Emanuel Raschi1, Elisabetta Poluzzi1, Ariola Koci1, Paolo Caraceni1, Fabrizio De Ponti1. 1. Emanuel Raschi, Elisabetta Poluzzi, Ariola Koci, Paolo Caraceni, Fabrizio De Ponti, Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, I-40126 Bologna BO, Italy.
Abstract
AIM: To inform clinicians on the level of hepatotoxic risk among antimycotics in the post-marketing setting, following the marketing suspension of oral ketoconazole for drug-induced liver injury (DILI). METHODS: The publicly available international FAERS database (2004-2011) was used to extract DILI cases (including acute liver failure events), where antimycotics with systemic use or potential systemic absorption were reported as suspect or interacting agents. The reporting pattern was analyzed by calculating the reporting odds ratio and corresponding 95%CI, a measure of disproportionality, with time-trend analysis where appropriate. RESULTS: From 1687284 reports submitted over the 8-year period, 68115 regarded liver injury. Of these, 2.9% are related to antimycotics (1964 cases, of which 112 of acute liver failure). Eleven systemic antimycotics (including ketoconazole and the newer triazole derivatives voriconazole and posaconazole) and terbinafine (used systemically to treat onychomicosis) generated a significant disproportionality, indicating a post-marketing signal of risk. CONCLUSION: Virtually all antimycotics with systemic action or absorption are commonly reported in clinically significant cases of DILI. Clinicians must be aware of this aspect and monitor patients in case switch is considered, especially in critical poly-treated patients under chronic treatment.
AIM: To inform clinicians on the level of hepatotoxic risk among antimycotics in the post-marketing setting, following the marketing suspension of oral ketoconazole for drug-induced liver injury (DILI). METHODS: The publicly available international FAERS database (2004-2011) was used to extract DILI cases (including acute liver failure events), where antimycotics with systemic use or potential systemic absorption were reported as suspect or interacting agents. The reporting pattern was analyzed by calculating the reporting odds ratio and corresponding 95%CI, a measure of disproportionality, with time-trend analysis where appropriate. RESULTS: From 1687284 reports submitted over the 8-year period, 68115 regarded liver injury. Of these, 2.9% are related to antimycotics (1964 cases, of which 112 of acute liver failure). Eleven systemic antimycotics (including ketoconazole and the newer triazole derivatives voriconazole and posaconazole) and terbinafine (used systemically to treat onychomicosis) generated a significant disproportionality, indicating a post-marketing signal of risk. CONCLUSION: Virtually all antimycotics with systemic action or absorption are commonly reported in clinically significant cases of DILI. Clinicians must be aware of this aspect and monitor patients in case switch is considered, especially in critical poly-treated patients under chronic treatment.
Entities:
Keywords:
Antimycotics; Drug safety; Drug-induced hepatotoxicity; Pharmacovigilance; Spontaneous reporting systems
Authors: P Zarb; B Amadeo; A Muller; N Drapier; V Vankerckhoven; P Davey; H Goossens Journal: Clin Microbiol Infect Date: 2012-07-24 Impact factor: 8.067
Authors: Rolf Teschke; Albrecht Wolff; Christian Frenzel; Alexander Schwarzenboeck; Johannes Schulze; Axel Eickhoff Journal: World J Hepatol Date: 2014-01-27
Authors: Patrick B Ryan; Martijn J Schuemie; Emily Welebob; Jon Duke; Sarah Valentine; Abraham G Hartzema Journal: Drug Saf Date: 2013-10 Impact factor: 5.606
Authors: Alberto Corsini; Patricia Ganey; Cynthia Ju; Neil Kaplowitz; Dominique Pessayre; Robert Roth; Paul B Watkins; Mudher Albassam; Baolian Liu; Saray Stancic; Laura Suter; Michele Bortolini Journal: Drug Saf Date: 2012-12-01 Impact factor: 5.606
Authors: Preciosa M Coloma; Paul Avillach; Francesco Salvo; Martijn J Schuemie; Carmen Ferrajolo; Antoine Pariente; Annie Fourrier-Réglat; Mariam Molokhia; Vaishali Patadia; Johan van der Lei; Miriam Sturkenboom; Gianluca Trifirò Journal: Drug Saf Date: 2013-01 Impact factor: 5.606
Authors: David E Kleiner; Naga P Chalasani; William M Lee; Robert J Fontana; Herbert L Bonkovsky; Paul B Watkins; Paul H Hayashi; Timothy J Davern; Victor Navarro; Rajender Reddy; Jayant A Talwalkar; Andrew Stolz; Jiezhun Gu; Huiman Barnhart; Jay H Hoofnagle Journal: Hepatology Date: 2013-12-18 Impact factor: 17.425
Authors: Robert John Fontana; Elizabeth Theresa Cirulli; Jiezhun Gu; David Kleiner; David Ostrov; Elizabeth Phillips; Ryan Schutte; Huiman Barnhart; Naga Chalasani; Paul Brent Watkins; Jay H Hoofnagle Journal: J Hepatol Date: 2018-08-21 Impact factor: 25.083
Authors: Vincent Lo Re; Dena M Carbonari; James D Lewis; Kimberly A Forde; David S Goldberg; K Rajender Reddy; Kevin Haynes; Jason A Roy; Daohang Sha; Amy R Marks; Jennifer L Schneider; Brian L Strom; Douglas A Corley Journal: Am J Med Date: 2015-11-17 Impact factor: 4.965
Authors: Mohamed Kadry Taher; Abdallah Alami; Christopher A Gravel; Derek Tsui; Lise M Bjerre; Franco Momoli; Donald R Mattison; Daniel Krewski Journal: JGH Open Date: 2021-06-04