Topical (Anti-fungals)

Butenafine HCl has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

Epidermophyton floccosum
Malassezia furfur
Trichophyton mentagrophytes
Trichophyton rubrum
Trichophyton tonsurans

INDICATIONS AND USAGE
Mentax® (butenafine HCl) Cream, 1% is indicated for the topical treatment of the dermatologic infection, tinea (pityriasis) versicolor due to M. furfur (formerly P. orbiculare).

Butenafine HCl cream was not studied in immunocompromised patients.

DOSAGE AND ADMINISTRATION
Patients with tinea (pityriasis) versicolor should apply Mentax® once daily for two weeks. In the treatment of interdigital tinea pedis , Mentax® should be applied twice daily for 7 days OR once daily for 4 weeks (NOTE: in separate clinical trials, the 7 day dosing regimen was less efficacious than the 4 week regimen. While the clinical significance of this difference is unknown, these data should be carefully considered before selecting the dosage regimen for patients at risk for the development of bacterial cellulitis of the lower extremity associated with interdigital cracking/fissuring).

Patients with tinea corporis or tinea cruris should apply Mentax® once daily for two weeks.

Sufficient Mentax® Cream should be applied to cover affected areas and immediately surrounding skin of patients with tinea versicolor, interdigital tinea pedis, tinea corporis, and tinea cruris. If a patient shows no clinical improvement after the treatment period, the diagnosis should be reviewed.

HOW SUPPLIED
Mentax® (butenafine HCl cream) Cream, 1%, is supplied in tubes in the following sizes:

15-gram tube (NDC 62794-151-02)
30-gram tube (NDC 62794-151-03)

Pharmacokinetic studies in men with tagged ciclopirox solution in polyethylene glycol 400 showed an average of 1.3% absorption of the dose when it was applied topically to 750 cm2 on the back followed by occlusion for 6 hours. The biological half-life was 1.7 hours and excretion occurred via the kidney. Two days after application only 0.01% of the dose applied could be found in the urine. Fecal excretion was negligible.

Penetration studies in human cadaverous skin from the back, with ciclopirox cream 0.77% with tagged ciclopirox showed the presence of 0.8 to 1.6% of the dose in the stratum corneum 1.5 to 6 hours after application. The levels in the dermis were still 10 to 15 times above the minimum inhibitory concentrations.

Autoradiographic studies with human cadaverous skin showed that ciclopirox penetrates into the hair and through the epidermis and hair follicles into the sebaceous glands and dermis, while a portion of the drug remains in the stratum corneum

INDICATIONS AND USAGE
Ciclopirox Cream is indicated for the topical treatment of the following dermal infections: tinea pedis, tinea cruris, and tinea corporis due to Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum canis; candidiasis (moniliasis) due to Candida albicans; and tinea (pityriasis) versicolor due to Malassezia furfur.

CONTRAINDICATIONS
Ciclopirox Cream is contraindicated in individuals who have shown hypersensitivity to any of its components.

WARNINGS
Ciclopirox Cream is not for ophthalmic use. Keep out of reach of children

Ciclopirox Shampoo, 1% is indicated for the topical treatment of seborrheic dermatitis of the scalp in adults.

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Superficial Dermotophyte Infections - Ciclopirox gel 0.77% is indicated for the topical treatment of interdigital tinea pedis and tinea corporis due to Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum. Seborrheic Dermatitis - Ciclopirox gel 0.77% is indicated for the topical treatment of seborrheic dermatitis of the scalp.
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Ciclopirox topical solution, 8% (nail lacquer), as a component of a comprehensive management program, is indicated as topical treatment in immunocompetent patients with mild to moderate onychomycosis of fingernails and toenails without lunula involvement, due to Trichophytonrubrum. The comprehensive management program includes removal of the unattached, infected nails as frequently as monthly, by a health care professional who has special competence in the diagnosis and treatment of nail disorders, including minor nail procedures.

