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Ketoconazole (Topical)


General


Pronunciation

(kee toe KOE na zole)


Brand Names: U.S.

  • Extina
  • Ketodan
  • Nizoral
  • Nizoral A-D [OTC]
  • Xolegel

Indications


Use: Labeled Indications

Cream: Treatment of tinea corporis (ringworm), tinea cruris (jock itch), and tinea pedis (athletes foot) caused by Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum; treatment of tinea (pityriasis) versicolor caused by Pityrosporum orbiculare (also known as Malassezia furfur); treatment of cutaneous candidiasis caused by Candida sp; treatment of seborrheic dermatitis

Foam, gel: Treatment of seborrheic dermatitis in immunocompetent adults and children 12 years and older

Limitations of use: Safety and efficacy for the treatment of fungal infections have not been established.

Shampoo:

US labeling: Treatment of tinea versicolor caused by or presumed to be caused by P. orbiculare (M. furfur or Malassezia orbiculare)

Canadian labeling: Treatment and prophylaxis of conditions caused by Pityrosporum (eg, pityriasis capitis [dandruff]); treatment of seborrheic dermatitis

OTC labeling: Controls flaking, scaling, and itching associated with dandruff


Contraindications


Hypersensitivity to ketoconazole or any component of the formulation.

OTC labeling: When used for self-medication, do not use on scalp that is broken or inflamed.

Documentation of allergenic cross-reactivity for azole antifungals is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.


Dosing and Administration


Dosing: Adult

Cutaneous candidiasis: Topical: Cream: Apply once daily to cover the affected and immediate surrounding area for 2 weeks. Note: Canadian labeling recommends a duration of 2 to 3 weeks.

Dandruff: Topical:

Shampoo 1% (OTC labeling): Apply to wet hair, lather, and rinse thoroughly; repeat. Use every 3 to 4 days for up to 8 weeks; then apply only as needed to control dandruff.

Shampoo 2% (Canadian product only): Apply 5 to 10 mL to wet scalp, lather, leave on 3 to 5 minutes, and rinse; apply once every 1 to 2 weeks (prophylaxis) or twice weekly for 2 to 4 weeks (treatment).

Seborrheic dermatitis: Topical:

Cream: Apply to the affected area twice daily for 4 weeks or until clinical response is noted

Foam: Apply to affected area twice daily for 4 weeks

Gel: Apply to the affected area once daily for 2 weeks

Shampoo 2% (Canadian product only; OTC labeling): Apply 5 to 10 mL to wet scalp, lather, leave on 3 to 5 minutes, and rinse; apply twice weekly for 2 to 4 weeks.

Tinea corporis, tinea cruris, tinea pedis: Topical: Cream: Apply to the affected and immediate surrounding area once daily.

Duration of treatment:

US labeling: Tinea corporis, cruris: 2 weeks; tinea pedis: 6 weeks.

Canadian labeling: Tinea corporis: 3 to 4 weeks; tinea cruris: 2 to 4 weeks; tinea pedis: 4 to 6 weeks.

Tinea versicolor: Topical:

Cream: Apply once daily to cover the affected and immediate surrounding area for 2 weeks. Note: Canadian labeling recommends a duration of 2 to 3 weeks.

Shampoo 2%: Apply to affected area of damp skin, lather, leave on 5 minutes, and rinse (one application is usually sufficient)

Susceptible fungal infections in the oral cavity (candidiasis, oral thrush, and chronic mucocutaneous candidiasis) (off-label use): Topical: Cream: Apply locally as directed with a thin coat to inner surface of denture and affected areas after meals


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Dandruff: Topical:

Shampoo 1% (OTC labeling): Children ≥12 years and Adolescents: Refer to adult dosing.

Shampoo 2% (Canadian product only): Children >12 years and Adolescents: Refer to adult dosing.

Seborrheic dermatitis: Topical:

Foam, gel: Children ≥12 years and Adolescents: Refer to adult dosing.

Shampoo 2% (Canadian product only): Children >12 years and Adolescents: Refer to adult dosing.


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturers labeling. However, dosage adjustment unlikely due to low systemic absorption.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturers labeling. However, dosage adjustment unlikely due to low systemic absorption.


Administration

Topical: For external use only; not for ophthalmic, oral, or intravaginal use. Avoid contact with the eyes and other mucous membranes. Wash hands after application.

Cream: Apply to the affected and immediate surrounding area.

Foam: Dispense foam into the cap of the can or other cool surface; do not dispense directly onto hands (foam will begin to melt upon contact with warm skin). Pick up small amounts of foam with the fingertips and gently massage into the affected area until the foam disappears. For hair-bearing areas, part the hair so that foam may be applied directly to the skin (rather than on the hair). Avoid exposure to flame or smoking during and immediately following application.

Gel: Apply a thin layer to affected area with fingertips. Do not wash affected area for at least 3 hours after application; wait at least 20 minutes after gel application before applying makeup or sunscreen to the treated areas.

