Ciclopirox olamine: salt form of a topical antifungal

Ciclopirox olamine is the olamine salt form of the topical broad-spectrum antifungal ciclopirox. The salt formation with ethanolamine increases water solubility and improves galenic handling in creams, gels, shampoos and powders. The antifungal activity is identical with that of the free ciclopirox base; the salt form differs mainly in formulation.

Pharmacologically, ciclopirox belongs to the hydroxypyridinones and thus differs fundamentally from imidazoles, triazoles and allylamines. This special status gives ciclopirox an unusually broad spectrum against dermatophytes, yeasts, moulds, plus additional antibacterial and anti-inflammatory properties.

Mechanism of action

Ciclopirox binds trivalent metal ions such as iron and aluminium in the fungal cell and thereby disrupts central enzymatic processes. Specific targets include:

• Inhibition of cytochrome-dependent enzymes of the respiratory chain and sterol synthesis
• Interference with the assembly of the fungal cell membrane and mitochondrial function
• Blockade of mycostatic cell respiration with a subsequent energy crisis in the fungal cell

Unlike imidazoles and triazoles, which specifically inhibit the cytochrome P450 dependent enzyme 14 alpha demethylase, ciclopirox attacks at several points simultaneously. This multi-target action hinders resistance development. The substance is active against the most important dermatophytes (Trichophyton, Microsporum, Epidermophyton), yeasts (Candida), moulds (Aspergillus, Scopulariopsis) and against some gram-positive and gram-negative bacteria. In addition, ciclopirox shows anti-inflammatory effects via inhibition of 5 lipoxygenase and cyclooxygenase.

Indications

• Tinea pedis (athlete's foot): cream or solution for local therapy
• Tinea corporis and cruris: fungal infections of the body and groin
• Pityriasis versicolor: superficial yeast infection with characteristic pigment change
• Cutaneous candidiasis: nappy thrush, intertrigo, oral thrush in topical preparations
• Onychomycosis: nail fungus, used as a nail lacquer (alternatives to Penlac, Loceryl)
• Seborrhoeic dermatitis: shampoo formulation acts against Malassezia and reduces dandruff
• Vaginal candidiasis: vaginal cream or vaginal tablets

Dosing and administration

Cream or solution 1 %: apply once or twice daily to the affected skin, spread thinly, do not cover. Treatment duration depends on location: tinea pedis 2 to 4 weeks, pityriasis versicolor 2 weeks, onychomycosis several months.

Shampoo 1.5 %: for seborrhoeic dermatitis two to three times a week, leave on for several minutes, rinse. Treatment duration 4 weeks, then individual maintenance.

Vaginal cream or tablets: once a day in the evening for 6 days.

Nail lacquer 8 %: apply once a day to the affected nail. Once a week file off residues and remove with alcoholic wipes, then reapply. Treatment duration 6 to 12 months until a healthy nail has fully grown back.

Even after symptoms improve, therapy should be continued to prevent relapse. With onychomycosis patience is particularly important, as success only becomes visible after months.

Side effects

Common: local burning, pruritus, redness, rash at the site of application.

Uncommon: contact dermatitis, allergic reactions, eczema at the treated site, dryness.

Rare: systemic allergic reactions, anaphylactoid reactions.

Notes:

• Local irritation occurs mainly in the first days and usually improves over time
• If skin reaction does not heal or redness increases, interrupt therapy and seek medical advice
• Vaginally a slight, short-lasting burning sensation may occur
• For nail lacquer, careful application is important: remove residues before each new application, otherwise drug and solvent will not reach the nail sufficiently

Interactions

Due to exclusively topical use and minimal systemic absorption, clinically relevant interactions are hardly to be expected.

• Other topical substances: apply to the same area with a time interval to avoid dilution and irritation
• Cosmetics: with nail lacquer, no normal nail polish during therapy; with shampoo, other hair care products are normally fine
• Latex: vaginal cream can weaken latex condoms and diaphragms

Special considerations

Pregnancy: systemic absorption is low, use during pregnancy possible after individual assessment. Avoid large-area application in the first trimester if possible.

Breastfeeding: possible, do not apply to the breast directly before feeding.

Children: use established from age 6, individual decision in younger children.

Use in the eye and mucosal area: not approved, avoid contact. After accidental eye contact, rinse with plenty of water.

Check therapy success: if improvement is insufficient after 4 weeks, reassess and consider mycological diagnostics (swab, fungal culture). For onychomycosis, fungal diagnostics before starting therapy is sensible.

Hygiene: alongside drug therapy, hygienic measures are important: change socks and shoes, disinfect shoes, wash towels, avoid walking barefoot in damp communal areas.

Related substances

• Ciclopirox, free base, identical action
• Ciclopiroxolamin, alternative spelling without hyphen
• Ketoconazole, imidazole antifungal in seborrhoeic dermatitis
• Clioquinol, combined antibacterial and antifungal topical

Frequently asked questions

Sources

• BfArM Federal Institute for Drugs and Medical Devices
• EMA European Medicines Agency
• AWMF guidelines onychomycosis and tinea
• Gelbe Liste ciclopirox monograph