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104 ITRACONAZOLE HEPATOTOXICITY IN PATIENTS WITH ALLERGIC FUNGAL SINUSITIS N Mahmoudi1, O Marglani2, AR Javer2, A Ramji3 BACKGROUND: Allergic Fungal Sinusitis (AFS) was first described in early 1980's. Treatment modalities include both surgical and medical. The latter comprises antifungal agents as well as topical and systemic steroids. Although hepatotoxicity is associated with itraconazole, few studies have evaluated itraconazole-associated hepatotoxicity.
1Department of Medicine, University of British Columbia; 2Department of Otolaryngology, St Paul's Hospital, ENT Clinic; 3Department of Gastroenterology, St Paul's Hospital, Vancouver, British Columbia
OBJECTIVES: To evaluate incidence of hepatotoxicity associated with systemic itraconazole therapy in patients with AFS in an outpatient ENT clinic.
METHODS: A retrospective study of all patients in an ENT clinic with a clinical diagnosis of AFS who were treated with itraconazole. Inclusion criteria were: adult patients with AFS who have been on 3 months of treatment with itraconazole. Liver enzymes were followed at baseline and through itraconazole therapy. Hepatotoxicity was defined as elevation of ALT or GGT twice the normal range. Those patients with hepatotoxicity were followed during and after discontinuation of antifungal therapy.
RESULTS: Thirty-four patients on itraconazole were identified, one patient was excluded as itraconazole was used for less than 3 months. From the 33 patients included, the mean age was 49.1 (range 15-78) years, 58% of patients were male. The dose of itraconazole ranged between 100-400 mg/d. Five patients (15%) developed transaminitis for which itraconazole was stopped. In those patients with itraconazole hepatotoxicity the liver enzymes returned to normal upon discontinuation of therapy. Two patients developed isolated elevation of GGT, one of whom had elevated GGT prior to treatment and who was diagnosed with non-alcoholic steatohepatitis secondary to hyperlipidemia. Itraconazole was stopped in both patients.
CONCLUSIONS: Hepatotoxicity is common in patients treated with systemic itraconazole occurring in 18% (6/33) of our study population after 3 months of therapy. The hepatotoxic effects of itraconazole are, reversible upon discontinuation of treatment.