Usage
Ketoconazole is usually prescribed for topical infections such as athlete’s foot, ringworm, candidiasis (yeast infection or thrush), and jock itch. The over-the-counter shampoo version can also be used as a body wash for the treatment of tinea versicolor.[3][4]
Ketoconazole is used to treat eumycetoma, the fungal form of mycetoma.
The side-effects of ketoconazole are sometimes used to treat non-fungal problems. The decrease in testosterone caused by the drug makes it useful for treating prostate cancer and for preventing post-operative erections[5] following penile surgery. Another use is the suppression of glucocorticoid synthesis, where it is used in the treatment of Cushing’s disease.[6] These side effects have also been studied for use in reducing depressive symptoms[7] and drug addiction;[8] however, it has not succeeded in either of these roles.[9][10]
Ketoconazole can be prescribed as a 200 mg pill, a 2% cream, a 2% gel,a 2% foam,or 2% shampoo for the treatment of dandruff or seborrhoeic dermatitis, or as a 1% over-the-counter shampoo (Perkhotal) & (Nizoral). However, 2% shampoo is sold over-the-counter in many countries as well.
Ketoconazole is also available as a topical mousse marketed under the brand name Ketomousse. In clinical studies, this preparation proved to be a superior mechanism of delivery to the shampoo.[citation needed] Currently it is only available in Europe.
Ketoconazole is also used in combination with other drugs such as zinc pyrithione in rinse-off products.
The anti-dandruff shampoo is designed for people who have a more serious case of dandruff where symptoms include, but are not limited to constant non-stop flaking, and severe itchiness.
It is a pregnancy category C drug because animal testing has shown it to cause teratogenesis in high dosages. Until recently, there were two human test cases on record (both during the treatment of Cushing’s syndrome)[11][12] and no adverse effects were reported, but this is not a broad enough data sample to draw any meaningful conclusions. A subsequent trial in Europe failed to show a risk to infants of mothers receiving ketoconazole.[13]
This medication is also sometimes prescribed by veterinarians for use on pets, often as 200 mg unflavored tablets that may need to be cut to smaller size for correct dosage.[14]
[edit]Mechanism of action
As an antifungal, ketoconazole is structurally similar to imidazole and interferes with the fungal synthesis of ergosterol, a constituent of fungal cell membranes, as well as certain enzymes. As with all azole antifungal agents, ketoconazole works principally by inhibiting the enzyme cytochrome P450 14-alpha-demethylase (P45014DM). This enzyme participates in the sterol biosynthesis pathway that leads from lanosterol to ergosterol. 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.
As an antiandrogen, ketoconazole operates through at least two mechanisms of action. First, and most notably, high oral doses of ketoconazole (e.g. 400 mg 3x/day) block both testicular and adrenal androgen biosynthesis, leading to a reduction in circulating testosterone levels.[15] Ketoconazole produces this effect through inhibition of cytochrome P450 and 17,20-lyase, which are involved in the synthesis and degradation of steroids, including the precursors of testosterone. Due to its efficacy at reducing systemic androgen levels, ketoconazole has been used as a treatment for androgen-dependent prostate cancer.[16] Second, ketoconazole is an androgen receptor antagonist, competing with androgens such as testosterone and DHT for androgen receptor binding. This effect is thought to be quite weak, even with high oral doses of ketoconazole.[17]
