NIZORAL- ketoconazole shampoo

Nizoral by

Drug Labeling and Warnings

Nizoral by is a Prescription medication manufactured, distributed, or labeled by Janssen Pharmaceuticals, Inc., Janssen Pharmaceutica NV, Noramco, Inc., Janssen Pharmaceutical Sciences Unlimited Company. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

DESCRIPTION

NIZORAL® (ketoconazole) 2% Shampoo is a red-orange liquid for topical application, containing the broad spectrum synthetic antifungal agent ketoconazole in a concentration of 2% in an aqueous suspension. It also contains: coconut fatty acid diethanolamide, disodium monolauryl ether sulfosuccinate, F.D.&C. Red No. 40, hydrochloric acid, imidurea, laurdimonium hydrolyzed animal collagen, macrogol 120 methyl glucose dioleate, perfume bouquet, sodium chloride, sodium hydroxide, sodium lauryl ether sulfate, 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:

CLINICAL PHARMACOLOGY

Tinea (pityriasis) versicolor is a non-contagious infection of the skin caused by Pityrosporum orbiculare (Malassezia furfur). This commensal organism is part of the normal skin flora. In susceptible individuals the condition is often recurrent and may give rise to hyperpigmented or hypopigmented patches on the trunk which 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 skin exposure. The rate of recurrence of infection is variable.

NIZORAL® (ketoconazole) was not detected in plasma in 39 patients who shampooed 4–10 times per week for 6 months, or in 33 patients who shampooed 2–3 times per week for 3–26 months (mean: 16 months).

An exaggerated use washing test on the sensitive antecubital skin of 10 subjects twice daily for five consecutive days showed that the irritancy potential of ketoconazole 2% shampoo was significantly less than that of 2.5% selenium sulfide shampoo.

A human sensitization test, a phototoxicity study, and a photoallergy study conducted in 38 male and 22 female volunteers showed no contact sensitization of the delayed hypersensitivity type, no phototoxicity and no photoallergenic potential due to NIZORAL® (ketoconazole) 2% Shampoo.

Mode of Action: Interpretations of in vivo studies suggest that ketoconazole impairs the synthesis of ergosterol, which is a vital component of fungal cell membranes. It is postulated, but not proven, that the therapeutic effect of ketoconazole in tinea (pityriasis) versicolor is due to the reduction of Pityrosporum orbiculare (Malassezia furfur) and that the therapeutic effect in dandruff is due to the reduction of Pityrosporum ovale. Support for the therapeutic effect in tinea versicolor comes from a three-arm, parallel, double-blind, placebo controlled study in patients who had moderately severe tinea (pityriasis) versicolor. Successful response rates in the primary efficacy population for each of both three-day and single-day regimens of ketoconazole 2% shampoo were statistically significantly greater (73% and 69%, respectively) than a placebo regimen (5%). There had been mycological confirmation of fungal disease in all cases at baseline. Mycological clearing rates were 84% and 78%, respectively, for the three-day and one-day regimens of the 2% shampoo and 11% in the placebo regimen. While the differences in the rates of successful response between either of the two active treatments and placebo were statistically significant, the difference between the two active regimens was not.

Microbiology: NIZORAL® (ketoconazole) is a broad spectrum synthetic antifungal agent which inhibits the 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, C. tropicalis, Pityrosporum ovale (Malassezia ovale) and Pityrosporum orbiculare (M. furfur). Development of resistance by these microorganisms to ketoconazole has not been reported.

INDICATIONS AND USAGE

NIZORAL® (ketoconazole) 2% Shampoo is indicated for the treatment of tinea (pityriasis) versicolor caused by or presumed to be caused by Pityrosporum orbiculare (also known as Malassezia furfur or M. orbiculare).

Note: Tinea (pityriasis) versicolor may give rise to hyperpigmented or hypopigmented patches on the trunk which may extend to the neck, arms and upper thighs. Treatment of the infection may not immediately result in normalization 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 versicolor is not contagious, it may recur because the organism that causes the disease is part of the normal skin flora.

CONTRAINDICATIONS

NIZORAL® (ketoconazole) 2% Shampoo is contraindicated in persons who have known hypersensitivity to the active ingredient or excipients of this formulation.

PRECAUTIONS

Severe hypersensitivity reactions, including anaphylaxis, have been reported during post-marketing use of NIZORAL® (ketoconazole) Shampoo. If a reaction suggesting sensitivity or chemical irritation should occur, use of the medication should be discontinued.

Information for Patients:

Patients should be advised of the following:

• NIZORAL® (ketoconazole) 2% Shampoo may be irritating to mucous membranes of the eyes and contact with this area should be avoided.
• The following have been reported with the use of NIZORAL® (ketoconazole) 2% Shampoo: hair discoloration and abnormal hair texture, removal of the curl from permanently waved hair, itching, skin burning sensation and contact dermatitis, hypersensitivity, angioedema, alopecia, rash, urticaria, skin irritation, dry skin, and application site reactions.
• Patients who develop allergic reactions, such as generalized rash, skin reactions, severe swelling, angioedema, or shortness of breath should discontinue NIZORAL® (ketoconazole) 2% Shampoo and contact their physician immediately.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Long-term studies to assess the carcinogenic potential of NIZORAL® (ketoconazole) 2% Shampoo have not been conducted. A long-term feeding study of ketoconazole 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 were not genotoxic. The Ames Salmonella microsomal activator assay was also negative.

