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Candida infectionsand disseminated mycoses. Ketoconazole is usuallyeffective in the treatment of thrush, but fluconazoleis superior to ketoconazole for refractory thrush.Widespread dermatophyte infections on skin surfacescan be treated easily with oral ketoconazole when theuse of topical antifungal agents would be impractical.Treatment of vulvovaginal candidiasis with topical imidazolesis less expensive. Because of its effectiveness in blocking C17-20 lyaseactivities, ketoconazole does not enhance existing hirsutismassociated with metyrapone. On the other hand,the antiandrogenic effects of ketoconazole may provedisconcerting to male patients. Unwanted effects include nausea, vomiting, abdominalpain, headache, rashes, urticaria and pruritus. Transientabnormalities of liver enzymes, interference with testosteronesynthesis (leading to gynecomastia, alopecia andoligospermia) and rare fatal hepatic damage have beenreported. Nausea, vomiting, and anorexia occur commonly withketoconazole, especially when high doses are prescribed.Epigastric distress can be reduced by taking ketoconazolewith food. Pruritis and/or allergic dermatitisoccurs in 10% of patients. Liver enzyme elevations duringtherapy are not unusual and are usually reversible.Severe ketoconazole-associated hepatitis is rare. At high doses, ketoconazole causes a clinically significantreduction in testosterone synthesis and blocksthe adrenal response to corticotropin. Gynecomastia,impotence, reduced sperm counts, and diminished libidocan occur in men, and prolonged drug use can resultin irregular menses in women. These hormonal effectshave led to the use of ketoconazole as a potentialadjunctive treatment for prostatic carcinoma. Because of its comparative lack of toxicity when compared to amphotericinB, oral administration, and relatively good efficacy, ketoconazolehas been used to treat several fungal infections in dogs,cats, and other small species. Ketoconazole is often employed withamphotericin B to enhance the efficacy of ketoconazole, and byreducing the dose of amphotericin B, decreasing its risk of toxicity.See the Dosage section or Pharmacology section for specifics.Newer antifungal agents (fluconazole, itraconazole) have advantagesover ketoconazole, primarily less toxicity and/or enhancedefficacy however, ketoconazole can be significantly less expensivethan the newer agents. Ketoconazole is considered by some to stillbe the drug of choice for treating histoplasmosis in dogs. Use of ketoconazole in cats is controversial and some say it shouldnever be used that species.Ketoconazole is also used clinically for the medical treatment ofhyperadrenocorticism in dogs. Ketoconazoleappears to be a viableoption (although relatively expensive) to mitotane, particularly forpalliativetherapy in dogs with large, malignant, or invasive tumorswhere surgery is not an option. Ketoconazole is also used frequentlyin dogs for stabilization prior to surgery.

It is a reversible inhibitorof steroidogenesis, so it is usually not a viable option for long-termtreatment. Because it interferes with the metabolism of cyclosporine, it hasbeen used to reduce the dosage necessary for cyclosporine in dogs. Both rifampin and isoniazid lower plasma ketoconazolelevels, and concomitant administration should be avoided.Phenytoin serum levels should be monitored closelywhen ketoconazole is prescribed.Ketoconazole causes increasesin serum concentrations of warfarin, cyclosporine,and sulfonylureas. Because of its ability to increase serumcyclosporine levels, ketoconazole has been given to cyclosporine-dependent cardiac transplant recipients to reducethe dose of cyclosporine needed and as a cost-savingmeasure 2020.