Clotrimazole
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Clotrimazole: From Superficial Fungal Skin and Mucosal Infections to Acne
One-Sentence Summary
Clotrimazole is an azole antifungal originally used for tinea (athlete's foot, ringworm), cutaneous candidiasis, pityriasis versicolor, oral candidiasis and vulvovaginal candidiasis. The TxGNN model predicts it may be effective for acne, but direct support is very thin: 1 clinical trial (a suspended three-drug combination study) and 0 publications.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Tinea pedis, tinea corporis and other tinea infections, cutaneous candidiasis, pityriasis versicolor, oral candidiasis, vulvovaginal candidiasis (the Singapore licence records list no indication text, so this comes from the knowledge graph) |
| Predicted New Indication | Acne |
| TxGNN Prediction Score | 99.86% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 20 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, clotrimazole is a broad-spectrum azole antifungal. Its efficacy in superficial fungal infections is established, and published reviews describe it as blocking ergosterol synthesis in fungal membranes. Mechanistically it may be applicable to acne in a limited way.
The proposed link is indirect. Clotrimazole is described as having some antibacterial and anti-inflammatory activity. Malassezia or Candida may also contribute to acne-like (acneiform) eruptions, and an antifungal could help in those cases. This is not the same as treating classic acne vulgaris.
The only trial found tests a fixed combination of beclomethasone, gentamicin and clotrimazole. Clotrimazole's own contribution cannot be separated, the trial is suspended, and no results are available. The very high TxGNN score is therefore not backed by direct evidence.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01244256 | Phase 2/3 | Suspended | 80 | Compared a beclomethasone + gentamicin + clotrimazole cream in contaminated dermatosis with bilateral symmetrical lesions. The trial is not clearly in acne vulgaris, and no efficacy data are available. Relevance grade: C. |
Literature Evidence
Currently no related literature available.
Singapore Market Information
There are 20 valid single-ingredient registrations and no cancelled ones. The registration records do not include approved indication text. Five representative authorizations are shown below.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| SIN04743P | Canesten Cream 1% | Cream | Encube Ethicals Private Limited |
| SIN06398P | Clotrimazole Cream 1% w/w | Cream | Beacons Pharmaceuticals Pte. Ltd. |
| SIN03782P | Candid Cream 1% | Cream | Glenmark Pharmaceuticals Ltd |
| SIN06447P | Mycoril Spray 1% | Spray | Remedica Ltd |
| SIN04582P | Candid Dusting Powder 1% w/w | Powder | Glenmark Pharmaceuticals Ltd |
The full set of 20 includes creams, lotion, spray, dusting powder, vaginal tablets and ear drops. Topical formats exist, which would suit a skin indication such as acne.
Safety Considerations
- Knowledge-graph contraindication signals (from drug-disease links, not label text): adrenocortical insufficiency, Addison disease, skin atrophy, telangiectasis, capillary disease, hereditary hemorrhagic telangiectasia, peripheral vascular disease, intermittent claudication, peripheral arterial disease. These signals most likely come from corticosteroid-containing combination products rather than clotrimazole itself. Confirm against the product label.
- Drug Interactions: 100 interactions were recorded in total. Those in the data reviewed include:
- Major: fentanyl, alfentanil, hydrocodone, amiodarone
- Moderate: paclitaxel, abemaciclib, acalabrutinib, nifedipine, amlodipine, apixaban, alprazolam, aliskiren, aprepitant, alfuzosin, estradiol, levonorgestrel, norethisterone
- Minor: dolutegravir, amphotericin B
The interaction data do not specify the route of administration.
For warnings and contraindications from the package insert, please refer to the product label.
Conclusion and Next Steps
Decision: Hold
Rationale: The only evidence for acne is one suspended Phase 2/3 trial of a three-drug combination, with no results and no separate effect of clotrimazole. No supporting literature exists. The high TxGNN score reflects network proximity rather than demonstrated benefit. For context, other predicted indications with stronger support, such as vulvovaginitis (evidence level L1, Proceed with Guardrails), are essentially on-label or near-label rather than true repurposing.
To proceed, the following is needed:
- Clotrimazole-alone clinical or mechanistic data in acne, such as a randomized trial against placebo or standard acne therapy
- Clarification of the acne subtype, for example Malassezia folliculitis versus acne vulgaris
- Detailed mechanism of action data (MOA)
- Package insert warnings and contraindications from the Singapore regulator (HSA), to complete safety screening
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.