Which medications in the drug class Azole Antifungals are used in the treatment of Candidiasis?

Updated: Jan 17, 2020
  • Author: Jose A Hidalgo, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Azole Antifungals

These agents are synthetic compounds that include 2 groups, imidazoles and triazoles. Triazoles have 3 atoms of nitrogen in the azole ring. Imidazoles have only two. The primary mechanism of action is inhibition of lanosterol 14-alpha-demethylase, an enzyme required for the synthesis of ergosterol, the main component of fungal cell membranes. Imidazole agents include miconazole, ketoconazole, and clotrimazole.

In August 2013, the FDA announced that clinicians should no longer prescribe ketoconazole (Nizoral, Janssen Pharmaceuticals) tablets as a first-line therapy for any fungal infection, including Candida and dermatophyte infections, because of the risk for severe liver injury, adrenal insufficiency, and adverse drug interactions. [34, 35] The FDA also cautioned that ketoconazole tablets should not be prescribed for any patient with underlying liver disease. The labeling changes do not apply to topical formulations of ketoconazole in creams, shampoos, foams, and gels. Oral ketoconazole is now indicated only for endemic mycoses in patients who fail to respond to or cannot tolerate other treatments.

Ketoconazole tablets were also withdrawn from the market in the European Union in July 2013. [34, 35]

Triazole agents, which are now the most commonly used azoles, include fluconazole, itraconazole, econazole, terconazole, butoconazole, and tioconazole. Newer triazoles (ie, voriconazole, posaconazole, ravuconazole) are active against fluconazole-resistant strains of Candida. Voriconazole and posaconazole have shown high efficacy against candidiasis in recent clinical trials. [43, 50, 51]

Topical agents are frequently used as front-line agents to manage localized or superficial forms of candidiasis such as cutaneous candidiasis, oropharyngeal candidiasis (OPC), and vulvovaginal candidiasis (VVC). These preparations are available as a cream for topical use, as troches for OPC, and as a vaginal suppositories or tablets for vaginitis.

Fluconazole (Diflucan)

Triazole with less effect on human sterol metabolism. Does not decrease cortisol and testosterone levels, as occurs with ketoconazole. Has fewer adverse effects and better tissue distribution than older systemic imidazoles. Available PO/IV and has demonstrated efficacy in topical and invasive forms of candidiasis. Available in 50-, 100-, 150-, and 200-mg tabs.

Daily dose varies with indication.

Itraconazole (Sporanox)

Has fungistatic activity. Synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P450-dependent synthesis of ergosterol, a vital component of fungal cell membranes. Effective against broad range of fungi, including Candida species, and is indicated for treatment of cutaneous, oral, esophageal, and disseminated candidiasis.

Available IV, 100-mg caps, and oral solution at 10 mg/mL.

Caps require gastric acidity for absorption and should be taken with food to increase absorption. Liquid formulation increases bioavailability and decreases need for acidity for proper absorption.

Use of solution has been recommended in mucosal and invasive candidiasis, while caps can be used in onychomycosis and dermatophyte infections.

Voriconazole (Vfend)

Available as tablet, suspension and parenteral preparations. Effective as fluconazole against esophageal candidiasis, and as effective as amphotericin B deoxycholate in treatment of candidemia and invasive candidiasis. In Europe, it has been approved for "treatment of fluconazole-resistant serious invasive Candida infections (including C krusei)." Additionally, associated with fewer breakthrough fungal infections when used as empiric therapy in febrile neutropenic patients. FDA approved for esophageal candidiasis and candidemia.

Posaconazole (Noxafil)

Novel triazole antifungal agent. Blocks ergosterol synthesis of cell membrane by inhibiting enzyme lanosterol 14-alpha-demethylase and sterol precursor accumulation. Action results in cell membrane disruption. Available as oral susp (200 mg/5 mL). Approved for treatment of OPC, including OPC refractory to itraconazole and/or fluconazole and for prophylaxis of infections due to Candida and Aspergillus in patients who are at high risk, such as those undergoing stem cell transplants with graft versus host disease or with prolonged neutropenia due to a hematologic malignancy or its treatment.

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