Ketoconazole is the name given to a medicinal substance that is used to treat fungal diseases on the skin. In addition, the substance is used in anti-dandruff shampoos.
What is ketoconazole?
Ketoconazole can slow the growth of filamentous fungi such as dermatophytes and yeast fungi such as Candida albicans. Ketoconazole is one of the drugs belonging to the group of imidazoles. The drug is used for the treatment and prevention of fungal diseases caused by dermatophytes (skin fungi) as well as yeast fungi. The development of ketoconazole took place in the late 1970s by the German drug company Janssen-Cilag. The drug finally came onto the market in the early 1980s. It attracted attention as an antifungal agent that could be used orally for the first time. Ketoconazole is an imidazole derivative that belongs to the group of azole fungicides. Ketoconazole can inhibit the growth of filamentous fungi such as dermatophytes and yeasts such as Candida albicans. However, resistance to ketoconazole now exists in some strains of Candida albicans.
Pharmacologic action
The action of ketoconazole is suitable for both external and internal use. The drug has the property of inhibiting the growth of fungi and counteracting their multiplication. Physicians refer to this as a fungistatic effect. However, the preparation is nowadays almost only used externally, as it has greater side effects than similar agents. In addition, alternatives are available in the form of itraconazole and fluconazole, which achieve a more intensive effect and are also better tolerated. Since 2015, ketoconazole has been allowed to be used as an exceptional drug for Cushing’s syndrome in adult patients as well as children over 12 years of age. In Cushing’s syndrome, the adrenal gland produces an excess of the body’s own cortisol. Ketoconazole can inhibit the activities of a specific group of enzymes within the adrenal glands that is important for cortisol production. In this way, the active ingredient can lower the level of cortisol in the organism. The mode of action of ketoconazole is based on the fact that the drug reduces ergosterol production by pathogens. Ergosterol is the most important component of the cell membrane of fungi. It does so by inhibiting enzymes that are dependent on cytochrome P450.
Medical application and use
For use, ketoconazole is used in the therapy of fungal diseases. Use of the drug is considered particularly useful in people affected by autoimmune diseases or diseases of the immune system, such as AIDS. Ketoconazole is also administered against seborrheic dermatitis in the form of solutions and creams. Seborrheic dermatitis is an inflammatory disease of the skin associated with severe scaling. In most cases, the scalp is affected by this fungal infection. Another fungal disease that can be treated externally with ketoconazole is Kleienpilzflechte. This is caused by the yeast Malassezia furfur. In early years, ketoconazole was also used in tablet form for fungal diseases of the skin, yeast infections of the mouth and throat, and yeast infections of the skin and mucous membranes. The drug was always taken internally when local therapy was unsuccessful. However, since ketoconazole can severely affect the liver, the drug may no longer be administered internally as a rule. The only exception is for the treatment of Cushing’s disease. However, the physician must regularly check the patient’s liver values. Anti-dandruff shampoos are another form of ketoconazole application. The dosage of the drug can be varied. If it is rinsed out thoroughly after use, the ketoconazole shampoo can be used like a conventional shampoo. It is not recommended to use the shampoo during pregnancy. Thus, in the course of animal experiments, malformations occurred several times at high doses. Ketoconazole is available only in pharmacies. The tablets are also subject to prescription in several countries.
Risks and side effects
There are some contraindications to the use of ketoconazole. These include, first and foremost, hypersensitivity to the drug.In addition, the drug should not be administered if the patient suffers from liver disease or if his liver enzyme levels are more than twice the normal value. When used topically, ketoconazole should not come into contact with the eyes. In pregnancy, even if used topically, it is essential to consult with a physician. The use of antifungal agents such as clotrimazole or nystatin is considered more appropriate. The use of ketoconazole should also be avoided during breastfeeding, as the active ingredient passes into breast milk and is thus transferred to the baby. The use of ketoconazole may be associated with various side effects. These include nausea, vomiting, abdominal pain and itching when used internally. Occasionally, dizziness, headache, digestive problems, diarrhea, hair loss, enlargement of the breast, skin rash, as well as the increase in liver enzymes also show. In case of topical application, ketoconazole rarely shows disturbing side effects. These may include itching, burning, reddening of the skin, greasiness or drying of the hair, hair loss, and allergic skin reactions. Interactions with other medications are also in the range of possibility when taking ketoconazole at the same time. Thus, the effectiveness of the drug is increased by indinavir, ritonavir, erythromycin and clarithromycin, while it is decreased by carbamazepine, isoniazid, phenobarbital, rifabutin, rifampicin as well as phenytoin. Because of the significant side effects on the liver, the EMA (European Medicines Agency) is seeking a ban on oral ketoconazole. In contrast, the U.S. Food and Drug Administration (FDA) limits itself to warning statements.
