ketoconazole


Also found in: Dictionary, Thesaurus, Encyclopedia, Wikipedia.

ketoconazole

 [ke″to-kon´ah-zōl]
a synthetic imidazole that is a broad-spectrum antifungal agent used for treatment of chronic mucocutaneous candidiasis and systemic fungal infections due to species of Candida, Epidermophyton, Microsporum, Trichophyton, and others.

ketoconazole

Apo-Ketoconazole (CA), Dactarin Gold (UK), Dandrazol (UK), Extina, Kryoxolr, Nizoral, Nizoral A-D, Novo-Ketoconazole (CA), Nu-Ketocon (CA), Nu-Ketoconazole (CA), Ratio-Ketoconazole (CA), Xolegel

Pharmacologic class: Imidazole

Therapeutic class: Antifungal

Pregnancy risk category C

FDA Box Warning

• Oral form has been linked to hepatic toxicity, including some deaths. Inform patient of this risk, and monitor closely.

• Concurrent use of astemizole, cisapride, or terfenadine with ketoconazole tablets is contraindicated, because serious cardiovascular adverse events (including death, ventricular tachycardia, and torsades de pointes) have occurred.

Action

Alters fungal cell membranes, resulting in increased permeability, growth inhibition, and ultimately, cell death

Availability

Cream: 2%

Shampoo: 1%, 2%

Tablets: 200 mg

Indications and dosages

Blastomycosis; chronic mucocutaneous candidiasis; oral thrush; candiduria; coccidioidomycosis; histoplasmosis; chromomycosis; paracoccidioidomycosis; mucocutaneous or vaginal candidiasis

Adults: 200 to 400 mg P.O. daily

Children ages 2 and older: 3.3 to 6.6 mg/kg P.O. as a single daily dose. Duration depends on infection: for candidiasis, 1 to 2 weeks; other systemic mycoses, 6 months; recalcitrant dermatophyte infections involving glabrous skin, 4 weeks. Chronic mucocutaneous candidiasis requires maintenance therapy.

Scaling caused by dandruff or seborrheic dermatitis

Adults: 2% shampoo applied topically twice weekly for 4 weeks, then as needed to control symptoms, with at least 3 days between applications; or 1% shampoo applied topically q 3 to 4 days for up to 8 weeks, then as needed to control dandruff

Tinea corporis; tinea cruris; tinea versicolor; tinea pedis, cutaneous candidiasis

Adults: 2% cream applied topically to affected areas daily for 2 weeks (except for tinea pedis, which may require 6 weeks of therapy)

Contraindications

• Hypersensitivity to drug or its components
• Concurrent oral astemizole, cisapride, triazolam, or terfenadine therapy

Precautions

Use cautiously in:
• renal or hepatic disease, achlorhydria
• pregnant or breastfeeding patients
• children younger than age 2.

Administration

• Apply cream to damp skin of affected area and wide surrounding area.
• To use shampoo, wet hair, then apply shampoo and massage into scalp for 1 minute. Leave on for 5 minutes before rinsing. Rinse and repeat, this time leaving shampoo on scalp for 3 minutes before rinsing.
• Don't apply shampoo to broken or inflamed skin.
• In achlorhydria, dissolve 200-mg tablet in 4 ml of 0.2N hydrochloric acid solution.
• Withhold antacids for at least 2 hours after giving oral ketoconazole.

Don't give concurrently with cisapride, available in U.S. for compassionate use only. (Astemizole and terfenadine are not available in U.S.)

Adverse reactions

CNS: headache, nervousness, dizziness, drowsiness, severe depression, suicidal ideation

EENT: photophobia

GI: nausea, vomiting, diarrhea, abdominal pain, anorexia

GU: erectile dysfunction, gynecomastia

Hematologic: purpura, hemolytic anemia, thrombocytopenia, leukopenia

Hepatic: hepatotoxicity

Metabolic: hyperlipidemia

Skin: pruritus, rash, dermatitis, urticaria, severe irritation, stinging, alopecia, abnormal hair texture, scalp pustules, oily skin, dry hair and scalp

Other: fever, chills, allergic reaction

Interactions

Drug-drug.Antacids, anticholinergics, histamine2-receptor antagonists: decreased ketoconazole absorption

Cyclosporine: increased cyclosporine blood level

Isoniazid, rifampin: increased ketoconazole metabolism

Theophylline: decreased theophylline blood level

Topical corticosteroids: increased corticosteroid absorption

Triazolam (oral): increased triazolam effects

Drug-diagnostic tests.Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase: increased levels

Hemoglobin, platelets, white blood cells: decreased levels

Drug-herbs.Yew: inhibited ketoconazole metabolism

Patient monitoring

Assess for suicidal ideation and signs and symptoms of depression.

Monitor for evidence of hepatotoxicity, such as nausea, fatigue, jaundice, dark urine, and pale stools.
• With long-term therapy, stay alert for adrenal crisis.

Patient teaching

Advise patient to watch for signs and symptoms of depression and to immediately report suicidal thoughts.

