Ketoconazole (Tablet)

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.

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.

Vaginal candidiasis: 1 tablet (200 mg) tablet twice daily for 5 days.

All other indications: 1 tablet (200 mg) once daily until at least one week after the symptoms have disappeared and the cultures have become negative.

Administration

Ketoconazole should be taken at meal times for maximal resorption. Because resorption depends on intact gastric activity, the concomitant treatment with agents that reduce gastric secretion (anticholinergic drugs, antacids, H2 blockers) should be avoided. When indicated, such drugs should be taken not earlier than two hours after ketoconazole. If clinical responsiveness is insufficient within the expected time, the dose of ketoconazole may be doubled (400 mg once daily).

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.

Ketoconazole is contraindicated in pregnancy and in patients with acute liver pathology.

Ketoconazole is very well tolerated. Nausea and itching may occasionally occur. In some patients, an idosyncratic liver reaction may occur (incidence 1:10000).

Pregnancy category C. There is no adequate and well controlled studies in pregnant women. Ketoconazole Tablets should not be used during pregnancy and lactation.

In patients with a previous history of liver disease, liver enzyme levels should be monitored during treatment. When patients develop symptoms indicative of liver reaction, such as nausea or fatigue, accompanied with pale faeces, dark urine or jaundice, Ketoconazole therapy should be stopped immediately.

Drugs for subcutaneous and mycoses

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.