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 |
Ontology: Ketoconazole (C0022625)
| Definition (NCI_NCI-GLOSS) | A drug that treats infection caused by a fungus. It is also used as a treatment for prostate cancer because it can block the production of male sex hormones. |
| Definition (NCI) | A synthetic derivative of phenylpiperazine with broad antifungal properties and potential antineoplastic activity. Ketoconazole inhibits sterol 14-a-dimethylase, a microsomal cytochrome P450-dependent enzyme, thereby disrupting synthesis of ergosterol, an important component of the fungal cell wall. (NCI04) |
| Definition (MSH) | Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients. |
| Definition (CSP) | 1-acetyl-4-(2,4-dichlorophenyl-2-imidazolylmethyl- 1,3- dioxolanylmethoxyphenyl) piperazine; broad spectrum, oral antifungal. |
| Definition (PDQ) | A synthetic derivative of phenylpiperazine with broad antifungal properties and potential antineoplastic activity. Ketoconazole inhibits sterol 14-a-dimethylase, a microsomal cytochrome P450-dependent enzyme, thereby disrupting synthesis of ergosterol, an important component of the fungal cell wall. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39488&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39488&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C605" NCI Thesaurus) |
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | D007654 |
| SnomedCT | 326240002, 332902002, 324673001, 387216007, 40232005 |
| LNC | LP15862-3, MTHU002299 |
| English | Ketoconazole, Piperazine, 1-acetyl-4-(4-((2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-, cis-, Ketoconazole [gyn], Ketoconazole [infections], Ketoconazole [skin], Cis-1-Acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazole-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine, ketoconazole, Ketoconazole [gynaecological use], Ketoconazole [gynecological use], ketoconazole (medication), KETOCONAZOLE, Ketoconazole [Chemical/Ingredient], Ketoconazole [skin] (product), Ketoconazole [infections] (product), Ketoconazole [gynecological use] (product), Ketoconazole (product), Ketoconazole (substance), KCZ, Ketoconazole [gynecological use] (substance), Ketoconazole [infections] (substance), Ketoconazole [skin] (substance) |
| Swedish | Ketokonazol |
| Spanish | ketoconazol [infecciones], ketoconazol (piel), Cetoconazol, cetoconazol (uso dermatológico), ketoconazol [antiinfeccioso], ketoconazol [antiinfeccioso] (producto), ketoconazol (uso dermatológico) (producto), cetoconazol [uso ginecológico], ketoconazol (uso dermatológico), cetoconazol (uso dermatológico) (producto), ketoconazol [uso ginecológico] (producto), ketoconazol [uso ginecológico], cetoconazol [antiinfeccioso], Ketoconazol, cetoconazol (producto), cetoconazol (sustancia), cetoconazol, ketoconazol (piel) (producto), ketoconazol (producto), ketoconazol (sustancia), ketoconazol [infecciones] (producto), ketoconazol |
| Czech | ketokonazol |
| Finnish | Ketokonatsoli |
| Russian | KETOKONAZOL, КЕТОКОНАЗОЛ |
| Japanese | ケトコナゾール, ニゾラール, ニトラゼン, ケトパミン, プルナ |
| Croatian | KETOKONAZOL |
| Polish | Ketokonazol |
| Portuguese | Cetoconazol, Ketoconazol |
| French | Kétoconazole |
| German | Ketoconazol |
| Italian | Ketoconazolo |
Ontology: Nizoral (C0699439)
| Concepts | Pharmacologic Substance (T121) , Organic Chemical (T109) |
| MSH | D007654 |
| English | Janssen Brand of Ketoconazole, Ketoconazole Janssen Brand, nizoral, Nizoral |
