title: Management of voriconazole hepatotoxicity in a lung transplant patient.
abstract: Lung allograft airway colonization by Aspergillus species is common among lung transplant recipients. We report the case of a 46-year-old female lung transplant outpatient diagnosed with persistent pulmonary Aspergillus colonization (>50 colonies of Aspergillus terreus) 3 months after lung transplantation. Oral voriconazole 200 mg twice a day (b.i.d) was initiated shortly after diagnosis. Two days after voriconazole initiation, alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) were normal or slightly elevated (79, 37, and 21 UI/L, respectively). Ten days after the first voriconazole administration, these values started to increase. Maximum levels were reached after 20 days for ALP (369 UI/L) and at around 30 days for ALT and AST (223 and 188 UI/L, respectively). Instead of discontinuing antifungal therapy, it was decided to reduce the voriconazole dose to 100 mg b.i.d. This asymptomatic progressive cholestatic hepatitis resolved, and 10 days after dose reduction ALP, ALT, AST were at 136, 53, and 28 UI/L, respectively. Finally, therapeutic drug monitoring revealed adequate voriconazole plasma trough concentrations (0.98 mg/L) 30 days after dose reduction and no more colonies of Aspergillus were observed. Voriconazole-induced hepatotoxicity is a well known dose-dependent adverse drug reaction. This experience confirms the appropriateness of voriconazole dose reduction instead of therapy interruption in dose-dependent moderate liver toxicity. Voriconazole therapeutic drug monitoring before and after dose reduction may help to avoid drug accumulation and inappropriately low drug exposure, respectively.
authors.affiliation: Pharmacy Department, Grenoble University Hospital, Grenoble, France.
authors.forename: S
authors.initials: S
authors.lastname: Belaiche
authors.forename: M
authors.initials: M
authors.lastname: Roustit
authors.forename: P
authors.initials: P
authors.lastname: Bedouch
authors.forename: S
authors.initials: S
authors.lastname: Quetant
authors.forename: C
authors.initials: C
authors.lastname: Saint-Raymond
authors.forename: C
authors.initials: C
authors.lastname: Pison
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D055732:Pulmonary Aspergillosis / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D065819:Voriconazole