II. Indications
- Topical Ketoconazole (topical Ketoconazole is considered safe unlike its systemic formulations)
- Systemic Ketoconazole (third-line agent when less toxic azoles cannot be used)
- Blastomycosis
- Chomomycosis
- Coccidioidomycosis
- Histoplasmosis
- Paracoccidioidomycosis
III. Contraindications
- Systemic Ketoconazole is avoided in general unless other less toxic options (esp. other azoles) are unavailable
- See Drug Interactions below
IV. Mechanism
- Synthetic derivative of phenylpiperazine
- As with other azoles, inhibits the synthesis of ergosterol (key component of fungal cell wall)
- Blocks sterol 14-a-dimethylase (microsomal Cytochrome P450-dependent enzyme)
V. Precautions: Systemic Ketoconazole
- Hepatotoxicity risk (FDA black box warning)
- Oral formulation indicated only for severe, refractory systemic fungal infections due to Ketoconazole hepatotoxicity
- No longer indicated in skin or nail infections (risk does NOT outweigh benefit)
- If Ketoconazole is used, requires Liver Function Tests at baseline and again weekly
VI. Medications
- Tablets: 200 mg
- Topical
- Shampoo: 1% and 2%
- Gel 2%
- Foam 2%
- Cream: 2%
VII. Dosing: Topical
- Use in children is off label
-
Tinea Versicolor
- Apply Ketoconazole 2% Shampoo to affected area and then wash off after 5 minutes
- Apply Ketoconazole cream once daily to affected area
-
Tinea Corporis, Tinea Cruris or Cutaneous Candiasis
- Apply Ketoconazole cream once daily to affected area for 2 weeks
-
Tinea Pedis
- Apply Ketoconazole cream once daily to affected area for 6 weeks
- Seborrheic Dermatitis
VIII. Dosing: Systemic Ketoconazole
- Avoid unless serious systemic infection and other less toxic options (esp. other azoles) are unavailable
- Taking with food decreases gastric irritation
- Adult
- Take 200 to 400 mg orally daily
- Child
- Give 3.3 to 6.6 mg/kg orally daily
IX. Adverse Effects: Oral (systemic formulation)
- Common (esp. at doses >=400 mg/day)
- Nausea
- Anorexia
- Headache
- Pruritus
- Dizziness
- Photophobia
- Decreased Serum Testosterone
- Men: Gynecomastia, Erectile Dysfunction
- Women: Metrorrhagia
- Serious
- Liver toxicity (Hepatotoxicity)
- See precautions above
- Adrenal Insufficiency
- Occurs with doses at 400 mg/day or higher
- Hyperkalemia
- QTc Prolongation
- Liver toxicity (Hepatotoxicity)
XI. Drug Interactions: Oral (Systemic formulation)
- Multiple other Drug Interactions
- CYP2C9 Inhibitor
- CYP3A3 Inhibitor
- CYP3A4 Inhibitor (potent)
- Contraindicated with other medications that risk QTc Prolongation and Torsades de Pointes (esp. CYP3A4 agents)
- See Prolonged QT Interval due to Medication
- Alprazolam
- Colchicine
- Disopyramide
- Dofetilide
- Dronedarone
- Eplerenone
- Ergot Akaloids
- Felodipine
- Lovastatin
- Lurasidone
- Methadone
- Midazolam
- Nisoldipine
- Pimozide
- Quinidine
- Ranolazine
- Salmeterol
- Simvastatin
- Tolvaptan
- Triazolam
- Hismanal or Seldane (off market in U.S.)
- Agents that decrease Ketoconazole absorption
- Antacids
- H2 Blockers
- Proton Pump Inhibitors
- Buffered medications (e.g. Didanosine)
- Limit Ketoconazole dose to 200 mg with the following agents
- Agents that decrease Ketoconazole levels
XII. Lab monitoring: Oral (systemic formulation)
- Follow Liver Function Tests at baseline and weekly
XIII. Resources
- Ketoconazole Cream 2% (DailyMed)
- Ketoconazole Tablet (DailyMed)
XIV. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- (2012) Med Lett Drugs Ther 10(120): 61-8 [PubMed]
Images: Related links to external sites (from Bing)
Related Studies
| ketoconazole (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| KETOCONAZOLE 2% CREAM | Generic | $0.31 per gram |
| KETOCONAZOLE 2% SHAMPOO | Generic | $0.10 per ml |
| KETOCONAZOLE 200 MG TABLET | Generic | $0.68 each |