In the early 1990’s, we saw a mini-revolution in the available oral anti-fungal agents to treat onychomycosis. Since 1958, Griseofulvin had been the drug of choice – by 1990 it was an ageing drug which was only active against dermatophytes with a relatively low cure rate in onychomycosis of about 30% (1). Terbinafine, Itraconazole and fluconazole were then introduced into the UK for fungal nail infection in the early 1990’s with the promise of shorter treatment duration and better outcomes. And indeed, this was certainly the case. There was a flurry of publications examining each of the drugs and many trials comparing their effectiveness to see which was best.
It soon became apparent that fluconazole was out of the running due to a higher rate of hepatic complications which later saw the drug being no longer recommended for onychomycosis leaving itraconazole and terbinafine the main players in the market at that time as the Sporanox® and Lamisil® brands at that time.
As with many oral antifungals, the risk of hepatic damage is always a consideration and so studies always looked at ways to reduce the dosage and duration of these drugs. With this concept, we saw the arrival of “pulsed” therapies where drugs were taken for a week and then ceased until a second pulse was required a short time after (2, 3). In general, they were found to be effective but never quite so effective as continuous therapies.
In July this year, a revised systematic review was published which collated all the recently added studies to analyse which drugs are most effective, through the Cochrane Collaboration. The review looked at 48 trials which in included over 10 000 patients and found the following:
1. Terbinafine is more effective than placebo (48% v 6%)
2. Itraconazole is more effective than placebo (31% v 14%)
3. Terbinafine seemed to show superiority over itraconazole with 58% of people showing normal nails after taking the drug compared to just 47% with itraconazole.
4. Adverse effects and recurrence rates were similar between the two drugs.
Full summary : https://discover.dc.nihr.ac.uk/portal/article?id=SIG-5000494
References
1. Roberts DT. Oral therapeutic agents in fungal nail disease. J Am Acad Dermatol. 1994;31(3 Pt 2):S78-81.
2. De Doncker P, Decroix J, Pierard GE, Roelant D, Woestenborghs R, Jacqmin P, et al. Antifungal pulse therapy for onychomycosis. A pharmacokinetic and pharmacodynamic investigation of monthly cycles of 1-week pulse therapy with itraconazole. Arch Dermatol. 1996;132(1):34-41.
3. Pavlotsky F, Armoni G, Shemer A, Trau H. Pulsed versus continuous terbinafine dosing in the treatment of dermatophyte onychomycosis. J DermatolTreat. 2004;15(5):315-20.