Antifungal Agent, Oral; Antifungal Agent, Topical

Active against most strains of Trichophyton mentagrophytes, Trichophyton rubrum; may be effective for infections of Microsporum gypseum and M. nanum, Trichophyton verrucosum, Epidermophyton floccosum, Candida albicans, and Scopulariopsis brevicaulis

Topical: Antifungal for the treatment of tinea pedis (athlete's foot), tinea cruris (jock itch), and tinea corporis (ringworm)

Unlabeled use: Topical: Cutaneous candidiasis and pityriasis versicolor

B

Clinical effects on the fetus: Avoid use in pregnancy since treatment of onychomycosis is postponable

Breast-feeding/lactation: Although minimal concentrations of terbinafine cross into breast milk after topical use, oral or topical treatment during lactation should be avoided

Hypersensitivity to terbinafine, naftifine or any component; pre-existing liver or renal disease ( less than or equal to 50 mL/minute GFR)

While rare, the following complications have been reported and may require discontinuation of therapy: Changes in the ocular lens and retina, pancytopenia, neutropenia, Stevens-Johnson syndrome, toxic epidermal necrolysis. Discontinue if symptoms or signs of hepatobiliary dysfunction or cholestatic hepatitis develop. If irritation/sensitivity develop with topical use, discontinue therapy. Use caution in writing/filling Rx. Confusion between Lamictal® (lamotrigine) and Lamisil® (terbinafine) have occurred.

Oral: 1% to 10%:

Central nervous system: Headache, dizziness, vertigo

Dermatologic: Rash, pruritus, and alopecia with oral therapy

Gastrointestinal: Nausea, diarrhea, dyspepsia, abdominal pain, appetite decrease, taste disturbance

Hematologic: Neutropenia, lymphocytopenia

Hepatic: Cholestasis, jaundice, hepatitis, liver enzyme elevations

Ocular: Visual disturbance

Miscellaneous: Allergic reaction

Topical: 1% to 10%:

Dermatologic: Pruritus, contact dermatitis, irritation, burning, dryness

Local: Irritation, stinging

Decreased effect: Cyclosporine clearance is increased (~15%) with concomitant terbinafine; rifampin increases terbinafine clearance (100%)

Increased effect: Terbinafine clearance is decreased by cimetidine (33%) and terfenadine (16%); caffeine clearance is decreased by terfenadine (19%)

Cream: Store at 5°C to 30°C/41°F to 86°F

Synthetic alkylamine derivative which inhibits squalene epoxidase, a key enzyme in sterol biosynthesis in fungi. This results in a deficiency in ergosterol within the fungal cell wall and results in fungal cell death.

Absorption: Topical: Limited (<5%); Oral: >70%

Distribution: V_d: 2000 L; distributed to sebum and skin predominantly

Protein binding, plasma: >99%

Metabolism: Hepatic; no active metabolites

Bioavailability: Oral: 80% although undergoes first-pass metabolism (40%); does not involve significant (<5%) of total cytochrome P-450 capacity of liver; peak plasma levels occur at 1-2 hours

Half-life: 22-26 hours; very slow release of drug from skin and adipose tissues occurs

Elimination: ~75% of dose excreted in urine; 3.5% of a topically administered dose excreted in urine and feces

Adults:

Superficial mycoses: Fingernail: 250 mg/day for up to 6 weeks; toenail: 250 mg/day for 12 weeks; doses may be given in two divided doses

Systemic mycosis: 250-500 mg/day for up to 16 months

Topical Cream:

Athlete's foot: Apply to affected area twice daily for at least 1 week, not to exceed 4 weeks

Ringworm and jock itch: Apply to affected area once or twice daily for at least 1 week, not to exceed 4 weeks

Topical Gel:

Tinea versicolor, tinea corporis and tinea pedis: Apply to affected area once daily for 7 days

Dosing adjustment in renal impairment: Although specific guidelines are not available, dose reduction in significant renal insufficiency (GFR <50 mL/minute) is recommended

CBC and LFTs at baseline and repeated if use is for >6 weeks

None reported

None reported

Topical: Avoid contact with eyes, nose, or mouth during treatment with cream; nursing mothers should not use on breast tissue; advise physician if eyes or skin becomes yellow or if irritation, itching, or burning develops. Do not use occlusive dressings concurrent with therapy. Full clinical effect may require several months due to the time required for a new nail to grow.

Patients should not be considered therapeutic failures until they have been symptom-free for 2-4 weeks off following a course of treatment; GI complaints usually subside with continued administration

Cream: 1% (15 g, 30 g)

Gel, topical: 1% (5 g, 15 g, 30 g)

Tablet: 250 mg

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Amichai B and Grunwald MH, "Adverse Drug Reactions of the New Oral Antifungal Agents - Terbinafine, Fluconazole, and Itraconazole," Int J Dermatol, 1998, 37(6):410-5.

Angello JT, Voytovich RM, and Jan SA, "A Cost/Efficacy Analysis of Oral Antifungals Indicated for the Treatment of Onychomycosis: Griseofulvin, Itraconazole, and Terbinafine," Am J Manag Care, 1997, 3(3):443-50.

De Backer M, De Vroey C, Lesaffre E, et al, "Twelve Weeks of Continuous Oral Therapy for Toenail Onychomycosis Caused by Dermatophytes: A Double-Blind Comparative Trial of Terbinafine 250 mg/day Versus Itraconazole 200 mg/day," J Am Acad Dermatol, 1998, 38(5 Pt 3):S57-63.

Dwyer CM, White MI, and Sinclair TS, "Cholestatic Jaundice Due to Terbinafine," Br J Dermatol, 1997, 136(6):976-7.

Gupta AK and Shear NH, "Terbinafine: An Update," J Am Acad Dermatol, 1997, 37(6):979-88.

Gupta AK, Sibbald RG, Knowles SR, et al, "Terbinafine Therapy May Be Associated With the Development of Psoriasis De Novo or Its Exacerbation: Four Case Reports and a Review of Drug Induced Psoriasis," J Am Acad Dermatol, 1997, 36(5 Part 2):858-62.

Jones TC, "Overview of the Use of Terbinafine in Children," Br J Dermatol, 1995, 132(5):683-9.

Trepanier EF and Amsden GW, "Current Issues in Onchomycosis," Ann Pharmacother, 1998, 32(2):204-14.