Efinaconazole
[CAS# 164650-44-6]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Antifungal drugs
• Name: Efinaconazole
• Synonyms: (alphaR,betaR)-alpha-(2,4-Difluorophenyl)-beta-methyl-4-methylene-alpha-(1H-1,2,4-triazol-1-ylmethyl)-1-piperidineethanol; KP 103; KP 103 (pharmaceutical)
• Molecular Formula: C₁₈H₂₂F₂N₄O
• Molecular Weight: 348.39
• CAS Registry Number: 164650-44-6
• EC Number: 813-597-5
• SMILES: C[C@H]([C@](CN1C=NC=N1)(C2=C(C=C(C=C2)F)F)O)N3CCC(=C)CC3

Properties

• Solubility: Practically insoluble (0.027 g/L) (25 °C), Calc.^*
• Density: 1.26±0.1 g/cm³ (20 °C 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2014 ACD/Labs)

Safety Data

• Hazard Symbols: GHS08 Warning
• Risk Statements: H361
• Safety Statements: P203-P280-P318-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	2	H361

Discovery and Applications

Efinaconazole is an antifungal medication specifically developed for the treatment of onychomycosis, a fungal infection affecting the toenails or fingernails. Introduced in the early 2010s, efinaconazole has provided a new option for managing this common and often difficult-to-treat condition.

The discovery of efinaconazole stemmed from ongoing research into improving antifungal treatments. It belongs to the azole class of antifungals, which work by inhibiting the synthesis of ergosterol, a vital component of fungal cell membranes. By disrupting ergosterol production, efinaconazole compromises the integrity of the fungal cell membrane, leading to the death of the fungal cells.

Efinaconazole was developed to address the limitations of previous treatments for onychomycosis, such as oral antifungals and older topical agents. Oral antifungals, while effective, carry risks of systemic side effects and drug interactions. Older topical treatments, on the other hand, often had lower efficacy due to poor penetration into the nail and surrounding tissues.

One of the key advantages of efinaconazole is its formulation as a topical solution with enhanced penetration properties. It is applied directly to the affected nails and is designed to reach the infection site more effectively than many previous topical treatments. The drug’s high concentration and effective penetration into the nail plate allow it to treat the infection more efficiently, leading to improved outcomes.

Efinaconazole is typically used as a once-daily topical treatment for up to 48 weeks. This prolonged treatment duration is necessary because toenail infections, in particular, can be challenging to eradicate fully due to the slow growth of nails and the difficulty in achieving adequate drug levels in the infected area.

Clinical trials have demonstrated that efinaconazole is effective in treating onychomycosis caused by dermatophytes, yeasts, and molds. The drug has shown good efficacy in clearing fungal infections and improving nail appearance. Common side effects are generally mild and may include local reactions such as redness, itching, or irritation at the application site.

The introduction of efinaconazole has provided a valuable option for patients who either cannot tolerate oral antifungals or prefer a topical treatment. Its development represents a significant advancement in the management of onychomycosis, addressing some of the shortcomings of earlier therapies and offering a more targeted approach.

Overall, efinaconazole has become an important tool in the dermatological arsenal for treating fungal nail infections. Its targeted action and improved formulation offer hope for effective treatment of onychomycosis, enhancing patient outcomes and providing a practical solution for a challenging condition.

References

2024. Efinaconazole 10% solution: a comprehensive review of its use in the treatment of onychomycosis. Expert Opinion on Pharmacotherapy, 25(15), 1927-1935.
DOI: 10.1080/14656566.2024.2416924

2024. Fungal Fighters: A Comprehensive Guide to Antifungal Therapies of the Past, Present, and Future. Recent Advances in Human Fungal Diseases.
DOI: 10.1007/978-981-97-4909-6_2

2002. Therapeutic Efficacy of Topically Applied KP-103 against Experimental Tinea Unguium in Guinea Pigs in Comparison with Amorolfine and Terbinafine. Antimicrobial Agents and Chemotherapy, 46(12), 3797-3801.
DOI: 10.1128/aac.46.12.3797-3801.2002