Ketoconazole

DEA Class; Rx

Common Brand Names; Nizoral, Nizoral Topical, Extina, Ketozole, Xolegel

• Antifungals, Systemic; 

Imidazole antifungal
Used topically for fungal skin and skin structure infections; used orally for serious fungal infections only when no other antifungal therapies available
Oral use associated with fatal hepatotoxicity, adrenal gland suppression, and harmful drug interactions

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 (eg, 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 (eg, simvastatin, lovastatin); ketoconazole inhibits CYP3A4 and may increase risk of myopathy associated with statins

• Nausea and vomiting (3-10%)
• Pruritus (2%)
• Abdominal pain (1%)
• Alopecia
• Headache
• Dizziness
• Hyperlipidemia
• Somnolence
• Fever
• Chills
• Bulging fontanelles
• Depression
• Gynecomastia
• Diarrhea
• Impotence
• Thrombocytopenia
• Leukopenia
• Hemolytic anemia
• Erythema multiforme
• Orthostatic hypotension
• Jaundice
• Dyspepsia
• Dysgeusia
• Hepatotoxicity
• Decreased platelet count
• Xeroderma
• Photophobia

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 (see Black Box Warnings)

Avoid prescribing tablets to treat skin and nail fungal infections owing to 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)

Use catuion in patients with hypersensitivity to other azoles

Increased long bone fragility reported with high dose in animal studies; choose dose carefully in patients susceptible to bone fragility, including the elderly and postmenopausal women

Absorption reduced in patients with achlorhydria, avoid coadministration with drugs that decrease gastric acidity

Not for the treatment of fungal meningitis; has poor penetration into cerebral spinal fluid

Hepatotoxicity reported, including fatalities or liver transplantation (see Black Box Warnings)

Ketoconazole decreases metabolism of midazolam PO, triazolam PO, or alprazolam and may result in prolonged hypnotic and sedative effects

Coadministration of CYP3A4 metabolized HMG-CoA reductase inhibitors (eg, simvastatin, lovastatin) increases risk for myopathy (see Contraindications)

Potential for gynecomastia (drug has antiandrogenic activity)

Pregnancy category: C

Lactation: Drug enters breast milk

Ketoconazole

tablet

• 200mg

cream/gel/foam

• 2%

shampoo

• 1%
• 2%