ketoconazole (systemic) (kee-toe-koe-na-zole)
ketoconazole (topical) (kee-toe-kon-a-zole)
Extina, Nizoral, Nizoral A-D, Xolegel
Therapeutic: antifungals (systemic)
Systemic: treatment of Candidiasis (disseminated and mucocutaneous), Chromomycosis, Coccidioidomycosis, Histoplasmosis, Paracoccidioidomycosis.
Unlabeled Use: Treatment of advanced prostate cancer. Treatment of Cushing's syndrome.
Topical: treatment of a variety of cutaneous fungal infections, including cutaneous candidiasis, tinea pedis (athlete's foot), tinea cruris (jock itch), tinea corporis (ringworm), dandruff (as a shampoo), seborrheic dermatitis, and tinea versicolor.
Disrupts fungal cell membrane. Interferes with fungal metabolism. Also inhibits the production of adrenal steroids. Therapeutic Effects: Fungistatic or fungicidal action against susceptible organisms, depending on organism and site of infection. Spectrum: Active against many pathogenic fungi, including Blastomyces, Candida, Coccidioides, Cryptococcus, Histoplasma, Many dermatophytes.
Adverse Reactions/Side Effects
CNS: dizziness, drowsiness. EENT: photophobia. GI: DRUG-INDUCED HEPATITIS, nausea, vomiting, abdominal pain, constipation, diarrhea, flatulence. GU: azoospermia, ↓ male libido, menstrual irregularities, oligospermia. Derm: rashes, ↑ hair loss (shampoo). Endo: gynecomastia. Local: burning, itching, local hypersensitivity reactions, redness, stinging.
PHYSICAL THERAPY IMPLICATIONS
Examination and Evaluation
Be alert for signs of drug-induced hepatitis, including anorexia, abdominal pain, severe nausea and vomiting, yellow skin or eyes, fever, sore throat, malaise, weakness, facial edema, lethargy, and unusual bleeding or bruising. Notify physician immediately of these signs.
Monitor rashes or other severe skin reactions such as exfoliation, hives, itching, raised patches of red or white skin (welts), burning, acne, and abnormal sweating. Notify physician immediately because certain skin responses may indicate serious hypersensitivity reactions.
Assess dizziness or drowsiness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician and nursing staff, and caution the patient and family/caregivers to guard against falls and trauma.
For cutaneous infections, assess healing of skin lesions to help document drug effectiveness.
Avoid contact with cutaneous lesions when treating patient.
Always wash hands thoroughly and disinfect equipment (whirlpools, electrotherapeutic devices, treatment tables, and so forth) to help prevent the spread of infection. Use universal precautions or isolation procedures as indicated for specific patients.
Advise patient to take or apply this drug as directed for the full course of treatment even if feeling better.
Advise patient to report any increased local sensitivity to topical application of this drug (pain, burning, itching, swelling) or extensive hair loss when used as a shampoo.
Instruct patients with cutaneous infections about proper hygiene; e.g., thoroughly wash and dry the affected area, wear clean socks and ventilated shoes for tinea pedis, and so forth.
Inform patient that early relief of cutaneous symptoms may be seen in 2–3 days. Full therapeutic response may take 2 wk for candidiasis, tinea cruris, tinea corporis, and tinea versicolor, and 4–6 wk for tinea pedis.
Advise patient to seek medical help if infections persist or recur after the full treatment. Recurrent fungal infections may be a sign of systemic illness.
Instruct patient on systemic doses to report other troublesome side effects such as prolonged or severe headache, increased visual sensitivity to light (photophobia), fever, ringing/buzzing in the ears (tinnitus), decreased libido, breast enlargement in men, menstrual irregularities, skin problems (rash, itching), or GI reactions (diarrhea, nausea, vomiting, constipation, flatulence, abdominal pain).
Absorption: Absorption from the GI tract is pH dependent; increasing pH decreases absorption.
Distribution: Widely distributed. CNS penetration is unpredictable and minimal. Crosses the placenta; enters breast milk.
Metabolism and Excretion: Partially metabolized by the liver. Excreted in feces via biliary excretion.
TIME/ACTION PROFILE (blood levels)
|ROUTE ||ONSET ||PEAK ||DURATION |
|PO ||rapid ||1–4 hr ||24 hr |
|topical ||unknown ||unknown ||Unknown |
Systemic use contraindicated in: Hypersensitivity; Pregnancy or lactation; Concurrent triazolam.
Use Cautiously in: Systemic—History of liver disease; Achlorhydria or hypochlorhydria; Alcoholism. Topical—Nail and scalp infections (may require additional systemic therapy); OB/Lactation: Safety not established.
Drug-Drug: Ketoconazole inhibits the hepatic P4503A4 enzyme system, which results in ↓ metabolism and possibly ↑ effects and/or toxicity from cyclosporine, tacrolimus, corticosteroids (dosage reduction may be necessary), calcium channel blockers, sulfonylurea, oral hypoglycemic agents, quinidine, buspirone, clarithromycin, troleandomycin, erythromycin, cyclophos-phamide, phenytoin, warfarin (↑ risk of bleeding), tamoxifen, tricyclic antidepressants, carbamazepine, nisoldipine, zolpidem, vinca alkaloids, ifosfamide, some benzodiazepines (effect may persist for several days; use of triazolam is contraindicated), alfentanil, fentanyl, sufentanil, donepezil, atorvastatin, lovastatin, simvastatin, amprenavir, indinavir (dosage ↓ of indinavir recommended), nelfinavir, ritonavir, saquinavir, quinidine, sildenafil and vardenafil (dosage adjustments may be necessary). May alter the effectiveness of hormonal contraceptives (alternative method of contraception recommended). Drugs that ↑ gastric pH, including antacids, histamine H2 antagonists, didanosine (chewable tablets, because of buffer), and gastric acid–pump inhibitors ↓ absorption (wait 2 hr before administration of ketoconazole). Sucralfate and isoniazid also ↓ bioavailability. ↑ hepatotoxicity with other hepatotoxic agents, including alcohol. Disulfiram-like reaction may occur with alcohol. Rifampin or isoniazid may ↓ levels and effectiveness. May ↓ absorption and effectiveness of theophylline.
PO (Adults): Antifungal—200–400 mg/day, single dose. Prostate cancer—400 mg tid (unlabeled).
PO (Children >2 yr): 3.3–6.6 mg/kg/day, single dose.
Topical (Adults and Children ≥12 yr): Apply cream once daily for cutaneous candidiasis, tinea corporis, tinea cruris, tinea pedia, and tinea versicolor. Apply cream twice daily for seborrheic dermatitis. Patients with cutaneous candidiasis, tinea cruris, tinea corporis, and tinea versicolor should be treated for 2 wk. Patients with tinea pedis should be treated for 6 wk. Patients with seborrheic dermatitis should be treated for 4 wk (2 wk with gel). For dandruff, use shampoo twice weekly (wait 3–4 days between treatments) for 4 wk, then intermittently.
Availability (generic available)
Tablets: 200 mg. Oral suspension: 100 mg/5 mL. Cream: 2%. Shampoo: 1% OTC. Foam: 2%. Gel: 2%.