Voriconazole dosage

Voriconazole 6 mg/kg IV loading dose every 12 hours on day 1 followed by 4 mg/kg PO/IV every 12 hours Dosage adjustment in hepatic dysfunction IV formulation contraindicated if creatinine clearance less than 50 mDminute multiple drug interactions. 

Coadministration with phenytoin Phenytoin may be coadministered with voriconazole if the IV maintenance dosage of voriconazole is increased to 5 mg/kg every 12 hours. 

Voriconazole is the newest triazole to be licensed in the USA. It is available in intravenous and oral formulations. The recommended dosage is 400 mg/d. The drug is well absorbed orally, with a bioavailability exceeding 90%, and exhibits less protein binding than itraconazole. Metabolism is predominantly hepatic, but the propensity for inhibition of mammalian P450 appears to be low. Observed toxicities include rash, elevated hepatic enzymes, and transient visual disturbances. 

Although the disposition of voriconazole in children aged 12 years and over is similar to that in adults, children aged 2-11 years need larger dosages to achieve the same exposure that was effective in interventional trials in adults (13). 

Fluconazole only interacts to a small and clinically irrelevant extent with H2-receptor antagonists and is therefore a possible alternative to ketoconazole and itraconazole. Similarly, no dosage adjustments are neees-sary if voriconazole is used with any of the Hj-receptor antagonists. ... 

No pharmacokinetic interaction appears to occur between anidulafungin and voriconazole or between caspofungin and itraconazole. No dosage adjustment of these drugs is necessary if they are used in combination. 

No dosage adjustment of the corticosteroid is said to be necessary if voriconazole is given with prednisolone, and this also appears to be the case if voriconazole is given with hydrocortisone. ... 

The concurrent use of sirolimus is contraindicated by the manufacturers of voriconazole. The rises in sirolimus levels caused by voriconazole are probably too large to be easily accommodated by reducing the dosage of the sirolimus. One study found that an initial empiric reduction in... 

Voriconazole is not recommended for use in combination with efavirenz however, if they are co-administered, the dosage of voriconazole should be increased to 400 mg 12-hourly and the dosage of efavirenz reduced to 300 mg/day, in order to provide systemic exposure similar to standard-dose monotherapy [SEDA-32, 498]. The combination of voriconazole and efavirenz in doses adjusted according to steady-state plasma concentrations has been studied in a 40-year-old man with AIDS, cryptococcosis, and mild liver cirrhosis [154 ]. Adequate concentrations of voriconazole in both plasma and cerebrospinal fluid were obtained and target plasma concentrations of efavirenz were achieved at the final dosage adjustment (oral voriconazole 200 mg bd plus oral efavirenz 300 mg/day). There was stable suppression of cryptococcosis and plasma HIV viremia at long-term follow-up (66 weeks), with no significant adverse events. 

The management of a pharmacokinetic interaction of voriconazole with everolimus has been described in a 65-year-old man who underwent orthotopic liver transplantation complicated by intestinal perforation, sepsis, and acute renal insufficiency [32 ]. He received intravenous fluconazole 400 mg followed by 100 mg/day and oral everolimus 0.75 mg bd the steady-state Cmin of everolimus was satisfactory. On day 72 after transplantation, because of invasive aspergillosis, antifungal therapy was switched to intravenous voriconazole 400 mg bd on the first day followed by 200 mg bd to prevent drug toxicity the dosage of... 

The oral dose of voriconazole does not have to be adjusted in patients who have renal impairment. However, intravenous administration of voriconazole should be avoided in these patients as the carrier vehicle sulfobu-tyl ether P-cyclodextrin sodium can accumulate in these patients. Dosage adjustment is required in patients who have chronic hepatic impairment. As voriconazole is a substrate for a number of cytochrome P450 enzymes, a number of clinically important dmg interactions occur with dmgs including ciclospotin, tacrolimus, phenytoin, warfarin, HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors. 

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