Emerging Concepts In Treating Onychomycosis

Author(s): 
John D. Mozena, DPM, and Joshua P. Mitnick, DPM

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.

   PinPointe FootLaser has received FDA approval for use in podiatry, dermatology and plastic surgery but it does not have a specific indication for onychomycosis at this time. However, in Europe, it recently received the CE Mark approval (certifying that it has met EU consumer and health safety standards) for the treatment of toenail fungus. The cost of the procedure is approximately $1,000.24

Comments

For professionals in the Podiatric community that are interested, here is the current Pivotal Study information on the Noveon from Nomir Medical Technologies

There were 36 subjects (53 Toes) enrolled in the study.

Starting after the completion of the second of the four treatments, all subjects were required to use a non-prescriptive topical agent: 1% topical terbinafine cream applied only between the toes to control or prevent tinea interdigitalis.

Patients were instructed to not get any cream on the nails.

Use of this topical between the toes only, was in accordance with the current listed product information and is neither FDA indicated, nor FDA cleared as a treatment for onychomycosis. Other adjunctive actions that are "standard of care", such as nail debridement or nail trimming, were allowed at each investigator’s discretion.

Control subjects were handled identically in all respects to those who were treated, except for, of course, with sham “treatment” there was no energy delivery. The highest treatment site temperature was 100.5°F.

All study subjects had to have laboratory confirmation of onychomycosis by either positive culture using a selective dermatophyte test medium, or positive periodic acid-Schiff staining (PAS) from a toenail sample.

The mycology was followed and data taken for the 180 day balance of the study.

The top-line preliminary 120-day data analysis that was presented at the Council for Nail Disorders 13th Annual Scientific Meeting, and demonstrated that after Noveon treatment, 76.3 percent of the treated toes showed evidence of clinical improvement (p

This data was based on at least 120 days of follow-up on all enrolled patients. Additionally, no significant adverse events were reported.

The final 180 day data, is currently under review by the FDA in an application for 510(k) approval for Onychomycosis treatment, and has been accepted for publication with a Podiatric peer-review journal.

Completed pilot study data with this device can be found at:

Bornstein, E.S., A.H. Robbins, M. Michelon (2008) Photo-inactivation of fungal pathogens that cause onychomycosis in vitro and in vivo with the noveon dual wavelength laser system. 2008 New Cardiovascular Horizons Meeting Abstracts.

http://www.nomirmedical.com/pdf/NCH_...L_08-26-08.pdf

A lengthy discussion on this and other light-based onychomycosis technologies can be found at:

http://www.podiatry-arena.com/podiat...ad.php?t=22925

Eric Bornstein
Chief Science Officer
Nomir Medical Technologies

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