What are the newer antifungal (antifungals) drugs used in dermatology for treating fungal infections?

Newer Antifungal Drugs in Dermatology

The second-generation triazoles—posaconazole, voriconazole, ravuconazole, albaconazole, and pramiconazole—represent the newest class of antifungal agents in dermatology, offering broad-spectrum activity against dermatophytes, yeasts, and nondermatophyte moulds with improved safety profiles and fewer drug interactions compared to first-generation triazoles. 1

Second-Generation Triazoles: The Newest Antifungal Class

Posaconazole

Posaconazole demonstrates the strongest clinical evidence among newer agents, with phase II data showing complete cure rates of 54% at 200 mg daily for 24 weeks and 45.5% at 400 mg daily for 24 weeks for toenail onychomycosis, comparable to terbinafine (37%). 1

• Exhibits MICs comparable to terbinafine against dermatophytes, with broad-spectrum activity against yeasts and moulds 1
• Most common adverse effects include headaches (6%), diarrhea (5%), nausea (4%), and fatigue (4%) 1
• Seven patients (3%) withdrew due to asymptomatic liver enzyme elevations in clinical trials 1
• Particularly valuable for recalcitrant infections caused by nondermatophyte moulds 1

Voriconazole

Voriconazole shows high in vitro activity against dermatophytes, Candida species, Scopulariopsis, Neoscytalidium, and Fusarium species, making it a useful salvage therapy for recalcitrant nail infections. 1

• FDA-approved for invasive fungal infections, with demonstrated efficacy against Aspergillus (44% success rate) and Candida species (41% success rate in candidemia) 2
• Successfully treated 15 of 24 patients (63%) with Scedosporium apiospermum infections and 9 of 21 patients (43%) with Fusarium infections 2
• Clinicians should monitor for visual disturbances, a characteristic adverse effect of voriconazole 3

Albaconazole

Albaconazole's long half-life permits weekly dosing (400 mg weekly for 36 weeks), achieving cure rates of 21-54% for toenail onychomycosis, with efficacy being dose-dependent. 1

• Treatment-related adverse effects occurred in <3% of patients and were mild to moderate 1
• Most common side effects: headache, nausea, diarrhea, and transient mild liver enzyme elevations 1
• Weekly dosing schedule significantly improves compliance compared to daily regimens 1

Ravuconazole

Ravuconazole achieved 59% mycological cure rates at 200 mg daily for 12 weeks in phase I/II trials for toenail onychomycosis, with high tolerability. 1

• Has not yet undergone phase III trials, limiting its current clinical availability 1

Pramiconazole

Pramiconazole demonstrates similar or superior antifungal activity to itraconazole and ketoconazole in preclinical studies, with excellent bioavailability and long half-life permitting once-daily dosing. 1

• Phase II trials showed encouraging results against cutaneous dermatophyte and yeast infections 1
• Specifically developed for superficial infections of skin, mucosae, and nails 1

Newest Agents for Candida Infections

Ibrexafungerp and Oteseconazole

The 2025 global Candida guideline identifies ibrexafungerp and oteseconazole as new additions to the antifungal armamentarium specifically for superficial candidiasis. 1

• These agents complement existing therapies for mucocutaneous Candida infections 1
• Represent alternatives when first-line azoles are contraindicated or ineffective 1

Rezafungin (Echinocandin Class)

Rezafungin, a new echinocandin, is recommended as first-line treatment for candidemia and invasive candidiasis (except CNS and ocular infections) due to broad activity and safety profile. 1

• Echinocandins inhibit glucan synthesis in fungal cell walls, providing fungicidal effects against yeasts 1
• Available only as intravenous formulations, limiting use for superficial dermatologic infections 1

Key Advantages of Second-Generation Triazoles

These newer agents offer improved safety profiles with fewer drug interactions compared to first-generation triazoles like itraconazole and ketoconazole. 1

• Particularly valuable for treating nondermatophyte mould infections, which are often resistant to terbinafine 1
• Broader spectrum activity against yeasts and moulds compared to allylamines 1

Critical Limitations and Caveats

High cost restricts utility of second-generation triazoles, which have been reserved primarily for treatment-refractory cases. 1

• Clinical trial data for onychomycosis remain limited or ongoing for most agents 1
• None have replaced terbinafine or itraconazole as first-line therapy for common dermatophyte infections 1
• Weekly dosing regimens (albaconazole, pramiconazole) may improve compliance but require longer treatment durations 1

Clinical Application Algorithm

For recalcitrant nail infections:

• Consider posaconazole 200 mg daily for 24 weeks if terbinafine or itraconazole have failed 1
• Reserve voriconazole for infections caused by nondermatophyte moulds (Scopulariopsis, Fusarium, Neoscytalidium) 1, 2

For improved compliance:

• Albaconazole 400 mg weekly for 36 weeks offers the most convenient dosing schedule among newer agents 1

For superficial Candida infections:

• Consider ibrexafungerp or oteseconazole when first-line azoles are contraindicated 1