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Concurrent administration of sirolimus and voriconazole: a pilot study assessing safety and approaches to appropriate management.

Abstract：

STUDY OBJECTIVES:To assess the use and safety of concurrent administration of voriconazole and sirolimus-which is contraindicated-and to determine approaches for appropriately managing patients who receive both drugs. DESIGN:Retrospective medical record review. SETTING:University-affiliated medical center. PATIENTS:Thirty-one cases in 23 inpatients who received at least one dose of voriconazole and sirolimus concomitantly within a 24-hour period. MEASUREMENTS AND MAIN RESULTS:Data on sirolimus and voriconazole indications, doses, routes, frequencies, and administration times; number of days of coadministration; and sirolimus dosage adjustments were collected. In addition, data on laboratory values, adverse events, sirolimus concentrations, and concomitant drugs, including cytochrome P450 (CYP) 3A isoenzyme and P-glycoprotein inhibitors and inducers, were collected for 7 days before, during, and for 14 days after coadministration. No cases of elevated sirolimus concentrations (>20 mg/ml) occurred in patients stabilized with voriconazole before starting low-dose sirolimus 0.5-1 mg/day, or in those stabilized with sirolimus 0.5-2 mg/day who had baseline sirolimus concentrations of 12 ng/ml or lower and whose sirolimus dose was decreased by 50% before the addition of voriconazole. In contrast, elevated sirolimus concentrations were experienced in patients receiving sirolimus doses of 4 mg/day or higher who had sirolimus concentrations of 12 ng/ml or higher and whose sirolimus dose was not decreased before addition of voriconazole. In a patient who received sirolimus with itraconazole, a strong CYP3A isoenzyme inhibitor, one case of only a minimal increase in the sirolimus concentration occurred after the addition of voriconazole. CONCLUSIONS:Sirolimus and voriconazole can be safely coadministered as long as consideration is given to which agent the patient receives first, the sirolimus dosage, sirolimus concentrations, and concurrent disease states and CYP3A isoenzyme inhibitors. Sirolimus concentrations should be closely and routinely monitored before, during, and after coadministration of voriconazole and other CYP3A isoenzyme inhibitors. Based on the results of this pilot study, a protocol on the management of this drug combination will be implemented and prospectively evaluated for efficacy and safety.

journal_name

Pharmacotherapy

journal_title

Pharmacotherapy

authors

Surowiec D,DePestel DD,Carver PL

doi

10.1592/phco.28.6.719

subject

Has Abstract

pub_date

2008-06-01 00:00:00

pages

719-29

issue

eissn

0277-0008

issn

1875-9114

pii

10.1592/phco.28.6.719

journal_volume

pub_type

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Concurrent administration of sirolimus and voriconazole: a pilot study assessing safety and approaches to appropriate management.