Description

Simple

A medication used to treat fungal skin infections.

Clinical

A broad spectrum antifungal used to treat seborrheic dermatitis and fungal skin infections.

Overview

Ketoconazole is an imidazole antifungal agent used in the prevention and treatment of a variety of fungal infections.[FDA Label] It functions by preventing the synthesis of ergosterol, the fungal equivalent of cholesterol, thereby increasing membrane fluidity and preventing growth of the fungus.[5,11] Ketoconazole was first approved in an oral formulation for systemic use by the FDA in 1981.[9] At this time it was considered a significant improvement over previous antifungals, [miconazole] and [clotrimazole], due to its broad spectrum and good absorption. However, it was discovered that ketoconazole produces frequent gastrointestinal side effects and dose-related hepatitis.[Read more

Pharmacology

Indication

Ketoconazole is used in the treatment or prevention of fungal infections including blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis.[FDA Label] In Europe, it is also used in the treatment of endogenous Cushing's syndrome.[ Read more

Pharmacodynamic

Ketoconazole, similarly to other azole antifungals, is a fungistatic agent which causes growth arrest in fungal cells thereby preventing growth and spread of the fungus throughout the body.[ Read more

Mechanism of action

Ketoconazole interacts with 14-α-sterol demethylase, a cytochrome P-450 enzyme necessary for the conversion of lanosterol to ergosterol.[ Read more

Absorption

Ketoconazole requires an acidic environment to become soluble in water.[6] At pH value... Read more

Protein binding

Ketoconazole is approximately 84% bound to plasma albumin with another 15% associated with blood cells for a total of 99% binding within the plasma.[ Read more

Volume of distribution

Ketoconazole has an estimated volume of distribution of 25.41 L or 0.36 L/kg.[ Read more

Clearance

Ketoconazole has an estimated clearance of 8.66 L/h.[ Read more

Half life

Ketoconazole experiences biphasic elimination with the first phase having a half-life of 2 hours and a terminal half life of 8 hours.[ Read more

Route of elimination

Only 2-4% of the ketoconazole dose is eliminated unchanged in the urine.[ Read more

Toxicity

Symptoms of overdose include acute liver injury, which may include both hepatocellular and cholestatic injury, accompanied by anorexia, fatigue, nausea, and jaundice.[14, Read more

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Severe irritation US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Stinging US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Pruritus US
  • Kind: experimental
    • Percent: 5%
  • Kind: placebo
    • Percent: 5%
  • Clinical Trial
    Painful allergic reaction US
  • Kind: experimental
    • Percent: 0.1
  • Kind: placebo
    • Percent: 0
  • Serious hepatotoxicity US
    Post Marketing
    Erectile Dysfunction US
    Post Marketing
    Azoospermia US
    Post Marketing
    Arthralgia US
    Post Marketing
    Photosensitivity US
    Post Marketing
    Acute Generalized Exanthematous Pustulosis US
    Post Marketing
    Hepatic Failure US
    Post Marketing
    Cirrhosis US
    Post Marketing
    Hepatitis cholestatic US
    Post Marketing
    Hepatotoxicity US
    Post Marketing
    Fontanelle bulging US
    Post Marketing
    Papilloedema US
    Post Marketing
    Reversible intracranial pressure increased US
    Post Marketing
    Adrenocortical Insufficiency US
    Post Marketing
    Angioneurotic Edema US
    Post Marketing
    Anaphylactic Reaction US
    Post Marketing
    Anaphylactic shock US
    Post Marketing
    Thrombocytopenia US
    Post Marketing
    Hyperlipidemia US
    Clinical Trial
    Anorexia US
    Clinical Trial
    Alcohol intolerance US
    Clinical Trial
    Gynecomastia US
    Clinical Trial
    Headache US
    Clinical Trial
    Nervousness US
    Clinical Trial
    Insomnia US
    Clinical Trial
    Increased appetite US
    Clinical Trial
    Anaphylactoid reaction US
    Clinical Trial
    Contact Dermatitis US
    Post Marketing
    Nausea US
    Clinical Trial
    Constipation US
    Clinical Trial
    Abdominal Pain US
    Clinical Trial
    Abdominal Pain Upper US
    Clinical Trial
    Dry Mouth US
    Clinical Trial
    Dysgeusia US
    Clinical Trial
    Dyspepsia US
    Clinical Trial
    Flatulence US
    Clinical Trial
    Dizziness US
    Clinical Trial
    Paresthesia US
    Clinical Trial
    Somnolence US
    Clinical Trial
    Photophobia US
    Clinical Trial
    Orthostatic Hypotension US
    Clinical Trial
    Epistaxis US
    Clinical Trial
    Vomiting US
    Clinical Trial
    Diarrhea US
    Clinical Trial
    Pruritus US
    Clinical Trial
    Urticaria US
    Clinical Trial

