General

Pronunciation
kee-toe-KOE-na-zole

Trade Name(s)

• Nizoral

Pregnancy Category
Category C

Ther. class.
antifungals
(systemic)

Indications

Treatment of

» Candidiasis (disseminated and mucocutaneous)

» Chromomycosis

» Coccidioidomycosis

» Histoplasmosis

» Paracoccidioidomycosis

Unlabelled Use(s):

• Treatment of advanced prostate cancer

• Treatment of Cushing's syndrome

Action

• Disrupts fungal cell membrane

• Interferes with fungal metabolism

• Also inhibits the production of adrenal steroids

Therapeutic Effect(s):
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

Pharmacokinetics

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

Protein Binding: 99%

Metabolism and Excretion: Partially metabolized by the liver. Excreted in feces via biliary excretion

Half-life: 8 hr

TIME/ACTION PROFILE (blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	1–4 hr	24 hr

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity

• Pregnancy or lactation

• Concurrent triazolam

Use Cautiously in:

• History of liver disease

• Achlorhydria or hypochlorhydria

• Alcoholism

Adverse Reactions/Side Effects

CNS: dizziness, drowsiness.

EENT: photophobia.

GI: DRUG-INDUCED HEPATITIS, nausea, vomiting, abdominal pain, constipation, diarrhea, flatulence.

GU: azoospermia, decreased male libido, menstrual irregularities, oligospermia.

Derm: rashes.

Endo: gynecomastia.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• Ketoconazole inhibits the hepatic P450 3A4 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, cyclophosphamide, 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

Route/Dosage

• PO (Adults):
Antifungal—200–400 mg/day, single dose.
Prostate cancer—400 mg 3 times daily (unlabeled).

• PO (Children >2 yr): 3.3–6.6 mg/kg/day, single dose.

Availability

• Tablets: 200 mg

• Oral suspension: 100 mg/5 ml[canada]

Assessment

• Assess patient for symptoms of infection prior to and periodically during therapy

• Specimens for culture should be taken prior to instituting therapy. Therapy may be started before results are obtained

Lab Test Considerations

• Monitor hepatic function tests prior to and monthly for 3–4 mo and then periodically during therapy. May cause AST, ALT, serum alkaline phosphatase, and bilirubin concentrations. Ketoconazole should be discontinued if even minor abnormalities occur

» May cause serum testosterone concentrations

Potential Nursing Diagnoses

• Risk for infection (Indications)

• Noncompliance (Patient/Family Teaching)

Implementation

• Do not confuse Nizoral (ketoconazole) with Neoral (cyclosporine)

• PO: Administer with meals or snacks to minimize nausea and vomiting.

» Shake suspension well prior to administration

» Do not administer histamine H₂ antagonists or antacids within 2 hr of ketoconazole

» For patients with achlorhydria, dissolve each tablet in 4 ml of aqueous solution of 0.2 N hydrochloric acid. Use a glass or plastic straw to avoid contact with teeth and follow with a glass of water, swished in mouth and swallowed

Patient/Family Teaching

Instruct patient to take medication as directed, at the same time each day,even if feeling better. Take missed doses as soon as remembered; if almost time for next dose, space missed dose and next dose 10–12 hr apart

» May cause dizziness or drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.

» Advise patient to avoid taking OTC antacids within 2 hr of ketoconazole.

» Caution patient to wear sunglasses and to avoid prolonged exposure to bright light to prevent photophobic reactions

» Advise patient to use a nonhormonal form of contraception during ketoconazole therapy

» Advise patient to avoid concurrent use of alcohol while taking ketoconazole; may cause a disulfiram-like reaction (flushing, rash, peripheral edema, nausea, headache) and increase the risk of hepatotoxicity

» Instruct patient to notify health care professional if abdominal pain, fever, or diarrhea becomes pronounced or if signs and symptoms of liver dysfunction (unusual fatigue, anorexia, nausea, vomiting, jaundice, dark urine, or pale stools) occur

Evaluation/Desired Outcomes

• Resolution of clinical and laboratory indications of fungal infections

• Minimal treatment for candidiasis is 1–2 wk and for other systemic mycoses is 6 mo

» Chronic mucocutaneous candidiasis usually requires maintenance therapy

ketoconazole (systemic) is a sample topic found in Davis's Drug Guide. All other sections of this record are viewable by clicking on the index in the left column, or by clicking on "Display all Sections" in the "Content Manager".

To find other Davis's Drug Guide topics, please login or purchase a subscription.