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Generic Name: Naftifine Hydrochloride
Class: Allylamines
ATC Class: D01AE22
VA Class: DE102
Chemical Name: (E)-N-Methyl-N-(3-phenyl-2-propenyl)-1-naphthalenemethanamine hydrochloride
Molecular Formula: C21H21N•HCl
CAS Number: 65473-14-5

Introduction

Antifungal; synthetic allylamine structurally and pharmacologically related to terbinafine.1 3 4 5 9 11 13 14 16 21 22 23 25 29 31 35 36 37 38 41 42 43 48 63 64 65 66 67 68 69

Uses for Naftin

Dermatophytoses

Treatment of tinea corporis (body ringworm)1 22 39 46 48 49 50 51 54 55 63 and tinea cruris (jock itch)1 22 23 39 45 48 49 50 51 54 55 63 caused by Epidermophyton floccosum,1 39 45 47 49 50 51 53 63 Microsporum canis,49 50 55 Trichophyton mentagrophytes,1 39 47 49 50 51 53 55 63 T. rubrum,1 T. tonsurans,a T. verrucosum,50 51 53 or T. violaceum.50

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Treatment of tinea pedis (athlete's foot)1 15 28 47 48 49 51 54 55 63 or tinea manuum51 54 55 caused by Epidermophyton floccosum,1 39 45 47 49 50 51 53 63 Microsporum canis,49 50 55 Trichophyton mentagrophytes,1 39 47 49 50 51 53 55 63 T. rubrum,1 T. tonsurans,a T. verrucosum,50 51 53 or T. violaceum.50

Topical antifungals usually effective for treatment of uncomplicated tinea corporis and tinea cruris.69 70 71 72 73 An oral antifungal may be necessary when tinea corporis or tinea cruris 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.69 70 71 72 73

Topical antifungals usually effective for treatment of uncomplicated tinea pedis.69 70 71 72 73 An oral antifungal may be necessary for the treatment of hyperkeratotic areas on the palms and soles,70 73 for chronic moccasin-type (dry-type) tinea pedis,69 70 72 and for tinea unguium (fingernail or toenail dermatophyte infections, onychomycosis).69 70 71 72

Gel has been used in the treatment of tinea unguium (onychomycosis).57

Cutaneous Candidiasis

Treatment of cutaneous candidiasis caused by Candida albicans.47 50 51 53 54 55 56 62 Less active than imidazole derivatives.36 37 56

Naftin Dosage and Administration

Administration

Topical Administration

Apply topically to the skin as a cream or gel.1 63

Do not apply to the eye, nose, mouth, or other mucous membranes.1 63

Do not use with occlusive dressings or wrappings, unless otherwise directed by clinician.1 63

Apply a sufficient amount of topical cream or gel; rub gently into the affected area and surrounding skin.1 22 33 39 46 47 49 50 51 53 54 60 63

Wash hands after applying.1 63

Dosage

Available as naftifine hydrochloride; dosage expressed in terms of naftifine.a

Adults

Dermatophytoses
Tinea Corporis or Tinea Cruris
Topical

Cream: Apply once daily for 2–4 weeks.1 15 22 25 33 39 45 46 49 53 54 60

Gel: Apply twice daily (morning and evening) for 2–4 weeks.22 25 39 45 46 49 a

Clinical improvement usually occurs within the first week of treatment.22 25 39 45 If clinical improvement does not occur after 4 weeks of treatment, reevaluate diagnosis.1 63 Severe infections may require prolonged treatment.50 60 61

Tinea Pedis
Topical

Cream: Apply once daily for 4–6 weeks.1 15 22 15 25 33 39 45 46 47 49 53 54 60

Gel: Apply twice daily (morning and evening) for 4–6 weeks.15 22 25 39 45 46 47 49 a

Clinical improvement usually occurs within the first week of treatment.22 25 39 45 If clinical improvement does not occur after 4 weeks of treatment, reevaluate diagnosis.1 63 Severe infections may require prolonged treatment.50 60 61

Special Populations

No special population dosage recommendations at this time.a

Cautions for Naftin

Contraindications

  • Known hypersensitivity to naftifine or any ingredient in the formulation. 1 63

Warnings/Precautions

Warnings

Administration Precautions

For external use only.1 63 Use only for topical application to the skin; not for ophthalmic use.1 63

Avoid contact with eyes, nose, mouth, and other mucous membranes.1 63

Sensitivity Reactions

Contact dermatitis has been reported occasionally.20 39 49 54 56

If irritation or sensitivity occurs, discontinue drug and initiate appropriate therapy.1 63

General Precautions

Selection and Use of Antifungals

Prior to use, confirm diagnosis by direct microscopic examination of scrapings from infected tissue mounted in potassium hydroxide (KOH) or by culture.1 63

Specific Populations

Pregnancy

Category B.a

Lactation

Not known whether distributed into milk following topical application.1 63 Use with caution.1 63

Pediatric Use

Safety and efficacy not established.a

Common Adverse Effects

Burning, stinging.1 22 32 39 46 47 50 51 55 63

Interactions for Naftin

No formal drug interaction studies to date.

