Ciclopirox Topical Solution 8% (Penlac Nail Lacquer)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

The fda has approved ciclopirox, a topical broad-spectrum antifungal agent, for the treatment of fungal infections of the fingernails and toenails. Ciclopirox is formulated in a 8% topical solution and will be marketed as Penlac Nail Lacquer by Dermik. It is manufactured by Aventis in Germany where it is already available. The vehicle contains volatile (flammable) solvents such as isopropyl alcohol and ethyl acetate that vaporize after application. Daily application results in a build up on the nail which must be removed on a weekly basis. Ciclopirox has also been marketed worldwide for years in cream, lotion, and gel formulations.

Indications

Ciclopirox topical solution is approved as topical treatment of mild to moderate onchomycosis of fingernails and toenails without lunular involvement, due to Trichophyton rubrum. Treatment should be a component of a comprehensive management program that includes removal of the unattached, infected nails as frequently as monthly by a trained health care professional.1

Dosage

Ciclopirox should be applied once daily evenly over the entire affected nail plate. Application is preferable at bedtime or eight hours before washing. Where possible, the solution should be applied to the underside of the nail and to the skin beneath it.1 Daily application should be applied over the previous coat. Layers should be removed with alcohol every seven days.

Potential Advantages

Bioavailability studies in human volunteers suggest that ciclopirox formulated as an 8% nail lacquer can penetrate the nail.2 In vitro studies demonstrated penetration up to a depth of about 0.4 mm.1 Efficacy with nail lacquers appears to be better than other topical therapy.3 Microbiologic cure has been reported in the range of 29-36% after 48 weeks of therapy.1

Potential Disadvantages

Complete clear nail may not be achieved with ciclopirox nail lacquer even after 48 weeks of therapy along with the comprehensive nail care program which includes weekly trimming of the nails by the patient and monthly removal of unattached nail by a professional.1 Less than 12% of patients with oychomycosis of the great toenail achieve either a completely clear or almost clear toenail. Common side effects include rash-related side effects (periungual erythema and erythema of the proximal nail fold), 5%.1

Comments

Ciclopirox is a hydroxy-pyridone that is chemically distinct from the azoles or other antifungals. It has a broad spectrum of action including fungicidal activity against T. rubrum.4 Ciclopirox has been available as a cream and solution for many years as a 1% strength. The 8% nail lacquer has been available in Europe and has now been introduced in the United States. The nail lacquer appears to improve nail penetration and is well tolerated. However, in patients with 20-65% involvement of the great toenail plate, complete cure was less than 10% and mycological cure ranged from 29% to 36% after 48 weeks based on intent-to-treat and last observation carried forward. Relapse rates have not been reported. There does not appear to be any published comparative trials with other topical or oral regimens. Dermik is expected to launch Penlac within the next few months.

Clinical Implications

Onychomycoses, or infections of the nail, are common, and can be caused by a number of organisms including dermatophytes, yeast, or molds. Dermatophytes with T. rubrum as the major pathogen are responsible for about 90-95% of the infections.3 Pharmacologic treatment involves oral and topical routes.

Topical therapy, which has the advantage of few systemic side effects, is generally limited by diffusion of the drug through the horny layers of the nail which may be enhanced with lacquer formulations. Ciclopirox in a nail lacquer formulation is reported to enhance nail penetration, but its long duration of therapy may be problematic. Oral therapy with antifungals such as fluconazole, itraconazole, and terbinafine are more effective and involve shorter courses of therapy. For example, the cure rates for terbinafine (250 mg daily) range from 60% to 80% after three months of therapy and that of fluconazole (150-450 mg weekly) 77-86%.3 A recent comparative study (n =137) suggested that terbinafine (250 mg for 12 weeks and evaluated at week 60) was more effective than fluconazole (150 mg weekly for 12 or 24 weeks).

Mycological cure was 89% vs. 51% and 49% and complete clinical cure was 67% vs. 21% and 32%.5 As for topical therapy, it may be reasonable for less severe infections (e.g., involvement of < 30% of the nail).3

Combined topical and systemic therapy is also being evaluated.

References

1. Penlac Product Information. Dermik Laboratories, Inc. December 1999.

2. Ceschin-Roques CG, et al. Skin Pharmacol 1991;4(2):89-94.

3. Niewerth M, et al. Drugs 1999;58(2):283-296.

4. Gupta AF, et al. Drugs 1998;55(5):645-674.

5. Havu V, et al. Br J Dermatol 2000;142(1):97-102.