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In the Literature, Clinical Infectious Diseases, Volume 55, Issue 6, 15 September 2012, Pages iii–iv, https://doi.org/10.1093/cid/cis619
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Intravenously Administered Voriconazole in Patients With Renal Insufficiency
Oude Lashof AML, Sobel JD, Ruhnke M, et al. Safety and tolerability of voriconazole in patients with baseline renal insufficiency and candidemia. Antimicrob Agents Chemother 2012; 56:3133–7.
Voriconazole is not itself nephrotoxic. It is, however, poorly soluble in water, resulting in the need for the addition of a solubilizing excipient in the intravenous preparation of this triazole antifungal agent. For this reason, the administration of intravenous voriconazole also involves the administration of sulfobutylether-β-cyclodextrin (SBECD). SBECD has an elimination half-life of 1.6 hours and its clearance is linearly related to that of creatinine. The molecule is cleared by hemodialysis and, in one study, this procedure resulted in a decrease in its serum half-life from 79 hours to 5 hours [1]. Because SBECD has been associated with renal tubular vacuolation in experimental animals when administered in high doses and because the SBECD component accumulates in patients in the presence of renal insufficiency, the package insert for intravenous voriconazole states: “In patients with moderate or severe renal insufficiency (creatinine clearance <50 mL/minute), accumulation of the intravenous vehicle, SBECD, occurs. Oral voriconazole should be administered to these patients, unless an assessment of the benefit/risk to the patient justifies the use of intravenous voriconazole. Serum creatinine levels should be closely monitored in these patients, and, if increases occur, consideration should be given to changing to oral voriconazole therapy” [2].
