Onychomycosis Clinical Considerations and Recommendations

Mickey Hart, PharmD Candidate 2015; Lynne Fehrenbacher, PharmD, BCPS-AQ ID

Disclosures

US Pharmacist 

In This Article

Treatment

Dosage and duration, mycological cure rate, and clinical considerations (including adverse effects) for each antifungal agent discussed are listed in Table 1.

Oral Pharmacotherapy

In general, using an oral antifungal is the most effective treatment option for onychomycosis.[1] However, oral antifungals may be inappropriate for some populations, particularly those with liver dysfunction.[1] Griseofulvin, which has an FDA indication for onychomycosis, and ketoconazole, which does not, were commonly used before the introduction of the newer antifungals discussed in this article.[4] However, the newer antifungals have shorter treatment durations, improved efficacy, and improved safety profiles, leading to the replacement of griseofulvin and ketoconazole, which are no longer recommended for use in this indication. For any agent chosen, treatment duration will be long (at least 12 weeks), and time to complete regrowth of healthy, disease-free nails can take up to 6 months for fingernails and 12 to 18 months for toenails.[4]

Terbinafine is a fungicidal allylamine derivative with an antifungal spectrum that includes dermatophytes and molds.[4] In one study, FDA-approved continuous terbinafine therapy was found to be significantly more effective than pulse terbinafine therapy (patients take the drug for only 1 week per month), which is not an FDA-approved regimen (71% and 59%, respectively; P = .03).[6] Continuous terbinafine therapy offers the highest efficacy of any available therapy (71%-89% when used for 12 weeks for onychomycosis of the toenails) and should be recommended first-line for most patients without contraindications to therapy.[6–8]

Itraconazole is a fungistatic triazole with an antifungal spectrum that includes dermatophytes and molds.[4] A continuous itraconazole regimen is FDA-approved for onychomycosis involving the toenails, and a pulse-dosing regimen (patients take the drug for only 1 week per month) is FDA-approved for onychomycosis with only fingernail involvement.[9] Itraconazole therapy is generally longer than terbinafine therapy and has been investigated for up to 48 weeks of continuous use for onychomycosis of the toenails; however, it is still less effective than terbinafine.[10] Itraconazole also has a higher rate of adverse drug reactions than terbinafine and fluconazole. For these reasons, it is recommended that itraconazole be reserved for use as a second-line therapy for patients who do not have success with terbinafine.

Fluconazole is a fungistatic triazole with an antifungal spectrum that is largely limited to Candida species and some dermatophytes.[4] Fluconazole is not FDA-approved for the treatment of onychomycosis but has been studied for use off-label. One study compared a 12-week treatment regimen of fluconazole 150-mg once weekly to a 24-week regimen and found no significant difference in efficacy.[7] Another study found no significant difference in efficacy between 150-mg, 300-mg, and 450-mg weekly regimens.[11] Based on these results, to minimize risk of adverse effects while maintaining efficacy, the recommended dosing regimen for fluconazole is 150 mg once weekly for 12 weeks for onychomycosis of the toenails. Because of its similar efficacy, lower incidence of adverse events, and once-weekly dosing regimen, fluconazole may be considered a second-line option alongside itraconazole, despite its lack of FDA-approval for onychomycosis.

Topical Pharmacotherapy

Nonprescription topical antifungals marketed for athlete's foot (e.g., terbinafine, tolnaftate) are not recommended for treating onychomycosis of the toenails.[4] These topical antifungals are unable to penetrate the nail, a requirement to eradicate the infection; however, they may be useful for prophylaxis.[4,5]

Ciclopirox is a fungicidal pyridone with an antifungal spectrum that includes dermatophytes, molds, and yeasts.[12] Although less effective than the oral antifungal agents, ciclopirox nail lacquer is associated with a lower incidence and severity of adverse effects than the oral antifungals.[12] Ciclopirox represents a valid option for patients who cannot tolerate other options due to adverse effects or contraindications or for those who are hesitant to start long-term oral antifungal therapy.[12] Concomitant use of systemic therapy (e.g., terbinafine) with topical ciclopirox may offer improved efficacy and decreased time to cure compared to either agent alone, although further research is required before this practice can be recommended routinely.[4]

Nonpharmacologic Treatment

Nail trimming and debridement can be used concurrently with pharmacologic treatments including topical therapies, to increase efficacy.

Several laser devices are FDA-approved for the treatment of onychomycosis, including neodymium: yttrium-aluminum-garnet (Nd:YAG) devices and dual-wavelength near-infrared lasers.[13] In one study, 61% of participants achieved mycological and cosmetic cure at week 16 of Nd:YAG therapy (mycological cure alone was not assessed).[14] A second study demonstrated that 30% of participants with onychomycosis of the toenails achieved mycological cure at day 180 of dual-wavelength infrared laser therapy.[15] Participants reported no adverse effects in either study.[14,15]

These therapies are much more expensive than pharmacologic methods and typically are not covered by insurance plans.[13] For this reason, it may be prudent to recommend laser therapy for those patients who are unable or unwilling to use conventional pharmacologic options, those who have experienced treatment failure, or those for whom out-of-pocket expense is not an issue.

Alternative Options

Dosing and duration, mycological cure rate, and clinical considerations for each alternative option are listed in Table 2.

Vicks VapoRub (Procter & Gamble), which contains camphor, eucalyptus oil, menthol, and thymol, was investigated in a small study of toenail onychomycosis (N = 18).[16] The authors noted better outcomes for participants with positive cultures for Trichophyton mentagrophytes and Candida parapsilosis than for other organisms.[16] Adverse effect rates and safety in pregnancy have not been established for this regimen. Although the Vicks VapoRub treatment showed similar efficacy to prescription-only ciclopirox 8% nail lacquer and is relatively low-cost (especially when factoring in appointment-related costs for prescription options), further research is needed before it can be routinely recommended to patients.[16] Vicks VapoRub has not been researched for treatment of fingernail onychomycosis and may be inappropriate for that use because of the risk of irritation of the eyes or mucous membranes if touched by a fingernail that is being treated.

Tea tree (Melaleuca alternifolia) oil has been investigated as a potential onychomycosis treatment. In one study, 18% of participants achieved a negative culture after twice-daily application for 24 weeks.[17] Adverse effects associated with tea tree oil treatment included erythema and irritation at the application site.[17] The safety of topical tea tree oil during pregnancy has not been well established. Like Vicks VapoRub, tea tree oil has not been tested for treatment of fingernail onychomycosis and may be inappropriate for such use because of the risk of irritation of the eyes or mucous membranes. Further study is needed before this therapy can be routinely recommended to patients.

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