No studies have been conducted to determine whether ciclopirox might reduce the effectiveness of systemic antifungal agents for onychomycosis. Therefore, the concomitant use of 8% ciclopirox topical solution and systemic antifungal agents for onychomycosis, is not recommended.
Ciclopirox topical solution, 8% (nail lacquer), should be used only under medical supervision as described above.
The effectiveness and safety of ciclopirox topical solution, 8% (nail lacquer), in the following populations has not been studied. The clinical trials with use of ciclopirox topical solution, 8% (nail lacquer), excluded patients who: were pregnant or nursing, planned to become pregnant, had a history of immunosuppression (e.g., extensive, persistent, or unusual distribution of dermatomycoses, extensive seborrheic dermatitis, recent or recurring herpes zoster, or persistent herpes simplex), were HIV seropositive, received organ transplant, required medication to control epilepsy, were insulin dependent diabetics or had diabetic neuropathy. Patients with severe plantar (moccasin) tinea pedis were also excluded.
The safety and efficacy of using ciclopirox topical solution, 8% (nail lacquer), daily for greater than 48 weeks have not been established.

DOSING AND ADMINISTRATION:
Topical:
Children >10 years and Adults: Tinea pedis, tinea cruris, tinea corporis, cutaneous candidiasis, and tinea versicolor: Cream/suspension: Apply twice daily, gently massage into affected areas; if no improvement after 4 weeks of treatment, re-evaluate the diagnosis

Children >16 years and Adults:

Tinea pedis, tinea corporis, seborrheic dermatitis of the scalp: Gel: Apply twice daily, gently massage into affected areas and surrounding skin; if no improvement after 4 weeks of treatment, re-evaluate diagnosis

Seborrheic dermatitis of the scalp: Shampoo: Apply to wet hair, lather, and leave in place ~3 minute; rinse. Repeat twice weekly for 4 weeks; allow a minimum of 3 days between applications.

Onychomycosis of the fingernails and toenails: Children >/= 12 years and Adults: Lacquer (solution): Apply to adjacent skin and affected nails daily (as a part of a comprehensive management program for onychomycosis). Remove with alcohol every 7 days

SUPPLIED:
Cream, as olamine (Loprox®): 0.77% (15 g, 30 g, 90 g)
Gel (Loprox®): 0.77% (30 g, 45 g, 100 g)
Shampoo (Loprox®): 1% (120 mL)
Solution, topical [nail lacquer] (Penlac®): 8% (6.6 mL)
Suspension, topical, as olamine (Loprox®): 0.77% (30 mL, 60 mL)

In vitro, clotrimazole exhibits fungistatic and fungicidal activity against isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum canis and Candida species including Candida albicans. In general, the in vitro activity of clotrimazole corresponds to that of tolnaftate and griseofulvin against the mycelia of dermatophytes (Trichophyton, Microsporum, and Epidermophyton), and to that of the polyenes (amphotericin B and nystatin) against budding fungi (Candida). Using an in vivo (mouse) and an in vitro (mouse kidney homogenate) testing system, clotrimazole and miconazole were equally effective in preventing the growth of the pseudomycelia and mycelia of Candida albicans.

Strains of fungi having a natural resistance to clotrimazole are rare. Only a single isolate of Candida guilliermondi has been reported to have primary resistance to clotrimazole.

No single-step or multiple-step resistance to clotrimazole has developed during successive passages of Candida albicans and Trichophyton mentagrophytes. No appreciable change in sensitivity was detected after successive passage of isolates of C. albicans, C. krusei, or C. pseudotropicalis in liquid or solid media containing clotrimazole. Also, resistance could not be developed in chemically induced mutant strains of polyene-resistant isolates of C. albicans. Slight, reversible resistance was noted in three isolates of C. albicans tested by one investigator. There is a single report that records the clinical emergence of C. albicans strain with considerable resistance to flucytosine and miconazole, and with cross-resistance to clotrimazole, the strain remained sensitive to nystatin and amphotericin B.

In studies of the mechanism of action, the minimum fungicidal concentration of clotrimazole caused leakage of intracellular phosphorus compounds into the ambient medium with concomitant breakdown of cellular nucleic acids and accelerated potassium efflux. Both these events began rapidly and extensively after addition of the drug.

Clotrimazole appears to be well absorbed in humans following oral administration and is eliminated mainly as inactive metabolites. Following topical and vaginal administration, however, clotrimazole appears to be minimally absorbed.

INDICATIONS AND USAGE
Clotrimazole Cream is indicated for the topical treatment of candidiasis due to Candida albicans and tinea versicolor due to Malassezia furfur.

Clotrimazole is also available as a nonprescription item which is indicated for the topical treatment of the following dermal infections: tinea pedis, tinea cruris, and tinea corporis due to Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, and Microsporum canis.

CONTRAINDICATIONS
Clotrimazole Cream is contraindicated in individuals sensitive to its components.

