There is weak evidence from randomized controlled trials (RCT) that adding topical amorolfine to oral terbinafine is more effective than oral treatment alone. No RCTs have assessed adding topical tioconazole to oral terbinafine.

Oral terbinafine compared with oral terbinafine plus topical amorolfine

• An unblinded RCT (n = 96) found no benefit from adding topical amorolfine hydrochloride 5% to oral terbinafine for onychomycosis [Jaiswal et al, 2007].
• Participants were treated for 4 months with one of three regimens:
• Oral terbinafine pulse therapy 250 mg twice daily for 1 week in every 4 weeks (48 participants), or
• Oral terbinafine pulse therapy plus topical amorolfine hydrochloride 5% applied once weekly at night on all the affected nails (24 participants), or
• Oral terbinafine pulse therapy plus topical ciclopirox olamine 8% applied once daily at night on all affected nails (24 participants) — results for this group are omitted because ciclopirox olamineis not licensed in the UK.
• At 36 weeks, cure rates for oral terbinafine alone compared with oral terbinafine plus topical amorolfine were:
• Clinical cure rates: 72% compared with 74%.
• Mycological cure rates for dermatophyte infection: 89% compared with 86%.
• Mycological cure rates for Candida infection: 67% compared with 50%.
• Mycological cure rates for non-dermatophyte infection: 50% compared with 0% (but the numbers of cases were very small: n = 2 and n = 1 respectively).
• An unblinded RCT (n = 249) found that adding topical amorolfine to oral terbinafine for onychomycosis resulted in similar mycological cure rates but improved clinical cure rates [Baran et al, 2007].
• All participants were treated with oral terbinafine 250 mg daily for three months. About half the participants (n = 120) were randomized to also use amorolfine hydrochloride 5% nail lacquer once weekly for 12 months.
• About 16% of the participants did not complete the study.
• Cure rates at 18 months for terbinafine alone compared with combined treatment were:
• Complete cure (clinical cure and mycological cure): 45% compared with 59% (p < 0.03, intention-to-treat analysis).
• Clinical cure: 54% compared with 67% (p < 0.03, intention-to-treat analysis).
• Mycological cure: 79.9% compared with 80% (values read from the published graph).
• An unblinded RCT (n = 147) found that adding topical amorolfine to oral terbinafine for onychomycosis resulted in similar mycological cure rates but improved clinical cure rates [Baran et al, 2000; Baran, 2001].
• Participants were treated with one of the following regimens
• T-12: Oral terbinafine 250 mg daily for 12 weeks, or
• AT-6: Oral terbinafine 250 mg daily for 6 weeks plus amorolfine hydrochloride 5% nail lacquer once weekly for 15 months, or
• AT-12: Oral terbinafine 250 mg daily for 12 weeks plus amorolfine hydrochloride 5% nail lacquer once weekly for 15 months.
• About 46% of the participants did not complete the study.
• Cure rates at 18 months were:
• Complete cure (clinical cure and mycological cure) for the T-12, AT-6, and AT-12 groups: 38%, 44%, and 72% respectively (statistical significance was not reported).
• Mycological cure: about 70% (T-12), 72% (AT-6), and 89% (AT-12) (values read from the published graph).

Oral terbinafine compared with oral terbinafine plus topical tioconazole

• CKS found no RCTs.