Ketoconazole

Indications
Treatment of superficial and deep mycoses:
Infections of the skin, hair and nails by dermatophytes and/or yeasts (dermatomycosis, onychomycosis, perionyxis, pityriasis versicolor, chronic mucocutaneous candidiasis etc.) especially when topical treatment is difficult or not very effective, owing to involvement of large skin surfaces or to lesions affecting deeper dermal layers, nails and hairs
Yeast infection of the mouth (oral thrush, perleche) and the gastrointestinal tract
Vaginal candidiasis, especially chronic recurrent cases or cases responding poorly to topcial treatment
Systemic mycotic infections such as systemic candidiasis, paracoccidioidomycosis, histoplasmosis, coccidioidomycosis etc.
Maintenance treatment to prevent recurrence in systemic mycotic infections and in chronic mucocutaneous candidiasis.
Prophylactic treatment to prevent mycotic infection in patients with reduced host defenses, e.g., patients with cancer, organ transplant and burns.

Therapeutic Class
Drugs for subcutaneous and mycoses

Pharmacology
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.

Dosage & Administration
Oral-
Fungal infections:
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.
Topical (Adult)-
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.
Seborrhoeic dermatitis:
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.

Interaction
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.

Contraindications
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).

Side Effects
Ketoconazole is very well tolerated. Nausea and itching may occasionally occur. In some patients, an idosyncratic liver reaction may occur (incidence 1 : 10,000).

Pregnancy & Lactation
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.

Precautions & Warnings
Predisposition to adrenocortical insufficiency. Admin with acidic drink in patients with achlorhydria. Pregnancy and lactation.

Use in Special Populations
Renal Impairment: Oral: No dosage adjustment needed.
Hepatic Impairment: Oral: Contraindicated.
Duration of Treatment
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
Paracoccidioidomycosis,histoplasmosis
and other systemic mycosis: 1 month to 2 years

Storage Conditions
Store between 15-25° C. Protect from moisture and light.