Emerging Concepts In Treating Onychomycosis
- Volume 22 - Issue 10 - October 2009
- 28846 reads
- 1 comments
MacroChem Corporation is currently in the midst of a phase II open-label trial of EcoNail (econazole 5%/SEPA 18% nail lacquer), a topical lacquer with SEPA (2-n-1,3 dioxolane) as a drug release enhancer to increase the delivery of econazole to the nail matrix. A total of 37 patients with mild to moderate great toenail infection underwent treatment for 48 weeks with the topical nail lacquer. After 48 weeks of once-a-day treatment, 100 percent of patients had cultures that were negative for dermatophyte growth.15
Pertinent Insights On Oral Medications
Griseofulvin (Gris-PEG, Pedinol) was introduced in 1958. It is fungistatic and effective against dermatophytes. However, due to low cure rates, high relapse rates and poor safety profile, the use of griseofulvin has been limited.
The azoles are a drug class that includes itraconazole, ketoconazole and fluconazole. This drug group is effective against dermatophytes, yeast and other fungi. Ketoconazole (Nizoral) fell out of favor due to its high toxicity rates. Fluconazole (Diflucan, Pfizer) never was approved for toenails and has a high rate of resistance.
Itraconazole (Sporanox, Ortho-McNeil) was approved for continuous therapy for onychomycosis and has proven effective when physicians use it in a pulsing fashion as well.16 Recently, itraconazole received a black box warning due to cardiac concerns.16
The best of the oral antifungals is terbinafine, the first oral antifungal approved for treatment of onychomycosis. Unlike the other antifungals, it is fungicidal and is currently the most effective of the antifungal oral medications.
Before starting any oral antifungal, it is important to take into account the other medications a patient is taking due to the fact that azoles inhibit P-450 cytochrome, which could interfere with other medications. Also, a past history of liver dysfunction may preclude the patient from taking these medications due to the fact that the medications are metabolized in the liver and could lead to further liver damage.17-19
There are a plethora of new triazoles at different stages of clinical trial. These include voriconazole (Vfend, Pfizer), isavuconazole (Basilea Pharmaceutica), ravuconazole (Eisai/Bristol-Myers Squibb), pramiconazole (Barrier Therapeutics/Stiefel Laboratories), posaconazole (Schering-Plough) and albaconazole (Stiefel Laboratories).20
One promising new azole is pramiconazole. This new addition to the family of triazole antifungal agents works by inhibiting fungal cell membrane ergosterol synthesis, thereby leading to increased cell permeability and cell destruction.21 In pre-clinical studies, pramiconazole showed similar or superior antifungal activity to ketoconazole and itraconazole. This new azole was absorbed rapidly and had a long half-life, allowing for once-daily dosing.21 Promising pre-clinical and early phase II clinical data warrant further development.
Can New Devices Have An Impact For Onychomycosis?
Noveon (Nomir Technologies) is a low power laser that is currently in use for dental work, cataract surgery and even hair removal. The laser beam has two different wavelengths of near-infrared light, which causes photo inactivation of the fungi that cause onychomycosis. The device uses specific infrared wavelengths that have the ability to cause photo damage to microbes.
In a pilot study, Noveon treatment had a 76 percent clinical improvement. At this time, Nomir Medical has a FDA 510(k) clearance for the Noveon laser and is pursuing approval for onychomysosis.23
PinPointe FootLaser (Patholase) is a new high powered pulse laser that targets the fungus responsible for causing onychomycosis and related fungal infections. According to Patholase, usually only one treatment is necessary although further study is ongoing. No anesthesia or other drugs are necessary. Patients who have undergone the treatment report very little pain and promising results have been reported.24 A new trial will evaluate the efficacy and safety of this new modality.