Keys To Managing Severe Onychomycosis

Myron Bodman, DPM

Current And Emerging Insights On Systemic Management

Due to an increased risk of subungual ulceration, one should consider oral antifungal therapy for onychomycosis of moderate to severe severity. The gold standard treatment for onychomycosis is basically systemic. Combination therapy with topical agents, such as nail lacquer and/or chemical nail avulsion, may produce better results than systemic treatment alone. Excluding minor cases, topical treatment as monotherapy is not efficient.12

   Oral therapy is the most effective treatment, especially in severe onychomycosis. In addition, studies have shown that patients with diabetes tolerate oral terbinafine (Lamisil, Novartis) just as well as other patients.15 Hall and coworkers reviewed over 25,000 patients taking terbinafine with the oldest patient being 78.15 They found no increased risk of adverse drug reactions, regardless of age. The authors also found that in their experience in Europe, there was no increase in adverse drug reactions that required terbinafine cessation. The incidence of adverse events was 10.5 percent with the majority involving the gastrointestinal system (4.9 percent) or skin (2.3 percent). These adverse events tended to be mild, transient and reversible. Researchers considered terbinafine as a possible or probable cause of 11 (0.04 percent) serious adverse events.

   Continuous therapy with cephalexin (Keflex, Eli Lilly) and naproxen can cause hepatic elevations at similar rates as terbinafine. Cephalexin can commonly cause mild elevations (less than two- to threefold) in serum transaminases but severe hepatocellular injury is very rare.14,16 Although the liver metabolizes terbinafine like most medications, terbinafine is not intrinsically hepatotoxic like acetaminophen.17

   It is important to carefully review the patient history for alcohol abuse and hepatitis. Ordering alanine aminotransferase and aspartate aminotransferase hepatic function tests before the beginning of continuous therapy establishes a baseline. If there is a history of living overseas where hepatitis is endemic, one can add a hepatitis antigen screening panel to the workup. Follow-up hepatic function tests at five weeks serve to detect the less than 2 percent of idiosyncratic responders. If the follow-up tests are significantly elevated, one can stop the drug and retest.

   Concurrent medications may preclude the use of oral antifungals. Terbinafine may alter the metabolism of a number of drugs so monitoring is appropriate. There is controversy regarding the risk of terbinafine with concurrent warfarin (Coumadin, Bristol-Myers Squibb) as there have been reports of elevated international normalized ratios.18-20 It is wise to monitor the international normalized ratio if it is necessary to use the drugs concurrently. There has been some controversy with concurrent statin therapy. Concerns regarding drug-to-drug interactions with statin therapy and systemic antifungal therapy are actually with the azole class of antifungals and not terbinafine.21 It might be best to avoid systemic therapy in patients on psychotropic medications. Terbinafine carries a contraindication for concurrent use with the phenothiazines and pimozide (Orap, Teva) for increased risk of QT prolongation.22

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