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| Introduction | Ketoconazole is the first orally active azole compound. It is a synthetic imidazole. It was first studied in the early 80's and licensed for use in 1985. It interfers with the synthesis of ergosterol like fluconazole and itraconazole. | |
| Dose & Delivery | Ketocanazole is only available as oral capsules or as a topical preparation such as Nizoral shampoo. | |
| Fungi - the drug is active against. | Ketoconazole is active against Candida infection, Blastomyces, Coccidioides, Histoplasma and Paracoccidioides. It is also active against skin fungi, but not to the degree of itraconazole or terbinafine. | |
| Typical regimens. | Ketoconazole is used for the treatment of oral thrush in a dose of 200mg per day, or 400mg per day in patients with AIDS and resistant strains. Doses of 400mg per day are used for blastomycosis, histoplasmosis, coccidioidomycosis and paracoccidioidomycosis (given as 200mg twice a day, but is inferior to itraconazole in these indications). The same dose is used for skin infections. As Ketoconazole is not as active as itraconazole, longer courses of therapy are typically given for endemic mycoses. | |
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| Metabolism distribution and excretion. | Ketoconazole is well absorbed after oral administration and there is no impact of food. Almost all the drug is metabolised in the liver and the metabolites excreted in bile. | |
| Drug/ Drug interactions |
Ketoconazole levels are slightly lower in those on
anti-ulcer drugs. Rifampicin (rifampin) reduces the
concentrations of Ketoconazole in the blood because of
accelerated metabolism. Ketoconazole must not be given with terfenadine, astemizole or cisapride as it causes increased levels of these drugs which can cause abnormal heart rhythms. Ketoconazole also can prolong the action of certain sedatives such midazolam and triazolam. It increases the blood level of cyclosporin and in fact has been used in some transplant centres to reduce the cost of cyclosporin. Ketoconazole also prolongs the effect of warfarin. |
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| Side effects |
Loss of appetite, feeling sick and vomiting are the most
common side effects and occur in about 1 in 10
patients. The side effects are particularly a problem
with high doses - above 400mg per day. Ketoconazole had
caused severe liver reactions, about 1 in 20 patients
get slight elevations of liver function tests on
Ketoconazole. If the treatment is given for longer than
two weeks there is a rare side effect of severe liver
disease, carrying a 1-10,000 - 1-15,000 risk. Ketoconazole also may have inhibited human adrenal and testicular steroid synthesis, particularly at high doses. This has consequences of loss of hair, breast swelling and lack of sexual function. There is a possibility that these effects may be more problematic in teenagers during puberty and Ketoconazole should be avoided in this age group if possible. |
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| Other information |