Pregnancy: Teratogenic effects:

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. In humans, ketoconazole is not detected in plasma after chronic shampooing on the scalp.

Ketoconazole has been shown to be teratogenic (syndactylia and oligodactylia) in the rat when given orally in the diet at 80 mg/kg/day (a dose 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.

Nursing mothers: There are no adequate and well-controlled studies in nursing women. Ketoconazole is not detected in plasma after chronic shampooing on the scalp. Caution should be exercised when NIZORAL® (ketoconazole) 2% Shampoo is administered to a nursing woman.

Pediatric Use: Safety and effectiveness in children have not been established.

ADVERSE REACTIONS

Clinical Trials Experience

In 11 double-blind trials in 264 patients using ketoconazole 2% shampoo for the treatment of dandruff or seborrheic dermatitis, an increase in normal hair loss and irritation occurred in less than 1% of patients. In three open-label safety trials in which 41 patients shampooed 4–10 times weekly for six months, the following adverse experiences each occurred once: abnormal hair texture, scalp pustules, mild dryness of the skin, and itching. As with other shampoos, oiliness and dryness of hair and scalp have been reported. In a double-blind, placebo-controlled trial in which patients with tinea versicolor were treated with either a single application of NIZORAL® (ketoconazole) 2% Shampoo (n=106), a daily application for three consecutive days (n=107), or placebo (n=105), drug-related adverse events occurred in 5 (5%), 7 (7%) and 4 (4%) of patients, respectively. The only events that occurred in more than one patient in any one of the three treatment groups were pruritus, application site reaction, and dry skin; none of these events occurred in more than 3% of the patients in any one of the three groups.

Post-marketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency. The following adverse drug reactions have been identified during post-marketing experience with NIZORAL® (ketoconazole) Shampoo: there have been reports of hair discoloration and abnormal hair texture, itching, skin burning sensation, contact dermatitis, hypersensitivity, angioedema, alopecia, rash, urticaria, skin irritation, dry skin, and application site reactions.

OVERDOSAGE

NIZORAL® (ketoconazole) 2% Shampoo is intended for external use only. In the event of accidental ingestion, supportive and symptomatic measures should be employed. Induced emesis and gastric lavage should not be performed to avoid aspiration.

DOSAGE AND ADMINISTRATION

Apply the shampoo to the damp skin of the affected area and a wide margin surrounding this area. Lather, leave in place for 5 minutes, and then rinse off with water.

One application of the shampoo should be sufficient.

HOW SUPPLIED

NIZORAL® (ketoconazole) 2% Shampoo is a red-orange liquid supplied in a 4-fluid ounce (120 mL) nonbreakable plastic bottle (NDC: 50458-680-08).

Storage conditions: Store at a temperature not above 25°C (77°F). Protect from light.

Keep out of reach of children

SPL UNCLASSIFIED SECTION

Product of Belgium

Manufactured by:
Janssen Pharmaceutica NV
Beerse, Belgium

Manufactured for:
Janssen Pharmaceuticals, Inc.
Titusville, NJ 08560

©2004 Janssen Pharmaceutical Companies

Revised: December 2017

PRINCIPAL DISPLAY PANEL - 120 mL Bottle Carton

NDC 50458-680-08

NIZORAL®
(ketoconazole) 2%
Shampoo

For topical application only.
Rx only.
4 fl. oz. (120 mL)

janssen

INGREDIENTS AND APPEARANCE

NIZORAL 
ketoconazole shampoo

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 50458-680
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 mL

Inactive Ingredients
Ingredient Name	Strength
COCO DIETHANOLAMIDE (UNII: 92005F972D)
DISODIUM LAURETH SULFOSUCCINATE (UNII: D6DH1DTN7E)
FD&C RED NO. 40 (UNII: WZB9127XOA)
HYDROCHLORIC ACID (UNII: QTT17582CB)
IMIDUREA (UNII: M629807ATL)
PEG-120 METHYL GLUCOSE DIOLEATE (UNII: YM0K64F20V)
SODIUM CHLORIDE (UNII: 451W47IQ8X)
SODIUM HYDROXIDE (UNII: 55X04QC32I)
SODIUM LAURETH-3 SULFATE (UNII: BPV390UAP0)
WATER (UNII: 059QF0KO0R)

Product Characteristics
Color	RED (red-orange)	Score
Shape		Size
Flavor		Imprint Code
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 50458-680-08	1 in 1 CARTON	08/31/1990
1		120 mL in 1 BOTTLE; Type 0: Not a Combination Product

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA019927	08/31/1990

Labeler - Janssen Pharmaceuticals, Inc. (063137772)

Establishment
Name	Address	ID/FEI	Business Operations
Janssen Pharmaceutica NV		370005019	MANUFACTURE(50458-680) , ANALYSIS(50458-680)

Establishment
Name	Address	ID/FEI	Business Operations
Janssen Pharmaceutica NV		374747970	API MANUFACTURE(50458-680)

Establishment
Name	Address	ID/FEI	Business Operations
Noramco, Inc.		057234486	API MANUFACTURE(50458-680)

Establishment
Name	Address	ID/FEI	Business Operations
Janssen Pharmaceutical Sciences Unlimited Company		985639841	API MANUFACTURE(50458-680)