Clioquinol
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Clioquinol: From Topical Antiseptic to Cutaneous Candidiasis
One-Sentence Summary
Clioquinol (Vioform) is a halogenated hydroxyquinoline derivative historically used as a topical antiseptic and antifungal agent, included in combination preparations such as Locacorten-Vioform for the treatment of infected dermatoses. The TxGNN model predicts it may be effective for Cutaneous Candidiasis, with 0 clinical trials and 6 publications currently supporting this direction. Evidence is based on older clinical comparison studies from the 1970s–1980s, and Clioquinol is currently not marketed in Singapore.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Topical antiseptic / infected dermatoses (historical combination preparations) |
| Predicted New Indication | Cutaneous Candidiasis |
| TxGNN Prediction Score | 99.84% |
| Evidence Level | L3 |
| Singapore Market Status | ✗ Not Marketed |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Clioquinol (iodochlorhydroxyquin, brand name Vioform) is a chelating agent with broad-spectrum antimicrobial properties. Its principal mechanism of antifungal action involves metal chelation — it binds divalent and trivalent metal ions (Zn²⁺, Cu²⁺, Fe³⁺) that are essential cofactors for fungal metalloenzymes, disrupting cell membrane integrity and inhibiting fungal metabolic pathways. This mechanism is biologically plausible for activity against Candida albicans, which relies on metal-dependent enzymatic systems for growth and virulence.
Historically, clioquinol was a component of commercially available topical combination preparations — most notably Locacorten-Vioform (flucortolone + clioquinol 3%) and iodochlorhydroxyquin-hydrocortisone (I-HC). These products were used in clinical practice for dermatoses complicated by secondary bacterial or fungal infection, including cutaneous candidiasis. Several clinical studies from the 1970s–1980s directly compared clioquinol-containing preparations against other topical regimens in patients with confirmed cutaneous candidiasis, providing a historical basis for its anti-candidal efficacy.
The TxGNN prediction therefore reflects a pharmacologically coherent and historically validated mechanism. However, because all supporting studies are decades old, were performed with combination formulations (not clioquinol alone), and lack modern RCT designs, the evidence base is categorised as L3. No registered clinical trials are currently exploring this indication.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
The following publications are relevant to clioquinol's use in cutaneous candidiasis. Note that most studies examined clioquinol as part of combination topical formulations (e.g., iodochlorhydroxyquin-hydrocortisone, Locacorten-Vioform), not as a monotherapy.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 128475 | 1975 | Clinical study (double-blind) | Dermatologica | Locacorten (flucortolone 0.02%) + Vioform (clioquinol 3%) cream showed significantly superior microbiological conversion and clinical improvement compared to clioquinol alone, corticosteroid alone, or placebo in 430 patients with dermatoses complicated by secondary bacterial infection |
| 155507 | 1979 | Clinical comparison study | Current Medical Research and Opinion | Iodochlorhydroxyquin-hydrocortisone (I-HC) used as active control; overall therapeutic response in cutaneous candidiasis was 43% (17/40 patients), substantially lower than the comparator HNA cream (95%), highlighting the limitations of clioquinol combination preparations |
| 6459255 | 1981 | Randomised parallel study | Journal of International Medical Research | Randomised study of 154 patients (67 with cutaneous candidiasis); a combination containing iodochlorhydroxyquin showed equivalent therapeutic response to an HNN-containing cream, supporting the anti-candidal role of clioquinol in topical formulations |
| 136333 | 1976 | Clinical evaluation | Current Therapeutic Research | Clinical evaluation of a halcinonide-antifungal topical combination; limited abstract available |
| 4220930 | 1965 | Pathology/aetiology study | Zeitschrift fur Haut- und Geschlechtskrankheiten | Examined the role of yeasts in acrodermatitis enteropathica (Danbolt-Closs); contextual background on cutaneous candidal aetiology |
| 2978600 | 1988 | Occupational prevention study | Przeglad Dermatologiczny | In vitro assessment of additives to soap against Candida albicans strains; demonstrated strong fungicidal effect of clioquinol in alkaline soap solutions, providing mechanistic support for topical anti-candidal activity |
Singapore Market Information
Clioquinol currently has no registered products in Singapore. There are no HSA-issued licences on record.
Safety Considerations
Detailed safety data (package insert warnings, contraindications, and drug interaction data) were not available in this evidence pack. The following considerations are drawn from publicly known information about this compound:
- Historical neurological concern: Systemic use of clioquinol was associated with subacute myelo-optic neuropathy (SMON) in Japan (1960s–1970s), which led to the withdrawal of oral formulations in most countries. Topical formulations are generally considered to have a different safety profile due to limited systemic absorption, but this should be verified.
- Topical absorption: Although systemic absorption via intact skin is low, absorption through broken or inflamed skin is possible.
Please refer to the package insert and regulatory guidance for complete safety information before any clinical consideration.
Conclusion and Next Steps
Decision: Hold
Rationale: Although clioquinol has a biologically plausible antifungal mechanism (metal chelation targeting Candida metalloenzymes) and historical clinical use in combination topical preparations for cutaneous candidiasis, all supporting literature dates from the 1970s–1980s and involves combination products rather than clioquinol monotherapy. There are no registered clinical trials, and the drug has no Singapore market presence, making regulatory and clinical development pathways unclear.
To proceed, the following is needed:
- Mechanism of action data: Formal DrugBank/literature review to confirm the metal chelation mechanism and its relevance to C. albicans specifically
- Modern safety assessment: Systematic review of topical safety profile, including systemic absorption risk via inflamed/broken skin in candidiasis patients
- Regulatory status clarification: Confirm global regulatory status of topical clioquinol preparations and whether any jurisdiction maintains an approved topical indication
- Comparative efficacy data: Head-to-head comparison with current standard-of-care topical antifungals (e.g., clotrimazole, miconazole) — clioquinol would need to demonstrate a meaningful advantage to justify further development
- Formulation feasibility: Assess whether a standalone clioquinol topical preparation (not in combination) is viable, given that all historical preparations used it in fixed-dose combinations
- Singapore registration pathway: If evidence supports continuation, consult HSA on the regulatory pathway for a product with no current Singapore registration
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.