AHFS Class:

• Allylamines 84:04.08.04

Generic Name(s):

• Terbinafine Hydrochloride

Terbinafine hydrochloride is a synthetic allylamine antifungal agent.1,2,8,12,19,28

Dermatophytoses

Tinea Corporis and Tinea Cruris

Terbinafine hydrochloride (1% cream, 1% spray solution) and terbinafine (1% gel) are used topically for the treatment of tinea corporis (ringworm of the body)1,2,7,8,9,10,14,15,19,20,22,23,26,27,28,32,33,34,37 and tinea cruris (jock itch, ringworm of the groin)1,2,6,7,8,9,10,14,15,19,20,21,22,23,25,26,27,28,32,33,34,37 caused by Epidermophyton floccosum , Trichophyton mentagrophytes , or T. rubrum .1,7,8,9,14,32,33

In clinical trials evaluating a 1-week regimen of terbinafine hydrochloride 1% cream in patients with tinea corporis or tinea cruris, clinical improvement and mycologic cure was observed at completion of treatment and 3 weeks later in 21 and 83%, respectively, of those with tinea corporis and in 43 and 92%, respectively, of those with tinea cruris.1 Additional data indicate that once- or twice-daily topical application of terbinafine hydrochloride 1% cream for 1-3 weeks generally results in clinical improvement and mycologic cure within 4 weeks in 80-100% of patients with tinea corporis or tinea cruris.1,2,6,25,26,27,28,33

In a clinical trial evaluating a 1-week regimen of topical terbinafine hydrochloride 1% solution in patients with tinea corporis or tinea cruris, “effective” treatment (defined as mycologic cure and a total clinical score representing minimal residual signs and symptoms) was attained in 37.7% of patients at the end of treatment and in 70.8% of patients at the end of the study.19 Complete cure, defined as mycologic cure and a total clinical score of 0 (i.e., no residual signs or symptoms), was attained in 5.7% of patients at the end of treatment and in 52.8% of patients at the end of the study.19

Tinea corporis and tinea cruris generally can be effectively treated using a topical antifungal; however, an oral antifungal may be necessary if the disease is extensive, dermatophyte folliculitis is present, the infection is chronic or does not respond to topical therapy, or the patient is immunocompromised because of coexisting disease or concomitant therapy.7,8,9,10,14,32,37 Topical imidazole-derivative azole antifungals (e.g., clotrimazole, econazole, ketoconazole, luliconazole, miconazole, oxiconazole, sertaconazole, sulconazole) or topical allylamine antifungals (e.g., naftifine, terbinafine) usually are used for the topical treatment of tinea corporis and tinea cruris, although other topical antifungals (e.g., butenafine hydrochloride, ciclopirox olamine, tolnaftate, undecylenic acid) also are effective for treatment of these infections.7,8,9,14,15,32

Tinea Pedis

Terbinafine hydrochloride (1% cream, 1% spray solution) and terbinafine (1% gel) are used topically for the treatment of tinea pedis (athlete's foot, ringworm of the foot)1,2,3,4,5,7,8,10,14,19,20,22,23,26,27,28,32,35 caused by E. floccosum , T. mentagrophytes , or T. rubrum .1,7,8,14,32,36,37 Topical terbinafine is not indicated for the treatment of dermatophyte infections involving the nails, including onychomycosis of the toenails (tinea unguium, ringworm of the nail).1,2,16,17,18

Clinical studies indicate that twice-daily topical application of terbinafine hydrochloride 1% cream for 1-4 weeks results in clinical improvement and mycologic cure within 6 weeks in about 65-90% of patients with uncomplicated tinea pedis.2,7,16,17,28 Response to short-course (1-2 weeks) topical therapy with the drug in uncomplicated infections is not improved substantially with more prolonged (e.g., 4 weeks) treatment.2,7,16,17,28

