Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections.

[11][13] It is an imidazole and works by hindering the production of ergosterol required for the fungal cell membrane, thereby slowing growth.

[23][24] Ketoconazole is used orally in dosages of 200 to 400 mg per day in the treatment of superficial and deep fungal infections.

[25] Ketoconazole shampoo in conjunction with an oral 5α-reductase inhibitor such as finasteride or dutasteride has been used off label to treat androgenic alopecia.

[26] Limited clinical studies suggest ketoconazole shampoo used either alone[27][28] or in combination with other treatments[29] may be useful in reducing hair loss in some cases.

While ketoconazole blocks the synthesis of the sterol ergosterol in fungi, in humans, at high dosages (>800 mg/day), it potently inhibits the activity of several enzymes necessary for the conversion of cholesterol to steroid hormones such as testosterone and cortisol.

[34] However, in the treatment of prostate cancer, concomitant glucocorticoid administration is needed to prevent adrenal insufficiency.

[25] Ketoconazole has additionally been used, in lower dosages, to treat hirsutism and, in combination with a GnRH analogue, male-limited precocious puberty.

[25] Ketoconazole has been used to prevent the testosterone flare at the initiation of GnRH agonist therapy in men with prostate cancer.

These formulations include creams, shampoos, foams, and gels applied to the skin, unlike the ketoconazole tablets, which are taken by mouth.

[38] A subsequent trial in Europe failed to show a risk to infants of mothers receiving ketoconazole.

Lower doses of fluconazole and itraconazole are required to kill fungi compared to ketoconazole, as they have been found to have a greater affinity for fungal cell membranes.

Resistance to ketoconazole has been observed in a number of clinical fungal isolates, including Candida albicans.

Defects in the sterol 5-6 desaturase enzyme reduce the toxic effects of azole inhibition of the 14-alpha demethylation step.

First, and most notably, high oral doses of ketoconazole (e.g. 40 mg three times per day) block both testicular and adrenal androgen biosynthesis, leading to a reduction in circulating testosterone levels.

[25][42] It produces this effect through inhibition of 17α-hydroxylase and 17,20-lyase, which are involved in the synthesis and degradation of steroids, including the precursors of testosterone.

[25] Due to its efficacy at reducing systemic androgen levels, ketoconazole has been used with some success as a treatment for androgen-dependent prostate cancer.

[47][48][49] Numerous small studies have investigated the effects of oral ketoconazole on hormone levels in humans.

[61] Due to incidence of serious liver toxicity, the use of oral ketoconazole was suspended in France in July 2011, following review.

[58][65] In 2013, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) recommended that a ban be imposed on the use of oral ketoconazole for systemic use in humans throughout the European Union, after concluding that the risk of serious liver injury from systemic ketoconazole outweighs its benefits.

[68] Ketoconazole is sometimes prescribed as an antifungal by veterinarians for use in pets, often as unflavored tablets that may need to be cut to smaller size for correct dosage.