Ciclopirox olamine, an intriguing active ingredient against fungal nail infections?

Onychomycoses, more commonly known as nail fungus, are a frequent fungal condition primarily affecting the toes. They are responsible for thickening, yellowish or brownish discolouration and occasionally progressive deformation of the nail plate. This condition, often seemingly trivial, can nevertheless prove persistent and significantly impair quality of life, not least because of its visibility. Most fungal nail infections are caused by dermatophytes, in particularTrichophyton rubrum, but other pathogens, such as yeasts, for example those of the genus Candida, may also be implicated. Treatment of onychomycoses generally relies on oral and/or topical antifungals, such as ciclopirox olamine.

If your nails are affected by symptoms indicative of a fungal infection, do not hesitate to seek advice from your pharmacist or doctor to guide you towards an appropriate treatment.

Among the topical antifungal agents available for the treatment of nail mycoses, ciclopirox olamine stands out by virtue of an original mode of action that may offer certain advantages over the limitations of conventional therapies. Unlike azoles or allylamines, which target the biosynthesis of ergosterol—a molecule present in most fungi and playing a role similar to that of cholesterol in humans—ciclopirox olamine acts by disrupting the intracellular homeostasis of fungi, particularly by chelating the metal cations essential to their metabolism, such as iron. This activity, both fungistatic and fungicidal, confers on this agent a particularly broad antifungal spectrum. It is effective against dermatophytes, the principal agents responsible for onychomycoses, but also against yeasts Candida and moulds, often involved in atypical or recalcitrant forms.

Another advantage of ciclopirox olamine is its excellent capacity to penetrate nail keratin, enabling it to reach the deeper layers.

Several studies have investigated the effects of ciclopirox olamine in onychomycoses. In particular, two parallel, double-blind clinical trials can be cited. The first involved 223 patients (8 % ciclopirox olamine group: 112; placebo group: 111) and the second 237 patients (8 % ciclopirox olamine group: 119; placebo group: 118). Treatment consisted of applying one of the formulations daily for 48 weeks to the toenails affected by onychomycosis, with monthly clinical assessments and mycological evaluations every three months. At the end of the protocol, the mycological cure rates were significantly higher in the ciclopirox olamine group: 29 % vs 11 % in the first study and 36 % vs 9 % in the second. Although these figures remain modest, they confirm the superiority of ciclopirox olamine over placebo. Moreover, the treatment was very well tolerated, with the adverse effects reported were rare, localised (erythema, irritation) and transient.

Another study confirmed these favourable results. In this trial, an 8% ciclopirox olamine formulation, known as P-3051, was compared with a placebo and a reference varnish, which also contained 8% ciclopirox olamine. The difference between the test solution and the reference lay in the improved affinity for keratin of the new formulation. In total, 467 patients with onychomycosis were divided into three groups to receive a daily application of P-3051, the reference varnish or a placebo for 48 weeks. A further 12-week follow-up was then carried out to evaluate the stability of the results.

The results demonstrate a superior cure rate for products containing ciclopirox olamine.

Ciclopirox olamine is not, however, a panacea for nail fungal infections, which remain particularly difficult to manage. This observation is reflected in the relatively low cure rate observed in the previous study. It is nevertheless noteworthy that the improvement appears to continue beyond the follow-up period : it is therefore possible that additional patients were cured after the study concluded without being accounted for in the final results.

One of the reasons why fungal nail infections are so complex to eradicate is the necessity of eliminating all pathogenic agents. Indeed, spores, the resting forms of fungi, are highly resistant and represent a major cause of therapeutic failure and relapse. For example, the dermatophyte Trichophyton interdigitale produces numerous arthrospores in and beneath the infected nail plate when colonising a host. Ciclopirox olamine is now regarded as a gold standard therapy, notably because of its sporicidal properties. These were demonstrated during an in vitro study that compared the sporicidal effect of several antifungal agents, including ciclopirox olamine, on spores of Trichophyton rubrum. The results, presented in the graphs below, indicate that ciclopirox olamine displays a good efficacy against fungal spores.

While onychomycoses remain difficult to treat even today, ciclopirox olamine remains the benchmark antifungal agent.

• WANG B. & al. A clinical and laboratory study of ciclopirox olamine (8% Batrafen) in the treatment of onychomycosis. Chinese Medical Sciences Journal (1991).

• BARAN R. & al. Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis. Journal of the American Academy of Dermatology (2000).

• BARAN R. & al. An innovative water-soluble biopolymer improves efficacy of ciclopirox nail lacquer in the management of onychomycosis. Journal of the European Academy of Dermatology and Venereology (2009).

• POLAK A. & al. Sporicidal effect of amorolfine and other antimycotics used in the therapy of fungal nail infections. Mycoses (2015).

• BUDZISZ E. & al. Ciclopirox and ciclopirox olamine: Antifungal agents in dermatology with expanding therapeutic potential. Applied Sciences (2024).