    Contraindications

    • Route:
      • Oral
    • Regions: US
    • With Categories:
        • Name: Cytochrome P-450 CYP3A4 Substrates
        • Drugbank Id: DBCAT002646
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Solifenacin
        • Drugbank Id: DB01591
    • Route:
      • Oral
    • Regions: EU
    • Patient Conditions:
        • Name: Renal Impairment
        • Drugbank Id: DBCOND0031781
    • With Drugs:
        • Name: Fesoterodine
        • Drugbank Id: DB06702
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Ombitasvir
        • Drugbank Id: DB09296
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Paritaprevir
        • Drugbank Id: DB09297
    • Sex Group: male
    • Regions: EU
    • Above Age:
      • Amount: 75
      • Unit: year
    • With Drugs:
        • Name: Vardenafil
        • Drugbank Id: DB00862
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Sirolimus
        • Drugbank Id: DB00877
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Everolimus
        • Drugbank Id: DB01590
    • Route:
      • Oral
    • Regions: EU
    • Patient Conditions:
        • Name: Renal Impaired
        • Drugbank Id: DBCOND0056408
    • With Drugs:
        • Name: Clarithromycin
        • Drugbank Id: DB01211
    • Route:
      • Oral
    • Regions: EU
    • Patient Conditions:
        • Name: Renal Impairment
        • Drugbank Id: DBCOND0031781
    • With Drugs:
        • Name: Telithromycin
        • Drugbank Id: DB00976
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Quetiapine
        • Drugbank Id: DB01224
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Lurasidone
        • Drugbank Id: DB08815
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Halofantrine
        • Drugbank Id: DB01218
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Mizolastine
        • Drugbank Id: DB12523
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Saquinavir
        • Drugbank Id: DB01232
    • Route:
      • Oral
    • Regions: EU
    • With Drugs:
        • Name: Sertindole
        • Drugbank Id: DB06144
    • Route:
      • Oral
    • Regions: EU
    • Patient Conditions:
        • Name: Acquired long QT syndrome
        • Drugbank Id: DBCOND0121753
    • Route:
      • Oral
    • Regions: EU
    • Patient Conditions:
        • Name: Congenital long QT syndrome
        • Drugbank Id: DBCOND0107917
    • Route:
      • Oral
    • Sex Group: female
    • Regions: EU
    • Patient Conditions:
        • Name: Breastfeeding
        • Drugbank Id: DBCOND0031330
    • Route:
      • Oral
    • Sex Group: female
    • Regions: EU
    • Patient Conditions:
        • Name: Pregnancy
        • Drugbank Id: DBCOND0018394
    • Route:
      • Oral
    • Regions: Canada
    • Patient Conditions:
        • Name: Hepatic dysfunction
        • Drugbank Id: DBCOND0094733
    • Route:
      • Oral
    • Regions: Canada
    • With Drugs:
        • Name: Astemizole
        • Drugbank Id: DB00637
    • Route:
      • Oral
    • Regions: Canada
    • With Drugs:
        • Name: Terfenadine
        • Drugbank Id: DB00342
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Colchicine
        • Drugbank Id: DB01394
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Atorvastatin
        • Drugbank Id: DB01076
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Simvastatin
        • Drugbank Id: DB00641
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Lovastatin
        • Drugbank Id: DB00227
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Eplerenone
        • Drugbank Id: DB00700
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Tolvaptan
        • Drugbank Id: DB06212
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Ranolazine
        • Drugbank Id: DB00243
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Nisoldipine
        • Drugbank Id: DB00401
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Felodipine
        • Drugbank Id: DB01023
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Triazolam
        • Drugbank Id: DB00897
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Alprazolam
        • Drugbank Id: DB00404
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Midazolam
        • Drugbank Id: DB00683
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Irinotecan
        • Drugbank Id: DB00762
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Methylergometrine
        • Drugbank Id: DB00353
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Ergometrine
        • Drugbank Id: DB01253
    • Route:
      • Oral
    • Regions: US
    • With Categories:
        • Name: Ergot Alkaloids and Derivatives
        • Drugbank Id: DBCAT000606
        • Mesh Id: D004876
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Dronedarone
        • Drugbank Id: DB04855
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Disopyramide
        • Drugbank Id: DB00280
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Methadone
        • Drugbank Id: DB00333
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Pimozide
        • Drugbank Id: DB01100
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Cisapride
        • Drugbank Id: DB00604
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Quinidine
        • Drugbank Id: DB00908
    • Route:
      • Oral
    • Regions: US
    • With Drugs:
        • Name: Dofetilide
        • Drugbank Id: DB00204
    • Dose Form:
      • Cream
      • Shampoo
      • Tablet
    • Hypersensitivity:
      • true
    • Regions: US

    Food Interactions

    Avoid alcohol. Drinking alcohol while on ketoconazole treatment may cause liver injury.

    Avoid multivalent ions. They may decrease ketoconazole concentrations.

    Take with food. Food decreases gastrointestinal irritation caused by ketoconazole.