Ketoconazole

What is ketoconazole?

Ketoconazole is an imidazole medication used to treat fungal infections. Ketoconazole binds to fungus p450 enzymes and stops cells from producing ergosterol, the main component of the cell wall. In New Zealand, it is available as a shampoo and cream.

Ketoconazole is effective against a broad spectrum of fungi including:

• Dermatophytes (ringworm infections)

• Yeasts such as candida and malassezia.

Ketoconazole 2% Cream (Nizoral Cream®) daily and 2% Shampoo (Nizoral®, Sebizole®) twice weekly are used to seborrheic dermatitis, a common scaly eruption affecting the scalp and face. They are subsidized by prescription, but can also be obtained on the counter In a pharmacy. Current ketoconazole is safe.

oral ketoconazole

Oral ketoconazole was discontinued in New Zealand on December 1, 2013. As it may still be available elsewhere, product information is included below.

Ketoconazole reaches the skin surface through normal blood circulation, sweat and tallow (skin oils). Very high concentrations of the drug develop within the skin, making it effective in treating superficial fungal infections.

The oral dose of ketoconazole in adults is 200 to 400 mg daily, taken for two to eight weeks (a single dose may be effective for pityriasis versicolor). Nail infections are treated for up to twelve months.

The dose in children is usually 50 mg per day for those weighing less than 20 kg and 100 mg per day for those 20 to 40 kg.

Oral medication is better absorbed when taken with a fatty meal or acidic drink (for example, orange juice). It binds to proteins such as albumin in the circulating blood and is widely distributed in body tissues. It takes three to ten hours for half of the drug to be cleared from the bloodstream. The remainder is eliminated in the feces and urine unchanged or after conversion by the liver to inactive compounds.

Side effects of oral ketoconazole.

The main concern with ketoconazole is the risk of liver problems, usually after it has been taken for long periods (weeks). Side effects can include:

• Nausea and vomiting.
• Constipation.
• Headache.
• Dizziness.
• Abnormal liver function tests (15%); serious hepatitis it can occur in 1: 10,000 patients. It can rarely be fatal.
• Adrenal insufficiency: Ketoconazole reduces the production of cortisol in the body.
• Allergic skin rash including urticaria.
• Endocrine effects including enlarged breasts (in men), alopecia and impotence can exacerbate adrenal insufficiency (Addison's disease)

ketoconazole should no be taken in pregnancy. Although it is only excreted in small amounts in breast milk, it should only be taken by a nursing mother if it is essential.

Drug interactions of ketoconazole.

Ketoconazole is a p-glycoprotein inhibitor and can have serious interactions with other medications.

• Ketonazole should not be taken with the HMG Co-A reductase inhibitor simvastatin, and the dose of atorvastatin should be reduced. Toxicity causes muscle pain and weakness, which can be severe. If long-term treatment with a statin and ketoconazole is required, suitable alternatives are fluvastatin, pravastatin, and rosuvastatin.
• It is also contraindicated with the anticoagulant, dabigatran due to the risk of bleeding.

Since ketoconazole requires acid for absorption, antacids, H2 antagonists (cimetidine, famotidine, ranitidine), and omeprazole should not be taken within 2 hours of ketoconazole.

Ketoconazole interacts with alcohol such as disulfiram (Antabuse®) and can cause severe nausea and vomiting.

Ketoconazole can increase the concentration of these drugs and enhance their effect:

• Warfarin
• methyl prednisolone
• Cisapride
• The antihistamines astemizole (Hismanal®) and terfenadine (Teldane®)
• cyclosporine
• Midazolam, triazolam
• Busulfan
• Antidiabetic sulfonylurea drugs (tolbutamide, glibenclamide, gliclazide, glipizide

The following drugs markedly decrease the concentration of ketoconazole:

• Rifampicin
• Isoniazid
• Phenytoin
• Carbamazepine

Ketoconazole is no it is thought to interact with the oral contraceptive pill.