In clinical trials evaluating a 1-week regimen of terbinafine hydrochloride 1% cream in patients with interdigital tinea pedis, clinical improvement (e.g., resolution of erythema, desquamation, pruritus) and mycologic cure was observed in 14% of patients at treatment completion and in 51 and 65% of patients at 3 and 5 weeks after treatment, respectively.1 Following a 4-week regimen, clinical improvement and mycologic cure were observed in 71 and 73% of patients at treatment completion and 2 weeks later (i.e., at 6 weeks), respectively, in patients treated with terbinafine hydrochloride 1% cream compared with 63 and 59%, respectively, of patients treated with topical clotrimazole.1,16 Likewise, in a study comparing 1- and 4-week courses of treatment with topical terbinafine cream and topical clotrimazole for interdigital tinea pedis, a 1-week course of terbinafine was substantially more effective at 6 weeks than a 1-week course of clotrimazole and comparably effective to a 4-week course of clotrimazole.11 In this study, mycologic cure at 6 weeks was observed in 83 or 81% of patients receiving a 1- or 4-week course of topical terbinafine, respectively, and in 51 or 83% of those receiving a 1- or 4-week course of topical clotrimazole, respectively; at 12 weeks, the rate of relapse or reinfection was 9 or 11% with 1 or 4 weeks of terbinafine and 47 or 30% with 1 or 4 weeks of clotrimazole.7 Results from a study comparing a 1-week course of topical terbinafine cream and a 4-week course of topical clotrimazole for interdigital tinea pedis also indicate that terbinafine is more effective in terms of both clinical improvement and mycologic response at 4-6 weeks than clotrimazole.18

In a clinical trial evaluating a 1-week regimen of topical terbinafine hydrochloride 1% spray solution in patients with tinea pedis, “effective treatment” (defined as mycologic cure and a total clinical score representing minimal residual signs and symptoms) was observed in 17.9% of patients at the end of treatment and in 65.5% of patients at the end of the study (7 weeks after completion of treatment or last examination before leaving the study).19 Complete cure, defined as mycologic cure and a total clinical score of 0 (i.e., no residual signs or symptoms), was reported in 1.8% of patients at the end of treatment and in 20.7% of patients at the end of the study.19

While topical antifungals usually are effective for treatment of uncomplicated tinea pedis, an oral antifungal may be necessary if the disease is extensive, the infection is chronic or does not respond to topical therapy, the patient is immunocompromised because of coexisting disease or concomitant therapy, or the infection involves hyperkeratotic areas on the soles or chronic moccasin-type (dry-type) tinea pedis.7,8,9,10,14,32,37

Pityriasis Versicolor

Terbinafine hydrochloride (1% cream, 1% spray solution) has been used topically for the treatment of pityriasis versicolor (also known as tinea versicolor) caused by Malassezia furfur (formerly Pityrosporum ovale ).14,19,30,31

In a clinical trial in adults and adolescents 14 years of age or older with a clinical diagnosis of pityriasis versicolor confirmed by potassium hydroxide (KOH) microscopy, patients who had skin lesions involving no more than 10% of body surface area were randomized to a 2-week regimen of terbinafine hydrochloride 1% cream (twice daily) or ketoconazole 2% cream (twice daily).31 Cure was defined as negative mycologic examination and clearance of skin lesions or presence of only mild residual disease.31 The cure rate in those treated with topical terbinafine or topical ketoconazole was 72 or 64%, respectively, at the end of week 2 (completion of treatment) and 81 or 69%, respectively, at the end of week 4 (2 weeks after completion of treatment).31 At the end of week 8 (6 weeks after completion of treatment), the recurrence rate was 1% in those who had been treated with topical terbinafine and 2% in those who had been treated with topical ketoconazole.31

Efficacy of a 1-week regimen of topical terbinafine hydrochloride 1% solution (twice daily) was evaluated in clinical trials in patients with pityriasis versicolor and “effective treatment” (defined as mycologic cure and a total clinical score representing minimal residual signs and symptoms) was reported in 39% of patients at the end of treatment and in 74% of patients at the end of the study (7 weeks after completion of therapy or last examination before leaving the study).19 Complete cure, defined as mycologic cure and a total clinical score of 0 (i.e., no residual signs or symptoms), was reported in 19% of patients at the end of treatment and in 58% of patients at the end of the study.19

Administration

Topical Administration

Terbinafine hydrochloride is applied topically to the skin as a 1% cream20 or 1% spray.21,22

