Nitozol

Nitozol contains broad-spectrum synthetic antifungal agent ketoconazole in a concentration of 2% in an aqueous suspension. It also contains the following: Polyoxyethylene lauryl ether sodium sulfate, coconut oil fatty-acid diethanolamide, potassium coco-hydrolyzed collagen, hydrolyzed keratin, cocamidopropyl betaine, sodium hydroxide, hydrochloric acid, erythrosin, apple flavour, mentha herb oil, prophyllen glycol, glycerin and purified water.

Pharmacology: 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 1 hr before being washed away, there were no detctable plasma ketoconazole levels using an assay method having a lower detection limit 5 ng/mL.
Nitozol was not detected in plasma in 39 patients who shampooed 4-10 times/week to 6 months or in 33 patients who shampooed 2-3 times/week for 3-26 months (mean: 16 months). Twelve hours after a single shampoo, hair samples taken from 6 patients showed that high amounts of ketoconazole were present on the hair but only about 5% had penetrated into the hair keratin. Chronic shampooing (twice weekly for 2 months) increased the ketoconazole levels in the hair keratin 20% but did not increase levels on the hair. There were no detectable plasma levels.
An exaggerated use washing test on the sensitive antecubital skin of 10 subjects twice daily for 5 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 hypersensitvity type, no phototoxicity and no photoallergenic potential due to Nitozol.
Mode of Action: Interpretations of in vitro studies suggests 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 dandruff is due to the reduction of Pityrosporum ovale (Malassezia ovale), but this has not been proven. Support for this hypothesis comes from a 4-week, double-blind, placebo-controlled clinical trial, in which the decrease in P. ovale on the scalp was significantly greater with ketoconazole (36 patients) than with placebo (20 patients) and was comparable to that with selenium sulfide (42 patients). In the same study, ketoconazole and selenium sulfide reduced the severity of adherent dandruff significantly more than the placebo did.
Ketoconazole produced significantly higher proportions of patients with at least 50% reductions in adherent dandruff (50% versus 15%) and in loose dandruff (67% versus 15%) than did the placebo.
Microbiology: Nitozol 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; yeast: Candida albicans, C. tropicalis, Pityrosporum ovale (Malassezia ovale) and Pityrosporum orbiculare (M. furfur). Development of resistance by these microorganism to ketoconazole has not been reported.

For the reduction of scaling due to dandruff.

Moisten hair and scalp thoroughly with water. Apply sufficient shampoo to produce enough lather to wash the scalp and hair and gently massage it over the entire scalp area for approximately 1 min. Rinse the hair thoroughly with warm water. Repeat, leaving the shampoo on the scalp for an additional 3 min.
After the second thorough rinse, dry the hair with a towel or warm air flow. Shampoo twice a week for 4 weeks with at least 3 days between each shampooing and then intermittently as needed to maintain control.

Nitozol 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.

Hypersensitivity to the ketoconazole or to any of the excipients of Nitozol.

General: If a reaction suggesting sensitivity of chemical irritation should occur, use of Nitozol should be discontinued.
Information for Patients: May be irritating to mucous membranes of the eyes and contact with this area should be avoided. There have been reports that the use of the shampoo resulted in removal of the curl from permanently waved hair.
Carcinogenicity, Mutagenicity & Impairment of Fertility: The dominant lethal mutation test in male and female mice revealed that single oral doses of ketconazole 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 ketconazole in swiss albino mice in Wistarrats showed no evidence of oncogenic activity.
Use in pregnancy: Teratogenic Effects: Pregnancy Category C: Ketconazole is not detected in plasma after chronic shampooing. Ketconazole 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.
Use in lactation: Ketoconazole is not detected in plasma after chronic shampooing. Nevertheless, caution should be exercised when Nitozol is administered to a nursing woman.
Used in children: Safety and effectiveness in children have not been established.

Use in pregnancy: Teratogenic Effects: Pregnancy Category C: Ketconazole is not detected in plasma after chronic shampooing. Ketconazole 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.
Use in lactation: Ketoconazole is not detected in plasma after chronic shampooing. Nevertheless, caution should be exercised when Nitozol is administered to a nursing woman.

In 11 double-blind trials in 264 patients using ketoconazole 2% shampoo, an increase in normal hair loss and irritation occurred in <1% of patients. In 3 open-label safety trials in which 41 patients shampooed 4-10 times weekly for 6 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.

Store at a temperature not above 25°C. Protect from light.

Psoriasis, Seborrhea & Ichthyosis Preparations

D01AC08 - ketoconazole ; Belongs to the class of imidazole and triazole derivatives. Used in the topical treatment of fungal infection.

GSL