Sirolimus with voriconazole

Select azole antifungals (e.g., itraconazole, voriconazole, and posaconazole) and the echinocandins are available for IA treatment. For initial therapy of IA, voriconazole had higher response and survival rates than c-AMB.102 An advantage of voriconazole is its 96% oral bioavailability, making use of this oral drug an attractive and less expensive alternative. The dose of voriconazole was 6 mg/kg IV every 12 hours for two doses, followed by 4 mg/kg IV every 12 hours for at least 7 days, at which time oral voriconazole 200 mg every 12 hours could be administered. Common toxicities reported with voriconazole include infusion-related, transient visual disturbances (i.e., blurred vision, altered color perception, photophobia, and visual hallucinations), skin reactions (i.e., rash, pruritus, and photosensitivity), elevations in hepatic transaminases and alkaline phosphatase, nausea, and headache.102 In addition, voriconazole increases the serum concentrations of medications cleared by cytochrome P-450 2C9, 2C19, and 3A4 (e.g., cyclophosphamide and calcineurin inhibitors) concomitant voriconazole-sirolimus should be avoided.103... 

Clinically important, potentially hazardous interactions with abacavir, atorvastatin, bepridil, bupropion, carbamazepine, clarithromycin, cyclosporine, dexamethasone, digoxin, felodipine, fluticasone propionate, fosamprenavir, itraconazole, ketoconazole, lovastatin, methadone, midazolam, nicardipine, nifedipine, phenobarbital, phenytoin, rifabutin, simvastatin, sirolimus, St John s wort, systemic lidocaine, tacrolimus, tenofovir, trazodone, vinblastine, vincristine, voriconazole, warfarin, zidovudine... 

Sirolimus levels are markedly raised by ketoconazole, and itraconazole, posaconazole and voriconazole appear to interact similarly. Clotrimazole is are also predicted to interact with sirolimus. A case report suggests that fluconazole also raises sirolimus levels. In theory it is possible that miconazole oral gel may also interact with sirolimus. 

A case report describes a patient with a heart transplant who was given two doses of voriconazole 400 mg then 200 mg twice daily for 16 days. When sirolimus was started a dose of 1 mg gave a sirolimus trough level of 12.8 nanograms/mL, but after the voriconazole was stopped a dose of 3 mg only gave trough sirolimus levels of 7.4 nanograms/mL. Voriconazole has been seen to markedly raise sirolimus levels in a number of other patients. ... 

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