1. Introduction
Ketoconazole is an imidazole antifungal agent used to treat fungal infections of the skin, scalp, and systemic fungal infections. It works by inhibiting the synthesis of ergosterol, a vital component of fungal cell membranes, leading to cell death.
2. Indications
- Approved Indications:
- Topical:
- Seborrhoeic dermatitis.
- Tinea infections (ringworm, jock itch, athlete’s foot).
- Candidiasis (cutaneous).
- Dandruff caused by Malassezia species.
- Oral:
- Chronic mucocutaneous candidiasis.
- Systemic fungal infections (e.g., histoplasmosis, blastomycosis) – only if alternative treatments are unavailable.
- Topical:
- Off-Label Uses:
- Hormonal disorders (oral ketoconazole, for Cushing’s syndrome, due to its adrenal-suppressive properties).
3. Dosage
- Topical Formulations:
- Cream: Apply a thin layer to the affected area once or twice daily for 2–4 weeks.
- Shampoo (2%):
- Dandruff: Use twice weekly for 2–4 weeks.
- Seborrhoeic Dermatitis: Use twice weekly for 4 weeks, then reduce to maintenance once weekly or as needed.
- Foam: Apply as directed, usually once daily.
- Oral Tablets:
- Adults: 200–400 mg once daily with a meal.
- Children (≥2 years): 3.3–6.6 mg/kg/day.
4. Administration
- Topical: Apply to clean, dry skin or scalp.
- Oral: Take with food to enhance absorption. Avoid antacids or medications that reduce stomach acid for at least 2 hours before or after.
5. Forms Available
- Topical: Cream (2%), shampoo (1% or 2%), foam (2%).
- Oral: Tablets (200 mg).
6. Side Effects
6.1. Common Side Effects
- Topical: Skin irritation, itching, redness, or burning.
- Oral: Nausea, vomiting, abdominal pain, headache.
6.2. Less Common Side Effects
- Topical: Dryness or peeling of the skin.
- Oral: Diarrhoea, dizziness, menstrual irregularities (with long-term use).
6.3. Rare but Serious Side Effects
- Oral:
- Hepatotoxicity (severe liver damage).
- QT prolongation and cardiac arrhythmias.
- Adrenal insufficiency.
7. Warnings
- Liver Toxicity: Oral ketoconazole can cause severe liver injury. Monitor liver function regularly, and use only if no safer alternatives are available.
- Hormonal Effects: Oral ketoconazole may interfere with steroid hormone synthesis, causing adrenal insufficiency or menstrual irregularities.
- QT Prolongation: Avoid use with other QT-prolonging medications.
8. Precautions
- Avoid prolonged use of oral ketoconazole due to potential toxicity.
- For topical products, avoid application to broken skin or open wounds.
- Use cautiously in patients with liver disease.
9. Interactions
- Drug-Drug Interactions:
- CYP3A4 substrates (e.g., midazolam, statins): Increased drug levels may cause toxicity.
- Antacids, proton pump inhibitors (PPIs): Reduced absorption of oral ketoconazole.
- QT-prolonging drugs (e.g., amiodarone): Increased risk of arrhythmias.
- Drug-Food Interactions:
- Avoid alcohol, as it increases the risk of hepatotoxicity.
10. Monitoring Parameters
- Topical Use: Improvement in symptoms (e.g., reduced scaling, itching).
- Oral Use:
- Liver function tests (LFTs) periodically.
- Monitor for adrenal insufficiency (e.g., fatigue, low blood pressure).
- ECG monitoring if there is a risk of QT prolongation.
11. Use in Children
- Topical ketoconazole is safe for use in children.
- Oral ketoconazole should be used cautiously and only when benefits outweigh risks.
12. Use in Pregnancy
- Category C: Use only if clearly needed. Topical formulations are considered safer than oral forms due to minimal systemic absorption.
13. Use in Elderly
- Topical formulations are safe; monitor for skin irritation.
- Oral formulations should be used cautiously due to increased risk of liver toxicity and drug interactions.
14. Use in Kidney Disease
- No dose adjustment is necessary for topical use.
- For oral use, monitor closely as ketoconazole is metabolised in the liver.
15. Use in Liver Disease
- Avoid oral ketoconazole in patients with active liver disease due to the risk of hepatotoxicity.
16. Patient Counselling Points
- For topical use: Apply as directed, avoiding contact with eyes, mouth, or mucous membranes.
- For shampoo: Leave on the scalp for 3–5 minutes before rinsing.
- For oral use: Take with food, and avoid antacids or acid-reducing drugs for 2 hours before and after.
- Report symptoms of liver damage (e.g., yellowing of the skin, dark urine, severe fatigue) immediately.
- Do not consume alcohol while on ketoconazole to avoid liver-related side effects.
17. Table of Brand Names, Manufacturers, and Prices
Brand Name | Manufacturer | Price (USD) |
---|---|---|
Nizoral (shampoo) | Janssen Pharmaceuticals | $10–20 (100 mL, 2%) |
Extina (foam) | Stiefel/GSK | $50–100 (100 mL, 2%) |
Ketoconazole Tablets | Generic manufacturers | $20–50 (30 tablets, 200 mg) |
18. FAQs (15 Questions)
- What is ketoconazole used for?
Ketoconazole is used to treat fungal infections, dandruff, and seborrhoeic dermatitis. - How does ketoconazole work?
It inhibits fungal cell membrane synthesis by blocking ergosterol production. - Can ketoconazole shampoo cure dandruff?
Yes, ketoconazole shampoo is highly effective in controlling dandruff caused by Malassezia species. - How often should I use ketoconazole shampoo?
Use twice weekly for 2–4 weeks, then reduce to once weekly or as needed for maintenance. - Can ketoconazole cause side effects?
Common side effects include skin irritation (topical) or nausea and liver enzyme changes (oral). - Is ketoconazole safe during pregnancy?
Topical formulations are safer than oral forms; consult your doctor before use. - How should I take ketoconazole tablets?
Take with food, and avoid antacids or acid-reducing medications for 2 hours before and after. - Can ketoconazole treat athlete’s foot?
Yes, ketoconazole cream is effective for athlete’s foot (tinea pedis). - Does ketoconazole interact with other medications?
Yes, it interacts with CYP3A4 substrates, QT-prolonging drugs, and antacids. - What should I do if I miss a dose of ketoconazole?
For oral forms, take it as soon as you remember unless it is close to the next dose. For topical use, apply as soon as possible. - How long does it take for ketoconazole to work?
Improvement is usually seen within 1–2 weeks for topical use and 4–6 weeks for oral therapy. - Can ketoconazole be used in children?
Yes, topical ketoconazole is safe for children. Oral ketoconazole should be used cautiously. - What are the risks of oral ketoconazole?
Oral ketoconazole can cause severe liver toxicity and should only be used if no safer alternatives are available. - Can ketoconazole foam be used for scalp psoriasis?
No, it is not specifically indicated for psoriasis, but it may help if fungal involvement is suspected. - How should ketoconazole products be stored?
Store at room temperature, away from heat and moisture.