Ketoconazole

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.
  • 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 NameManufacturerPrice (USD)
Nizoral (shampoo)Janssen Pharmaceuticals$10–20 (100 mL, 2%)
Extina (foam)Stiefel/GSK$50–100 (100 mL, 2%)
Ketoconazole TabletsGeneric manufacturers$20–50 (30 tablets, 200 mg)

18. FAQs (15 Questions)

  1. What is ketoconazole used for?
    Ketoconazole is used to treat fungal infections, dandruff, and seborrhoeic dermatitis.
  2. How does ketoconazole work?
    It inhibits fungal cell membrane synthesis by blocking ergosterol production.
  3. Can ketoconazole shampoo cure dandruff?
    Yes, ketoconazole shampoo is highly effective in controlling dandruff caused by Malassezia species.
  4. How often should I use ketoconazole shampoo?
    Use twice weekly for 2–4 weeks, then reduce to once weekly or as needed for maintenance.
  5. Can ketoconazole cause side effects?
    Common side effects include skin irritation (topical) or nausea and liver enzyme changes (oral).
  6. Is ketoconazole safe during pregnancy?
    Topical formulations are safer than oral forms; consult your doctor before use.
  7. How should I take ketoconazole tablets?
    Take with food, and avoid antacids or acid-reducing medications for 2 hours before and after.
  8. Can ketoconazole treat athlete’s foot?
    Yes, ketoconazole cream is effective for athlete’s foot (tinea pedis).
  9. Does ketoconazole interact with other medications?
    Yes, it interacts with CYP3A4 substrates, QT-prolonging drugs, and antacids.
  10. 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.
  11. 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.
  12. Can ketoconazole be used in children?
    Yes, topical ketoconazole is safe for children. Oral ketoconazole should be used cautiously.
  13. 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.
  14. 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.
  15. How should ketoconazole products be stored?
    Store at room temperature, away from heat and moisture.