Teach patient to recognize and immediately report signs and symptoms of hepatotoxicity, such as unusual tiredness or yellowing of skin or eyes.
• Advise patient not to take antacids for at least 2 hours after oral ketoconazole.
• Instruct patient to apply cream to damp skin of affected area and wide surrounding area.
• Tell patient to wet hair before applying shampoo and to massage into scalp for 1 minute; then leave on for 5 minutes before rinsing off. Tell him to shampoo again, leaving it on for 3 minutes this time before rinsing.
• Caution patient not to apply shampoo to broken or inflamed skin.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.

ketoconazole

/ke·to·co·na·zole/ (ke″to-kon´ah-zōl) a derivative of imidazole used as an antifungal agent.

ketoconazole

(kē′tō-kə-nā′zōl′)
n.
A broad-spectrum antifungal agent, C26H28Cl2N4O4, administered as a topical treatment or as a second-line oral treatment for a variety of fungal infections.

ketoconazole

[-kō′nəzōl]
an antifungal agent.
indications It is prescribed for the treatment of candidiasis, coccidioidomycosis, histoplasmosis, and other fungal diseases.
contraindications Known hypersensitivity to this drug prohibits its use. It should not be used for fungal meningitis. Because it is also an inhibitor of some important drug metabolizing enzymes and can cause toxic intermediates from other drugs to accumulate, the safe use of ketoconazole with other prescribed medications should be verified.
adverse effects The most serious adverse effects are liver disorders.

ketoconazole

Nizoral Infectious disease An oral imidazole that inhibits fungal cytochrome P450-dependent steroid synthesis, which is effective against candidiasis, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, paracoccidioidomycsis Adverse effects Liver problems, ↓ production of hormones–eg, testosterone

ketoconazole

An imidazole antifungal drug. Ketoconazole is absorbed into the blood from the intestine and can be used to treat internal (systemic) fungal infections as well as skin fungal infections. It can, however, damage the liver. Brand names are Daktarin Gold and Nizoral.

ketoconazole

; Nizoral imidazole antifungal agent, not effective against toenail onychomycosis; patients on systemic ketoconazole should be monitored for liver function; systemic dose = 200 mg daily for 14 days

antifungal agent 

Any substance which destroys or prevents the growth of fungi. It is one of the antibiotic groups. There are several classes of antifungal drugs: Polyenes, which cause an increase in fungal cell wall permeability leading to its death. Examples: amphotericin B, natamycin, nystatin. Azoles, which act either by inhibiting the synthesis of ergosterol, a component of fungal cell wall or by causing direct wall damage. Examples: clotrimazole, econazole, fluconazole, itraconazole, ketoconazole, miconazole. Pyrimidines, which interfere with the normal function of fungal cells. Example: flucytosine. Syn antimycotic agent.

ketoconazole

(kē´tōkon´əzōl´),
n a broad-spectrum synthetic antifungal agent applied to the skin to inhibit the growth of dermatophytes and yeasts, effective in
Candida infections and in the treatment of seborrheic dermatitis;
brand name: Nizoral;
drug class: imidazole antifungal;
action: alters cell membranes and inhibits several fungal enzymes;
uses: systemic candidiasis, chronic mucocutaneous candidiasis, candiduria, coccidioidomycosis, histoplasmosis, chromomycosis, paracoccidioidomycosis, tinea pedis.

ketoconazole

an imidazole antifungal agent, used orally and topically as the nitrate in the treatment of cutaneous and systemic fungal infections. It also inhibits steroidogenesis and has been used in the treatment of canine hyperadrenocorticism; infertility and teratogenicity may occur.
References in periodicals archive ?
Although ketoconazole produced a slightly stronger drug-retention effect, grapefruit juice has the advantage that it is non-toxic, with no risk of overdose.
For ketoconazole and itraconazole controls, the inhibition diameter values obtained ranged from 23-32 mm and 16-20 mm with the mean inhibition diameter being 29.
Antiproliferative synergism of the allylamine SF 86-327 and ketoconazole on epimastigotes and amastigotes of Trypanosoma (Schizotrypanum) cruzi.
Medical agents for treating Cushing's syndrome Adrenal steroidogenesis Drugs modulating ACTH release inhibitors from the pituitary Metyrapone Dopamine agonists Ketoconazole Somatostatin analogues Mitotane Cyproheptadine Aminoglutethimide Ritanserine Trilostane Sodium valproate Etomidate PPAR agonists
Changes to the clinical pharmacology section of the label note that trazodone--indicated for the treatment of depression--is a substrate of the cytochrome P450 3A4 (CYP3A4) enzyme and that trazodone metabolism can be inhibited by the CYP3A4 inhibitors ketoconazole, ritonavir, and indinavir.
Taro's Ketoconazole Cream is bioequivalent to Nizoral(R) Cream, a product of Janssen Pharmaceutica Products, L.
Chronic graft dysfunction, while less frequent in the ketoconazole group in the first posttransplant year, was equally prevalent in both groups by the end of the study.
Ketoconazole 2% Cream is Teva's generic version of Janssen's anti-fungal drug Nizoral(R) 2% Cream, of which annual US sales are approximately $65 million.
Here are some of the better-known ones: the anti-ulcer drug and indigestion remedy cimetidine, water tablets like bendrofluazide, the anti-fungal ketoconazole, the heart pill digoxin, beta-blockers like propanolol and the hormonal treatments for prostate cancer (like cyproterone acetate).
In 1992, however, several deaths among liver patients and patients taking Seldane at the same time they were using ketoconazole or erythromycin caused the FDA and the drug company to warn doctors, pharmacists, and patients of the potential danger of taking Seldane at the same time as these other two drugs.
But in 1992, doctors discovered that people with liver disease or who took ketoconazole, an antifungal agent, or erythromycin, an antibiotic, could suffer heart rhythm problems by taking Seldane.
The drugs used in routine clinical management of HIV/AIDS in the Uganda health care system are the least expensive essential drugs on the national essential drugs list; for example, both nystatin and ketoconazole are on the list but only small quantities of ketoconazole are bought because of its greater cost.