Econazole
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Econazole: From Superficial Fungal Skin Infections (Tinea) to Majocchi Granuloma
One-Sentence Summary
Econazole is a topical imidazole antifungal, originally used for tinea (pedis, corporis, groin and perianal), cutaneous candidiasis and pityriasis versicolor. The TxGNN model predicts it may be effective for Majocchi granuloma (score 99.97%), but there are no registered clinical trials and only 1 case report for this top-ranked indication. The better-supported predicted indications are vulvovaginal candidiasis and vulvovaginitis (candidal), which have comparative clinical studies dating from 1976 to 1994.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Tinea pedis, tinea corporis, tinea infection, cutaneous candidiasis, pityriasis versicolor, dermatophytosis of groin and perianal area (the Singapore licence records contain no indication text) |
| Predicted New Indication | Majocchi granuloma (top-ranked); vulvovaginal candidiasis is the best-supported prediction |
| TxGNN Prediction Score | 99.97% (Majocchi granuloma); 99.50% (vulvovaginal candidiasis) |
| Evidence Level | L4 (Majocchi granuloma); L3 (vulvovaginal candidiasis, vulvovaginitis) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold (Majocchi granuloma); Proceed with Guardrails (vulvovaginal candidiasis) |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the data compiled for this report. Based on known information, econazole is an azole antifungal. Azoles inhibit fungal lanosterol 14-alpha-demethylase, which depletes ergosterol and damages the fungal cell membrane. This activity is established against dermatophytes, Candida and Malassezia.
Majocchi granuloma is a deep dermatophyte infection of hair follicles and dermis, typically caused by Trichophyton rubrum. It is closely related to the approved tinea indications, so the mechanistic link is plausible. However, deep follicular involvement generally requires systemic therapy, so topical econazole alone is unlikely to be adequate.
Other predictions follow the same pattern:
- Ectothrix and endothrix infections, dermatophytosis of the scalp or beard, and tinea profunda involve the same organisms. Hair-shaft and follicle penetration by topical agents is limited, and these usually need systemic therapy.
- Superficial mycosis is essentially an on-label match for econazole's existing indications rather than true repurposing.
- Vulvovaginal candidiasis and candidal vulvovaginitis are the most credible new uses. Econazole's anti-Candida activity is well established, and vaginal econazole is used in many markets.
- Acne likely reflects misclassified Malassezia (Pityrosporum) folliculitis rather than true acne vulgaris.
- Postmenopausal atrophic vaginitis is driven by estrogen deficiency, not infection. The prediction is probably a network-proximity artefact and has no mechanistic support.
Clinical Trial Evidence
Currently no related clinical trials registered for any of the predicted indications.
Literature Evidence
Majocchi granuloma (top-ranked prediction)
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37899944 | 2023 | Case report | Case Reports in Dermatology | Majocchi granuloma presenting as a "great mimicker" that can be mistaken for eczema or psoriasis; not specific to econazole |
Vulvovaginal candidiasis / vulvovaginitis (best-supported predictions)
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 7820892 | 1994 | Double-blind comparative study | Ceylon Medical Journal | Econazole compared with clotrimazole in vaginal candidiasis |
| 2257961 | 1990 | Randomised comparative trial | J Int Med Res | Butoconazole 2% cream for 3 days compared with econazole 1% cream for 7 days in 75 patients |
| 6761088 | 1982 | Multicentre comparative study | Chemotherapy | Clotrimazole vaginal tablets compared with econazole ovules over 3 days (randomised, 3 centres) |
| 7428415 | 1980 | Multicentre comparative study | Curr Med Res Opin | Same design as above; activity and tolerance compared |
| 7383476 | 1980 | Randomised comparison | Obstet Gynecol | 178 women; mycological cure rates were comparable between 1% econazole vaginal cream and clotrimazole tablets, with few local adverse reactions |
| 984105 | 1976 | Multicentre study (uncontrolled) | Am J Obstet Gynecol | 996 women given 150 mg econazole suppositories for 3 days; 93.4% cure rate in Studies I and II |
