Ketoconazole

Pharmacologic Category

Antifungal Agent, Imidazole Derivative; Antifungal Agent, Topical

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)

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

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

Dosing: Hepatic Impairment: Adult

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

Dosing: Pediatric

Dandruff (flaking, scaling, and itching):

Shampoo (ketoconazole 1%): Children ≥12 years and Adolescents: Topical: OTC labeling: Shampoo every 3 to 4 days for up to 8 weeks; then use only as needed to control dandruff

Shampoo (ketoconazole 2%): Canadian labeling: Children ≥12 years and Adolescents: Topical:

Prophylaxis: Shampoo with 5 to 10 mL once every 1 to 2 weeks

Treatment: Shampoo with 5 to 10 mL twice weekly for 2 to 4 weeks

Seborrheic dermatitis:

Foam: Children ≥12 years and Adolescents: Topical: Apply to affected area twice daily for 4 weeks

Gel: Children ≥12 years and Adolescents: Topical: Apply to affected area once daily for 2 weeks

Shampoo (ketoconazole 2%): Canadian labeling: Children ≥12 years and Adolescents: Topical: Shampoo with 5 to 10 mL twice weekly for 2 to 4 weeks

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; however, dosage adjustment unlikely necessary due to low systemic absorption.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment unlikely due to low systemic absorption.

Use: Labeled Indications

Cream: Treatment of tinea corporis (ringworm), tinea cruris (jock itch), and tinea pedis (athlete's 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

* See Uses in AHFS Essentials for additional information.

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.

Administration: Pediatric

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

Foam (Extina): Children ≥12 years and Adolescents: Hold the container upright and dispense foam into cap or other cool surface; do not dispense into hands as foam will begin to melt immediately upon contact with warm skin. If fingers are warm, rinse in cold water and dry thoroughly; pick up small amounts of foam with the fingers, and gently massage into the affected area(s) until foam disappears. For hair-bearing areas, part the hair, so foam may be applied directly to skin (rather than on the hair). Avoid fire, flame, and/or smoking during and immediately following application.

Gel (Xolegel): Children ≥12 years and Adolescents: Apply thin layer on affected skin; wait at least 3 hours after application before washing area(s). Avoid fire, flame, and/or smoking during and immediately following application. Wait at least 20 minutes after applying the gel before putting makeup or sunscreen on the affected areas.

Shampoo:

1% [OTC product]: Children ≥12 years and Adolescents: Apply to wet hair, lather, and rinse hair thoroughly; repeat

2%: Children ≥12 years and Adolescents: Apply to wet hair, lather, leave on for ~5 minutes, and rinse

Storage/Stability

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.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat fungal infections of the skin.

• It is used to control seborrheic dermatitis.

• It is used to treat dandruff.

Frequently reported side effects of this drug

• Burning

• Straight hair

• Hair loss

• Itching

• Dry skin

• Change in hair texture

• Hair discoloration

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe application site irritation or redness

• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

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.

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.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Instruct patient or caregiver on appropriate use of topical ketoconazole products.

Warnings: Additional Pediatric Considerations

Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Pregnancy Considerations

Ketoconazole is not detectable in the plasma following chronic use of the shampoo.

Topical ketoconazole may be used for the treatment of infectious atopic dermatitis complications in pregnant women (Vestergaard 2019).

Breast-Feeding Considerations

Ketoconazole has been detected in breast milk following oral dosing. Although it is not detected in the plasma following chronic use of the shampoo, and concentrations in the plasma following application of the gel are <250 times those observed with oral dosing, the manufacturers recommend the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Do not apply to the nipple or surrounding area to avoid direct contact with infants who are breastfeeding.

Lexicomp Pregnancy & Lactation, In-Depth

• Ketoconazole (Systemic)

Briggs' Drugs in Pregnancy & Lactation

• Ketoconazole

Adverse Reactions

1% to 10%:

Dermatologic: Application-site pruritus (cream: ≤5%; shampoo: 1% to 3%; foam, gel: <1%), stinging of the skin (cream: ≤5%), xeroderma (shampoo: 1% to 3%; foam, gel: <1%)

Local: Application site reaction (foam: 6%; shampoo: 1% to 3%), local irritation (cream: ≤5%; foam, shampoo <1%), application site burning (gel: 4%; foam, shampoo: <1%)

Frequency not defined: Dermatologic: Dry hair, dry scalp, oily hair

<1%, postmarketing, and/or case reports: Abnormal hair texture, acne vulgaris, alopecia, anaphylaxis, angioedema, application-site dermatitis, application site discharge, application site erythema, application site pain, cheilitis, contact dermatitis, dizziness, eye irritation, facial swelling, hair discoloration, headache, hypersensitivity reaction, impetigo, keratoconjunctivitis sicca, localized warm feeling, nail discoloration, paresthesia, pustules, pyogenic granuloma, skin irritation, skin rash, swelling of eye, urticaria

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Azole Antifungal Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

There are no known significant interactions.

Advanced Practitioners Physical Assessment/Monitoring

Teach patient proper administration or application and necessity of completing full therapy.

Nursing Physical Assessment/Monitoring

Teach patient proper administration or application and necessity of completing full therapy.

