Should You Use Oral Drugs For Onychomycosis?

Author(s): 
By Richard Pollak, DPM, MS

Patients with onychomycosis are becoming increasingly aware that oral antifungals have the potential to cure their underlying infections, yet a recent study finds the majority of podiatrists continue to rely largely on debridement to provide symptomatic relief. As a profession, we’re quite knowledgeable about the various approaches to treating onychomycosis, but this study reveals that current treatment practices are aligned only partially with patients’ attitudes and behaviors regarding their infections. The study, a survey of over 900 onychomycosis patients and over 600 doctors conducted by the research firm Lieberman Research Associates, suggests that in addition to providing the symptomatic relief our patients desire, we should start treating onychomycosis as we would any other infection — medically.
A Review Of Treatments For Onychomycosis
The therapeutic approaches to managing onychomycosis range from palliative to curative and include nail debridement, topical therapy, oral antifungals or some combination of these treatments.1 For DPMs, debridement and topical medications have long been the most popular forms of treating onychomycosis.1,2
When you debride, you can effectively relieve the patient’s pain, help prevent subungual ulceration, reduce the fungal load and improve the appearance of the nail.2 While debriding mycotic nails does not cure the underlying infection, it does help address a patient’s desire for symptomatic relief, plays a role in managing the infection and helps avoid serious morbidity.1,3
Topical preparations for nail infections also are generally regarded as palliative therapy due mainly to their questionable efficacy. The low cure rates probably result from the inability of these agents to penetrate the nail plate keratin and contact the target tissue in sufficient quantity and duration to kill the invading fungi effectively.1
I should note that one topical treatment for onychomycosis, 8 percent ciclopirox topical solution, reportedly is more effective than older topical agents. Double-blind, placebo-controlled clinical trials found that once-a-day application of this FDA-approved modality for 48 straight weeks caused mycological cure rates ranging between 29 percent and 36 percent and complete cure rates (no nail involvement and negative mycology) between 5.5 percent and 8.5 percent.4
In general, you’ll find topical therapies show their most beneficial effects when your patient has a small degree of clinical involvement.3 Using topical preparations can help you treat onychomycosis as they can soften the nail plate and help contain the infection. However, be aware the long treatment courses frequently required often result in poor patient compliance.1,2
Griseofulvin and ketoconazole, the older-generation oral antifungal agents that have been used to treat onychomycosis, suffer from low efficacy and high relapse rates.2,5 Pharmacodynamic characteristics of both of these agents require that you administer these drugs in prolonged treatment regimens lasting up to 18 months for toenail onychomycosis.1,2 The long-term dosing regimens, potential for adverse experiences, poor efficacy and frequent recurrences have caused many physicians to avoid prescribing griseofulvin and ketoconazole for onychomycosis.
What You Should Know
About Itraconazole And Terbinafine
Within the last six years, the FDA has approved two newer oral antifungal agents (itraconazole and terbinafine) for treating onychomycosis. These current-generation oral antifungal agents offer a favorable safety profile, shorter courses of treatment, lower relapse rates and superior efficacy compared to griseofulvin and ketoconazole.
Based on pivotal trials, itraconazole boasts a mycological cure rate of 54 percent (complete cure rate of 14 percent), while terbinafine has a 70 percent mycological cure rate (complete cure rate of 38 percent).6,7 Unlike the older-generation oral antifungals, itraconazole and terbinafine rapidly enter the nail bed and diffuse into the entire nail plate where they accumulate. Given this “reservoir effect,” which allows these agents to remain active long after you’ve ceased providing treatment, you can give patients shorter courses of therapy.2,5
Newer-generation oral antifungals also have substantially better safety profiles than older-generation oral agents. A prospective, multicenter, open-label study evaluated the safety of oral terbinafine in 1,508 patients who received at least 12 weeks of therapy. The study confirmed the safety of terbinafine in the population at large, and showed no differences for either elderly patients or patients with diabetes.8
Additional trials of terbinafine and itraconazole have confirmed both agents are safe to use. Since the liver metabolizes both agents, it is recommended that you perform a simple blood test of liver enzyme function when considering each drug.6,7 A difference between the two treatments with respect to safety is the potential for drug-drug interactions. Imidazole antifungals (including itraconazole, fluconazole and ketoconazole) have a greater potential for clinically significant drug interactions than the allylamine terbinafine.7,9,10
Editor’s Note: The Food And Drug Administration (FDA) has issued a health advisory on the oral antifungals, itraconazole and terbinafine. It noted that a small risk of developing congestive heart failure is associated with using itraconazole. The FDA also noted that, in rare cases, severe liver problems may be associated with using itraconazole or terbinafine.
Be aware patient groups (including elderly patients, immunocompromised patients and patients with diabetes) who are at increased risk for developing onychomycosis also have a greater risk of drug-drug interactions due to a generally higher rate of prescription drug use.
Should DPMs Re-Evaluate
Their Approach To Onychomycosis?
Despite the aforementioned research, the Lieberman study found that DPMs recommend debridement to three-fourths of our onychomycosis patients and oral antifungals to fewer than one-third, even though we perceive oral compounds to be far more effective. By comparison, 64 percent of dermatologists and 65 percent of primary care physicians prescribed oral antifungals, with neither group recommending debridement.
What accounts for this discrepancy? Most likely, it stems from our desire to improve the nail’s appearance and provide rapid symptomatic relief of pain as only a good debridement can do.1 When asked to indicate their reasons for treating onychomycosis, 69 percent of DPMs surveyed felt pain was an important factor compared to only 49 percent of dermatologists or primary care physicians. Somewhat surprisingly, however, neither cosmetic concerns nor the desire to be free from pain was a primary motivating factor for patients seeking treatment, according to the survey.
In fact, the majority of patients surveyed said the main reason why they sought treatment for onychomycosis was because it was an infection that wouldn’t go away on its own. By the time patients come to us seeking treatment, they are generally frustrated with their condition and motivated to find a solution to the problem. Six out of 10 survey participants found their infection somewhat bothersome (40 percent) or extremely/very bothersome (22 percent).
Clearly, there is a disconnect between the perception of different treatments and the reality of what is actually prescribed for onychomycosis patients. Despite the substantial risk of secondary infection among diabetic and immunocompromised patients, the study revealed an alarming 30 to 38 percent of these patients had not received any onychomycosis treatment during the preceding 12 months (see Table 1). Surprisingly, only 8 percent of these high-risk patients benefitted from the superior efficacy of oral antifungal agents, a value nearly identical to otherwise healthy low-risk patients.
Overall, the greatest number of surveyed patients, including high-risk patients, used the least effective treatments for onychomycosis, while the fewest number of patients used the most effective treatments. The high degree of efficacy and safety of oral antifungals makes them an ideal choice for treating onychomycosis, yet, according to the Lieberman study, only 2 percent (itraconazole) to 5 percent (terbinafine) of patients have used oral antifungals in the past year. On the other hand, 30 percent of patients have received debridement and trimming in the preceding 12 months, even though debridement constitutes palliative management only and will not eliminate the infection.2,3
It is understandable why patients with onychomycosis are frustrated with their infections and increasingly request their physicians prescribe curative therapy in addition to palliative relief. By prescribing oral medication that can eliminate onychomycosis, podiatric physicians undoubtedly will increase patient satisfaction by accurately addressing patients’ desires and their medical needs.3
Addressing Misgivings
DPMs May Have Over Oral Antifungals
The results of the Lieberman survey reveal patients’ attitudes about onychomycosis have shifted following the introduction of current-generation oral antifungals. Patients realize oral antifungals now have the potential to eliminate their infections once and for all and they may no longer be satisfied with periodic debridements as their sole form of therapy. However, I should note that performing debridement may help you maximize the efficacy of oral antifungals when you’re treating patients with refractive infection or onycholytic nails.11
One obvious question that emerges from the Lieberman data is why podiatrists, in general, seem reluctant to prescribe oral antifungals for their patients. Perhaps, in the past, we have failed to perceive or misinterpreted our patients’ desires for a cure. By providing immediate symptomatic relief, we kept our patients happy, but why not use the tools at our disposal to eliminate the underlying disease?
Perhaps some DPMs feel oral antifungals are unnecessarily risky treatment choices. From my point of view, these new oral antifungals are sufficiently safe to use, as long as we take drug interactions into account and follow recommendations for liver enzyme testing. Maybe the “hassle factor” of ordering liver function tests has caused some podiatrists to shy away from oral agents, but keep in mind we routinely order blood tests for our surgical patients.
Granted, treatment costs can be a factor for patients who don’t have adequate insurance coverage. However, it’s important to properly evaluate treatments for onychomycosis on a cost-to-cure formula that emphasizes the cost of unsuccessful therapy. No matter how inexpensive the therapy, if you don’t cure the infection, the treatment costs have been wasted.
Lastly, perhaps some podiatrists are concerned that oral antifungals will diminish their patient base by eliminating onychomycosis. On the contrary, many more patients are likely to find their way to your practice as your successfully treated patients spread the word. I believe podiatrists who continue to manage patients through debridement alone are likely to lose patients to physicians who provide effective therapy to their patients in the form of oral antifungals.
Final Notes
Both the study findings and a wealth of scientific data suggest we need to rethink our approach to treating onychomycosis. By combining debridement with potentially curative therapy via oral antifungals, we can achieve an excellent clinical outcome and increase our patients’ satisfaction with their therapy.

Dr. Pollak is a Clinical Assistant Professor in the Department of Orthopedics at the University of Texas Health Science Center. He also has a private practice in San Antonio, Texas.




References:

References
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