Fluconazole

The introduction of fluconazole in 1990 was a break-through in antifungal pharmacotherapy. Fluconazole is highly bioavailable, available in both oral and IV formulations, and highly active against many species of Candida. Before this, clinicians were faced with the toxicity and inconvenience of amphotericin B for serious forms of candidiasis. Fluconazole has a low incidence of serious adverse reactions, and converting from IV to oral therapy is simple. Though a shift toward non-albicans species of Candida has affected the use of fluconazole, it remains an important, frequently utilized agent.

Spectrum

Good: Candida albicans, Candida tropicalis, Candida parapsilosis, Candida lusitaniae, Crypto-coccus neoformans, Coccidioides immitis

Moderate: Candida glabrata (can be susceptible dose-dependent, or resistant)

Poor: moulds, many dimorphic fungi,  Candida krusei

Adverse Effects

Though fluconazole is generally well tolerated, it can cause hepatotoxicity or rash. It has a lower propensity for serious drug interaction than many other azoles, but interactions still occur with many drugs metabolized by the cytochrome P450 system.   QTc prolongation is also possible.

Dosing Issues

Fluconazole doses for systemic fungal infections have been escalated, particularly for the treatment of Candida glabrata. Be sure to adjust dosing with regard to renal function, because the drug is eliminated through the urine. Vulvovaginal candidiasis requires only a one-time dose of 150 mg of fluconazole.

Important Facts

• Fluconazole is poorly active against all  Candida krusei and some Candida glabrata. If you are using it for the latter infection, it is best to check susceptibilities and give 800 mg per day of fluconazole. If your lab does not do susceptibility testing of fungi, consider an alternative agent such as an echinocandin.

• Fluconazole is often given as prophylaxis against Candida infections in susceptible populations like intensive care unit patients. Are you treating a patient who was receiving it and now has yeast in the blood? Try an echinocandin instead.

• The high bioavailability of fluconazole makes it an excellent therapy to transition to as patients tolerate oral medications.

What It’s Good For

Fluconazole remains a drug of choice for many susceptible fungal infections, including invasive and noninvasive candidiasis and cryptococcal disease.  It is also used for some dimorphic fungal infections,  such as coccidioidomycosis.

Don’t Forget!

Not all species of  Candida are fluconazole-susceptible. Ensure that you check your patient’s isolate before committing to a definitive course of therapy with it.

References

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

مواضيع ذات صلة

Antifungal Chemotherapy

Pimaricin

Echinocandins

Posaconazole

Voriconazole

Itraconazole

Introduction to Azoles

Antimetabolites

Polyenes

Introduction to Antifungal Drugs