Ketoconazole

Ketoconazole is used to treat certain serious fungal infections in the body. Ketoconazole belongs to the class of drugs called azole antifungals. It works by stopping the growth of the fungus.

• Ketoconazole should not be used to treat fungal infections on the skin and nails due to the risk of serious side effects and drug interactions. Talk to your doctor about other medications you can use to treat these types of infection.
• Ketoconazole is available under the following different brand names: Nizoral.

Adult and Pediatric Dosage Forms and Strengths

Tablet

• 200 mg

Dosage Considerations – Should be Given as Follows:

Fungal Infections

Indicated for the treatment of the following systemic fungal infections in patients who have failed or who are intolerant to other therapies: blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis

• Adult: 200-400 mg/day orally
• Children under 2 years old: Safety and efficacy not established
• Children 2 years old and older: 3.3-6.6 mg/kg/day orally

Dosage Modifications

Renal impairment: No dosage modifications provided in manufacturer's labeling

Hepatic impairment

• No dosage modifications were provided in the manufacturer's labeling
• If hepatotoxicity occurs during treatment (ALT levels above UNL or ALT 30% above baseline): Interrupt dosing and order a full set of liver tests

Cushing Syndrome (Off-label)

Used off-label to inhibit steroidogenesis in patients with Cushing syndrome

• 600-800 mg/day orally
• Used rarely and often toxic at doses required to reduce cortisol secretion

Recurrent Tinea Versicolor (Off-label)

• 400 mg orally monthly

Dosing Considerations

• Do not use tablets as first-line treatment; should be used only when other effective antifungal therapy is not available or tolerated and the potential benefits are considered to outweigh the potential of hepatotoxicity
• Avoid prescribing tablets to treat skin and nail fungal infections owing to the risk of serious liver damage, adrenal gland problems, and harmful interactions with other medicines that outweigh its benefit in treating these conditions, which are not approved uses of the drug (these indications were removed from labeling by the FDA in 2013)
• Do not use for fungal meningitis because of poor penetration into the cerebrospinal fluid (CSF)

Common side effects of Ketoconazole include:

• Nausea and vomiting
• Itching or skin rash
• Abdominal or stomach pain

Less common side effects of ketoconazole include:

• Hair loss
• Headache
• Dizziness
• High levels of fat in the blood (hyperlipidemia)
• Drowsiness
• Fever
• Chills
• Bulging fontanelles
• Depression
• Swollen breast tissue in males
• Diarrhea
• Impotence
• Low blood platelet count (thrombocytopenia)
• Low white blood cell count (leukopenia)
• Hemolytic anemia
• Erythema multiforme
• Orthostatic hypotension
• Yellow skin and eyes (jaundice)
• Indigestion
• Changes in taste
• Liver damage
• Decreased platelet count
• Dry skin
• Sensitivity to sunlight
• Loss of interest in sex

Serious side effects of ketoconazole include:

• Vision changes
• Mental/mood changes (such as depression, thoughts of suicide)

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ketoconazole has severe interactions with at least 33 different drugs.
• Ketoconazole has serious interactions with at least 202 different drugs.
• Ketoconazole has moderate interactions with at least 241 different drugs.
• Ketoconazole has mild interactions with at least 105 different drugs.

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns, or for more information about this medicine.

Warnings

• Tablets should be used only when other effective antifungal therapy is not available or tolerated and the potential benefits are considered to outweigh the potential risks
• Liver damage (hepatotoxicity) has occurred with oral use, including some fatalities or requiring liver transplantation; reported with oral administration of the drug; some patients had no obvious risk factors for liver disease
• May cause QT prolongation; coadministration with dofetilide, quinidine, pimozide, cisapride, methadone, disopyramide, dronedarone, and ranolazine is contraindicated; ketoconazole can cause elevated plasma concentrations of these drugs (by CYP3A4 inhibition) and may prolong QT intervals, sometimes resulting in life-threatening ventricular dysrhythmias such as torsades de pointes
• This medication contains ketoconazole. Do not take Nizoral if you are allergic to ketoconazole or any ingredients contained in this drug
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately

Contraindications

• Hypersensitivity
• Contraindicated with dofetilide, quinidine, pimozide, cisapride, methadone, disopyramide, dronedarone, and ranolazine; can cause elevated plasma concentrations of these drugs and may prolong QT intervals, sometimes resulting in life-threatening ventricular dysrhythmias (e.g., torsades de pointes)
• Concurrent therapy with cisapride, ergot derivatives, or triazolam (fatal cardiac arrhythmias may occur)
• Acute or chronic liver disease
• CYP3A4 metabolized HMG-CoA reductase inhibitors (e.g., simvastatin, lovastatin); ketoconazole inhibits CYP3A4 and may increase risk of myopathy associated with statins

Effects of Drug Abuse

• No information provided

Short-Term Effects

• See "What Are Side Effects Associated with Using Ketoconazole?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Ketoconazole?"

Cautions

• Do not use tablets as first-line treatment; should be used only when other effective antifungal therapy is not available or tolerated and the potential benefits are considered to outweigh the potential of liver damage (hepatotoxicity)
• Avoid prescribing tablets to treat skin and nail fungal infections owing to the risk of serious liver damage, adrenal gland problems, and harmful interactions with other medicines that outweigh its benefit in treating these conditions, which are not approved uses of the drug (these indications were removed from labeling by the FDA in 2013)
• Hypersensitivity to other azoles
• Liver damage (hepatotoxicity) reported, including fatalities or liver transplantation
• Ketoconazole decreases the metabolism of oral midazolam, oral triazolam, or alprazolam and may result in prolonged hypnotic and sedative effects
• Coadministration of CYP3A4 metabolized HMG-CoA reductase inhibitors (e.g., simvastatin, lovastatin) increases the risk for myopathy
• Potential for breast tissue enlargement in males (gynecomastia) (the drug has anti-androgenic activity)
• Adrenal insufficiency:
  • Decreases adrenal corticosteroid secretion at doses 400 mg or greater
  • This effect is not shared with other azoles
  • Do not exceed the recommended dose of 200-400 mg/day
  • Monitor adrenal function in patients with adrenal insufficiency or with borderline adrenal function, and in patients under prolonged periods of stress (e.g., major surgery, intensive care)

Pregnancy and Lactation

• Use ketoconazole with caution during pregnancy if benefits outweigh risks
• Animal studies show risk and human studies are not available or neither animal nor human studies were done
• Ketoconazole enters breast milk; consult your doctor before breastfeeding