Supratherapeutic posaconazole concentrations associated with hyperlipidemia in a patient with HSCT

Posaconazole is a potent, extended-spectrum triazole antifungal used for the treatment and prophylaxis of serious fungal infections. Previous reports have demonstrated hyperlipidemia resulted in significant changes in posaconazole pharmacokinetics and tissue distribution in rats. However, the effect of hyperlipidemia on the pharmacokinetics of posaconazole in patients has not yet been reported. We report a case of a 34-year-old woman who experienced a supratherapeutic posaconazole trough concentration (PTC) associated with hyperlipidemia after haploidentical hematopoietic stem cell transplantation (HSCT). The patient was admitted 13 months after HSCT for recurrent cough and sputum. She was treated with caspofungin due to developing invasive fungal infection of Candida tropicalis. After 10 days, caspofungin was discontinued due to the poor therapeutic efficacy and replaced with amphotericin B. Afterwards, the condition of the patient improved significantly and she was switched to daily oral posaconazole tablet. Therapeutic drug monitoring (TDM) of posaconazole showed a PTC was 3.2 mg/L. After discharge, she continued to receive posaconazole tablet as antifungal treatment. Two months later, laboratory tests at outpatient showed her blood lipid levels were significantly elevated and PTC was increased to 9.38 mg/L. Therefore, the posaconazole tablet was discontinued and she received lipid-lowering therapy. A few days later, the PTC was down to 5.22 mg/L. No medication errors and significant drug interactions were found. Hence, supratherapeutic PTC for this patient may be caused by hyperlipidemia which altered pharmacokinetics of posaconazole. Our findings highlight the need for close TDM in order to avoid supratherapeutic PTC if hyperlipidimia occurs during posaconazole use.