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OVERVIEW

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Voriconazole and posaconazole are broad-spectrum triazole antifungal agents. They decrease ergosterol synthesis by interfering with the lanosterol-14α-demethylase (P450 enzyme) activity leading to a malformation of the fungal cell membrane. These agents have activity against most yeasts, such as fluconazole-resistant Candida spp. and molds, such as Aspergillus spp. and Fusarium spp. Unlike voriconazole, posaconazole has activity against the Mucorales order.1,2 Posaconazole and voriconazole play a significant role in both the prevention and treatment of opportunistic invasive fungal infections, especially in immunocompromised patients. Because of its wide spectrum of activity, posaconazole is indicated for prophylaxis of invasive Aspergillus and Candida infections in patients who are at high risk of developing these infections due to prolonged immunosuppression after stem cell transplant or prolonged neutropenia after chemotherapy for a hematologic malignancy.1,3 Voriconazole is considered the drug of choice for treatment of most invasive aspergillosis infections.2,4 Voriconazole is also approved for use in nonneutropenic candidemia and as salvage therapy for Scedosporium apiospermum and Fusarium spp. infections.2 Although posaconazole is FDA-indicated for the treatment of refractory oropharyngeal candididasis, the suspension formulation also has positive data to support its use at higher doses for the treatment of other invasive fungal infections including mucormycosis and cryptococcal infections.5,6 Refer to Table 16-1 for FDA-approved treatment and prophylactic dosing recommendations for voriconazole and posaconazole. To date, the data for posaconazole delayed-release (DR) tablets and intravenous formulations are limited to prophylactic indications.1 Voriconazole and posaconazole therapeutic drug monitoring (TDM) can be utilized to improve patient outcomes and, in the case of voriconazole, to limit toxicity.

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TABLE 16-1Pharmacokinetic Parameters of Voriconazole and Posaconazole1,2,8,12,15,31,46,47
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BIOAVAILABILITY (F)

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Posaconazole oral suspension has variable bioavailability that is significantly influenced by dose and food intake. This formulation has saturable absorption requiring a smaller, multiple daily dosing schedule despite the drug's long half-life. For example, dosing posaconazole 400 mg every 12 hours versus 800 mg once doubles the bioavailability and dosing it 200 mg every 6 ...

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