Ketoconazole
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Ketoconazole: From Antifungal Use to Acne
One-Sentence Summary
Ketoconazole is an azole antifungal, and two topical or related products are registered in South Africa (the supplied registration data does not state the approved indication text). The TxGNN model predicts it may be useful for acne, but the supporting evidence is thin: 1 clinical trial (phase not applicable, 52 patients, no results yet) and 15 publications, of which only a few are directly relevant and none is a randomised trial. The prediction is best treated as a research question, not a treatment recommendation.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Fungal infections (azole antifungal class); registration indication text not provided in the supplied data |
| Predicted New Indication | Acne |
| TxGNN Prediction Score | 99.80% |
| Evidence Level | L4 |
| South Africa Market Status | Marketed |
| Number of SAHPRA Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, ketoconazole is an azole antifungal, and its antifungal activity is well established. Mechanistically it may be applicable to acne, but this link is not confirmed by the supplied data.
Three routes are plausible from general pharmacology:
- Yeast suppression. Malassezia (Pityrosporum) yeasts are implicated in acne-like folliculitis and neonatal pustulosis. Ketoconazole could help where yeast is part of the picture.
- Bacterial and lipase effects. Laboratory studies report that ketoconazole inhibits the growth of Cutibacterium (Propionibacterium) acnes, the bacterium associated with acne vulgaris, and inhibits its lipase activity. This may matter given rising antibiotic resistance.
- Androgen lowering. Ketoconazole inhibits steroid synthesis, which could matter in hyperandrogenic acne such as that seen in PCOS. This route relates to systemic use.
The high TxGNN score is a computational prediction, not clinical evidence. Pityrosporum folliculitis is often misdiagnosed as acne vulgaris, so any benefit seen in “acne” may partly reflect misdiagnosed yeast folliculitis.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07237763 | Not applicable | Active, not recruiting | 52 | Randomised trial of topical ketoconazole 2% cream vs adapalene 2% cream for 12 weeks in mild comedonal and papulopustular acne. It aims to test whether ketoconazole can be an alternative to a topical retinoid with fewer side effects and better compliance. No results available. |
No SANCTR or PACTR registrations were found in the supplied data.
Literature Evidence
No randomised trials were identified. The directly relevant items are laboratory studies and a small clinical series. The rest is background.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28111792 | 2017 | In vitro study | Microbiol Immunol | Ketoconazole inhibits P. acnes lipase activity and growth, suggesting a possible alternative to antibiotics for acne vulgaris. |
| 20045949 | 2010 | In vitro study | Biol Pharm Bull | Azole antifungals were tested against P. acnes isolated from acne patients, motivated by rising antibiotic resistance. |
| 8593718 | 1995 | Clinical series | Clin Exp Dermatol | 62 patients with Pityrosporum folliculitis were evaluated. The condition is frequently misdiagnosed as acne vulgaris, leading to unnecessary prolonged treatment. |
| 12566804 | 2003 | Review | Dermatology | Systemic acne treatment update. Antibiotics remain the agents of choice for papulopustular acne, with resistance a growing problem. |
| 32872149 | 2020 | Review | Pharmaceuticals (Basel) | Adapalene is used in first-line acne treatment. It is relevant as the comparator in NCT07237763. |
| 8255067 | 1993 | Review | Keio J Med | Pityrosporum ovale is linked to Pityrosporum folliculitis, seborrhoeic dermatitis and other skin diseases. |
| 8629828 | 1996 | Case report | Arch Dermatol | Neonatal papulopustular facial eruptions may be associated with Malassezia furfur infection. |
| 19445767 | 2009 | Review | BMJ Clin Evid | PCOS is associated with hirsutism, infertility and acne. Indirect relevance to the androgen route. |
| 8090657 | 1993 | Review | Pol Tyg Lek | Treatment of hyperandrogenic manifestations in PCOS, including acne and seborrhoea. Indirect relevance. |
Several other retrieved papers (Cushing’s syndrome case reports, levoketoconazole, infant rash and free-clinic formulary papers) do not address ketoconazole in acne and are not listed.
South Africa Market Information
| Registration Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Reg. No. 33/20.2.2/0503 | Ketazol | Cream (topical) | Not stated in supplied data |
| Reg. No. 34/20.2.2/0244 | Adco-dermed | Listed as “Sha” (form unclear in source) | Not stated in supplied data |
Both registrations sit under the same category code (20.2.2), and the supplied data lists no oral formulation. The Essential Medicines List (EML) status of ketoconazole was not included in the supplied data.
Safety Considerations
Please refer to the SAHPRA-approved Professional Information (PI) for safety information. Report adverse drug reactions to SAHPRA.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence is at model-prediction and laboratory level (L4): one small, unreported trial of topical ketoconazole for acne and no randomised results. The safety review is also blocked because package insert information is missing. Systemic ketoconazole carries known liver and endocrine safety concerns, so any repurposing question should focus on topical use. A topical cream is already registered in South Africa, which makes the topical route feasible.
To proceed, the following is needed:
- Results of NCT07237763 (topical ketoconazole vs adapalene), and confirmation of the exact condition studied
- Larger randomised trials in well-defined acne vulgaris, ideally excluding Pityrosporum folliculitis
- Download and review of the SAHPRA package inserts for both registered products (blocking data gap)
- Mechanism of action data from DrugBank
- Confirmation of the approved indications and EML status of the registered products
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any clinical use.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.