Shampoo:

Thoroughly wet affected area, apply shampoo, lather generously, and rinse thoroughly; the Canadian labeling recommends leaving on for 3 to 5 minutes before rinsing. Do not use on areas that are broken or inflamed.

For tinea versicolor, apply shampoo to damp skin of the affected area; leave on skin for 5 minutes before rinsing.


Storage

Cream: Store at <25 ‚ °C (<77 ‚ °F).

Foam: Store at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F). Do not refrigerate. Do not expose container to heat and/or store at >49 ‚ °C (120 ‚ °F). Do not store in direct sunlight. Contents are flammable; do not puncture or incinerate.

Gel: Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Contents are flammable; avoid fire, flame, or smoking during and immediately following application.

Shampoo:

Rx: Store at ≤25 ‚ °C ( ≤77 ‚ °F). Protect from light.

OTC: Store at 2 ‚ °C to 30 ‚ °C (35 ‚ °F to 86 ‚ °F); protect from light and freezing.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Cream, External:

Generic: 2% (15 g, 30 g, 60 g)

Foam, External:

Extina: 2% (50 g, 100 g) [contains alcohol, usp, cetyl alcohol, propylene glycol]

Ketodan: 2% (100 g) [contains alcohol, usp, cetyl alcohol, propylene glycol]

Generic: 2% (50 g, 100 g [DSC])

Gel, External:

Xolegel: 2% (45 g) [contains alcohol, usp, fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow), propylene glycol]

Kit, External:

Ketodan: 2% [contains cetyl alcohol, edetate disodium, propylene glycol]

Shampoo, External:

Nizoral: 2% (120 mL) [contains fd&c red #40]

Nizoral A-D: 1% (125 mL, 200 mL)

Generic: 2% (120 mL)


Drug Interactions

There are no known significant interactions.


Adverse Reactions


Topical cream/gel:

1% to 10%:

Central nervous system: Localized burning (4%)

Dermatologic: Stinging of the skin (5%)

Frequency not defined:

Central nervous system: Dizziness, headache, pain, paresthesia

Dermatologic: Acne vulgaris, erythema, facial swelling, impetigo, nail discoloration, pruritus, pustules, pyogenic granuloma, xeroderma

Hypersensitivity: Hypersensitivity reaction, contact dermatitis (possibly related to sulfites or propylene glycol)

Local: Application site discharge, local irritation (severe)

Ophthalmic: Eye irritation, keratoconjunctivitis sicca, swelling of eye

Topical foam:

1% to 10%: Local: Application site burning (10%), application site reaction (6%)

Frequency not defined: Dermatologic: Contact dermatitis, erythema, pruritus, skin rash, xeroderma

Shampoo:

1% to 10%:

Dermatologic: Pruritus ( ≤3%), xeroderma ( ≤3%), abnormal hair texture (<1%), loss of scalp hair (<1%), scalp pustules (<1%)

Local: Application site reaction ( ≤3%), local irritation (<1%)

Frequency not defined:

Central Nervous System: Burning sensation

Dermatologic: Alopecia, dry hair, hair discoloration, oily hair, skin rash, urticaria

Hypersensitivity: Anaphylaxis, angioedema, hypersensitivity reaction


Warnings/Precautions


Concerns related to adverse effects:

- Hypersensitivity reactions: Severe hypersensitivity reactions, including contact sensitization, photoallergenicity, and anaphylaxis (rare) have been reported; discontinue use if hypersensitivity occurs.

- Irritation: May cause irritation at the site of application; discontinue use if irritation occurs.

Dosage form specific issues:

- Foam: Formulation contains alcohol and propane/butane; do not expose to open flame and/or smoking during or immediately after application. Do not puncture and/or incinerate container.

- Gel: Flammable; avoid exposure to fire, flames, or smoking during or immediately after application.

- Shampoo: Use may remove curl from permanently wavy hair, cause hair discoloration, and changes in hair texture.

- Sulfites: Some dosage forms contain sulfites which may cause allergic-type reactions (including anaphylaxis) as well as life-threatening or less severe asthmatic episodes in certain individuals.

Other warnings/precautions:

- Appropriate use: Avoid contact with the eyes and other mucous membranes. Not for ophthalmic, oral, or intravaginal use. If condition worsens or does not improve after the treatment period, discontinue use and contact health care provider.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events have been observed in animal reproduction studies with oral ketoconazole. Ketoconazole is not detectable in the plasma following chronic use of the shampoo.


Actions


Pharmacology

Alters the permeability of the cell wall by blocking fungal cytochrome P450; inhibits biosynthesis of triglycerides and phospholipids by fungi; inhibits several fungal enzymes that results in a build-up of toxic concentrations of hydrogen peroxide; also inhibits androgen synthesis


Absorption

Shampoo: None; Cream, Foam, Gel: Minimal


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience burning, straight hair, hair loss, or hair discoloration. Have patient report immediately to prescriber severe skin irritation, redness, or severe scalp irritation (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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