Naftin Pharmacokinetics

Absorption

Bioavailability

Following topical application, approximately 3–6% absorbed.1 43 63

Distribution

Extent

Not known whether naftifine crosses the placenta.60

Distributed into milk in rats; not known whether distributed into human milk.1 43 60 63

Elimination

Metabolism

Metabolized by oxidation and by N-dealkylation.18

Elimination Route

Systemically absorbed drug excreted in urine (40–60%) as unchanged drug and metabolites and in feces.1 18 43 63

Half-life

2–3 days.1 60 63

Stability

Storage

Topical

Cream

<30°C;1 cream is stable for 24 months after the date of manufacture.60

Gel

Room temperature.63

Actions and Spectrum

  • Allylamine antifungal.1 3 4 5 9 11 13 14 16 21 22 23 25 29 31 35 36 37 38 41 42 43 48 63

  • Usually fungicidal against susceptible dermatocytes.1 9 14 41 42 Usually fungistatic against Candida; may be fungicidal at high concentrations.1 3 9 14 41 42

  • Exact mechanism unknown; 1 3 11 16 41 43 appears to interfere with sterol biosynthesis by inhibiting the enzyme squalene monooxygenase (squalene 2,3-epoxidase).1 11 13 14 16 21 41 43 The resulting accumulation of squalene (the usual substrate of the enzyme) in the cells and decreased amounts of sterols, especially ergosterol,1 3 10 11 16 41 may contribute to the antifungal effects.41

  • Spectrum of antifungal activity includes many fungi, including dermatophytes and yeasts.1 2 3 4 5 8 9 12 22 23 31 37 42 Also may have in vitro activity against some gram-positive and -negative bacteria,58 60 61 and Leishmania.27

  • Candida: Active in vitro against Candida albicans,1 3 4 12 36 C. krusei,4 C. parapsilosis,4 12 31 41 and C. tropicalis;12 however, less active than imidazole derivatives against Candida.36 37 56

  • Dermatophytes and other fungi: Active in vitro against Aspergillus flavus,12 A. fumigatus,12 Blastomyces dermatitidis,12 Cryptococcus neoformans,12 Epidermophyton floccosum,1 4 8 12 38 42 Histoplasma capsulatum,12 Microsporum audouinii,1 M. canis,1 8 38 42 M. gypseum,1 8 Petriellidium boydii,12 Sporothrix schenckii,4 12 Trichophyton mentagrophytes,1 2 8 38 41 42 T. rubrum,1 8 38 42 T. tonsurans,1 38 T. verrucosum,42 and T. violaceum.8 38

  • Also has anti-inflammatory activity when applied topically.51 52

  • No reports to date of resistance in organisms originally susceptible to naftifine.60 61

Advice to Patients

  • Importance of completing full course of treatment, even if symptoms improve.1

  • Importance of contacting clinician if improvement does not occur within 4 weeks.1 63

  • Importance of notifying clinician if condition worsens or treated area shows signs of increased irritation.a

  • Importance of applying to affected areas as directed and avoiding contact with eyes, nose, mouth, or other mucous membranes.1 63

  • Advise patients to wash their hands after touching the affected areas.a

  • Importance of not using occlusive dressings, unless otherwise directed by clinician.1 63

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.a

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.a

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Naftifine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Topical

Cream

1%

Naftin (with benzyl alcohol)

Merz

Gel

1%

Naftin (with alcohol 52% v/v)

Merz

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Naftin 1% Cream (MERZ PHARMACEUTICAL): 30/$302.00 or 90/$839.98

Naftin 1% Cream (MERZ PHARMACEUTICAL): 60/$301.00 or 180/$885.95

Naftin 1% Cream (MERZ PHARMACEUTICAL): 90/$280.39 or 270/$789.82

Naftin 1% Gel (MERZ PHARMACEUTICAL): 40/$297.32 or 120/$830.95

Naftin 1% Gel (MERZ PHARMACEUTICAL): 60/$296.84 or 180/$810.79

Naftin 1% Gel (MERZ PHARMACEUTICAL): 90/$292.00 or 270/$835.97

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Allergan. Naftin (naftifine hydrochloride) 1% cream prescribing information (dated 1996). In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:501-2.

2. Meingassner JG, Sleytr U, Petranyi G. Morphological changes induced by naftifine, a new antifungal agent, in Trichophyton mentagrophytes. J Invest Dermatol. 1981; 77:444-51. [IDIS 141591] [PubMed 7310168]

3. Ryder NS, Seidl G, Troke PF. Effect of the antimycotic drug naftifine on growth of and sterol biosynthesis in Candida albicans. Antimicrob Agents Chemother. 1984; 25:483-7. [IDIS 184282] [PubMed 6375557]

4. Georgopoulos A, Petranyi G, Mieth H et al. In vitro activity of naftifine, a new antifungal agent. Antimicrob Agents Chemother. 1981; 19:386-9. [IDIS 134653] [PubMed 7247366]

5. Kerridge D. Mode of action of clinically important antifungal drugs. Adv Microbiol Physiol. 1986; 27:1-64.

6. Dittmar W, Jovic N. Laboratory techniques alternative to in vivo experiments for studying the liberation, penetration and fungicidal action of topical antimycotic agents in the skin, including ciclopiroxolamine. Mykosen. 1987; 30:326-42. [PubMed 3657856]

7. Gehse M, Kuster S, Gloor M. On the effective dimension of inhibition of ciclopiroxolamine and naftifine in the horny layer with regard to the galenic preparation. Mykosen. 1987; 30:322-5. [PubMed 3657855]

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51. Tronnier H. Inflammatory dermatomycoses: comparative study of naftifine and a combination of a corticosteroid and an imidazole derivative. Mykosen. 1987; 30(Suppl 1):78-87.

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56. Paetzold OH, Engst R, Kneist W et al. Yeast infections of the skin: comparative double-blind therapeutic trial with naftifine and clotrimazole. Mykosen. 1987; 30(Suppl 1):112-8.

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58. Nolting S. Investigation of the antibacterial effect of the antifungal agent naftifine: left versus right clinical comparative study between naftifine and gentamycin in pyoderma. Mykosen. 1987; 30(Suppl 1):124-8.

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61. Reviewers’ comments (personal observations); 1988 Dec.

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a. Merz Pharmaceuticals. Naftin (naftifine hydrochloride 1%) gel and cream prescribing information. Greensboro, NC; 2007 May.

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