There has been a rise in tinea infections among infants and pregnant women. Ciclopirox olamine (CPO) though an old molecule has stood the test of time. Ciclopirox is a pregnancy category B drug and safe to use in children above 3 months of age. CPO can be used for treating tinea, pityriasis versicolor and vulvovaginal candidiasis (VVC). VVC is commonly encountered in pregnant women at late gestation. The use of ciclopirox in the population renders good results and confers mild and minor local side effects in only a few patients. Based on animal trials, no significant fetal adverse effects are apparent when used during pregnancy. Besides, the potential of dermatophytes for developing resistance to CPO by biochemical or molecular means is extremely low – owing to its fungicidal mode of action, unique anti-fungal mechanism of action, and a steep dose-response curve.

A phase III study on the use of CPO cream in pediatric population reported excellent safety profile in 95% of the children. Meanwhile, 92% cases showed clinical improvement within a week of application. Hence, it was concluded that 1% CPO cream to be a safe and effective treatment for superficial cutaneous mycotic infections, particularly Candida spp. infection, in children aged between 3 months and 10 years.

CPO is used as a topical antimycotic agent and is a hydroxypyridone derivative. The drug received its US FDA approval in the year 2004. It has a broad-spectrum antimicrobial profile that includes nearly all of the clinically relevant dermatophytes, yeasts and molds, and is therefore broader than that of most other antimycotics. It is also active against certain frequently azole-resistant Candida species and against some bacteria, as well as azole-resistant Candida species, like Candida glabrata and Candida krusei.

A study conducted in 49 patients suffering with onychomycosis and/or tinea pedis reported that patients with onychomycosis had a cure rate of 14% with CPO and the therapy showed improvement in 36% of the patients. In addition, patients with tinea pedis had a cure rate of 42% with an improvement rate of 45%. The good tolerability favors management of recalcitrant superficial fungal infections with topical CPO.

The mechanism of action of ciclopirox is different from that of other topical antifungal drugs, which generally act through ergosterol inhibition. The authors reported that the high affinity of ciclopirox for trivalent metal cations, resulting in inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell, appears to be the major determinant of its antimicrobial activity. This unique and multilevel mechanism of action provides a very low potential for the development of resistance in pathogenic fungi, with little or no incidence of resistance.

Additionally, ciclopirox displays mild anti-inflammatory effects in biochemical and pharmacological models, which have also been demonstrated in small clinical studies. Scavenging of reactive oxygen species released from inflammatory cells is a likely contributor to these anti-inflammatory effects. Ciclopirox and its olamine salt are available in multiple topical formulations suitable for administration onto the skin and nails and into the vagina. The pharmaceutical forms most widely investigated are 1% ciclopirox olamine cream and 8% ciclopirox acid nail lacquer. Lotion, spray, shampoo, pessary, solution, gel and douche formulations have also been used.

Ciclopirox penetrates into the deep layers of the skin, mucosal membranes and nail keratin, reaching concentrations exceeding the minimal fungicidal concentrations for most pathogenic fungi. This agent was first developed for fungal skin infections and vaginal candidiasis and is currently well established in these indications. More recently, the drug has been clinically investigated in seborrheic dermatitis and onychomycosis—showing good efficacy and excellent tolerability in both conditions.

Ciclopirox has recently revealed interesting novel features in both nonclinical and clinical studies. The therapeutic role of this topical drug in the management of superficial skin infections is well established. The efficacy of the drug was also confirmed in an evaluation of more than 4000 patients with vaginal candidiasis. The broad antimicrobial activity of ciclopirox – especially against yeasts of the genus Malassezia, and its anti-inflammatory properties are the likely reason for its beneficial effects in these diseases. Ciclopirox containing nail lacquer is based on an original technology and has superior properties in terms of its affinity to keratin and nail permeation. It has been found to have superior efficacy and safety to another commercially available formulation in the treatment of onychomycosis. Topical ciclopirox is well-tolerated and is devoid of systemic adverse reactions. Most side effects with this drug are mild and local reactions and is reported in less than 5% of treated patients.

Thus, ciclopirox compares very well in the benefit/risk ratio to other antimycotic agents due to its excellent tolerability, complete absence of serious adverse effects and a very low potential for the development of microbial resistance.

Source: Drugs. 2010; 70 (16): 2133-2152. 0012-6667/10/0016-2133/$55.55/0 Indian Dermatology Online Journal. 2019 Jul-Aug; 10(4): 481–485. doi: 10.4103/idoj.IDOJ_29_19: 10.4103/idoj.IDOJ_29_19