API: Ketoconazole

What Is Ketoconazole and How Does It Work?

Ketoconazole belongs to a class of antifungals called triazoles and can be administered orally or through topical preparations. The drug essentially works by inhibiting the synthesis of ergosterol (a key component of fungal cell membranes) via the cytochrome P450. The drug has a broad spectrum of activity and is well-tolerated, but also inhibits testosterone production.1 This side effect has been exploited in terms of using the drug as an anti-androgen therapy to treat prostate cancer2 and Cushing’s disease, but is mainly used as an antifungal therapy.

Approved Indications3

Ketoconazole can be formulated for systemic or topical use. Taken orally, the drug is used to treat:

  • Candidiasis: Ketoconazole is most effective in treating chronic mucocutaneous Candidiasis, but can also be used to treat candidiasis of the mouth, esophagus, vagina, and nails that have had poor response to topical therapies.
  • Others: Ketoconazole may also be effective against other systemic mycoses, including histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis. The hormonal effects of this drug make it a possible off-label treatment for Cushing’s Disease and prostate cancer. The drug may also aid in inhibiting hepatic microsomal enzymes in organ transplant patients.

Taken topically, the drug is used to treat:

  • Skin Conditions: Ketoconazole is effective against dermatophyte infections, seborrheic dermatitis, and dandruff.
  • Tinea Infections: Ketoconazole is often used to treat fungal infections such as tinea versicolor, tinea corporis (ringworm), tinea cruris (jock itch), and tinea pedis (athlete’s foot).4

Side Effects and Drug Interactions

Common side effects in patients taking oral ketoconazole include5:

  • Headache
  • Stomach pain, diarrhea, constipation, or gas
  • Heartburn
  • Changes in ability to taste food, or in tongue color
  • Dry mouth
  • Sleep changes
  • Anxiety
  • Numbness, burning, or tingling in hands or feet
  • Muscle pain, flushes, or chills
  • Hair loss
  • Sensitivity to light
  • Nosebleeds
  • Breast enlargement in men or decrease in sexual ability

Patients who suffer from severity of these common side effects should contact their pharmacist or physician right away. Patients who experience an allergic reaction (hives, trouble breathing, swelling of the face, lips, tongue, or throat), hoarseness, or fatigue should contact their physician right away. Oral use of ketoconazole may cause a decrease sperm production, especially at high doses.

Patients who are allergic to ketoconazole should not take this drug. This drug is contraindicated against a number of CYP3A4 substrates, such as dofetilide, quinidine cisapride and pimozide.6 The drug is also contraindicated against:

  • Methadone
  • Disopyramide
  • Dronedarone
  • Ergot alkaloids such as
    • Dihydroergotamine
    • Ergometrine
    • Ergotamine
    • Methylergometrine
    • Irinotecan
    • Lurasidone
    • Oral midazolam
    • Alprazolam
    • Triazolam
    • Felodipine
    • Nisoldipine
    • Ranolazine
    • Tolvaptan
    • Eplerenone
    • Lovastatin
    • Simvastatin
    • Colchicine

Use of ketoconazole may not be indicated in pregnant or nursing patients. The drug has not been studied for use in children under 2 years of age, but can be used in older children. Patients with liver dysfunction should let their physician know before starting this medication.

Common side effects in patients taking topical formulations of ketoconazole include7:

  • Mild skin itch or irritation
  • Dry or flaky skin
  • Headache

Patients who suffer from severity of these common side effects should contact their pharmacist or physician right away. Patients who experience an allergic reaction (hives, trouble breathing, swelling of the face, lips, tongue, or throat) or severe itching, burning, or irritation at application site, oily or dry scalp, hair loss, redness or pain at application site, and oozing or swelling at application site should contact their physician right away. Note that topical formulations of ketoconazole may not be for ophthalmic use.

Patients who are allergic to ketoconazole should not take this drug. This drug has not been studied in pregnant or nursing patients, or in juveniles.

Latest News and Research

In general, ketoconazole is indicated only when other, safer antifungal medications are ineffective. Other uses for the drug are currently being studied. For example, as ketoconazole inhibits cortisol, its antiglucocorticoid properties may make the drug suitable for treating depression.8 The drug is currently prescribed off-label for Cushing’s Disease and prostate cancer, both of which are under increased scrutiny to see if the drug can formally be approved for treatment. The drug’s hormonal side effects also makes it a promising candidate for treating alopecia in men.9

Buying Guide

Many compound pharmacists prefer Itraconazole or Fluconazole as safer alternatives. Please find more information about our Bulk APIs here.

Show 9 footnotes

  1. “Ketoconazole. Mechanism of action, spectrum of activity, pharmacokinetics, drug interactions, adverse reactions and therapeutic use,” November-December 1984, http://onlinelibrary.wiley.com/doi/10.1002/j.1875-9114.1984.tb03398.x/abstract
  2. “Hormone (androgen deprivation) therapy for prostate cancer,” March 12, 2015, http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-hormone-therapy
  3. “Ketoconazole: Indications,” http://www.infomed.ch/100drugs/ketoind.html
  4. “ketoconazole topical (Rx),” 2016, http://reference.medscape.com/drug/nizoral-xolegel-ketoconazole-topical-343488
  5. “Ketconazole,” June 15, 2014, https://www.nlm.nih.gov/medlineplus/druginfo/meds/a682816.html#other-information
  6. ” LABEL: KETOCONAZOLE- ketoconazole tablet,” Nivember 24, 2015, http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=91fffa92-709a-4e16-9335-e6f0338a5eb9
  7. “Ketoconazole Cream,” May 6, 2015, http://www.rxlist.com/ketoconazole-cream-side-effects-drug-center.htm
  8. “GLUCOCORTICOID INHIBITION IN THE TREATMENT OF DEPRESSION: CAN WE THINK OUTSIDE THE ENDOCRINE HYPOTHALAMUS?,” May 1, 2009, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640810/
  9. “Promising Therapies for Treating and/or Preventing Androgenic Alopecia,” 2012, http://www.skintherapyletter.com/2012/17.6/1.html