Terbinafine is applied topically to the skin as a 1% gel.23

Terbinafine hydrochloride 1% cream20 or 1% spray21,22 and terbinafine 1% gel23 are for external use only.20,21,22,23 These topical preparations should not be administered intravaginally and should not be applied in or near the mouth or eyes.20,21,22,23 In addition, these preparations should not be used on the nails or scalp.20,21,22,23

Prior to topical application of the cream, spray, or gel in adults and children 12 years of age or older, the affected area should be washed with soap and water and dried completely.20,21,22,23

When terbinafine hydrochloride 1% spray solution is used, the container should be held 4-6 inches from the skin and a thin layer of the solution sprayed over the affected areas.22 The solution spray should not be used on the face.19

Occlusive dressings or wrappings should be avoided unless otherwise directed by a clinician.1,19

The cream, spray, and gel should not be used for self-medication in children younger than 12 years of age without consulting a clinician.20,21,22,23

Dosage

Tinea Corporis and Tinea Cruris

For topical treatment, including self-medication , of tinea corporis or tinea cruris in adults and children 12 years of age or older, a sufficient amount of terbinafine hydrochloride 1% cream or 1% spray or terbinafine 1% gel should be applied to affected areas and surrounding skin once daily (morning or night) for 1 week or as directed by a clinician.20,21,22,23

Tinea Pedis

For topical treatment, including self-medication , of interdigital tinea pedis (only involving areas between the toes) in adults and children 12 years of age or older, a sufficient amount of terbinafine hydrochloride 1% cream or 1% spray should be applied to affected areas between the toes twice daily (morning and night) for 1 week or as directed by a clinician.20,22 Alternatively, a sufficient amount of terbinafine 1% gel should be applied to affected areas between the toes once daily (at bedtime) for 1 week or as directed by a clinician.23

If tinea pedis involves the bottom or sides of the foot, a sufficient amount of terbinafine hydrochloride 1% cream should be applied to all affected areas twice daily (morning and night) for 2 weeks or as directed by a clinician.20

Pityriasis Versicolor

For topical treatment of pityriasis versicolor (also known as tinea versicolor), terbinafine hydrochloride 1% cream or 1% spray has been applied to affected areas twice daily for 1-2 weeks.19,30,31

Contraindications

Topical preparations containing terbinafine are contraindicated in patients hypersensitive to the drug or any ingredient in the formulation.1,19

Warnings/Precautions

Sensitivity Reactions

If irritation or sensitivity occurs, topical preparations containing terbinafine should be discontinued and appropriate therapy initiated.1,19,20,21,22,23

Selection and Use of Antifungals

Prior to initiation of treatment of dermatophytoses, the diagnosis can be confirmed by direct microscopic examination of scrapings from infected tissue mounted in potassium hydroxide (KOH) or by culture using an appropriate medium.1,7,9,14,19,32

Prior to initiation of treatment for pityriasis versicolor (also known as tinea versicolor), the diagnosis should be confirmed by direct microscopic examination of scrapings from infected tissue mounted in potassium hydroxide.1,19

Clinical improvement usually is evident within the first week of treatment with topical terbinafine, and patients treated for 1-2 weeks usually show continued improvement for several weeks after completion of treatment.1,2,4,6,8,11,14,18 If clinical improvement is not evident within 2-6 weeks after completion of topical treatment, the diagnosis should be reevaluated.1

Specific Populations

Pregnancy

Category B.1,19

Lactation

Terbinafine is distributed into milk following oral administration.1,19 A decision should be made to discontinue nursing or the drug.1,19

Pediatric Use

Topical terbinafine should not be used for self-medication in children younger than 12 years of age unless directed by a clinician;20,21,22,23 safety and efficacy have not been established in children in this age group.1,19,20,21,22,23

Common Adverse Effects

The most frequent adverse effects reported with topical terbinafine are irritation, burning/tingling, pruritus, dryness, skin exfoliation, and erythematous rash.1,19

Description

Terbinafine hydrochloride is a synthetic allylamine antifungal agent.1,2,3,4,6,12,18,19,25,26,27,28,29 Terbinafine is derived from naphthalenemethanamine,1 and is structurally and pharmacologically related to naftifine.2,6,12,28,29

