Drugs

, Volume 69, Issue 3, pp 339–359 | Cite as

Sertaconazole

A Review of Its Use in the Management of Superficial Mycoses in Dermatology and Gynaecology
Adis Drug Evaluation

Summary

Abstract

Sertaconazole (Dermofix®, Ertaczo™, Ginedermofix®, Monazol, Mykosert® or Zalain®), an imidazole antifungal agent, inhibits the synthesis of ergosterol, an essential cell wall component of fungi. It is indicated in the EU for the treatment of superficial skin mycoses such as dermatophytosis (including tinea corporis, tinea cruris, tinea manus, tinea barbae and tinea pedis), cutaneous candidiasis, pityriasis versicolor and seborrhoeic dermatitis of the scalp, and in the US for tinea pedis only.

Sertaconazole has broad-spectrum antifungal activity against dermatophytes of the Trichophyton, Epidermophyton and Microsporum genera, and yeasts of the genera Candida and Cryptococcus; additionally, it is effective against opportunistic filamentous fungi and Gram-positive bacteria. Moreover, the antifungal activity of sertaconazole is maintained in clinical isolates of dermatophytes that show reduced susceptibility to other azoles. While the drug has good dermal penetration, this is not associated with systemic absorption. In clinical trials in patients with superficial mycoses, 2% sertaconazole cream applied twice daily was effective in the eradication of a range of dermatophytoses, and a significantly greater proportion of patients were cured compared with those receiving 2% miconazole cream twice-daily treatment. In patients with vulvovaginal candidiasis, sertaconazole as a single-dose ovule or tablet was effective in the eradication of Candida spp., and achieved both a more rapid and a higher cure rate compared with a triple dose of econazole. Both as a topical cream and suppository preparation, sertaconazole was generally well tolerated. Sertaconazole is a well established antifungal agent, which is now available in a variety of formulations, and remains a useful treatment option particularly in patients with fungal infections resistant to other azoles.

Pharmacological Properties

Like other azoles, sertaconazole inhibits the synthesis of ergosterol, an essential component of fungal cell walls, resulting in disruption of mycelial growth and replication. However, at higher concentrations, sertaconazole binds directly to nonsterol lipids in the fungal cell wall, which leads to increased permeability and subsequent lysis of the mycelium. Thus, depending on the concentration, sertaconazole may exhibit both fungistatic and fungicidal activities.

Sertaconazole shows good in vitro fungistatic activity against a broad range of dermatophytes of the Trichophyton, Epidermophyton and Microsporum genera, and yeasts of the genera Candida and Cryptococcus. The geometric minimum inhibitory concentration (MIC) of sertaconazole ranged from 0.06 to 1 mg/mL against a variety of dermatophyte isolates (n = 456), which included 114 isolates with reduced susceptibility to fluconazole (MICs ≥16μg/mL). Similarly, against a variety of Candida spp., MIC values at which 90% of cultures were inhibited (MIC90) for sertaconazole were ≤0.1–4μg/mL compared with MIC90 of 0.1 to >100 μg/mL for fluconazole. Furthermore, fungicidal activity of sertaconazole was apparent against a variety of Candida spp., with minimum fungicidal concentration values of 0.5–64 μg/mL.

Additionally, sertaconazole showed antibacterial activity with a geometric MIC of 0.88μg/mL against 21 isolates of Gram-positive bacteria. When applied topically in experimental models of inflammation, sertaconazole showed some evidence of anti-inflammatory action. Only 4% of 250 clinical isolates of dermatophytes and Scopulariopsis brevicaulis from Spanish hospitals showed resistance to sertaconazole, and continuous culture of Candida spp. in sertaconazole-containing media failed to induce resistance. Following application of sertaconazole as a topical cream or vaginal suppository, plasma levels of the drug remained undetectable in healthy volunteers.

Therapeutic Efficacy

In randomized, double-blind, multicentre trials of 3–6 weeks’ duration (n= 127–383), a significantly greater number of patients with tinea of the glabrous skin and tinea pedis receiving topical 2% sertaconazole cream once or twice daily achieved a successful mycological cure compared with recipients of a placebo cream. Moreover, the clinical cure rate and the mycological cure rate of 2% sertaconazole cream twice daily was significantly higher than that of 2% miconazole cream twice daily in patients with a range of cutaneous mycoses (n = 631) in a randomized, double-blind, multicentre, phase III, comparator trial of 35 days’ duration. Furthermore, a greater proportion of patients receiving sertaconazole achieved the category of clinically cured at a significantly earlier timepoint than recipients of miconazole. An open-label, noninferiority trial of 28 days’ duration in 313 patients with tinea corporis, tinea pedis or a corresponding candidiasis showed that sertaconazole as a 2% solution was as effective as treatment with a 2% cream preparation.

Sertaconazole as a single-dose 300 mg vaginal ovule or 500 mg tablet was successful in the eradication of Candida spp. in 65–100% of patients with vaginal candidiasis in trials that evaluated clinical and mycological cure rates up to 1 year after the last treatment application (n = 37–327). Furthermore, the clinical cure rate and the mycological cure rate of single-dose sertaconazole 500 mg tablet was significantly greater than that of triple-dose econazole 150 mg in the eradication of Candida albicans and also achieved a more rapid response rate in patients with vaginal candidiasis (n=37).

Tolerability

Sertaconazole was generally well tolerated in patients with dermatological and gynaecological mycoses. Adverse events associated with topical application of sertaconazole cream were mostly cutaneous-related and included contact dermatitis, dry or burning skin, application-site reaction, eczema, itch and skin tenderness. However, the frequency of adverse events did not differ from that of the placebo vehicle treatment arm. Furthermore, sertaconazole showed no evidence of a sensitizing action in causing contact dermatitis in healthy volunteers. Sertaconazole administered as a vaginal suppository was generally associated with an absence of adverse events and, where reported, included only local irritation after insertion.

Keywords

Tinea Pedis Econazole Vaginal Candidiasis Mycological Cure Tinea Corporis 

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Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Wolters Kluwer Health | AdisMairangi Bay, North Shore 0754, AucklandNew Zealand
  2. 2.Wolters Kluwer HealthConshohockenUSA

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