Ketoconazole interferes with biosynthesis of triglycerides and phopholipids by blocking fungal CYP450, thus altering cell membrane permeability in susceptible fungi. It also inhibits other fungal enzymes resulting in the accumulation of toxic concentrations of hydrogen peroxide.
Adult: 200 mg once daily; may increase to 400 mg once daily if clinical response is insufficient. Continue treatment until symptoms have cleared and cultures have become negative.
Child: ?2 yr 3.3-6.6 mg/kg once daily. Treatment duration: 1-2 wk for candidiasis; at least 4 wk in recalcitrant dermatophyte infections and up to 6 mth for other systemic mycoses.
Elderly: No dosage adjustment needed.
Pityriasis versicolor, Skin fungal infections:
As 2% cream: Apply 1-2 times daily to cover affected and surrounding area until at least a few days after disappearance of symptoms.
As 2% shampoo: Apply on scalp once daily for up to 5 days. For prophylaxis: As 2% shampoo, use once daily for a max of 3 days before exposure to sunlight.
As 2% foam: Apply to the affected area bid for 4 wk.
As 1 or 2% shampoo: Apply on the scalp twice wkly for 2-4 wk. For prophylaxis: As 2% shampoo, use once every 1-2 wk.
Reduced absorption with antimuscarinics, antacids, H2-blockers, PPIs and sucralfate. Reduced plasma concentrations with rifampicin, isoniazid, efavirenz, nevirapine, phenytoin. May also reduce concentrations of isoniazid and rifampicin. May reduce efficacy of oral contraceptives. May increase serum levels of CYP3A4 substrates e.g. digoxin, oral anticoagulants, sildenafil, tacrolimus.
Hypersensitivity; preexisting liver disease. Concurrent use with CYP3A4 substrates e.g. HMG-CoA reductase inhibitors (e.g. lovastatin, simvastatin), midazolam, triazolam, cisapride, dofetilide, eplerenone, nisoldipine, pimozide, quinidine, terfenadine, astemizole, ergot alkaloids (e.g. ergotamine, dihydroergotamine).
Ketoconazole is very well tolerated. Nausea and itching may occasionally occur. In some patients, an idosyncratic liver reaction may occur (incidence 1 : 10,000).
Category C: Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.
Predisposition to adrenocortical insufficiency. Admin with acidic drink in patients with achlorhydria. Pregnancy and lactation.
Renal Impairment: Oral: No dosage adjustment needed.
Hepatic Impairment: Oral: Contraindicated.
Pityriasis versicolor: 1 to 6 weeks
Dermatomycoses: 2 to 8 weeks
Onychomycoses: 1 to 12 months
Mycoses of hair and scalp: 1 to 2 months
Chronic mucocutaneous candidiasis : 1 to 12 months
Oral mycoses: 5 to 10 days
Systemic candidiasis: 1 to 2 months
and other systemic mycosis: 1 month to 2 years
Store between 15-25? C. Protect from moisture and light.