DOSING:
Apply twice daily; if no improvement occurs after 4 weeks of therapy, re-evaluate diagnosis

SUPPLIED:
Cream, topical: 1% (15 g, 30 g, 45 g)

CONTRAINDICATIONS
Econazole Nitrate Cream, 1% is contraindicated in individuals who have shown hypersensitivity to any of its ingredients.

WARNINGS
Econazole Nitrate Cream, 1% is not for ophthalmic use

DOSAGE AND ADMINISTRATION
Sufficient SPECTAZOLE Cream should be applied to cover affected areas once daily in patients with tinea pedis, tinea cruris, tinea corporis, and tinea versicolor, and twice daily (morning and evening) in patients with cutaneous candidiasis.

Early relief of symptoms is experienced by the majority of patients and clinical improvement may be seen fairly soon after treatment is begun; however, candidal infections and tinea cruris and corporis should be treated for two weeks and tinea pedis for one month in order to reduce the possibility of recurrence. If a patient shows no clinical improvement after the treatment period, the diagnosis should be redetermined. Patients with tinea versicolor usually exhibit clinical and mycological clearing after two weeks of treatment.

HOW SUPPLIED
SPECTAZOLE (econazole nitrate 1%) Cream is supplied in tubes of

15 grams (NDC 0062-5460-02),
30 grams (NDC 0062-5460-01), and
85 grams (NDC 0062-5460-03).

 ------------CREAM-------------------

INDICATIONS
Ketoconazole cream, 2% is indicated for the topical treatment of tinea cor-poris, tinea cruris and tinea pedis caused by Trichophyton rubrum, T. mentagrophytes and Epidermophyton floccosum; in the treatment of tinea (pityriasis) versicolor caused by Malassezia furfur (Pityrosporum orbiculare); in the treatment of cutaneous candidiasis caused by Candida spp. and in the treatment of seborrheic dermatitis.

DOSAGE AND ADMINISTRATION
Cutaneous candidiasis, tinea corporis, tinea cruris, tinea pedis, and tinea (pityriasis) versicolor: It is recommended that ketoconazole cream, 2% be applied once daily to cover the affected and immediate surrounding area. Clinical improvement may be seen fairly soon after treatment is begun; however, candidal infections and tinea cruris and corporis should be treated for two weeks in order to reduce the possibility of recurrence.

Patients with tinea versicolor usually require two weeks of treatment. Patients with tinea pedis require six weeks of treatment.

If a patient shows no clinical improvement after the treatment period, the diagnosis should be redetermined.

Seborrheic dermatitis: Ketoconazole cream, 2% should be applied to the affected area twice daily for four weeks or until clinical clearing.

HOW SUPPLIED
Ketoconazole cream, 2% is supplied in 15, 30, and 60 gram tubes.

 ------------FOAM-------------------

INDICATIONS
Extina Foam is indicated for the topical treatment of seborrheic dermatitis in immunocompetent patients 12 years of age and older. Safety and efficacy of Extina Foam for treatment of fungal infections have not been established.

DOSAGE AND ADMINISTRATION
Extina Foam should be applied to the affected area(s) twice daily for four weeks. Hold the container upright, and dispense Extina Foam into the cap of the can or other cool surface in an amount sufficient to cover the affected area(s). Dispensing directly onto hands is not recommended, as the foam will begin to melt immediately upon contact with warm skin. Pick up small amounts of Extina Foam with the fingertips, and gently massage into the affected area(s) until the foam disappears. For hair-bearing areas, part the hair, so that Extina Foam may be applied directly to the skin (rather than on the hair). Avoid contact with the eyes and other mucous membranes. Extina foam is not for ophthalmic, oral or intravaginal use.

HOW SUPPLIED
Extina Foam contains 2% ketoconazole in a thermolabile hydroethanolic foam, and is provided in 50 g and 100 g aluminum containers.

 ------------SHAMPOO-------------------

INDICATIONS
Ketoconazole 2% shampoo is indicated for the reduction of scaling due to dandruff.

DOSAGE AND ADMINISTRATION
Moisten hair and scalp thoroughly with water.

Apply sufficient shampoo to produce enough lather to wash the scalp and hair gently massage it over the entire scalp area for approximately one minute.

Rinse the hair thoroughly with warm water.

Repeat, leaving the shampoo on the scalp for an additional 3 minutes.

After the second thorough rinse, dry the hair with a towel or warm air flow.

