When you’re trying to really “nail” down a treatment option for onychomycosis, it can be difficult navigating through new therapies and insurance restrictions. The newest kid on the block for treatment is Jublia (efinaconazole), joining Ciclopirox and Tavaborole on our shelves as an option for fungal nail infections. However, despite its excellent treatment success, it’s not always feasible for patients to afford. Jublia’s success in treatment trials can be tied to its small molecular size and reduced keratin binding, ensuring the medication makes it completely through the nail and into the colonized nail bed[1]. The difficulty in treating onychomycosis is achieving therapeutic concentrations of medication at the site of infection, and our main physical barrier is the keratinized nail itself.
Evidence suggests that we may be able to facilitate the movement of medication by utilizing excipients, like DMSO, that improve diffusion through the nail and alter keratin organization[2,3]. Using creative compounding, we offer an Itraconazole/Terbinafine/Ibuprofen compound that uses DMSO to allow these medications to reach that nail bed. When used alone, compounded terbinafine has shown to reach therapeutic concentrations of 0.4mg in the nail bed when applied consistently[4]. Additionally terbinafine with itraconazole has a higher statistically significant rate of cure over monotherapy with terbinafine alone[5]. Finally, ibuprofen has been utilized as an antidermatophytic medication, and can reduce the activity of efflux pumps in candida species, allowing the medication to build up to achieve both fungicidal and fungistatic levels [6.7].
By compounding these three medications together, we may be able to deliver therapeutic levels of medication to the nail bed to treat onychomycosis. While treatment times likely still need to be 48-52 weeks, our compound is offered at a cash price of $49 per 15mL. This can present an additional option for prescribers interested in prescribing an -azole antifungal for treatment.
1.)Tatsumi Y, Nagashima M, Shibanushi T, Iwata A, Kangawa Y, Inui F, Siu WJ, Pillai R, Nishiyama Y. Mechanism of action of efinaconazole, a novel triazole antifungal agent. Antimicrob Agents Chemother. 2013 May;57(5):2405-9. doi:10.1128/AAC.02063-12. Epub 2013 Mar 4. PMID: 23459486; PMCID: PMC3632939.
2.) Malode, Pranjali & Hiwe, Kanchan & Hatwar, Pooja & Bakal, Ravindra & Kohale, Nitin. (2024). “A REVIEW ON TRANSUNGUAL DRUG DELIVERY SYSTEM”. International Journal of Novel Research and Development. 9. 569.
3.) Amichai B, Mosckovitz R, Trau H, Sholto O, Ben-Yaakov S, Royz M, Barak D, Nitzan B, Shemer A. Iontophoretic terbinafine HCL 1.0% delivery across porcine and human nails. Mycopathologia. 2010 May;169(5):343-9. doi: 10.1007/s11046-009-9265-x. Epub 2009 Dec 13. PMID: 20012894.
4.) Hoffman K, Gorski M, Frey CP. Innovation in Onychomycosis Treatment Through Creative Compounding. Cureus. 2025 Sep 2;17(9):e91475. doi: 10.7759/cureus.91475. PMID: 41049944; PMCID: PMC12491616.
5.) Ramzi SHT, Arif SA, Majid A, Kumar S, Shumail H, Qudsia F, Zainab Y, Varrassi G, Khatri M. Efficacy of Terbinafine and Itraconazole Combination Therapy Versus Terbinafine or Itraconazole Monotherapy in the Management of Fungal Diseases: A Systematic Review and Meta-Analysis. Cureus. 2023 Nov 14;15(11):e48819. doi: 10.7759/cureus.48819. PMID: 38106696; PMCID: PMC10722332.
6.) Abdul Hussein A, Al-Janabi S. Investigation of anti-dermatophytic effects of non-steroidal anti-inflammatory drugs on trichophyton mentagrophytes and epidermophyton floccosum. Iran J Pharm Res. 2011 Summer;10(3):547-52. PMID: 24250387; PMCID: PMC3813025.
7.) Ricardo E, Costa-de-Oliveira S, Dias AS, Guerra J, Rodrigues AG, Pina-Vaz C. Ibuprofen reverts antifungal resistance on Candida albicans showing overexpression of CDR genes. FEMS Yeast Res. 2009 Jun;9(4):618-25. doi: 10.1111/j.1567-1364.2009.00504.x. Epub 2009 Mar 30. PMID: 19416368.
