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Action/Kinetics:
Inhibits synthesis of sterols (e.g., ergosterol), damaging the cell membrane and resulting in loss of essential intracellular material. Also inhibits biosynthesis of triglycerides and phospholipids and inhibits oxidative and peroxidative enzyme activity. When used to treat
Candida albicans it inhibits transformation of blastospores into the invasive mycelial form. Inhibits growth of
Pityrosporum ovale when used to treat dandruff. Use in Cushing's syndrome is due to its ability to inhibit adrenal steroidogenesis.
Peak plasma levels: 3.5 mcg/mL after 1-2 hr after a 200-mg dose.
t
1/2 [biphasic]: first, 2 hr; second, 8 hr. Requires acidity for dissolution. Metabolized in liver to inactive metabolites and most excreted through feces.
Uses:
PO: Candidiasis, chronic mucocutaneous candidiasis, candiduria, histoplasmosis, chromomycosis, oral thrush, blastomycosis, coccidioidomycosis, paracoccidioidomycosis. Recalcitrant cutaneous dermatophyte infections not responding to other therapy.
Cream: Tinea pedis. Tinea corporis and tinea cruris due to
Trichophyton rubrum, T. mentagrophytes and
Epidermophyton floccosum. Tinea versicolor caused by
Microsporum furfur; cutaneous candidiasis caused by
Candida species; seborrheic dermatitis.
Shampoo: To reduce scaling due to dandruff and tinea versicolor.
Investigational: Onychomycosis due to
Candida and
Trichophyton. High doses to treat CNS fungal infections. Advanced prostate cancer, Cushing's syndrome.
Contraindications:
Hypersensitivity, fungal meningitis. Topical product not for ophthalmic use. Use during lactation.
Special Concerns:
Use tablets with caution in children less than 2 years of age. The safety and effectiveness of the shampoo and cream have not been determined in children. Use with caution during lactation.
Side Effects:
GI: N&V;, abdominal pain, diarrhea.
CNS: Headache, dizziness, somnolence, fever, chills, suicidal tendencies, depression (rare).
Hematologic: Thrombocytopenia, leukopenia,
hemolytic anemia.
Miscellaneous: Hepatotoxicity, photophobia, pruritus, gynecomastia, impotence, bulging fontanelles, urticaria, decreased serum testosterone levels, anaphylaxis (rare).
Topical cream: Stinging, irritation, pruritus.
Shampoo: Increased hair loss, irritation, abnormal hair texture, itching, oiliness or dryness of the scalp and hair, scalp pustules.
Laboratory Test Alterations:
Transient
serum liver enzymes.
Serum testosterone.
Drug Interactions:
-
Antacids /
Absorption of ketoconazole R/T
pH
-
Anticoagulants /
Anticoagulant effect
-
Anticholinergics /
Absorption of ketoconazole R/T
pH
-
Cisapride /
Risk of serious cardiac arrhythmias
-
Corticosteroids /
Risk of drug toxicity R/T
bioavailability
-
Cyclosporine /
Cyclosporine levels (ketaconazole may be used therapeutically to decrease cyclosporine dose)
-
Donepezil /
Plasma levels of donepezil R/T
liver metabolism
-
Histamine H
2 antagonists /
Ketoconazole absorption R/T
pH
-
Isoniazid /
Bioavailability of ketoconazole
-
Nisoldipine /
Nisoldipine plasma levels R/T
liver metabolism
-
Rifampin /
Serum levels of both drugs
-
Theophyllines /
Serum theophylline levels
-
Zolpidem /
Half-life of zolpidem R/T
liver metabolism
How Supplied:
Cream: 2%;
Shampoo: 1%, 2%;
Tablet: 200 mg
Dosage
?Tablets
Fungal infections.
Adults: 200 mg once daily; in serious infections or if response is not sufficient, increase to 400 mg once daily.
Pediatric, over 2 years: 3.3-6.6 mg/kg once daily. Dosage has not been established for children less than 2 years of age.
CNS fungal infections.
Adults: 800-1,200 mg/day.
Advanced prostate cancer.
400 mg q 8 hr.
Cushing's syndrome.
800-1,200 mg/day.
?Topical Cream (2%)
Tinea corporis, tinea cruris, tinea versicolor, tinea pedis, cutaneous candidiasis.
Cover the affected and immediate surrounding areas once daily (twice daily for more resistant cases). Duration of treatment is usually 2 weeks.
Seborrheic dermatitis.
Apply to affected area b.i.d. for 4 weeks or until symptoms clear.
?Shampoo (1%, 2%)
Use twice a week for 4 weeks with at least 3 days between each shampooing.
Then, use as required to maintain control.