Terbinafine is active in vitro against dermatophytes, including Epidermophyton floccosum , Trichophyton mentagrophytes , T. rubrum , T. verrucosum , Microsporum canis , and M. gypseum .1,2,13,19 The drug also is active in vitro against Malassezia furfur 13 and some Candida , including C. albicans and C. parapsillosis .2,13 The antifungal spectrum of activity of terbinafine is similar to that of naftifine.2,3,28,29

Terbinafine usually is fungicidal in action against susceptible dermatophytes,1,2,3,4,13,28,29 but may be fungicidal or fungistatic against Candida .2,13,28 Terbinafine is more active than azole antifungals (e.g., itraconazole, ketoconazole) against dermatophytes,2,5,15,25 but is less active than these drugs against Candida .2,26,28

Following topical application of terbinafine hydrochloride 1% cream or 1% solution to healthy skin, percutaneous absorption occurs and terbinafine concentrations attained in the stratum corneum are similar with both preparations.1,19 Terbinafine is absorbed systemically following topical application to intact skin, and low concentrations of the drug are attained in plasma.1,19 Systemically absorbed terbinafine is extensively metabolized.1,19 Approximately 75% of percutaneously absorbed terbinafine is eliminated in urine, principally as metabolites.1,19 Following topical application to skin, the half-life of systemically absorbed terbinafine is approximately 21 hours.19

Advice to Patients

Importance of using topical preparations containing terbinafine as directed;1,19,20,21,22,23 importance of completing full course of treatment, even if symptoms improve.1,19,20,21,22,23

The cream, solution, and gel are for external use only;20,21,22,23 contact with the vagina, mouth, and eyes should be avoided.20,21,22,23 If accidental contact with eyes occurs, importance of rinsing eyes thoroughly with water and consulting a clinician if symptoms persist.19,20,21,22,23

Importance of washing the affected areas with soap and water and drying completely before applying topical terbinafine;20,21,22,23 importance of washing hands after application.20,21,22,23

For patients with tinea pedis (athlete's foot, ringworm of the foot), importance of wearing well-fitting, ventilated shoes and changing shoes and socks at least once daily.20,22,23

Importance of consulting clinician if treated area shows signs of increased irritation or possible sensitization (e.g., erythema, pruritus, burning, blistering, swelling, oozing).1,19,20,21,22,23

Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1,19

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1,19

Importance of advising patients of other important precautionary information.1,19

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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3. Savin RC. Treatment of chronic tinea pedis (athlete's foot type) with topical terbinafine. J Am Acad Dermatol . 1990; 23:786-9. [PubMed 2229524]

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16. Sandoz Pharmaceutical Corporation, East Hanover, NJ: Personal communication.

17. Reviewers' comments (personal observations).

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20. Novartis Consumer Health, Inc. Lamisil AT^® (terbinafine hydrochloride) 1% cream patient information. Parsippany, NJ; 2008.

21. Novartis Consumer Health, Inc. Lamisil AT^® (terbinafine hydrochloride) 1% solution spray pump patient information. Parsippany, NJ; 2006.

22. Novartis Consumer Health, Inc. Lamisil AT^® (terbinafine hydrochloride) 1% solution continuous spray patient information. Parsippany, NJ.

23. Novartis Consumer Health, Inc. Lamisil AT^® (terbinafine) 1% gel patient information. Parsippany, NJ.

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33. Choudhary S, Bisati S, Singh A et al. Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris: A Comparative Therapeutic Trial. Indian J Dermatol . 2013; 58:457-60. [PubMed 24249898]

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35. Schopf R, Hettler O, Bräutigam M et al. Efficacy and tolerability of terbinafine 1% topical solution used for 1 week compared with 4 weeks clotrimazole 1% topical solution in the treatment of interdigital tinea pedis: a randomized, double-blind, multi-centre, 8-week clinical trial. Mycoses . 1999; 42:415-20. [PubMed 10536434]

36. Korting HC, Kiencke P, Nelles S et al. Comparable efficacy and safety of various topical formulations of terbinafine in tinea pedis irrespective of the treatment regimen: results of a meta-analysis. Am J Clin Dermatol . 2007; 8:357-64. [PubMed 18039018]

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