Shampoo twice a week for four weeks with at least three days between each shampooing and then intermittently as needed to maintain control.

HOW SUPPLIED
Nizoral 2% shampoo is a red-orange liquid supplied in a 4-fluid ounce nonbreakable plastic bottle.
Storage: Store at a temperature not above 25°C (77°F). Protect from light.

DOSAGE AND ADMINISTRATION:
 For topical use only. Not for ophthalmic, oral, or intravaginal use.

Interdigital Tinea Pedis: LUZU Cream, 1% should be applied to the affected and immediate surrounding area(s) once a day for two weeks.

Tinea Cruris and Tinea Corporis: LUZU Cream, 1% should be applied to the affected skin and immediate surrounding area(s) once a day for one week.

Local monograph

DOSING:
Topical: Children and Adults: Note: Not for OTC use in children <2 years:
Tinea pedis and tinea corporis: Apply twice daily for 4 weeks.
Tinea cruris: Apply twice daily for 2 weeks.

HOW SUPPLIED
Cream, topical, as nitrate: 2% (15 g, 30 g, 45 g)
Powder, topical, as nitrate: Lotrimin® AF, Micatin®, Micro-Guard®: 2% (90 g)
Ointment, topical, as nitrate: (Aloe Vesta® 2-n-1 Antifungal): 2% (60 g, 150 g)

*Efficacy for this organism in this organ system was studied in fewer than 10 infections.

DOSAGE AND ADMINISTRATION
GEL:
A sufficient quantity of Naftin® Gel, 1% should be gently massaged into the affected and surrounding skin areas twice a day in the morning and evening. The hands should be washed after application. If no clinical improvement is seen after four weeks of treatment with Naftin® Gel, 1%, the patient should be re-evaluated.

CREAM:
A sufficient quantity of Naftin® Cream, 1% should be gently massaged into the affected and surrounding skin areas once a day. The hands should be washed after application.

If no clinical improvement is seen after four weeks of treatment with Naftin® Cream, 1%, the patient should be re-evaluated .

HOW SUPPLIED
Naftin® (naftifine hydrochloride) 1% Gel is supplied in collapsible tubes in the following sizes:
20g - NDC 0259-4770-20
40g - NDC 0259-4770-40
60g - NDC 0259-4770-60

Naftin® (naftifine hydrochloride) 1% Cream is supplied in collapsible tubes in the following sizes :
15g_ NDC 0259-4126-15
30g_ NDC 0259-4126-30
60g_ NDC 0259-4126-60
60g (4x15g) - NDC 0259-4126-04

Nystatin acts by binding to sterols in the cell membrane of susceptible species resulting in a change in membrane permeability and the subsequent leakage of intracellular components. On repeated subculturing with increasing levels of nystatin, Candida albicans does not develop resistance to nystatin. Generally, resistance to nystatin does not develop during therapy. However, other species of Candida (C. tropicalis, C. guilliermondi, C. krusei, and C. stellatoides) become quite resistant on treatment with nystatin and simultaneously become cross resistant to amphotericin as well. This resistance is lost when the antibiotic is removed.

Nystatin exhibits no appreciable activity against bacteria, protozoa, or viruses.

INDICATIONS AND USAGE
Nystatin topical preparations are indicated in the treatment of cutaneous or mucocutaneous mycotic infections caused by Candida albicans and other susceptible Candida species

DOSAGE AND ADMINISTRATION
Nystatin preparations should be applied liberally to affected areas twice a day or as indicated until healing is complete, Nystatin cream is usually preferred to nystatin ointment in candidiasis involving intertriginous area; very moist lesions, however, are best treated with nystatin topical powder.

The preparations do not stain skin or mucous membranes and they provide simple, convenient means of treatment.

HOW SUPPLIED
As light yellow products Nystatin Cream USP, (100,000 USP Nystatin Units/gram), and Nystatin Ointment USP, (100,000 USP Nystatin Units/gram) are supplied in both 15 g and 30 g tubes.

OXISTAT Cream may be used in pediatric patients for tinea corporis, tinea cruris, tinea pedis, and tinea (pityriasis) versicolor; however, these indications for which OXISTAT Cream has been shown to be effective rarely occur in children below the age of 12.

