
KW - drug-induced liver injury
KW - hepatitis
KW - oral antifungal agents
UR - http://www.scopus.com/inward/record.url?scp=84891064488&partnerID=8YFLogxK
U2 - 10.1111/bcp.12178
DO - 10.1111/bcp.12178
M3 - 文章
C2 - 23750489
AN - SCOPUS:84891064488
SN - 0306-5251
VL - 77
SP - 180
EP - 189
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 1
ER -