Nizoral Shampoo

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:

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.

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

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: Pregnancy Category C:

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.

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.

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.

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.

NDC 50458-680-08

NIZORAL®
(ketoconazole) 2%
Shampoo

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

janssen

Applies to ketoconazole topical: topical cream, topical foam, topical gel, topical kit, topical shampoo

Dermatologic

Cream:
-Common (1% to 10%): Skin burning sensation
-Uncommon (0.1% to 1%): Bullous eruption, contact dermatitis, rash, skin exfoliation, sticky skin
-Frequency not reported: Severe irritation, pruritus, stinging, urticaria

Foam:
-Frequency not reported: Reactions to a photoallergenicity study, contact sensitization

Gel:
-Frequency not reported: Impetigo, pyogenic granuloma, acne, nail discoloration

Shampoo:
-Uncommon (0.1% to 1%): Alopecia, dry skin, abnormal hair texture, rash, skin burning sensation, folliculitis
-Rare (0.01% to 0.1%): Acne, contact dermatitis, skin disorder, skin exfoliation
-Frequency not reported: Normal hair loss increased, irritation, scalp pustules, mild skin dryness, oiliness/dryness of hair and scalp, pruritus
-Postmarketing reports: Hair discoloration/hair color changes, itching, angioedema, urticaria, skin irritation[Ref]

Rare reports of contact dermatitis have been associated with the cream or 1 of its excipients (i.e., sodium sulfite or propylene glycol) during postmarketing experience.

Alopecia, dry skin, abnormal hair texture, rash, skin burning sensation, and contact dermatitis have also been reported during postmarketing experience with the shampoo.[Ref]

Local

Cream:
-Common (1% to 10%): Application site pruritus, application site erythema
-Uncommon (0.1% to 1%): Application site bleeding, application site discomfort, application site dryness, application site inflammation, application site irritation, application site paresthesia, application site reaction

Foam:
-Common (1% to 10%): Application site burning, application site reaction
-Frequency not reported: Application site reactions (dryness, erythema, irritation, paresthesia, pruritus, rash, warmth)

Gel:
-Common (1% to 10%): Application site burning
-Frequency not reported: Treatment-related application site reactions (dermatitis, discharge, dryness, erythema, irritation, pain, pruritus, pustules)
-Postmarketing reports: Burning sensation, pain, skin irritation, erythema

Shampoo:
-Uncommon (0.1% to 1%): Application site erythema, application site irritation, application site pruritus, application site reaction
-Rare (0.01% to 0.1%): Application site hypersensitivity, application site pustules

Application site reactions have also been reported during postmarketing experience with the shampoo.

Hypersensitivity

Cream:
-Uncommon (0.1% to 1%): Hypersensitivity
-Frequency not reported: Painful allergic reaction

Shampoo:
-Rare (0.01% to 0.1%): Hypersensitivity
-Postmarketing reports: Hypersensitivity reactions (including anaphylaxis)[Ref]

Nervous system

Gel:
-Frequency not reported: Headache, dizziness, paresthesia

Shampoo:
-Rare (0.01% to 0.1%): Dysgeusia

Ocular

Gel:
-Frequency not reported: Eye irritation, eye swelling, keratoconjunctivitis sicca

Shampoo:
-Uncommon (0.1% to 1%): Increased lacrimation
-Rare (0.01% to 0.1%): Eye irritation

Other

Gel:
-Frequency not reported: Facial swelling

Shampoo:
-Frequency not reported: Removal of curl from permanently waved hair

Some side effects of Nizoral Shampoo may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.