| 98315 | 1978 | Review | Drugs | Review of econazole's antifungal activity and therapeutic efficacy |
| 39846759 | 2025 | In vitro susceptibility | Microbiol Spectrum | Local epidemiological cut-off values for Candida isolates from women with VVC |
| 37601561 | 2023 | In vitro study | Infect Drug Resist | Biofilm formation and aspartyl proteinase activity linked to azole resistance in C. albicans |
Superficial mycosis and scalp/beard dermatophytosis (class-level or indirect support)
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 7351270 | 1980 | Follow-up study | Dermatologica | 100 dermatomycosis patients treated with econazole 1%; 95% of those followed up had no relapse or reinfection |
| 24196340 | 2013 | Review | J Drugs Dermatol | Topical therapy suits most superficial fungal infections, except onychomycosis and tinea capitis |
| 37594096 | 2024 | Review | Pharm Nanotechnol | Nanotechnology-based delivery of topical antifungals |
| 12950911 | 2003 | Case report | Mycoses | Favus healed with 6 weeks of griseofulvin plus topical econazole |
| 153658 | 1978 | Uncontrolled clinical study | Z Hautkrankh | Econazole spray solution and powder in skin mycoses |
Acne: one 1995 small therapeutic study of Pityrosporum (Malassezia) folliculitis, a fungal condition often mistaken for acne (8593718, Clin Exp Dermatol).
No literature was retrieved for ectothrix infection, endothrix infection, tinea profunda or postmenopausal atrophic vaginitis.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN06601P | ECONAZINE CREAM | Cream | Not stated in the licence record |
| SIN10246P | ECOCORT CREAM | Cream | Not stated in the licence record |
Both licences are valid, single-ingredient topical creams. The ECOCORT product name suggests a corticosteroid combination, but the licence record lists it as single-ingredient, so this should be confirmed against the label.
Cytotoxicity
Not applicable. Econazole is not an antineoplastic drug, so this section is omitted.
Safety Considerations
- Drug Interactions: 41 potential interactions were recorded, but none has a severity level assigned. Examples include clotrimazole, fluconazole, omeprazole, lansoprazole, metformin, glipizide, rosiglitazone, clopidogrel, heparin, dexamethasone, fluticasone, diazepam, lorazepam, levothyroxine and cytarabine. These are mainly relevant when absorption is increased, for example with vaginal use or large treated areas.
Warnings and contraindications from the Singapore package insert were not available. Please refer to the package insert for these.
For the vaginal-use predictions, the following should be considered:
- Local resistance monitoring is needed, given reports of azole resistance and non-albicans Candida.
- Use should be restricted to confirmed candidal infection.
- Irritation risk should be assessed in atrophic tissue.
Conclusion and Next Steps
Decision: Hold for Majocchi granuloma and the other dermatophyte/hair-follicle predictions; Proceed with Guardrails for vulvovaginal candidiasis and candidal vulvovaginitis.
Rationale:
- Majocchi granuloma, ectothrix and endothrix infection, scalp/beard dermatophytosis and tinea profunda have high TxGNN scores but little or no direct evidence. Their evidence is a single case report or prediction only, and deep or follicular infection generally requires systemic therapy.
- Vulvovaginal candidiasis is supported by several comparative clinical studies, but these are old and have no trial registration, so the evidence is capped at L3.
- Acne and postmenopausal atrophic vaginitis are not supported mechanistically and should not be pursued.
To proceed, the following is needed:
- Singapore package insert warnings, contraindications and approved indications. This is currently a blocking gap for safety screening.
- Mechanism-of-action data from DrugBank.
- Confirmation that a vaginal econazole formulation is available or can be registered in Singapore. Current licences are for creams only, and route compatibility has not yet been assessed.
- Local Candida susceptibility and resistance data for Singapore.
- For Majocchi granuloma: clinical data on topical econazole as an adjunct to systemic antifungals.
- Review of the interaction data to assign severity levels.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.