Nizoral

Ni·zo·ral (nz-rl)

A trademark for a preparation of ketoconazole.

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Nizoral,

trademark for an antifungal agent (ketoconazole).

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ketoconazole

Dactarin Gold (UK), Dandrazol (UK), Dandrid (UK), Ketozole, Nizoral, Nizoral A-D

Pharmacologic class: Imidazole

Therapeutic class: Antifungal

Pregnancy risk category C

FDA Boxed 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 need-ed to control symptoms; 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

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.)

Route	Onset	Peak	Duration
P.O.	Unknown	1-2 hr	Unknown
Topical	Unknown	Unknown	Unknown

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.

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Nizoral®

Ketoconazole, see there