Clioquinol
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Clioquinol: From Topical Anti-infective Combination Products to Cutaneous Candidiasis
One-Sentence Summary
Clioquinol is a halogenated hydroxyquinoline with antifungal and antibacterial activity. In South Africa it is registered only in topical combination products, and the Evidence Pack does not record an approved indication text. The TxGNN model predicts it may be useful for cutaneous candidiasis, but there are 0 registered clinical trials and only 6 old publications (1965-1988), of which only 3 clearly involve a clioquinol-containing product. The evidence is indirect and confounded by corticosteroid and antibiotic co-components.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the registration data (approved indication text is blank for both licences) |
| Predicted New Indication | Cutaneous candidiasis |
| TxGNN Prediction Score | 99.84% |
| Evidence Level | L4 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not currently available. Based on drug class, clioquinol is a halogenated hydroxyquinoline. Its antifungal and antibacterial effect is plausibly due to chelation of copper, zinc and iron, and this link is inferred rather than confirmed.
Candida skin infection is a superficial fungal infection, so an agent with broad topical antifungal activity is a reasonable candidate. The predicted indication is also close to what these products are used for: the two registered products are topical corticosteroid combinations, and the retrieved literature is mostly on steroid-antimicrobial creams.
Two caveats matter here:
- Comparator data cuts against clioquinol. In the 1979 study (PMID 155507), the clioquinol-hydrocortisone cream (iodochlorhydroxyquin is a synonym of clioquinol) served as the control. It gave an excellent response in 43% of patients, compared with 95% for the halcinonide-neomycin-amphotericin cream. This is not a clioquinol-versus-placebo result, but it suggests the anti-candidal effect of the clioquinol combination is modest.
- Route. Only topical use is plausible. Oral clioquinol has a known neurotoxicity history (SMON).
For context, the strongest indication in the wider prediction set is superficial mycosis (also L4). It is supported by a 2021 in vitro study of clioquinol combined with ciclopirox and terbinafine (PMID 33772895) and a 1958 clinical report of a clioquinol-hydrocortisone cream (PMID 13521766). The clioquinol-specific evidence for that indication is stronger than for candidiasis, but it is still preclinical or historical.
Clinical Trial Evidence
Currently no related clinical trials registered (ClinicalTrials.gov, ICTRP). No SANCTR or PACTR identifiers were retrieved.
Literature Evidence
Design details below are taken from the titles and abstract excerpts only, and full texts have not been verified.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6459255 | 1981 | Randomised comparative study | J Int Med Res | 154 patients (67 with cutaneous candidiasis). Halcinonide-neomycin-nystatin cream and a betamethasone-gentamicin-iodochlorhydroxyquin-tolnaftate cream gave equivalent responses. |
| 128475 | 1975 | Double-blind clinical study | Dermatologica | 430 patients. A clioquinol-steroid cream was highly effective in dermatoses with secondary bacterial infection. The study concerns bacterial infection, not candidiasis. |
| 155507 | 1979 | Parallel clinical comparison | Curr Med Res Opin | The clioquinol-hydrocortisone control arm gave an excellent response in 17/40 (43%), against 38/40 (95%) for the comparator cream. |
| 136333 | 1976 | Clinical evaluation | Curr Ther Res | Steroid-antifungal combination. No abstract; clioquinol content not confirmed. |
| 4220930 | 1965 | Etiology article (indirect) | Z Haut Geschlechtskr | Role of yeasts in acrodermatitis enteropathica. Tangential. |
| 2978600 | 1988 | In vitro / prevention (indirect) | Przegl Dermatol | Soap additives against Candida albicans. Tangential. |
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| G1830 | Betnovate ‘c’ | Ointment | Not stated in registry data |
| G2331 (Act 101/1965) | Quadriderm | Cream | Not stated in registry data |
Safety Considerations
- Key caution (from the Evidence Pack rationale): oral clioquinol has a known neurotoxicity history (SMON), so only topical use is plausible.
- Confounding: the studied products also contain corticosteroids and antibiotics. Topical corticosteroids can worsen fungal skin infections if used without adequate antifungal cover.
Please refer to the SAHPRA-approved Professional Information (PI) for full warnings, contraindications and interactions. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high, but there are no registered trials. The retrieved studies are 1975-1981 combination-product studies, and the one head-to-head comparison involving a clioquinol product favoured the comparator. Without the SAHPRA PI safety information, the candidate cannot proceed to safety screening.
To proceed, the following is needed:
- SAHPRA package insert warnings and contraindications (blocking)
- Approved indication text for Betnovate ‘c’ and Quadriderm, to check whether candidiasis is already on-label
- Mechanism of action data (for example from DrugBank)
- Full-text review of PMIDs 6459255, 128475 and 155507 to confirm designs and clioquinol content
- A study design that separates clioquinol from the corticosteroid and antibiotic components, for example a clioquinol-only versus established topical azole comparison
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.