P02 - Therapeutic Drug Monitoring of Itraconazole in Dogs with Blastomycosis

Abstract: Background – Itraconazole is the treatment of choice for canine blastomycosis, but serum concentrations are highly variable. Therapeutic drug monitoring (TDM) could facilitate individualized therapy and optimize outcomes. Hypothesis/Objectives – To establish a protocol for itraconazole TDM for canine blastomycosis. Animals – 13 dogs with blastomycosis treated with itraconazole Methods – Single-arm, prospective study. The starting dose of itraconazole was 5 mg/kg/d. TDM was performed at two weeks and then monthly until clinical and antigenic remission of blastomycosis. Itraconazole doses were adjusted to maintain trough serum concentrations within the target range (2-7 mcg/mL) using a standardized formula. Results – Dogs were treated with itraconazole for a median of 7 months (range 2-10). The dose at disease remission (2.8 mg/kg/d, 0.9-5.0) was significantly lower than the initial dose (4.9 mg/kg/d, 4.0-5.4, p < 0.001). 11/13 dogs required at least one dose adjustment and 5/11 required three dose adjustments. The first dose adjustment occurred a median of 1 month (0.5-7) after treatment start and occurred in the first 2 months in 10/11 dogs. 5/11 dogs underwent only dose decreases, while 6/11 required both increases and decreases. All dogs successfully achieved and maintained remission of blastomycosis. The most common adverse effects were decreased appetite (4/11) and increased ALT activity (4/11) and were mild in all cases. Conclusions and Clinical Importance – Most dogs with blastomycosis require dose adjustments to maintain itraconazole concentrations in the target range. We recommend TDM be performed within 2 months of drug initiation and monitoring continued throughout treatment.