(1997; 132 pages) [French] [Spanish]
Tablet, 200 mg
Oral suspension, 100 mg / 5 ml
Ketoconazole is a synthetic imidazole derivative with fungistatic activity against dermatophytes, yeasts and other pathogenic fungi. It is widely used in the treatment of serious gastrointestinal and systemic mycoses as well as in the management of superficial infections. It acts by inhibiting the synthesis of ergosterol, an essential component of the surface membrane of fungal cells.
Ketoconazole is rapidly absorbed from the gastrointestinal tract and partially metabolized in the liver. It has a plasma half-life of approximately 8 hours and is largely excreted in the faeces via the bile.
• dermatophyte infections of the skin
• cutaneous candidosis and chronic Candida paronychia
• pityriasis (tinea) versicolor
• seborrhoeic dermatitis
• subcutaneous fungal infections, including mycetoma and subcutaneous zygomycosis
• oesophageal and resistant oropharyngeal candidosis in patients with HIV infection.1
1 For further information, see WHO model prescribing information: drugs used in sexually transmitted diseases and HIV infection. Geneva, World Health Organization, 1995.
Dosage and administration
Ketoconazole tablets and oral suspension should preferably be administered with, or immediately after, meals.
Dermatophyte infections of the skin, cutaneous candidosis, pityriasis (tinea) versicolor and seborrhoeic dermatitis:
A thin layer of cream should be applied to the affected areas once or twice daily until all signs have cleared for several days. The diagnosis should be reviewed if no clearing is evident after 4 weeks.
Chronic Candida paronychia:
A thin layer of cream should be massaged into the cuticles once or twice daily until remission is obtained. Treatment may have to be continued for several months.
Resistant dermatophyte infections of the skin, mycetoma and subcutaneous zygomycosis:
200-400 mg orally daily until remission is obtained.
Dermatophyte infections are usually cured within 2 weeks. Treatment may be extended in resistant cases, provided the results of intensified hepatic monitoring are reassuring.
200-400 mg daily until remission is obtained. The need for subsequent maintenance doses of 200 mg daily should be considered.
Resistant oropharyngeal candidosis:
200 mg once daily until remission is obtained.
Children over 2 years:
3-6 mg/kg orally daily until remission is obtained.
• Hypersensitivity to azole derivatives.
• Impaired hepatic function.
• Chronic alcohol dependence.
• Age less than 2 years.
• Dermatophyte infections of the nails that are of cosmetic significance only.
If potent topical corticosteroids have been used previously in the treatment of seborrhoeic dermatitis, a period of 2 weeks should be allowed to elapse before ketoconazole cream is applied to reduce the risk of skin sensitization.
When systemic administration is continued beyond 2 weeks the risk of hepatitis increases. The patient should be advised to report immediately any symptoms or signs indicative of liver disease such as fatigue with fever, dark urine, pale stools or jaundice. Liver function should be assessed before and at monthly intervals throughout treatment.
Use in pregnancy and lactation
Ketoconazole is fetotoxic in rats. It should be administered during pregnancy only when the need of the mother outweighs the risk of harm to the fetus. Breast-feeding should be suspended during treatment.
Nausea, vomiting, abdominal pain, constipation, diarrhoea and transient increases in plasma concentrations of hepatic enzymes are common. Treatment should be withdrawn immediately if there is evidence of more severe hepatocellular damage.
Rarely, anaphylactic reactions occur following the first dose. Hypersensitivity may also present as pruritus, purpura, urticaria or angio-oedema. Thrombocytopenia is rare.
Gynaecomastia and menstrual irregularities have also been reported.
Absorption of ketoconazole from the gastrointestinal tract is pH dependent. Concomitant administration of drugs that reduce gastric acid secretion, such as histamine H2-receptor antagonists, and of other antacids should be avoided whenever possible.
Ketoconazole is extensively bound to plasma proteins and induces hepatic enzymes. Both effects give rise to potential drug interactions. The anticoagulant effect of coumarin compounds may be enhanced, and use of ketoconazole with rifampicin or ciclosporin may alter the metabolism of one or both drugs. Ketoconazole should not be administered concomitantly with either astemizole or terfenadine, as cardiac irregularities including prolonged Q-T intervals and ventricular fibrillation may occur.
Induction of emesis or gastric lavage should be undertaken in the event of overdose.
Ketoconazole preparations should be kept in well-closed containers.