Therapeutic Update: Onychomycosis

The two main options for oral therapy are terbinafine (Lamisil) and itraconazole (Sporonox, Omnel). Terbinafine is taken daily for 12 weeks in the treatment of onychomycosis. Although effective, the use of terbinafine is limited by concerns regarding rare yet potentially severe side effects. The overall adverse event rate for terbinafine is about 10%, with gastrointestinal (GI) upset and nausea being most common. “Very rare” events which occur in <0.01% of patients include liver failure resulting in transplant or death, severe neutropenia, cutaneous and systemic lupus, prolonged taste loss, and toxic epidermal necrolysis (TEN). Temporary loss or disturbance in taste is considered “uncommon” occurring in 0.1 to 1% of patients.⁸ These side effects should be discussed with the patient, and the diagnosis must be confirmed with fungal culture prior to initiating treatment. Baseline laboratory testing including complete blood count and liver function tests should be performed with most practitioners repeating the liver function tests monthly during treatment.

Itraconazole is an alternative to terbinafine that is sometimes more cost effective yet not without its own limitations. It is a fungistatic, triazole antifungal that blocks ergosterol synthesis by inhibiting 14α-demethylase. Itraconazole carries a black box warning for both congestive heart failure and drug interactions. It is a potent inhibitor of the cytochrome P3A4 enzyme and thus can lead to dangerously high levels of many medications when administered together. It is strictly contraindicated for co-administration with at least 25 medications including statins. Other adverse effects include elevated liver functions tests, decreased white blood cell count, elevated triglycerides, and nephrotoxicity. For young healthy patients, however, who are not on many other medications it remains a viable alternative. Omnel (Merz Aesthetics, Greensboro, NC) is a relatively new formulation of itraconazole that utilizes a proprietary melt-extrusion or Meltrex technology designed to improve bioavailability and allow for steady and consistent GI absorption. It is administered 200mg a day for 12 weeks in the treatment of onychomycosis. Itraconazole can also be administered in a pulsed fashion, most commonly 200mg twice daily for 7 days, off for 21 days, repeated for 2 or 3 months. It is important to note, however, that the pulsed regimen is not FDA approved.

The use of lasers in the treatment onychomycosis has gained popularity as an answer to the need for a treatment with better efficacy than topicals but without the potential side effects of oral therapy. One such laser is the Pinpointe^® Foot Laser (Cynosure, Westford, MA), which is a patented 0.65ms 1064 Nd:YAG marketed for the treatment of onychomycosis. It is a fiber optic device that directs a matrix of 1mm spots that covers the nail plate and surrounding 2mm of epidermis. In a small study of 8 patients, 7 of 8 obtained a negative culture after 2 to 3 sessions.⁹ Another study of the 1064 Nd:YAG (6mm spot size, 5 J/cm² fluence, 0.3 ms pulse duration) yielded less impressive results with only 9.3% of the nails treated achieving a complete cure.¹⁰

Fractional CO₂ combined with topical therapy has also been utilized with a reasonable degree of success. A study of 24 subjects treated with fractional CO₂ laser three times at 4 week intervals in conjunction with topical amorolfine showed a 50% complete response rate with negative microscopic result.¹¹ The protocol consisted of 30 minutes of topical anesthesia on periungual skin followed by 2-3 passes at 160mJ with a density of 150 spots/cm² using static operating mode over the affected nail and surrounding 1mm of normal nail or skin. Topical therapy was initiated immediately post treatment.¹¹ As of yet, there is no data available regarding recurrence rates after laser therapy.

Photodynamic therapy (PDT) has also been utilized in the treatment of onychomycosis as it has been shown that T. rubrum can metabolize aminolevulinic acid (ALA) to protoporphyrin IX with a subsequent growth reduction of 50% after ALA PDT.¹² A study published in the Archives of Dermatology described the successful treatment of onychomycosis using 5-ALA and the excimer laser.¹³ In this case report of 2 patients, the application of 20% urea under occlusion was followed by 20% 5-ALA under foil for 5 hours. Affected nails were then treated with horizontal and vertical passes of the 630nmexcimer laser. A total of 6 to 7 treatments were required to obtain a cure.

Currently available treatments for onychomycosis remain suboptimal for various reasons. The most reliable treatment in terms of obtaining a cure remains oral therapy with either terbinafine or itraconazole. Many patients, however, are unwilling to accept even a small risk of a severe of life-threatening side effect for the sake of their toenails. Laser therapy is likely safer than oral therapy but data on efficacy, particularly long term efficacy, remains limited. The future of onychomycosis treatment may depend on improved drug delivery of existing topical agents.

The author has not disclosed any relevant conflicts.