Label: KETOCONAZOLE cream
- NDC Code(s): 0168-0099-15, 0168-0099-30, 0168-0099-60
- Packager: E. Fougera & Co. a division of Fougera Pharmaceuticals Inc.
- Category: HUMAN PRESCRIPTION DRUG LABEL
- DEA Schedule: None
- Marketing Status: Abbreviated New Drug Application
Updated June 7, 2018
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- SPL UNCLASSIFIED SECTION
Ketoconazole Cream 2%, for topical administration only, contains the broad-spectrum synthetic antifungal agent, ketoconazole 2%, formulated in an aqueous cream vehicle consisting of propylene glycol, stearyl and cetyl alcohols, sorbitan monostearate, polysorbate 60, isopropyl myristate, sodium sulfite anhydrous, polysorbate 80 and purified water.
Ketoconazole is cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine and has the following structural formula:
When Ketoconazole Cream 2% was applied dermally to intact or abraded skin of Beagle dogs for 28 consecutive days at a dose of 80 mg, there were no detectable plasma levels using an assay method having a lower detection limit of 2 ng/ml.
After a single topical application to the chest, back and arms of normal volunteers, systemic absorption of ketoconazole was not detected at the 5 ng/ml level in blood over a 72-hour period.
Two dermal irritancy studies, a human sensitization test, a phototoxicity study and a photoallergy study conducted in 38 male and 62 female volunteers showed no contact sensitization of the delayed hypersensitivity type, no irritation, no phototoxicity and no photoallergenic potential due to Ketoconazole Cream 2%.
Microbiology: Ketoconazole is a broad spectrum synthetic antifungal agent which inhibits the in vitro growth of the following common dermatophytes and yeasts by altering the permeability of the cell membrane: dermatophytes: Trichophyton rubrum, T. mentagrophytes, T. tonsurans, Microsporum canis, M. audouini, M. gypseum and Epidermophyton floccosum; yeasts: Candida albicans, Malassezia ovale (Pityrosporum ovale) and C. tropicalis; and the organism responsible for tinea versicolor, Malassezia furfur (Pityrosporum orbiculare). Only those organisms listed in the INDICATIONS AND USAGE Section have been proven to be clinically affected. Development of resistance to ketoconazole has not been reported.
Mode of Action:In vitro studies suggest that ketoconazole impairs the synthesis of ergosterol, which is a vital component of fungal cell membranes. It is postulated that the therapeutic effect of ketoconazole in seborrheic dermatitis is due to the reduction of M. ovale, but this has not yet been proven.
INDICATIONS AND USAGE
Ketoconazole Cream 2% is indicated for the topical treatment of tinea corporis, 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.
Ketoconazole Cream 2% is not for ophthalmic use.
Ketoconazole Cream 2% contains sodium sulfite anhydrous, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
General: If a reaction suggesting sensitivity or chemical irritation should occur, use of the medication should be discontinued. Hepatitis (1:10,000 reported incidence) and, at high doses, lowered testosterone and ACTH induced corticosteroid serum levels have been seen with orally administered ketoconazole; these effects have not been seen with topical ketoconazole.
Carcinogenesis, Mutagenesis, Impairment of Fertility: A long-term feeding study in Swiss Albino mice and in Wistar rats showed no evidence of oncogenic activity. The dominant lethal mutation test in male and female mice revealed that single oral doses of ketoconazole as high as 80 mg/kg produced no mutation in any stage of germ cell development. The Ames'Salmonella microsomal activator assay was also negative.
Pregnancy: Teratogenic effects: Pregnancy Category C:
Ketoconazole has been shown to be teratogenic (syndactylia and oligodactylia) in the rat when given orally in the diet at 80 mg/kg/day, (10 times the maximum recommended human oral dose). However, these effects may be related to maternal toxicity, which was seen at this and higher dose levels.
There are no adequate and well-controlled studies in pregnant women. Ketoconazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers: It is not known whether Ketoconazole Cream 2% administered topically could result in sufficient systemic absorption to produce detectable quantities in breast milk. Nevertheless, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
During clinical trials 45 (5.0%) of 905 patients treated with Ketoconazole Cream 2% and 5 (2.4%) of 208 patients treated with placebo reported side effects consisting mainly of severe irritation, pruritus and stinging. One of the patients treated with Ketoconazole Cream developed a painful allergic reaction.
In worldwide postmarketing experience, rare reports of contact dermatitis have been associated with Ketoconazole Cream or one of its excipients, namely sodium sulfite or propylene glycol.
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. Seborrheic dermatitis: Ketoconazole Cream 2% should be applied to the affected area twice daily for four weeks or until clinical clearing.
If a patient shows no clinical improvement after the treatment period, the diagnosis should be redetermined.
- HOW SUPPLIED
- PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 15 G CONTAINER
- PACKAGE LABEL – PRINCIPAL DISPLAY PANEL – 15 G CARTON
INGREDIENTS AND APPEARANCE
Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0168-0099 Route of Administration TOPICAL Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ketoconazole (UNII: R9400W927I) (ketoconazole - UNII:R9400W927I) ketoconazole 20 mg in 1 g Inactive Ingredients Ingredient Name Strength propylene glycol (UNII: 6DC9Q167V3) stearyl alcohol (UNII: 2KR89I4H1Y) cetyl alcohol (UNII: 936JST6JCN) sorbitan monostearate (UNII: NVZ4I0H58X) polysorbate 60 (UNII: CAL22UVI4M) isopropyl myristate (UNII: 0RE8K4LNJS) sodium sulfite (UNII: VTK01UQK3G) polysorbate 80 (UNII: 6OZP39ZG8H) water (UNII: 059QF0KO0R) Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0168-0099-15 1 in 1 CARTON 04/28/2004 1 15 g in 1 TUBE; Type 0: Not a Combination Product 2 NDC:0168-0099-30 1 in 1 CARTON 04/28/2004 2 30 g in 1 TUBE; Type 0: Not a Combination Product 3 NDC:0168-0099-60 1 in 1 CARTON 04/28/2004 3 60 g in 1 TUBE; Type 0: Not a Combination Product Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA076294 04/28/2004 Labeler - E. Fougera & Co. a division of Fougera Pharmaceuticals Inc. (043838424)