All you need to know about ciclopirox olamine.

Ciclopirox olamine is an antifungal agent commonly prescribed in dermatology to combat infections of the skin, nails and scalp. It has been used since the 1980s, both in prescription-only medicines and in over-the-counter gels and creams. The ciclopirox olamine is generally used at a concentration of 1%. It is indicated in the treatment of dermatophytoses, such as athlete’s foot, candidoses, dandruff and seborrhoeic dermatitis of the face or scalp. Ciclopirox olamine is also used as a nail lacquer to treat mild to moderate onychomycoses. Regarding its chemical structure, ciclopirox is a synthetic derivative of pyridone. When formulated as a salt with ethanolamine, it is termed ciclopirox olamine. This combination enhances the active ingredient’s solubility in water and its bioavailability.

The synthesis of ciclopirox olamine is based on the combination of two molecules: ciclopirox, an antifungal active ingredient, and ethanolamine, a basic agent acting as a solubiliser. Ciclopirox is obtained by substituting a pyridone core with specific lipophilic groups, including a cyclohexyl ring and a hydroxyl side chain. For this, two compounds can be used: methyl 5-oxo-5-cyclohexyl-3-methylpentenoate (I) or 6-cyclohexyl-4-methyl-2-pyrone (V), as shown in the figure below. Ciclopirox is then neutralised in its acidic form with a weak base, namely ethanolamine, to obtain the olamine salt. As mentioned above, this salified form is more stable in aqueous solution, exhibits improved bioavailability and is easier to incorporate into dosage forms such as creams, shampoos or varnishes.

The ciclopirox olamine is a noteworthy active ingredient in dermatology and cosmetics, capable of delivering benefits to the skin, scalp and nails alike. Its antifungal, antibacterial, anti-inflammatory and antioxidant properties, outlined below, enable it to act on mycoses of the skin or nails (onychomycoses), seborrhoeic dermatitis and dandruff.

Ciclopirox olamine is primarily renowned for its antifungal properties.

Ciclopirox olamine stands out for its particularly broad antifungal activity spectrum. It acts effectively against dermatophytes, such as Trichophyton, Microsporum or Epidermophyton, yeasts such as Candida, Malassezia or Cryptococcus, as well as certain moulds, notably Aspergillus and Fusarium. Depending on its concentration and the duration of application, its action may be fungistatic, meaning that it inhibits microbial growth, or fungicidal, indicating that it eradicates the pathogens. Its mode of action is based on the chelation of metal cations, notably iron and aluminium, metals essential for fungal enzymatic activity.

Indeed, this chelation by ciclopirox olamine inactivates metal-dependent enzymes such as cytochromes, catalases and peroxidases, which are essential for mitochondrial respiration, membrane transport and oxidative stress management in fungi. By depriving the cell of free iron, ciclopirox induces a state of intracellular iron deficiency and disrupts iron homeostasis. The FTR1 gene (high-affinity permease) is strongly overexpressed, whereas FTR2 (low-affinity permease) is inhibited. This multifaceted mechanism of action of ciclopirox olamine makes the emergence of resistance unlikely, in contrast to other classes of antifungals.

Ciclopirox olamine also exhibits antibacterial activity.

In addition to its antifungal efficacy, ciclopirox olamine exhibits a broad-spectrum antibacterial activity, affecting both Gram-positive bacteria, such as Staphylococcus aureus, Streptococcus pyogenes or Corynebacterium spp., and Gram-negative bacteria such as Pseudomonas aeruginosa, Escherichia coli or Klebsiella pneumoniae. Unpublished data indicated that daily application of a cream containing 1% ciclopirox olamine by patients with tinea pedis (athlete’s foot) complicated by bacterial infection achieved a two-log reduction in aerobic bacterial counts after fifteen days. No change in bacterial counts occurred with the cream without ciclopirox olamine, emphasising the role of this active compound.

Ciclopirox olamine also exhibits an anti-inflammatory effect.

Ciclopirox olamine also exhibits notable anti-inflammatory properties. It interferes with the arachidonic acid cascade, inhibiting the production of prostaglandins and leukotrienes, two key mediators of cutaneous inflammation. It has further been demonstrated that ciclopirox olamine prevents the activation of certain pro-inflammatory enzymes, such as cyclooxygenase and 5-lipoxygenase, which slows the release of pro-inflammatory cytokines, such as IL-1β, IL-6 or TNF-α. Coupled with its antifungal effects, this anti-inflammatory action of ciclopirox olamine makes it particularly effective in the management of seborrhoeic dermatitis and dandruff, conditions caused by an excessive presence of yeasts on the skin and associated inflammation.

Finally, ciclopirox olamine may limit oxidative stress.

The affinity of ciclopirox olamine for iron not only allows it to exert an antifungal effect but also to modulate oxidative stress. Indeed, by chelating free iron present in tissues, ciclopirox olamine limits its involvement in the so-called Fenton reaction. Catalysed by iron, this reaction involves the transformation of hydrogen peroxide (H₂O₂) into hydroxyl radicals, highly reactive molecules. These free radicals are known to cause cellular damage, particularly at the level of lipid membranes, thus disrupting the skin barrier. This imbalance may favour the emergence of inflammatory skin diseases such as eczema or the seborrhoeic dermatitis. This effect of ciclopirox olamine contributes to its overall anti-inflammatory action, particularly in contexts where oxidative stress is a driver of cutaneous inflammation.

Ciclopirox olamine is generally well tolerated, even when applied for extended periods and/or to sensitive areas.

Reported adverse events remain rare and generally mild. They typically manifest as redness, transient burning sensations or slight itching. These effects are often short-lived and do not necessarily require discontinuation of the product. A retrospective study involving 613 patients with dermatophytosis evaluated the efficacy and tolerability of ciclopirox olamine. Volunteers applied a 1% ciclopirox olamine cream twice a day for six weeks. Good outcomes were achieved, with 73.89% of patients completely cured. Regarding tolerability, only 5.7% of participants reported adverse events. The observed side effects were local and mild, dominated by itching followed by erythema and skin dryness. No systemic reactions or serious events were documented, which supports the idea that ciclopirox olamine is a safe active ingredient.

Note : No study in the available research indicates any teratogenic effects or dangers associated with the use of ciclopirox olamine during pregnancy. However, in the absence of robust clinical data, pregnant women are advised to consult their doctor before using it.

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• BARKATE H. & al. Effectiveness and safety of ciclopirox olamine in patients with dermatophytosis: A retrospective cohort analysis. International Journal of Research in Dermatology (2021).

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