Posaconazole

Posaconazole is the newest extended-spectrum azole. It is an analog of itraconazole that is substantially more active against many fungi. Currently, it is indicated only for the prophylaxis of fungal infections in neutropenic patients and the treatment of oropharyngeal candidiasis. It is unique among the azoles in that it has good activity against the Zygomycetes, a difficult-to-treat class of moulds that most antifungals (voriconazole included) do not treat.

Spectrum

Good: Candida albicans, Candida lusitaniae, Can-dida parapsilosis, Candida tropicalis, Candida krusei, Aspergillus species, Zygomycetes, many other moulds, dimorphic fungi

Moderate: Fusarium species, Candida glabrata Though posaconazole is active against these organ-isms, clinical data are lacking for many of them.

Adverse Reactions

Posaconazole seems to be well tolerated, though it can cause hepatotoxicity, nausea, and rash. It has the same propensity to cause drug interactions via cytochrome P450 as the other azoles. We will learn  more about the adverse effect spectrum of posaconazole as clinical experience with it grows.

Dosing Issues

Posaconazole is available only as an oral suspension. It should always be administered with food to increase its absorption; foods with a high fat con-centration improve absorption the most. An IV formulation is in development.

Important Facts

• Posaconazole’s primary use is in the prophylaxis of fungal infections in high-risk patients. As with voriconazole, many of these patients are taking immunosuppressants that interact with posaconazole, so keep close tabs on those drug concentrations.

• Clinical data with posaconazole for Zygomycete infections are growing, and posaconazole is emerging as a drug of choice for these infections.

• Posaconazole has issues with absorption. High-fat meals boost absorption substantially and may be required for adequate absorption in some patients.  Posaconazole drug concentrations are not standardly tested for in many labs, but tests are becoming available and may be a way to ensure that patients are absorbing enough of the drug for it to be effective.

What It’s Good For

Posaconazole is most commonly used as prophylaxis against fungal infections in susceptible hosts,  but it can also be used in zygomycosis, oropharyngeal candidiasis, and fungal infections refractory to other agents.

Don’t Forget!

Have your patients take posaconazole with meals to ensure adequate absorption. This is not always possible with neutropenic patients with mucositis.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.

مواضيع ذات صلة

Antifungal Chemotherapy

Pimaricin

Echinocandins

Voriconazole

Itraconazole

Fluconazole

Introduction to Azoles

Antimetabolites

Polyenes

Introduction to Antifungal Drugs