Pharm

Ketoconazole

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Ketoconazole, Nizoral, Extina, Xologel

  • See also
  1. Antifungal Medication
  2. Topical Antifungal
  3. Fluconazole
  4. Isavuconazole
  5. Itraconazole
  6. Posaconazole
  7. Voriconazole
  • Indications
  1. Topical Ketoconazole (topical Ketoconazole is considered safe unlike its systemic formulations)
    1. Tinea Versicolor
    2. Cutaneous Candidiasis
    3. Tinea Corporis
    4. Tine Cruris
    5. Seborrheic Dermatitis
  2. Systemic Ketoconazole (third-line agent when less toxic azoles cannot be used)
    1. Blastomycosis
    2. Chomomycosis
    3. Coccidioidomycosis
    4. Histoplasmosis
    5. Paracoccidioidomycosis
  • Contraindications
  1. Systemic Ketoconazole is avoided in general unless other less toxic options (esp. other azoles) are unavailable
  2. See Drug Interactions below
  • Mechanism
  1. Synthetic derivative of phenylpiperazine
  2. As with other azoles, inhibits the synthesis of ergosterol (key component of fungal cell wall)
    1. Blocks sterol 14-a-dimethylase (microsomal Cytochrome P450-dependent enzyme)
  • Precautions
  • Systemic Ketoconazole
  1. Hepatotoxicity risk (FDA black box warning)
    1. Oral formulation indicated only for severe, refractory systemic fungal infections due to Ketoconazole hepatotoxicity
    2. No longer indicated in skin or nail infections (risk does NOT outweigh benefit)
    3. If Ketoconazole is used, requires Liver Function Tests at baseline and again weekly
  • Medications
  1. Tablets: 200 mg
  2. Topical
    1. Shampoo: 1% and 2%
    2. Gel 2%
    3. Foam 2%
    4. Cream: 2%
  • Dosing
  • Topical
  1. Use in children is off label
  2. Tinea Versicolor
    1. Apply Ketoconazole 2% Shampoo to affected area and then wash off after 5 minutes
    2. Apply Ketoconazole cream once daily to affected area
  3. Tinea Corporis, Tinea Cruris or Cutaneous Candiasis
    1. Apply Ketoconazole cream once daily to affected area for 2 weeks
  4. Tinea Pedis
    1. Apply Ketoconazole cream once daily to affected area for 6 weeks
  5. Seborrheic Dermatitis
    1. For scalp involvement (Dandruff), apply Ketoconazole 1% Shampoo (e.g. Nizoral AD 1%) twice weekly
    2. Apply Ketoconazole 2% cream twice daily for 4 weeks
    3. Apply Ketoconazole foam twice daily for 4 weeks
    4. Apply Ketoconazole gel daily for 2 weeks
  • Dosing
  • Systemic Ketoconazole
  1. Avoid unless serious systemic infection and other less toxic options (esp. other azoles) are unavailable
  2. Taking with food decreases gastric irritation
  3. Adult
    1. Take 200 to 400 mg orally daily
  4. Child
    1. Give 3.3 to 6.6 mg/kg orally daily
  • Adverse Effects
  • Oral (systemic formulation)
  1. Common (esp. at doses >=400 mg/day)
    1. Nausea
    2. Anorexia
    3. Headache
    4. Pruritus
    5. Dizziness
    6. Photophobia
    7. Decreased Serum Testosterone
      1. Men: Gynecomastia, Erectile Dysfunction
      2. Women: Metrorrhagia
  2. Serious
    1. Liver toxicity (Hepatotoxicity)
      1. See precautions above
    2. Adrenal Insufficiency
      1. Occurs with doses at 400 mg/day or higher
    3. Hyperkalemia
    4. QTc Prolongation
  • Safety
  1. Pregnancy Category C (Teratogenic in animals)
  2. Unknown safety in Lactation
  • Drug Interactions
  • Oral (Systemic formulation)
  1. Multiple other Drug Interactions
    1. CYP2C9 Inhibitor
    2. CYP3A3 Inhibitor
    3. CYP3A4 Inhibitor (potent)
  2. Contraindicated with other medications that risk QTc Prolongation and Torsades de Pointes (esp. CYP3A4 agents)
    1. See Prolonged QT Interval due to Medication
    2. Alprazolam
    3. Colchicine
    4. Disopyramide
    5. Dofetilide
    6. Dronedarone
    7. Eplerenone
    8. Ergot Akaloids
    9. Felodipine
    10. Lovastatin
    11. Lurasidone
    12. Methadone
    13. Midazolam
    14. Nisoldipine
    15. Pimozide
    16. Quinidine
    17. Ranolazine
    18. Salmeterol
    19. Simvastatin
    20. Tolvaptan
    21. Triazolam
    22. Hismanal or Seldane (off market in U.S.)
  3. Agents that decrease Ketoconazole absorption
    1. Antacids
    2. H2 Blockers
    3. Proton Pump Inhibitors
    4. Buffered medications (e.g. Didanosine)
  4. Limit Ketoconazole dose to 200 mg with the following agents
    1. Ritonavir
    2. Saquinavir
    3. Kaletra
  5. Agents that decrease Ketoconazole levels
    1. Isoniazid
    2. Rifampin
    3. Efavirenz
  • Lab monitoring
  • Oral (systemic formulation)
  1. Follow Liver Function Tests at baseline and weekly
  • Resources
  1. Ketoconazole Cream 2% (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=cad7c647-34a9-4e4e-83b3-8d78e58f588f
  2. Ketoconazole Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=bc189ce2-3f10-260d-e053-2a95a90ae808
  • References
  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. (2012) Med Lett Drugs Ther 10(120): 61-8 [PubMed]