DOSAGE AND ADMINISTRATION
OXISTAT Cream or Lotion should be applied to affected and immediately surrounding areas once to twice daily in patients with tinea pedis, tinea corporis, or tinea cruris. OXISTAT Cream should be applied once daily in the treatment of tinea (pityriasis) versicolor. Tinea corporis, tinea cruris, and tinea (pityriasis) versicolor should be treated for 2 weeks and tinea pedis for 1 month to reduce the possibility of recurrence. If a patient shows no clinical improvement after the treatment period, the diagnosis should be reviewed.

Note: Tinea (pityriasis) versicolor may give rise to hyperpigmented or hypopigmented patches on the trunk that may extend to the neck, arms, and upper thighs. Treatment of the infection may not immediately result in restoration of pigment to the affected sites. Normalization of pigment following successful therapy is variable and may take months, depending on individual skin type and incidental sun exposure. Although tinea (pityriasis) versicolor is not contagious, it may recur because the organism that causes the disease is part of the normal skin flora.

HOW SUPPLIED
OXISTAT Cream, 1% is supplied in 15-g tubes (NDC 0173-0423-00), 30-g tubes (NDC 0173-0423-01), and 60-g tubes (NDC 0173-0423-04). Store between 15° and 30°C (59° and 86°F).

OXISTAT Lotion, 1% is supplied in a 30-mL bottle (NDC 0173-0448-01). Store between 15° and 30°C (59° and 86°F). Shake well before using.

Terbinafine has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections.

Trichophyton mentagrophytes
Trichophyton rubrum

The following in vitro data are available, but their clinical significance is unknown. In vitro, terbinafine exhibits satisfactory MIC’s against most strains of the following microorganisms; however, the safety and efficacy of terbinafine in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials:

Candida albicans
Epidermophyton floccosum
Scopulariopsis brevicaulis

INDICATIONS AND USAGE  [Tablets]
LAMISIL® (terbinafine hydrochloride) Tablets are indicated for the treatment of onychomycosis of the toenail or fingernail due to dermatophytes (tinea unguium).

Prior to initiating treatment, appropriate nail specimens for laboratory testing (KOH preparation, fungal culture, or nail biopsy) should be obtained to confirm the diagnosis of onychomycosis.

DOSAGE AND ADMINISTRATION:
Children >/= 12 years and Adults:
Topical cream, solution:
Athlete's foot (tinea pedis): Apply to affected area twice daily for at least 1 week, not to exceed 4 weeks [OTC/prescription formulations]

Ringworm (tinea corporis) and jock itch (tinea cruris): Apply cream to affected area once or twice daily for at least 1 week, not to exceed 4 weeks; apply solution once daily for 7 days.

Topical solution:
Tinea versicolor: Apply to affected area twice daily for 1 week

===================
Tablets:
DOSAGE AND ADMINISTRATION
Terbinafine hydrochloride tablets, one 250 mg tablet, should be taken once daily for 6 weeks by patients with fingernail onychomycosis. Terbinafine hydrochloride, one 250 mg tablet, should be taken once daily for 12 weeks by patients with toenail onychomycosis. The optimal clinical effect is seen some months after mycological cure and cessation of treatment. This is related to the period required for outgrowth of healthy nail.

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HOW SUPPLIED
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Cream (Lamisil® AT™): 1% (15 g, 30 g)
Solution [topical spray] (Lamisil®, Lamisil® AT™): 1% (30 mL)

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Terbinafine Hydrochloride Tablets
Supplied as white to off white round tablets debossed ‘AN’ above ‘543’ on one side and plain on other side.
Bottles of 30 tablets............ NDC 67405-543-03
Bottles of 100 tablets.......... NDC 67405-543-10

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (between 59°F and 86°F), in a tight container. Protect from light.

DOSING:
Children 2 years and Adults: Topical: Wash and dry affected area; spray aerosol or apply 1-3 drops of solution or a small amount of cream, gel, or powder and rub into the affected areas 2 times/day
Note: May use for up to 4 weeks for tinea pedis or tinea corporis, and up to 2 weeks for tinea cruris

[Avoid contact with the eyes; apply to clean dry area; consult the physician if a skin irritation develops or if the skin infection worsens or does not improve after 10 days of therapy; does not stain skin or clothing]

SUPPLIED:
Aerosol, liquid, topical:
Tinactin® Antifungal: 1% (120 mL)

Aerosol, powder, topical:
Tinactin® Antifungal: 1% (45 g, 90 g, 100 g, 150 g)

Cream, topical: 1% (15 g, 30 g)
Powder, topical: 1% (45 g)