Ketoconazole (Nizoral)

Description
An imidazole antifungal agent.
Indications
The treatment of systemic fungal infections and severe resistant mucocutaneous candidiasis.
Presentations
(i) A 200 mg tablet.
(ii) A suspension (100 mg/5 mL).
Dose
200 mg once daily for 14 days.
In children 3 mg/kg daily.
Contraindications
Previous hypersensitivity (plus see important drug interactions below).
History of porphyria.
Best avoided in pregnancy.
Precautions
Ketoconazole is more readily absorbed than miconazole and can lead to nephrotoxicity. It is not advised for superficial fungal infections.
Unwanted effects
Hypersensitivity reactions.
Gastrointestinal disturbances.
Drug interactions
Ketoconazole should not be prescribed to patients receiving the antihistamines astemizole and terfenadine as cardiac dysryhthmias may occur. Ketoconazole inhibits the metabolism of the anti-spasmodic drug cisapride and this can lead to ventricular arrhythmias; thus concurrent use should be avoided. Ketoconazole enhances the anticoagulant effect of warfarin even after topical use. Ketoconazole increases the plasma concentrations of benzodiazepines (including midazolam) and ciclosporin. Ketoconazole increases the hypoglycaemic effect of tolbutamide.
Phenytoin reduces the plasma concentration of ketoconazole.
Ketoconazole and amphotericin antagonize each others’ antifungal action. Anti-ulcer medications (including cimetidine, omeprazole, and sucralfate), and antimuscarinic drugs decrease the absorption of ketoconazole.
Other drugs which decrease the plasma concentration of ketoconazole include rifampicin and isoniazid.
Ketoconazole reduces the metabolism and excretion of methyl prednisolone.
Ketoconazole can lead to oral contraceptive failure. A disulfiram- like (antabuse) reaction can occur with alcohol consumption and thus alcohol intake is best avoided during ketoconazole therapy.