Introduction Oral ketoconazole Side effects Drug interactions Antifungal drug resistance
Ketoconazole is an imidazole medicine used to treat fungal infections. Ketoconazole binds to the fungal p450 enzymes and stops the cells making ergosterol, the main component of the cell wall. In New Zealand, it is available as shampoo and cream.
Ketoconazole is effective against a broad spectrum of fungi including:
Ketoconazole 2% Cream (Nizoral Cream®) daily and 2% Shampoo (Nizoral®, Sebizole®) twice weekly are used for seborrhoeic dermatitis, a common scaly rash affecting scalp and face. They are subsidised on prescription, but can also be obtained over the counter at a chemist. Topical ketoconazole is safe.
Oral ketoconazole was discontinued in New Zealand 1 December 2013. As it may still be available elsewhere, information about the product is included below.
Ketoconazole reaches the surface of the skin through normal blood circulation, sweat and sebum (skin oils). Very high concentrations of the drug develop within the skin, so it is 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 100mg daily for those 20-40 kg.
The oral medication is somewhat better absorbed when it is taken with a fatty meal or acidic drink (e.g. orange juice). It is bound 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 medication to be cleared from the blood stream. The rest is eliminated in faeces and urine either unchanged or after conversion by the liver into inactive compounds.
The main concern with ketoconazole is the risk of liver problems, usually after it has been taken for prolonged periods (weeks). Side effects may include:
Ketoconazole should not be taken in pregnancy. Although only excreted in tiny amounts from breast milk, it should only be taken by a breastfeeding mother if essential.
Ketoconazole is a p-glycoprotein inhibitor and can have serious interactions with other medications.
As ketoconazole needs acid for its absorption, antacids, H2 antagonists (cimetidine, famotidine, ranitidine) and omeprazole should not be taken for 2 hours after ketoconazole.
Ketoconazole interacts with alcohol rather like disulfiram (Antabuse®) and can cause severe nausea and vomiting.
Ketoconazole may increase the concentration of these drugs and enhance their effect:
The following drugs markedly decrease the concentration of ketoconazole:
Ketoconazole is not thought to interact with the oral contraceptive pill.
In recent years, both topical and oral allylamine and triazole antifungal drug resistance has become a problem, particularly in the Indian subcontinent.
Extensive therapy-resistant dermatophyte infection should prompt this as a possible problem. Where available, fungal culture and estimation of drug minimum inhibitory concentration determined to guide appropriate medication
For more information, see antifungal drug resistance.
Approved datasheets are the official source of information for medicines, including approved uses, doses, and safety information. Check the individual datasheet in your country for information about medicines.
We suggest you refer to your national drug approval agency such as the Australian Therapeutic Goods Administration (TGA), US Food and Drug Administration (FDA), UK Medicines and Healthcare products regulatory agency (MHRA) / emc, and NZ Medsafe, or a national or state-approved formulary eg, the New Zealand Formulary (NZF) and New Zealand Formulary for Children (NZFC) and the British National Formulary (BNF) and British National Formulary for Children (BNFC).
