Ketoconazole
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Ketoconazole: From Antifungal Use to Acne
One-Sentence Summary
Ketoconazole is an azole antifungal that is marketed in the US as oral tablets and as topical creams, shampoos and foams. The TxGNN model predicts it may be effective for acne, with 1 clinical trial (not phase-classified, still active) and 15 publications currently supporting this direction. Most of the literature is indirect (in vitro work, reviews, related conditions), so this remains a research question rather than a proven use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Antifungal use (the US license records supplied contain no indication text) |
| Predicted New Indication | Acne (disease) |
| TxGNN Prediction Score | 99.80% |
| Evidence Level | L4 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 total US licenses (the five listed below are ANDAs) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the source record. Based on published literature, ketoconazole is an azole antifungal, and several of its known effects could plausibly apply to acne.
- Effect on the acne bacterium: In vitro, ketoconazole inhibits the lipase of Propionibacterium (Cutibacterium) acnes and also inhibits its growth (PMID 28111792). This lipase breaks down sebum into free fatty acids that drive skin inflammation. A separate in vitro study tested azole antifungals against P. acnes isolates from acne patients (PMID 20045949). This matters because antibiotic-resistant strains are becoming more common.
- Effect on yeast: Ketoconazole’s activity against Malassezia/Pityrosporum yeast may help in follicular eruptions that look like acne. However, these conditions, such as Pityrosporum folliculitis, are often misdiagnosed as acne vulgaris and are not the same disease (PMID 8593718, 8255067).
- Anti-androgen effect: At systemic doses, ketoconazole inhibits steroid hormone synthesis. Acne improvement has been reported with its derivative levoketoconazole in Cushing’s syndrome (PMID 33216275). That population and mechanism differ from ordinary acne.
The high TxGNN score is a computational prediction only. The mechanistic link above comes from the literature, not from the source record. Only topical use appears to be a reasonable safety context for acne.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07237763 | NA (not phase-classified) | Active, not recruiting | 52 | Randomized trial of ketoconazole 2% cream vs adapalene 2% cream (a topical retinoid) in mild comedonal and papulopustular acne over 12 weeks. It asks whether ketoconazole could be an alternative with fewer side effects and better compliance. No results posted. |
This trial is directly on topic but small, and it cannot be counted as Phase 2/3 evidence.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28111792 | 2017 | Preclinical (in vitro) | Microbiol Immunol | Ketoconazole inhibits P. acnes lipase activity and growth, suggesting a possible alternative to antibiotics for acne. |
| 20045949 | 2010 | In vitro study | Biol Pharm Bull | Tested the in vitro activity of azole antifungals against P. acnes isolated from acne patients, motivated by rising antibiotic resistance. |
| 12566804 | 2003 | Review | Dermatology | Reviews systemic acne treatment, in which antibiotics such as tetracyclines and macrolides are the main agents. Useful background, but not specific to ketoconazole. |
| 8593718 | 1995 | Clinical study | Clin Exp Dermatol | 62 patients with Pityrosporum folliculitis, a condition often misdiagnosed as acne vulgaris. Includes therapeutic trials, but the condition is not acne. |
| 8255067 | 1993 | Review | Keio J Med | P. ovale is linked to several skin diseases (pityriasis versicolor, Pityrosporum folliculitis, seborrhoeic dermatitis). Indirect support. |
| 8629828 | 1996 | Case report | Arch Dermatol | Neonatal facial pustular eruptions were associated with Malassezia furfur infection. Not acne vulgaris. |
| 33216275 | 2021 | Clinical study (indirect) | Pituitary | Levoketoconazole improved clinical signs and symptoms in Cushing’s syndrome. This is a different drug form and condition. |
| 32872149 | 2020 | Review (comparator) | Pharmaceuticals (Basel) | Review of adapalene, the comparator in the ongoing trial. Provides context on first-line topical acne therapy. |
| 19445767 | 2009 | Review (indirect) | BMJ Clin Evid | Polycystic ovary syndrome (PCOS), a condition associated with acne. Indirect. |
| 39622522 | 2024 | Practice report (indirect) | South Med J | Analysis of dermatologic diagnoses and medication distribution at a free clinic. Indirect. |
No randomized controlled trial in the literature directly supports ketoconazole for acne.
US Market Information
The US license records supplied contain no approved-indication text. The manufacturer is shown instead. Of 20 total licenses, five are listed.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| ANDA075638 | Ketoconazole | Cream | Golden State Medical Supply, Inc. |
| ANDA075319 | Ketoconazole | Tablet | Sun Pharmaceutical Industries, Inc. |
| ANDA212443 | Ketoconazole Cream | Cream | Direct_Rx |
| ANDA075581 | Ketoconazole | Cream | Bryant Ranch Prepack |
| ANDA076942 | Ketoconazole | Shampoo, suspension | Cosette Pharmaceuticals, Inc. |
Other listed dosage forms include shampoo and foam (aerosol). Topical forms are already on the market, which is relevant to an acne indication.
Safety Considerations
Please refer to the package insert for safety information.
The source record has no warning, contraindication or interaction data. The package insert is a blocking data gap. The evidence pack’s own rationale notes that systemic ketoconazole carries known risks of liver toxicity, adrenal suppression, QT prolongation and drug interactions. It therefore treats only topical use as a reasonable safety context for acne.
Conclusion and Next Steps
Decision: Hold
Rationale: The only directly relevant evidence is one small, non-phase-classified trial that is still active and has no results. The rest is in vitro work and indirect literature. The FDA package insert safety data is missing, which blocks the safety screening step.
To proceed, the following is needed:
- Package insert warnings and contraindications, obtained from the FDA label
- Results from NCT07237763, or larger randomized trials of topical ketoconazole in acne vulgaris
- Confirmation that the indication is limited to topical formulations, with no systemic use for acne
- Mechanism of action data (from DrugBank)
- Approved-indication text for the US licenses, to confirm the original indication
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.