What clinical data supports the use of topical ketoconazole (antifungal) / ibuprofen (nonsteroidal anti-inflammatory drug (NSAID)) in dimethyl sulfoxide (DMSO) solution for onychomycosis (nail fungus)?

Limited Clinical Data for Ketoconazole/Ibuprofen in DMSO Solution for Nail Fungus

There is no established clinical evidence supporting the use of topical ketoconazole/ibuprofen in DMSO solution for onychomycosis treatment. The British Association of Dermatologists' guidelines do not mention this specific combination therapy for nail fungus treatment 1.

Standard Treatment Approaches for Onychomycosis

Topical Therapy

Topical therapy is generally recommended only for:

• Superficial white onychomycosis (SWO)
• Very early distal lateral subungual onychomycosis (DLSO)
• Cases where systemic therapy is contraindicated 1

Established topical treatments with clinical evidence include:

• Amorolfine 5% nail lacquer (approximately 50% efficacy in distal nail infections) 1, 2
• Ciclopirox 8% lacquer (34% mycological cure rate) 2, 3
• Tioconazole 28% solution (22% cure rate) 2
• Efinaconazole 10% solution (approximately 50% mycological cure rate) 2, 3

Systemic Therapy

Systemic therapy is more effective than topical treatment for most onychomycosis cases:

• Terbinafine: First-line treatment (250mg daily for 6 weeks for fingernails, 12-16 weeks for toenails) 1, 2
• Itraconazole: Alternative treatment (200mg daily for 12 weeks or pulse therapy) 1, 2
• Fluconazole: Not FDA-approved for onychomycosis but sometimes used 2
• Griseofulvin: No longer recommended as first-line due to lower efficacy 1, 2

DMSO as a Vehicle

While dimethyl sulfoxide (DMSO) is known for its penetration-enhancing properties that could theoretically improve topical antifungal delivery through the nail plate, there are no clinical studies in the provided evidence that specifically evaluate ketoconazole/ibuprofen in DMSO for onychomycosis.

Treatment Considerations for Specific Fungi

For non-dermatophyte mold infections (which may be relevant when considering alternative formulations):

• Scopulariopsis infections showed no efficacy with griseofulvin, low efficacy with fluconazole and ketoconazole, but high efficacy with itraconazole and terbinafine 1, 4
• Aspergillus has excellent susceptibility to itraconazole, followed by miconazole, ketoconazole and terbinafine 1

Potential Pitfalls and Caveats

1. Lack of evidence: Without clinical trials supporting this specific combination, its efficacy and safety remain unknown.

2. Potential for irritation: DMSO can cause skin irritation and has a distinctive odor that patients may find unpleasant.

3. Drug interactions: Topical medications with DMSO may have increased systemic absorption, potentially leading to unexpected drug interactions.

4. Treatment failure: Using unproven therapies may delay effective treatment, allowing the infection to progress and become more difficult to treat.

5. Recurrence risk: Onychomycosis has high recurrence rates (40-70%) even with established treatments 1.

Conclusion

Based on current evidence, established topical or oral antifungal medications should be used according to guidelines rather than unproven combinations. If topical therapy is preferred, amorolfine or ciclopirox nail lacquers have demonstrated efficacy in clinical trials 1, 2, 5.

For patients who cannot use systemic therapy, surgical approaches combined with topical antifungals have been studied but showed disappointing results (56% cure rate with high dropout rates) 6.