Everything 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 medications and in over-the-counter gels and creams. The ciclopirox olamine is generally used at a 1% concentration. It is employed in the treatment of dermatophytoses such as athlete’s foot, candidiasis, dandruff, and seborrheic dermatitis of the face or scalp. Ciclopirox olamine is also formulated as a nail lacquer to address mild to moderate onychomycosis. Regarding its chemical structure, ciclopirox is a synthetic derivative of pyridone. When formulated as a salt with ethanolamine, it is referred to as ciclopirox olamine. This combination enhances the solubility of the active ingredient in water and its bioavailability.

The synthesis of ciclopirox olamine relies on the combination of two molecules: ciclopirox, an antifungal active ingredient, and ethanolamine, a basic agent serving as a solubilizer. Ciclopirox is obtained by substituting a pyridone core with specific lipophilic groups, including a cyclohexyl ring and a hydroxylated side chain. For this purpose, two compounds may 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 neutralized in its acidic form with a weak base, ethanolamine, to obtain the olamine salt. As noted above, this salted form is more stable in aqueous solution, offers improved bioavailability, and is easier to incorporate into dosage forms such as creams, shampoos, or nail lacquers.

The ciclopirox olamine is an active ingredient of interest in dermatology and cosmetics, which can provide benefits to the skin, scalp, and nails. Its antifungal, antibacterial, anti-inflammatory, and antioxidant properties, detailed below, enable it to act against skin or nails (onychomycoses), seborrheic dermatitis and dandruff.

Ciclopirox olamine is primarily recognized for its antifungal properties.

Ciclopirox olamine stands out for its particularly broad antifungal spectrum. It acts effectively against dermatophytes, such as Trichophyton, Microsporum or Epidermophyton, yeasts such as Candida, Malassezia or Cryptococcus, as well as certain molds, notably Aspergillus and Fusarium. Depending on its concentration and the duration of application, its action can be fungistatic—meaning it inhibits the growth of microorganisms—or fungicidal, meaning it eliminates the pathogens. Its mode of action relies on the chelation of metal cations, notably iron and aluminum, metals essential for the enzymatic activity of fungi.

Indeed, this chelation of ciclopirox olamine deactivates metallodependent enzymes, such as cytochromes, catalases, or 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, while FTR2 (low-affinity permease) is inhibited. This multifaceted mechanism of action of ciclopirox olamine makes the emergence of resistance unlikely, unlike with 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 reduced the aerobic bacterial count by two logarithmic units after fifteen days. No change in bacterial counts occurred with the cream lacking ciclopirox olamine, highlighting 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 also been shown 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 managing seborrheic dermatitis and dandruff, conditions caused by the excessive presence of yeasts on the skin and inflammation.

Finally, ciclopirox olamine can limit oxidative stress.

The affinity of ciclopirox olamine for iron not only enables it to exert an antifungal effect, but also to modulate oxidative stress. Indeed, by chelating free iron present in tissues, ciclopirox olamine limits its participation in the so-called Fenton reaction. Catalyzed by iron, this reaction involves the conversion of hydrogen peroxide (H₂O₂) into hydroxyl radicals, highly reactive molecules. These free radicals are known to cause cellular damage, particularly to lipid membranes, thereby disrupting the skin barrier. This imbalance can promote the onset of inflammatory skin disorders, such as eczema or seborrheic dermatitis. This effect of ciclopirox olamine contributes to its overall anti-inflammatory action, especially in contexts where oxidative stress drives skin inflammation.

Ciclopirox olamine is a broadly well-tolerated active ingredient, even during prolonged applications and/or on sensitive areas.

Reported adverse effects remain rare and generally mild. They typically consist of redness, transient burning sensations, or mild pruritus. These effects are often temporary and do not necessarily require discontinuation of the product. A retrospective study of 613 patients with dermatophytosis evaluated the efficacy and tolerability of ciclopirox olamine. Twice daily for six weeks, volunteers applied a 1% ciclopirox olamine cream. Good results were achieved, with 73.89% of patients fully cured. Regarding tolerability, only 5.7% of participants reported adverse effects. Observed side effects were local and mild, dominated by pruritus followed by erythema and skin dryness. No systemic reactions or serious events were documented, supporting the idea that the ciclopirox olamine is a safe active ingredient.

Note : No studies from available research indicate teratogenic effects or hazards associated with using ciclopirox olamine during pregnancy. However, in the absence of robust clinical data, it is advisable for pregnant women to consult their physician before use.

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