Critically Ill Recipients of Weight-Based Fluconazole Meeting Drug-Induced Liver Injury Network Criteria

Merlyn Joseph; Rebecca Brady; Russell Attridge; Jason Cota; Cheryl Horlen; Kathleen Lusk; Rebecca L Attridge

doi:10.1177/0018578718802583

Critically Ill Recipients of Weight-Based Fluconazole Meeting Drug-Induced Liver Injury Network Criteria

Hosp Pharm. 2019 Dec;54(6):378-384. doi: 10.1177/0018578718802583. Epub 2018 Sep 29.

Authors

Merlyn Joseph^{1

2}, Rebecca Brady³, Russell Attridge^{2

4}, Jason Cota⁴, Cheryl Horlen⁴, Kathleen Lusk^{4

5}, Rebecca L Attridge^{4

5}

Affiliations

¹ Irma Lerma Rangel College of Pharmacy, Texas A&M University, Houston, TX, USA.
² South Texas Veterans Health Care System, Audie L. Murphy VA Hospital, San Antonio, TX, USA.
³ University Hospital, San Antonio, TX, USA.
⁴ Feik School of Pharmacy, University of the Incarnate Word, San Antonio, TX, USA.
⁵ University of Texas Health San Antonio, San Antonio, TX USA.

Abstract

Background: Fluconazole-associated liver injury is estimated to occur in <10% of patients; however, effect of weight-based fluconazole dosing on liver injury is unknown. Furthermore, no studies have systematically applied the Drug-Induced Liver Injury Network (DILIN) Criteria to identify patients who may have drug-induced liver injury in an intensive care unit (ICU) setting. Objective: This study evaluated how often patients met DILIN criteria when receiving fluconazole daily doses of <6 mg/kg versus ⩾6 mg/kg. Methods: This dual-center, retrospective cohort study was performed in hospitalized critically ill fluconazole recipients. We compared liver function tests (LFTs) upon fluconazole initiation to peak LFTs within 2 weeks after discontinuation using DILIN criteria. The primary objective was to evaluate the number of patients meeting DILIN criteria when receiving fluconazole daily doses of <6 mg/kg versus ⩾6 mg/kg. Secondary objectives were to evaluate incidence of patients meeting DILIN criteria in patients with renal dysfunction, cirrhosis, septic shock, or those receiving a loading dose. Results: Of 248 patients included, 90% had a documented fungal infection or received empiric therapy for suspected invasive candidiasis. In patients receiving <6 mg/kg of fluconazole, 55% (110/199) met DILIN criteria versus 46.9% (23/49) in the ⩾6 mg/kg cohort (P = .20). Only 14.5% of patients meeting DILIN criteria also met the definition for hepatocellular damage. Weight-based fluconazole dose and creatinine clearance <50 mL/min were not independent risk factors for meeting DILIN criteria. However, 77.3% of patients with cirrhosis met DILIN criteria (OR 4.84 [95% confidence interval, CI, 2.61-9.28]) and 76.3% with septic shock met DILIN criteria (OR 4.56 [95% CI, 2.44-8.88]). Conclusion: Weight-based fluconazole dosing did not affect the number of critically ill recipients who met DILIN criteria. However, DILIN criteria may overestimate the incidence of fluconazole-associated liver injury in critically ill patients.

Keywords: adverse drug reactions reporting/monitoring; critical care; drug-induced liver toxicity; fluconazole; hepatotoxicity; medication safety.