Clinical Pharmacology and Therapeutics
Clinical Pharmacology and Therapeutics
5 years ago

Everolimus-induced nephrotic syndrome precipitated by interaction with voriconazole in a patient with Hodgkin's lymphoma

Everolimus-induced nephrotic syndrome precipitated by interaction with voriconazole in a patient with Hodgkin's lymphoma
L. C. Pinter-Brown, P. N. Tran
What is known and objectives Everolimus is a small molecule that inhibits the mammalian target of rapamycin (mTOR) and is used for treatment of various solid tumours and renal transplant rejection prophylaxis. Whereas everolimus-induced proteinuria was previously observed in 3%-36% renal transplant recipients, nephrotic syndrome was not reported in cancer patients taking everolimus. However, nephrotic syndrome was reported in patients taking sirolimus. Case summary We report the case of a 32-year-old female with relapsed Hodgkin's lymphoma who was on everolimus for 5 years and developed nephrotic syndrome about 2 months after initiation of voriconazole. She was on 10 mg everolimus once a day and 200 mg voriconazole twice a day orally. Renal biopsy revealed thrombotic microangiopathic vasculopathy and thin basement membrane nephropathy. Discontinuation of everolimus and voriconazole rapidly improved her nephrotic syndrome. What is new and conclusion We provide in-depth analysis of the underlying mechanisms of everolimus-induced nephrotic syndrome and hypothesize that voriconazole likely decreased everolimus metabolism. In the era of targeted therapy for cancer, healthcare providers should be aware of the drug-drug interaction between everolimus (as well as tyrosine kinase inhibitors) and cytochrome P450 CYP3A4 inhibitors (ie voriconazole). Everolimus is a small molecule that inhibits the mammalian target of rapamycin (mTOR) and is used for treatment of for treatment of various tumors and transplant rejection prophylaxis. Everolimus can lead to proteinuria but rarely cause nephrotic syndrome. Here, we report a 32-year- old female with relapsed Hodgkin's lymphoma who developed everolimus-induced nephrotic syndrome precipitated by interaction with voriconazole in a patient with Hodgkin's lymphoma. His urine protein to creatinine ratio increased to 3.01 after two months of voriconazole initiation. About 10 days after discontinuation of everolimus and voriconazole, his nephrotic syndrome resolved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/jcpt.12572

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