Dosage Forms: US

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 [DSC], 100 g [DSC]) [contains alcohol, usp, cetyl alcohol, propylene glycol]

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

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

Generic: 2% (50 g, 100 g)

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)

Nizoral A-D: 1% (125 mL, 200 mL) [contains brilliant blue fcf (fd&c blue #1), edetate sodium (tetrasodium)]

Generic: 2% (120 mL)

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Cream, External:

Ketoderm: 2% (30 g) [contains cetyl alcohol, polysorbate 80, propylene glycol]

Anatomic Therapeutic Chemical (ATC) Classification

• D01AC08

Generic Available (US)

May be product dependent

Pricing: US

Cream (Ketoconazole External)

2% (per gram): $1.32 - $8.75

Foam (Extina External)

2% (per gram): $18.84

Foam (Ketoconazole External)

2% (per gram): $14.17

Foam (Ketodan External)

2% (per gram): $7.64

Gel (Xolegel External)

2% (per gram): $20.97

Kit (Ketodan External)

2% (per gram): $1.38

Shampoo (Ketoconazole External)

2% (per mL): $0.20 - $0.25

Shampoo (Nizoral A-D External)

1% (per mL): $0.08

Shampoo (Nizoral External)

2% (per mL): $0.67

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

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

Pharmacodynamics/Kinetics

Absorption: Shampoo: None; Cream, Foam, Gel: Minimal

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

References

American Academy of Pediatrics Committee on Drugs. "Inactive" ingredients in pharmaceutical products: update (subject review). Pediatrics. 1997;99(2):268-278.[PubMed 9024461]

Extina (ketoconazole foam) [prescribing information]. Newtown, PA: Prestium Pharma; June 2018.

Ketoconazole Cream [prescribing information]. North Wales, PA: Fougera; September 2018.

Ketodan Foam (ketoconazole) [prescribing information]. Fairfield, NJ: Medimetriks Pharmaceuticals, Inc; June 2019.

Ketoderm (ketoconazole cream) [product monograph]. Brampton, Ontario: TaroPharma; September 2003.

Moretti ME, Ito S, and Koren G, “Disposition of Maternal Ketoconazole in Breast Milk,” Am J Obstet Gynecol, 1995, 173(5):1625-6.[PubMed 7503214]

Nizoral (ketoconazole shampoo) [prescribing information]. Titusville, NJ: Janssen; received December 2018.

Nizoral (ketoconazole shampoo) [product monograph]. Markham, Ontario: Johnson & Johnson; October 2010.

Nizoral A-D (ketoconazole shampoo) [prescribing information]. Ridge, NJ: Kramer Laboratories, Inc; received July 2019.

Shehab N, Lewis CL, Streetman DD, Donn SM. Exposure to the pharmaceutical excipients benzyl alcohol and propylene glycol among critically ill neonates. Pediatr Crit Care Med. 2009;10(2):256-259.[PubMed 19188870]

Vestergaard C, Wollenberg A, Barbarot S, et al. European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period. J Eur Acad Dermatol Venereol. 2019;33(9):1644-1659. doi:10.1111/jdv.15709[PubMed 31231864]

Xolegel (ketoconazole gel) [prescribing information]. San Antonio, TX: DPT Laboratories; December 2019.

Xolegel (ketoconazole gel) [prescribing information]. San Antonio, TX: DPT Laboratories; May 2012.

Xolegel (ketoconazole gel) [prescribing information]. San Antonio, TX: DPT Laboratories; September 2017.

Brand Names: International

Amfazol (VN); Apodruff (IN); Aquarius (GR); Arcolane (CO); Curazole (EG); DaktaGOLD (AU, NZ); Danfree (BD); Dangel (LK); Dermatin (MT); Dermazole (PH, UA); Dezor (ID); Dezor Cream (MY, SG, TH); Dezor Kem (VN); Dezor Shampoo (MY, PH); Diazon (MY); Erazol (ID); Faction (BR); Fitonal (AR); Formyco (ID, SG); Fundan (SE); Fungarest (ES); Fungaway (TW); Fungiderm-K (TH); Fungium (CL, PY); Fungoral (IS, LV, NO); Kenazole (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, TW, YE); Ketazol (AE, BH, CY, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Ketoco (TW); Ketoconazol (CR, DO, GT, HN, NI, PA, SV); Ketoderm (FR, QA); Ketogin (CR, DO, GT, HN, NI, PA, SV); Ketoisdin (ES); Ketona (TW); Ketopine (NZ); Ketozol (PH); Ketozol Shampoo (IL); Kezon (TH); Larry (TH); Micoral (AR, BR); Micosin (EC); Mikanisal (LV); Mycofebrin (GR); Mycoral (LK); Nazole (KR); Nicoziral Cream (VN); Niz Creme (ZA); Niz Shampoo (ZA); Nizapex (EG); Nizoral (AE, AT, BB, BD, BE, BF, BG, BH, BJ, BM, BS, CH, CI, CN, CY, CZ, DE, DK, EE, EG, ET, FI, GH, GM, GN, GY, HK, ID, IE, IL, IQ, IR, IT, JM, JO, KE, KW, LB, LR, LT, LU, LV, LY, MA, ML, MR, MT, MU, MW, MY, NE, NG, NL, OM, PH, PK, PL, PR, QA, RO, RU, SA, SC, SD, SG, SK, SL, SN, SR, SY, TH, TN, TR, TT, TZ, UA, UG, UY, VE, VN, YE, ZA, ZM, ZW); Nizoral 2% Cream (NZ, PH); Nizoral Cream (GB, IE); Nizoral Shampoo (DE, NZ, PH); Oronazol (HR); Panfungol (ES); Pikangwang (CN); Pranzole (ET); Pristine (HK, MY); Pristinex (HK); Reduff (PH); Resolve (BD); Sebizole (AU, LK, NZ); Sporaxyl (TH); Sporium (CO); Terzolin (DE); Triatop Lotion (CN); Yucomy (MY, VN); Zakan (EG); Zhoulixin (CN)

Last Updated 2/19/20