Ketoconazole
| Evidence Level: L4 | Predicted Indications: 1 |
Table of Contents
Ketoconazole: Acne (disease)
One-Sentence Summary
Ketoconazole is an azole antifungal originally used for skin fungal infections (such as tinea, pityriasis versicolor and seborrheic dermatitis) and for some systemic mycoses (such as histoplasmosis and aspergillosis). The TxGNN model predicts it may be effective for acne, but the supporting evidence is thin: 1 clinical trial (small, no results posted) and a literature set made up mostly of reviews, case reports and laboratory studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Acne (disease) |
| TxGNN Prediction Score | 0.9980 |
| Evidence Level | L4 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Ketoconazole is an azole antifungal that inhibits fungal CYP51 (lanosterol 14-alpha-demethylase). It also inhibits human steroidogenic enzymes (CYP17A1, CYP11A1), which lowers androgen synthesis. Detailed mechanism-of-action data are not available in the data compiled for this report, so the reasoning below rests on general pharmacology rather than curated drug-database entries.
Two plausible links to acne follow from this:
- Less androgen-driven sebum production. Hyperandrogenism in conditions such as polycystic ovary syndrome is associated with acne, and lowering androgens could reduce sebum.
- Suppression of Malassezia (Pityrosporum) yeast. This yeast is implicated in some acne-like or follicular eruptions, including neonatal Malassezia pustulosis and Pityrosporum folliculitis, which is often misdiagnosed as acne vulgaris. Ketoconazole’s established use in seborrheic dermatitis, another sebaceous-site disease, supports this link.
Laboratory studies also report that ketoconazole inhibits growth and lipase activity of Propionibacterium acnes, the bacterium involved in acne.
The very high TxGNN score is a computational prediction and is not clinical evidence. Because systemic ketoconazole carries liver and adrenal risks, topical use is the only plausible route for acne.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT07237763 | Not applicable | Active, not recruiting | 52 | Randomized trial comparing topical ketoconazole 2% cream with topical adapalene 2% cream in mild comedonal and papulopustular acne over 12 weeks. It tests whether ketoconazole could be an alternative to a topical retinoid with fewer side effects and better compliance. No results posted. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 12566804 | 2003 | Review | Dermatology | Overview of systemic acne treatment; antibiotics are the agents of choice for papulopustular acne |
| 32872149 | 2020 | Review | Pharmaceuticals (Basel) | Adapalene is a first-line acne treatment (relevant as the trial comparator) |
| 8255067 | 1993 | Review | Keio J Med | Pityrosporum ovale is linked to pityriasis versicolor, folliculitis and seborrheic dermatitis |
| 8629828 | 1996 | Case report | Arch Dermatol | Neonatal acne-like pustular eruptions associated with Malassezia furfur infection |
| 8593718 | 1995 | Clinical study | Clin Exp Dermatol | Pityrosporum folliculitis in 62 patients, frequently misdiagnosed as acne vulgaris; therapeutic trials reported |
| 28111792 | 2017 | Laboratory study | Microbiol Immunol | Ketoconazole inhibits P. acnes lipase activity and growth |
| 20045949 | 2010 | Laboratory study | Biol Pharm Bull | In vitro activity of azole antifungals against P. acnes isolates from acne patients |
| 8090657 | 1993 | Review | Pol Tyg Lek | Treatment of hyperandrogenic features, including acne, in polycystic ovary syndrome |
No randomized controlled trial of ketoconazole in acne is among the retrieved publications. Several other retrieved papers (for example on Cushing’s syndrome and free-clinic formularies) are only indirectly related and are not listed.
India Market Information
Twenty single-ingredient ketoconazole licences are currently valid in India. The approved indication text is not available in the licence records. The main authorizations are:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 223281 | Tona 200mg Tablet | Strip of 10 tablets | Not stated |
| 118672 | Ketarich Tablet | Strip of 10 tablets | Not stated |
| 89462 | Funazole 200mg Tablet | Strip of 10 tablets | Not stated |
| 117372 | Ketosel Shampoo | Bottle of 60 ml shampoo | Not stated |
| 5437 | Atiket Tablet | Strip of 10 tablets | Not stated |
Nearly all registrations are oral 200 mg tablets. Only one shampoo is registered, and no topical cream appears in the licence list, even though the ongoing trial uses a 2% cream.
Safety Considerations
- Contraindications (from the knowledge graph, not label text): long QT syndrome (including familial), torsades de pointes, liver disease, gallbladder disease, adrenocortical insufficiency, Addison disease, skin atrophy, telangiectasis and related capillary disease, hereditary hemorrhagic telangiectasia, peripheral vascular and arterial disease, intermittent claudication, and achlorhydria.
- Drug Interactions: 658 interactions have been identified. Major-level interactions include loperamide, triamcinolone and budesonide. Moderate interactions include famotidine, ranitidine, omeprazole, rabeprazole, hydrocortisone, dexamethasone, betamethasone, pioglitazone, aprepitant and atropine.
- Other considerations: Systemic use carries risks of liver toxicity and adrenal suppression, so topical use is the only plausible route for acne.
Please refer to the package insert for the full warnings, as label-based safety data were not available for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is biologically plausible (anti-androgenic and anti-Malassezia effects, plus laboratory activity against P. acnes), but the only trial is small, has no results, and is a Phase “not applicable” study of a topical cream. The remaining literature is indirect, so this stays a research question (L4). Label-based safety data are also missing.
To proceed, the following is needed:
- Results from NCT07237763, and ideally larger randomized trials of topical ketoconazole in acne
- Confirmation of a suitable topical product and route in India, since most licences are oral tablets
- Package insert warnings and contraindications from the manufacturers
- Curated mechanism-of-action data
- A safety plan limiting use to topical application, given the systemic liver, adrenal, QT and interaction risks
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.