Products
Azole antifungals are approved in many countries for both topical and systemic treatment. They are available in numerous dosage forms-including creams, an oral gel, powders, sprays, tablets, capsules, injectables, vaginal creams, and vaginal tablets. The first azole antifungal came on the market in the 1950s.
Structure and properties
The name azole refers to heterocycles that contain nitrogen atoms. Most azole antifungals contain an imidazole (e.g., econazole), and some also contain a triazole (e.g., fluconazole, itraconazole). Accordingly, they are also referred to as imidazole antifungals and triazole antifungals. The nitrogen of the heterocycles binds to the heme iron of the drug target.
Effects
Azole antifungals (ATC D01AC, ATC J02AB) have antifungal (fungistatic to fungicidal) properties, meaning they are effective against fungi such as dermatophytes, yeasts, and molds. The effects are based on the inhibition of the enzyme lanosterol-14α-demethylase (CYP51A1) in fungi. This inhibits the synthesis of ergosterol from lanosterol, leading to accumulation of toxic precursors and disruption of fungal cell membrane assembly. Some representatives are also active against Gram-positive and Gram-negative bacteria, as well as parasites.
Indications
For the treatment of local and systemic fungal infections, such as:
- Athlete’s foot
- Nail fungus
- Fungal skin infections
- Candidamycoses
- Vaginal fungus
- Oral thrush
- Dandruff
- Pityriasis versicolor
- Systemic fungal infections, e.g. invasive candidamycosis, aspergillosis.
Dosage
According to the professional information. The application depends on the drug.
Active ingredients
Topical azole antifungals:
- Clotrimazole (Canesten, Gyno-Canesten, generics).
- Econazole (Pevaryl, Gyno-Pevaryl).
- Isoconazole (Travogen)
- Ketoconazole (Nizoral, Terzolin, generics).
- Miconazole, miconazole against nail fungus, miconazole mouth gel (Daktarin).
Systemic azole antifungals:
- Fluconazole (Diflucan, generic).
- Isavuconazonium sulfate (prodrug of isavuconazole, Cresemba).
- Itraconazole (Sporanox, generic).
- Ketoconazole (Nizoral tablets are out of trade).
- Posaconazole (Noxafil)
- Voriconazole (Vfend, generics)
Other representatives exist that are not or no longer available in many countries.
Contraindications
Contraindications include (selection):
- Hypersensitivity, including to other agents in this group.
- Combination with CYP450 substrates that prolong the QT interval (systemic therapy).
For complete precautions, see the drug label.
Interactions
Azole antifungals are inhibitors of CYP450 isozymes and have a high potential for drug-drug interactions when used systemically. With concomitant use of CYP substrates, their plasma concentrations may increase and the risk for adverse effects increases.
Adverse effects
The most common potential adverse effects with topical (dermal) use include skin reactions such as itching, a burning sensation on the skin, and pain may occur. With systemic treatment, skin reactions, headache, gastrointestinal disturbances, and elevated liver enzymes may occur. A problem is resistance, which the fungi can develop against the antifungal drugs.
