Efficacy and safety of 250 mg versus 500 mg oral terbinafine in the treatment of tinea corporis and cruris: A randomised, assessor-blinded comparative study

Abstract

Background Though higher doses of terbinafine are often prescribed to treat dermatophyte infections, it is unknown if such doses are more effective than the conventional dose because comparative data are unavailable. Aim To compare the efficacy and safety of a once-daily dose of oral terbinafine 250 mg with 500 mg along with topical clotrimazole in the treatment of tinea infections. Methods A randomised, assessor-blinded, comparative study was carried out. Each group of subjects were administered either 250 mg or 500 mg oral terbinafine once daily for four weeks, along with topical clotrimazole. Clinical improvement was assessed after two weeks and again after four weeks from treatment initiation. Result A total of 60 patients with tinea corporis and cruris were randomised into two groups receiving either 250 mg (group A) or 500 mg (group B) oral terbinafine, along with clotrimazole cream in both groups. Baseline clinical parameters such as lesional activity (papules, vesicles and pustules), degree of erythema, scaling and severity of itching were comparable between both treatment arms. At the first and second follow-ups, no significant differences were found in the clinical parameters between the two groups. At the end of two weeks 13.8% of group A and 14.3% of group B and after 4 weeks 25.9% of group A and 33.3% of group B participants became KOH negative (P = 1.00 and 0.76, respectively). No significant difference in culture negativity was reported at the end of therapy (four weeks) between the two treatment arms (P = 0.78). Overall cure rates were 20% and 33.3% in the two treatment arms respectively at the end of the study (P = 0.82). Conclusion Oral terbinafine 250 mg daily yielded a poor cure rate in tinea cruris and corporis after 4 weeks of treatment and an increased dose of 500 mg did not have any additional benefit.

Clinical Course, Antifungal Susceptibility, and Genomic Sequencing of Trichophyton indotineae

“…Data highlight that 100-mg or 200-mg daily dosing of itraconazole for 6 to 8 weeks is the current preferred therapy, yet longer durations and higher doses may be required with reported relapse occurring . Terbinafine at higher than standard doses (500 mg daily) may be effective for some patients . Griseofulvin and fluconazole show limited efficacy …”

“…11,12 Terbinafine at higher than standard doses (500 mg daily) may be effective for some patients. 17,19 Griseofulvin and fluconazole show limited efficacy. 7,13 Consistent with published literature, 9,15,16,29 T indotineae isolates recovered from patients in this study whose infections were unresponsive to terbinafine at standard doses and durations harbored variants at either position L393 (L393S; MIC values of 0.5 to 1.0 μg/mL) or position F397 (F397L; MIC values between 32 to >128 μg/mL).…”

“…Published data demonstrate that T indotineae isolates displaying terbinafine minimum inhibitory concentration (MIC) values of 0.5 μg/mL or higher are associated with treatment failure at standard doses and durations of therapy, and they harbor specific sequence variations in SQLE, including L393S and F397L . Daily doses of terbinafine at 500 mg per day may overcome mildly elevated terbinafine MICs, yet response rates vary . Isolates responsive to terbinafine therapy are correlated with SQLE alterations at position 448 (A448T) .…”

“…9,[14][15][16] Daily doses of terbinafine at 500 mg per day may overcome mildly elevated terbinafine MICs, 17,18 yet response rates vary. 19 Isolates responsive to terbinafine therapy are correlated with SQLE alterations at position 448 (A448T). 9,16 However, no established clinical breakpoints for antifungal medications exist for dermatophytes, and in vitro antifungal susceptibility testing (AFST) does not necessarily correspond to clinical response, creating additional treatment challenges.…”