The use of terbinafine in the treatment of onychomycosis in adults and special populations: a review of the evidence

Journal of Drugs in Dermatology, May-June, 2005 by Aditya K. Gupta, Jennifer E. Ryder, Lindsay E. Lynch, Amir Tavakkol

Special Patient Populations

Children

Onychomycosis is observed less frequently in children than in adults. In a North American study, the prevalence of onychomycosis in children was 0.16% (N = 2,500). (14) Although the safety and efficacy of terbinafine in pediatric patients is not yet established by large-scale RCTs, (10) preliminary data suggest the allylamine may be a consideration for use in this population. (15-19) In a retrospective study of 14 pediatric patients treated with terbinafine (mean dose 4 mg [kg.sup.-1] [day.sup.-1] for 2-5 months), Heikkila and Stubb (15) reported mycological and clinical cure rates of 77% and 69%, respectively, 1 to 9 years after treatment. Goulden and Goodfield (19) reported clinical and mycological success in the treatment of 3 cases of childhood onychomycosis with terbinafine 250 mg/day for 3 or 6 months. Similar results have been reported by other authors. (17)

Terbinafine may also be a consideration for the treatment of onychomycosis in pediatric patients with Down syndrome. In an open study, 32 Down syndrome patients diagnosed with onychomycosis were treated with terbinafine 250 mg daily for 16 weeks. (20) At week 40, mycological cure (negative culture and microscopy) was achieved in 94% of patients and clinical cure (no clinical signs of dermatophyte infection) in 78%. (20) Adverse events reported included abdominal cramps (N = 1), abdominal pain (N = 1), constipation (N = 1), and eczematous eruptions (N = 2); all were treatable. The authors of this study suggested that the decreased cellular immunity found in Down syndrome had no effect on the therapeutic effect of terbinafine. (20)

Elderly

The prevalence of onychomycosis increases with age and is higher in patients over 60 years of age. The management of this fungal infection with terbinafine has been reported to be safe and effective in this population. Smith et al, (21) in an open-label study, evaluated the efficacy and safety of terbinafine in patients 60 years or older with onychomycosis. At week 24, 93.3% (N = 15) of patients were mycologically cured and the cure rate between week 24 and 72 was greater than or equal to 92.9%. (21) A negative mycologic culture was used as the basis for efficacy. At week 72, 46.7% (N = 15) achieved a complete cure. Adverse events were mild to moderate in severity and transient in nature. Of the 30 patients evaluated for safety, investigators attributed a possible, probable, or definite causal relationship between an event and terbinafine in 13 patients. Smith et al (21) also found that no drug interactions occurred in patients taking terbinafine with drugs metabolized by cytochrome P-450 2D6 enzymes (eg, [beta]-blockers, tricyclic antidepressants, antiarrhythmic agents, antimicrobials, opioid analgesics, muscle relaxants, or cough/cold preparations).

In a single-blind, randomized, controlled study, patients greater than 60 years of age (mean age of 68 years) with toenail onychomycosis were treated with either terbinafine (250 mg/day for 12 weeks) or itraconazole pulse (200 mg twice daily given for 1 week each month for 3 pulses). (22) At month 18, mycological cure (negative culture and microscopy) was achieved in 64% (N = 50) and 62.7% (N = 51) in the terbinafine and itraconazole pulse groups, respectively. (22) Adverse events were reported in 5 terbinafine patients (GI and cutaneous) and 7 itraconazole pulse patients (GI, cutaneous, elevation of liver function tests, and drowsiness). (22)