TOPICAL ANTIFUNGALS

A drug may be classified by the chemical type of the active ingredient or by the way it is used to treat a particular condition. Each drug can be classified into one or more drug classes. Topical antifungal agents are applied locally to the skin, on the nail, onto mucus membranes or vaginally, to treat fungal infections. They kill or inactivate fungi and yeast. Topical antifungal agents are available as creams, ointments, shampoos, powders and other forms, which can be applied locally on the area that needs to be treated

PURPOSE
Dermatologic fungal infections are usually described by their location on the the body as for example: tinea pedis (infection of the foot), tinea unguium (infection of the nails), tinia capitis (infection of the scalp.) Three types of fungus are involved in most skin infections: Trichophyton, Epidermophyton, Microsporum Mild infections are usually susceptible to topical therapy, however severe or resistant infections may require systemic treatment. There are a large number of drugs currently available in topical form for fungal infections. Other than the imidazoles, (miconazole, clotrimazole , econazole, ketoconazole , oxiconazole , sulconazole and the allylamine derivatives (butenafine , naftifine , terbinafine ), the drugs in this therapeutic class are chemically distinct from each other. All drugs when applied topically have a good margin of safety, and most show a high degree of effectiveness. There are no studies comparing drugs on which to base a recommendation for drugs of choice. Although some of the topical antifungals are available over-the-counter, they may be as effective as prescription drugs for this purpose.

SOME ANTI FUNGALS (TOPICAL)

Butenafine (Mentax) Clotrimazole (Lotrimin) Ketoconazole (Nizoril) Naftifine (Naftin) Oxiconazole (Oxistat) Tolnaftate (Tinacitin) Ciclopirox (Loprox) Econazole(Spectrazole) Miconazole (Micatin) Nystatin

Terbenafine (Lamisil)

TOPICAL ANTIFUNGAL THERAPY

NYSTATIN
It is a polyene macrolide much like amphotericin B,it is too toxic for parenteral administration and is used only topically

MECHANISM OF ACTION
Nystatin is an antibiotic which is both fungistatic and fungicidal in vitro against a wide variety of yeasts and yeast-like fungi, including Candida albicans. Nystatin acts by binding to sterols in the cell membrane of susceptible 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 has a broad antifungal spectrum. Nystatin topical preparations are indicated in in the treatment of cutaneous or mucocutaneous mycotic infections caused by Candida albicans and other susceptible Candida species it may find a resurgence of use in azole resistant candidiasis in HIV/AIDS.

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
Nystatin is currently available in creams,ointments,suppositories and other forms for application to skin and mucous membrane

As light yellow products Nystatin Cream USP, (100000 USP Nystatin Units/gram), and Nystatin Ointment USP, (100,000 USP Nystatin Units/gram) are supplied in both 15 g and 30 g tubes.

TOPICAL AZOLES
MECHANISM OF ACTION
The antifungal activity of azole drugs results from the reduction of ergosterol synthesis by inhibition of fungal cytochrome P450 enzyme.these drugs have greater affinity for fungal then for human cytochrome P450 enzyme There are two azoles most commonly used topically are; Clotrimazole Miconazole

CLOTRIMAZOLE
Clotrimazole is a broad-spectrum antifungal agent that is used for the treatment of dermal infections caused by various species of pathogenic dermatophytes, yeasts, and Malassezia furfur. The primary action of clotrimazole is against dividing and growing organisms. 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. 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.. 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. . 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

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, and 45 g)

MICONAZOLE (MICATIN )
MECHANISM OF ACTION
Inhibits biosynthesis of ergosterol, damaging the fungal cell wall membrane, which increases permeability causing leaking of nutrients

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)

TOPICAL ALLYLAMINES
Topical allylamines are terbinafine and naftifine

TERBINAFINE (LAMISIL )
Terbinafine hydrochloride is a synthetic allylamine derivative. Terbinafine hydrochloride is hypothesized to act by inhibiting squalene epoxidase, thus blocking the biosynthesis of ergosterol, an essential component of fungal cell membranes. In vitro, mammalian squalene epoxidase is only inhibited at higher (4000-fold) concentrations than is needed for inhibition of the dermatophyte enzyme. Depending on the concentration of the drug and the fungal species test in vitro, terbinafine hydrochloride may be fungicidal. However, the clinical significance of in vitro data is unknown.

The following in vitro data are available, but their clinical significance is unknown. In vitro, terbinafine exhibits satisfactory MICs 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:

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

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

NAFTIFINE (NAFTIN )
INDICATIONS
Topical treatment of tinea pedis, tinea cruris and tinea corporis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans* and Epidermophyton floccosum.* *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

PRECAUTIONS
Most topical antifungal agents are well tolerated. The most common adverse effects are localized irritation caused by the vehicle or its components. This may include redness, itch, and a burning sensation. Some direct allergic reactions are possible. Topical antifungal drugs should only be applied in accordance with labeled uses. They are not intended or ophthalmic (eye) or otic (ear) use. Application to mucous membranes should be limited to appropriate formulations. The antifungal drugs have not been evaluated for safety in pregnancy and lactation on topical application under the pregnancy risk category system. Although systemic absorption is probably low, review specific references. Gentian violet is labeled with a warning against use in pregnancy.

INTERACTIONS
Topical antifungal drugs have no recognized drug-drug or food-drug interaction