Drug, Healthcare and Patient Safety (Sep 2017)
A suspected case of autoinduction of voriconazole metabolism in a patient with cerebral aspergillosis
Abstract
Martin J Ferguson,1 Maria L Randles,2 Declan G de Freitas3 1Pharmacy Department, Beaumont Hospital, Beaumont, Dublin, 2Pharmacy Department, Wexford General Hospital, Wexford, 3Department of Transplantation, Urology and Nephrology, Beaumont Hospital Kidney Centre, Dublin, Ireland Objective: This study aims to report a case of accelerated metabolism of voriconazole in a patient with cerebral aspergillosis.Case summary: A 36-year-old woman developed cerebral aspergillosis after immunosuppressive treatment for suspected atypical hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. She was treated with voriconazole using therapeutic drug monitoring to guide dosing. After an initial high level, her dose was reduced, but over the following weeks, she required several dose increases in order to achieve a voriconazole level within the target range. The patient’s dose requirements eventually stabilized at 700 mg twice daily. Cimetidine and omeprazole were added in an effort to inhibit the metabolism of voriconazole.Discussion: The metabolism of voriconazole is known to be highly variable among different patients depending on pharmacogenetic factors; however, an increasing rate of voriconazole metabolism in a single patient over time is not well recognized. Therapeutic drug monitoring of voriconazole in this case facilitated the use of large doses while controlling for toxicity.Conclusion: This case is further evidence of autoinduction in voriconazole metabolism. Therapeutic drug monitoring of voriconazole is useful in detecting variation in a patient’s metabolism of voriconazole over time. Keywords: voriconazole, therapeutic drug monitoring, metabolism, enzyme inhibition, autoinduction
