ketoconazole: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
ketoconazole: clinical details
Prescribing considerations
- Reserve tablets for specialist-supervised endogenous Cushing’s syndrome; oral ketoconazole is not indicated for fungal infection.
- Complete an interaction review before and throughout oral treatment.
- Assess pregnancy potential and provide pregnancy-prevention counselling for oral treatment.
- Consider excipient-related local reactions with cream and shampoo; tablets contain lactose.
Contraindications and cautions
- All formulations: hypersensitivity to ketoconazole or product excipients.
- Tablets: acute or chronic liver disease, significantly abnormal pretreatment liver enzymes, pregnancy, breastfeeding, congenital or acquired QTc prolongation, and specified interacting medicines.
- Cream: the selected product is licensed for adults; safety and efficacy have not been established in younger patients.
Monitoring
- Tablets: check liver enzymes and bilirubin before treatment and monitor during treatment; stop promptly for significant abnormalities or clinical hepatitis.
- Monitor clinical and biochemical cortisol response and assess for hypocortisolism, especially during physiological stress.
- Obtain an ECG before treatment, shortly after initiation and subsequently when clinically indicated.
- Review concurrent medicines when acid-suppressing or other interacting therapy changes.
Clinical pharmacology
Topical ketoconazole inhibits fungal membrane synthesis with negligible systemic exposure. Oral ketoconazole inhibits adrenal steroidogenic enzymes, strongly inhibits CYP3A4 and P-glycoprotein, requires gastric acidity for absorption and is extensively metabolised.
Formulation and product differences
- Shampoo is licensed for dandruff prevention and treatment and is rinsed from the scalp.
- Cream is licensed for athlete’s foot and fungal groin infection in adults and remains on the skin.
- Tablets are systemically absorbed, licensed for endogenous Cushing’s syndrome and require specialist monitoring because of hepatotoxicity, adrenal suppression, QT effects and interactions.
ketoconazole preparations and strengths
Cream
Route: Cutaneous
Strengths: 2%
Shampoo
Route: Cutaneous
Strengths: 2%, 2% w/w
Tablet
Route: Oral
Strengths: 200 mg
ketoconazole interactions
Topical products have few expected systemic interactions. Tablets have numerous clinically important interactions.
Simvastatin, atorvastatin and lovastatin
Oral ketoconazole can greatly increase exposure and the risk of severe muscle injury; the combination is contraindicated.
Methadone and several QT-prolonging medicines
Raised concentrations can cause dangerous QT prolongation and ventricular arrhythmias; several combinations are contraindicated.
Dabigatran
Oral ketoconazole increases exposure and bleeding risk; concomitant use is contraindicated.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.