Ketoconazole

As Ketoconazole is the name of a medicinal substance that is used against fungal diseases on the skin. The substance is also used in anti-dandruff shampoos.

What is ketoconazole?

Ketoconazole is one of the drugs that belong to the group of imidazoles. The agent is used to treat and prevent fungal diseases caused by dermatophytes (skin fungi) and yeasts.

Ketoconazole was developed in the late 1970s by the German drug company Janssen-Cilag. The preparation finally came onto the market at the beginning of the 1980s. It was noticed 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 slow down the growth of filamentous fungi such as dermatophytes and yeasts such as Candida albicans. However, some strains of Candida albicans are now resistant to ketoconazole.

Pharmacological effect

The effect of ketoconazole is suitable for both external and internal use. The medicinal substance has the property of inhibiting the growth of fungi and counteracting their reproduction. Doctors speak of a fungistatic effect. However, nowadays the preparation is almost only used externally, as it has greater side effects compared to similar agents. In addition, itraconazole and fluconazole alternatives are available that achieve a more intensive effect and are also better tolerated.

Since 2015, ketoconazole has been allowed to be used as an exceptional drug against Cushing's syndrome in adult patients and children over 12 years of age. In Cushing's syndrome, the adrenal gland produces an excess of its own cortisol. Ketoconazole can inhibit the activities of a certain group of enzymes within the adrenal glands that are important for the production of cortisol. In this way, the active ingredient can lower the cortisol level in the organism.

The mode of action of ketoconazole is based on the fact that the drug reduces the ergosterol production of the pathogens. Ergosterol is the most important component of the cell membrane in fungi.This inhibits enzymes that are dependent on the cytochrome P450.

Medical application & use

Ketoconazole is used in the treatment of fungal diseases. The use of the drug is particularly useful in people who are affected by autoimmune diseases or diseases of the immune system such as AIDS.

Ketoconazole is also given in the form of solutions and creams against seborrheic dermatitis. Seborrheic dermatitis is an inflammatory disease of the skin that is accompanied by severe flaking. In most cases, the scalp is affected by this fungal infection. Another fungal disease that can be treated externally with ketoconazole is bran fungus. This is caused by the yeast Malassezia furfur.

In early years, ketoconazole was also used in tablet form for fungal diseases on the skin, yeast infestation in the mouth and throat and yeast infections on the skin and mucous membranes. The remedy was always taken internally when local therapy was unsuccessful. However, since ketoconazole can severely affect the liver, the drug must usually no longer be administered internally. The only exception is for the treatment of Cushing's disease. However, the doctor must regularly check the patient's liver values.

Another application form of ketoconazole are anti-dandruff shampoos. The agent can be dosed in different amounts. If the ketoconazole shampoo is rinsed thoroughly after its use, it can be used like a conventional shampoo. The use of the shampoo during pregnancy is not recommended. In animal experiments at high doses, malformations occurred several times. Ketoconazole is compulsory in a pharmacy. The tablets are also subject to prescription in several countries.

Risks & side effects

There are some contraindications against the use of ketoconazole. This primarily includes an over-sensitivity to the drug. In addition, the drug must not be given if the patient has a liver disease or if his liver enzyme levels are more than double the normal value.

When used externally, ketoconazole should not come into contact with the eyes. During pregnancy, even with local use, it is essential to consult a doctor. The use of anti-fungal agents such as clotrimazole or nystatin is considered more sensible. You should also avoid the use of ketoconazole during breastfeeding, as the active ingredient passes into breast milk and is thus transferred to the baby.

The use of ketoconazole can be associated with various side effects. When used internally, these include nausea, vomiting, abdominal pain and itching. Occasionally, dizziness, headaches, digestive problems, diarrhea, hair loss, breast enlargement, skin rashes and an increase in liver values ​​are also evident.

In the case of external use, ketoconazole rarely has bothersome side effects. This can include itching, burning, reddening of the skin, greasiness or drying out of the hair, hair loss and allergic skin reactions.

Interactions with other drugs are also possible when taking ketoconazole at the same time. The effectiveness of the agent is increased by indinavir, ritonavir, erythromycin and clarithromycin, while it is decreased by carbamazepine, isoniazid, phenobarbital, rifabutin, rifampicin and phenytoin.

Due to the significant side effects on the liver, the EMA (European Medicines Agency) is aiming for a ban on oral ketoconazole. In contrast, the American FDA (Food and Drug Administration) restricts itself to warning notices.