Ketoconazole

Trade Names:Extina- Foam 2%

Trade Names:Ketoconazole- Tablets 200 mg

Trade Names:Kuric- Cream 2% in an aqueous vehicle

Trade Names:Nizoral- Shampoo 2% in an aqueous suspension

Trade Names:Nizoral A-D- Shampoo 1%

Trade Names:Xolegel- Gel 2%

Pharmacology

Impairs synthesis of ergosterol, allowing increased permeability in fungal cell membrane and leakage of cellular components.

Pharmacokinetics

Absorption

C _max is approximately 3.5 mcg/mL (with a 200 mg oral dose taken with a meal). T _max is 1 to 2 h. Requires acidity for dissolution and absorption. Absorbed in the GI.

Distribution

Approximately 99% protein bound (in vitro), mainly to the albumin fraction. Only a negligible proportion reaches the cerebrospinal fluid.

Metabolism

Major metabolic pathways are oxidation and degradation of the imidazole and piperazine rings, oxidative O-dealkylation, and aromatic hydroxylation. It is converted into several inactive metabolites.

Elimination

Approximately 13% of dose is excreted in urine; 2% to 4% is unchanged drug. The major route of excretion is through the bile into the intestinal tract. Plasma elimination is biphasic with t _½ of 2 h during the first 10 h, and t _½ of 8 h after 10 h.

Indications and Usage

Treatment of susceptible systemic and cutaneous fungal infections.

Treatment of seborrheic dermatitis in immunocompetent adults and children 12 yr of age and older.

Cutaneous candida; tinea corporis; tinea cruris; tinea pedis; tinea versicolor; seborrheic dermatitis ( Kuric ).

Scaling due to dandruff.

Tinea versicolor.

Contraindications

Oral ketoconazole coadministered with astemizole, cisapride, terfenadine, and/or triazolam; hypersensitivity to any components.

Dosage and Administration

PO 200 to 400 mg daily for 1 wk to 6 mo depending on infection.

PO A small number of children older than 2 yr of age have been treated with 3.3 to 6.6 mg/kg daily for 1 wk to 6 mo depending on infection.

Topical

Apply to affected and immediate surrounding areas every day for 2 wk (candidiasis, tinea cruris, tinea corporis, and tinea versicolor) or 6 wk (tinea pedis). For seborrheic dermatitis, apply to affected areas twice daily for 4 wk or until clinical clearing ( Kuric ).

Apply to affected area(s) twice daily for 4 wk.

Apply to affected area once daily for 2 wk.

Apply to affected area and a wide margin of surrounding area, lather, leave in place for 5 min, then rinse. One application only.

Apply to wet hair, lather, rinse thoroughly, and repeat. Use shampoo every 3 to 4 days for up to 8 wk.

• Holding the container upright, dispense into cap of the can or other cool surface in an amount sufficient to cover affected area(s).
• Because the foam will begin to melt immediately upon contact with warm skin, do not dispense directly onto hands.
• Pick up small amounts of foam with fingertips and gently massage into affected area(s) until foam disappears.
• For hair-bearing areas, part hair and apply foam directly to the skin.
• Avoid contact with eyes and/or mucous membranes.

• Avoid contact with the eyes and/or mucous membranes.

Storage/Stability

Store at 68° to 77°F. Store Kuric cream below 77°F.

Store at 68° to 77°F. Do not refrigerate. Do not expose container to heat or store at temperatures higher than 120°F. Do not store in direct sunlight. Contents are flammable and under pressure. Do not puncture or incinerate container.

Store at 59° to 86°F.

Store at 35° to 86°F. Protect from light.

Store below 77°F. Protect from light.

Store at controlled room temperature (59° to 77°F) in tightly closed container. Protect from moisture.

Drug Interactions

Rare cases of disulfiram-like reactions to alcohol have been reported.

Increased alfuzosin levels; avoid concomitant use.

Do not take almotriptan within 7 days of ketoconazole; do not take eletriptan within 72 h of ketoconazole.

Increased gastric pH may inhibit ketoconazole absorption; separate administration by at least 2 h.

Plasma levels may be elevated by ketoconazole; reduce aripiprazole dose by 50% during coadministration.

Plasma levels of benzodiazepines may be increased and prolonged.

Plasma levels may be elevated by ketoconazole, increasing the risk of adverse reactions.

Plasma levels may be elevated by ketoconazole; coadministration with ketoconazole is contraindicated.

Antiplatelet effect of clopidogrel may be inhibited.

Increased bioavailability and decreased clearance of corticosteroid.

May decrease ketoconazole absorption.

Elevated plasma levels of dofetilide may increase the risk of life-threatening cardiac arrhythmia.

Plasma levels may be increased by ketoconazole; if coadministration cannot be avoided, carefully monitor patient for rhabdomyolysis and consider using pravastatin.

Metabolism of one or both drugs may be altered. Monitor the clinical response.

Plasma levels may be elevated by ketoconazole; reduce dose of phosphodiesterase.

Decreased serum levels of either drug; avoid concomitant use.

Decreased theophylline serum concentrations.

Plasma levels may be elevated by ketoconazole; avoid coadministration.

Increased anticoagulant effect.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Increased intracranial pressure, neuropsychiatric disturbances, paresthesia (postmarketing).

Headache (1%).

Dermatologic

Pruritus (2%); alopecia (postmarketing).

GI

Nausea, vomiting (3%); abdominal pain (1%).

Genitourinary

Oligospermia (with high doses).

Hepatic

Hepatic function impairment.

Local

Pruritus, severe irritation, stinging; contact dermatitis (postmarketing).

Photo-allergenicity (17%); application-site burning (10%); application-site reaction (6%).

Application-site burning (4%).

Application-site reaction, dry skin, pruritus (3% or less).

Metabolic-Nutritional

Hypertriglyceridemia (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Safety and efficacy not established in children younger than 12 yr of age.

Sulfite Sensitivity

Cream contains sodium sulfite anhydrous, which may cause allergic-type reactions, including anaphylaxis.

Anaphylaxis

Has occurred after the first dose.

Gastric acidity

Oral ketoconazole requires acid environment for dissolution and absorption.

Hormone levels

May lower serum testosterone or suppress adrenal corticosteroid secretion.

Sensitization

Foam may cause contact sensitization, including photoallergenicity.

QT interval

Oral ketoconazole coadministration with terfenadine, astemizole, or cisapride has led to prolongation of the QT interval, resulting in life-threatening arrhythmias, including torsades de pointes.

Overdosage

Symptoms

No data available.

Patient Information

• Advise patient to read the patient information leaflet before using product the first time and with each refill.

• Oral
• Instruct patient that if a dose is missed, to take it as soon as possible. If several hours have passed or if it is close to the time of next dose, do not double the dose. Notify health care provider if more than 1 dose is missed.
• Advise patient not to take medication with antacids. If antacids are required, take ketoconazole 2 h before antacid.
• Emphasize importance of completing full course of therapy, even if signs and symptoms resolve. Advise patient that maintenance therapy may be required for chronic infections.
• Instruct patient to report the following symptoms to health care provider: abdominal pain, dark urine, diarrhea, fatigue, fever, loss of appetite, nausea, pale stools, vomiting, yellowing of skin.
• Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
• Instruct patient not to take OTC medications, including antihistamines, without consulting health care provider.

• Topical
• Inform patient that product is for external use only.
• Advise patients that product may be irritating to mucous membranes and to avoid contact with eyes, nostrils, and mouth.
• Instruct patients to wash hands after application.
• Instruct patient to notify health care provider if severe itching, irritation, or stinging occurs after application.

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