KETOCONAZOLE

KETOCONAZOLE (ke-to-con'a-zol) Extina, Kuric, Nizoral, Nizoral A-D, Xolegel Classifications: antibiotic; azole antifungal; Therapeutic: azole antifungal antibiotic Prototype: Fluconazole Pregnancy Category: C

Availability

200 mg tablets; 2% cream; 2% shampoo; 2% foam; 2% gel

Action

Fungistatic; may also be fungicidal depending on concentration. Interferes with formation of ergosterol, the principal sterol in the fungal cell membrane that, when depleted, interrupts membrane function by increasing its permeability.

Therapeutic Effect

Antifungal properties are related to the drug effect on the fungal cell membrane functioning.

Uses

Oral—Severe systemic fungal infections including candidiasis (e.g., oral thrush, candiduria), chronic mucocutaneous candidiasis, pulmonary and disseminated coccidioidomycosis, histoplasmosis, paracoccidioidomycosis, blastomycosis, and chromomycosis. Topical—Tinea corporis and tinea cruris (caused by Epidermophyton floccosum, Trichophyton mentagrophytes, and Trichophyton rubrum) and in treatment of tinea versicolor (pityriasis) caused by Malassezia furfur (Pityrosporum obiculare), seborrheic dermatitis.

Unlabeled Uses

Oral—Onychomycosis, vaginal candidiasis, Cushing's syndrome associated with adrenal or pituitary adenoma; precocious puberty, dysfunctional hirsutism, and as swish and swallow preparation for prophylaxis against fungal infections in patients with neutropenia induced by cancer chemotherapy and in patients with AIDS.

Contraindications

Hypersensitivity to ketoconazole or any component in the formulation; chronic alcoholism, fungal meningitis; onychomycosis; ocular exposure, ophthalmic administration; pregnancy (category C).

Cautious Use

Azole antifungal hypersensitivity; achlorhydria, hypochlorhydria; history of hepatic disease, HIV infection; alcoholism; azole antifungal hypersensitivity. Safe use in children <2 y is not established.

Route & Dosage

Fungal Infections Adult: PO 200–400 mg once/d Topical Apply 1–2 times/d to affected area and surrounding skin Child (>2 y): PO 3.3–6.6 mg/kg/d as single dose Dandruff Adult/Child: Topical Shampoo twice a week for 4 wk with at least 3 d between shampoos Topical (Extina) Apply b.i.d. x 4 wk (Xolegel) Apply q.d. x 2 wk

Administration

Oral

• Give with water, fruit juice, coffee, or tea; drug requires an acid medium for dissolution and absorption.
• Relieve nausea and vomiting during early therapy by taking drug with food and dividing into 2 daily doses.
• Do not give with antacids.
• Store in tightly covered container at 15°–30° C (59°–86° F) unless otherwise directed.

Topical

• Apply sufficient shampoo to produce lather to wash scalp and hair and gently massage over entire scalp area for 1 min, rinse hair thoroughly and repeat, leaving shampoo on scalp for 3 min. Rinse thoroughly.

Adverse Effects (≥1%)

Oral—Body as a Whole: Skin rash, erythema, urticaria, pruritus, angioedema, anaphylaxis. GI: Nausea, vomiting, anorexia, epigastric or abdominal pain, constipation, diarrhea, transient elevation in serum liver enzymes, fatal hepatic necrosis (rare). Hematologic: With high doses, lowers serum testosterone and ACTH-induced corticosteroid serum levels, transient decreases in serum cholesterol and triglycerides; hyponatremia (rare). Urogenital: Gynecomastia (males), breast pain; uterine bleeding, loss of libido, impotence, oligospermia, hair loss. Other: Acute hypoadrenalism (reduction of adrenal stress syndrome), renal hypofunction. Topical—Skin: Mild transient erythema, severe irritation, pruritus, stinging.

Interactions

Drug: Alcohol may cause sunburnlike reaction; antacids, anticholinergics, h₂-receptor antagonists decrease ketoconazole absorption; isoniazid, rifampin increase ketoconazole metabolism, thus decreasing its activity; levels of phenytoin and ketoconazole decreased; may increase levels of cyclosporine or carbamazepine, increasing the risk of toxicity; warfarin may potentiate hypoprothrombinemia; may increase ergotamine toxicity of dihydroergotamine, ergotamine; may increase concentration and toxicity of trazodone. Herbal: Echinacea may increase risk of hepatotoxicity.

Pharmacokinetics

Absorption: Erratically from GI tract (needs an acid pH); minimal absorption topically. Peak: 1–2 h. Distribution: Distributed to saliva, urine, sebum, and cerumen; CSF levels unpredictable; distributed into breast milk. Metabolism: In liver (CYP3A4). Elimination: Primarily in feces, 13% in urine. Half-Life: 8 h.

Nursing Implications

Assessment & Drug Effects

• Lab tests: Monitor baseline liver function tests (AST, ALT, alkaline phosphatase, and bilirubin) and repeat at least monthly throughout therapy.
• Monitor for S&S of hepatotoxicity (see Appendix F). Discontinue drug immediately to prevent irreversible liver damage and report to physician.

Patient & Family Education

• Report S&S of hepatotoxicity promptly to physician (see Appendix F).
• Note: Drowsiness and dizziness are early and time-limited adverse effects.
• Do not drive or engage in potentially hazardous activities until response to drug is known.
• Avoid OTC drugs for gastric distress, such as Rolaids, Tums, Alka-Seltzer and check with physician before taking any other nonprescription medicines.
• Do not alter dose or dose interval and do not stop taking ketoconazole before consulting the physician.
• Notify physician if skin condition fails to respond to topical therapy or worsens or if signs of irritation or sensitivity occur.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug