Nizoral® (ketoconazole) 2% 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:

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.

When ketoconazole 2% shampoo was applied dermally to intact or abraded skin of rabbits for 28 days at doses up to 50 mg/kg and allowed to remain one hour before being washed away, there were no detectable plasma ketoconazole levels using an assay method having a lower detection limit of 5 ng/mL. 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.

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 shown hypersensitivity to the active ingredient or excipients of this formulation.

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. A long-term feeding study of ketoconazole in Swiss Albino mice and in Wistar rats showed no evidence of oncogenic activity.

Ketoconazole is not detected in plasma after chronic shampooing. 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.

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 divure, 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.

In worldwide experience with NIZORAL® Shampoo there have been rare reports of hair discoloration.

NIZORAL® (ketoconazole) 2% Shampoo is intended for external use only. In the event of accidental ingestion, supportive measures should be employed. Induced emesis and gastric lavage should usually be avoided.

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.

NIZORAL® (ketoconazole) 2% Shampoo is a red-orange liquid supplied in a 4-fluid ounce nonbreakable plastic bottle (NDC 50580-380-08).