Ketoconazole topical

Class: Azoles
VA Class: DE102
Chemical Name: cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl] methoxy]phenyl] piperazine
Molecular Formula: C₂₆H₂₈Cl₂N₄O₄
CAS Number: 65277-42-1
Brands: Extina, Nizoral, Nizoral A-D, Xolegel

Introduction

Antifungal; azole (imidazole derivative).^{1 3 4 5 6 11 23 32 72 105 106 110}

Uses for Ketoconazole

Dermatophytoses

Treatment of tinea corporis, tinea cruris, and tinea pedis caused by Epidermophyton floccosum, Trichophyton mentagrophytes, or T. rubrum.^{1 2 25 27 28 56 58 59 60 61 62 66 78 79 110}

A drug of first choice for topical treatment of tinea corporis or tinea cruris.^{81 85} Oral antifungals preferred when tinea corporis or tinea cruris is extensive, dermatophyte folliculitis is present, infection is chronic or does not respond to topical therapy, or patient is immunocompromised or has coexisting disease.^{80 81 82 83 84}

Treatment of tinea manuum† caused by Trichophyton^{2 25 58 59 60 61 62} and tinea corporis caused by Microsporum†.^{2 25 59}

Cutaneous Candidiasis

Treatment of cutaneous candidiasis caused by Candida albicans.^{1 2 25 58 59 67 68 69 110}

Pityriasis (Tinea) Versicolor

Treatment of pityriasis (tinea) versicolor caused by or presumed to be caused by Malassezia furfur (Pityrosporum orbiculare or P. ovale).^{1 2 25 26 63 72 97 110}

Seborrheic Dermatitis and Dandruff

Treatment of seborrheic dermatitis, including seborrheic dermatitis of the scalp.^{1 12 42 43 44 67 71 73 76 98 99 101 103 105 106 107 108 109}

Self-medication (OTC use) for reduction of flaking, scaling, and itching associated with dandruff.^{74 75 77 99 100 101 102 104}

Ketoconazole Dosage and Administration

Administration

Topical Administration

Apply topically to skin as a 2% cream,^{1 110} foam,¹⁰⁶ gel,¹⁰⁵ or shampoo.^{72 97}

Apply topically to hair and scalp as a 1% shampoo.^{100 104} Also has been applied topically to hair† and scalp† as a 2% shampoo.^{76 98 99 101 103}

Cream, foam, gel, and shampoo are for external use only.^{1 72 104 105 106} Do not apply to eyes^{1 72 104 105 106} and do not administer orally^{105 106} or intravaginally.^{56 57 105 106}

If contact with eyes, mouth, or vagina occurs, rinse thoroughly with water.^{104 106}

When using the 2% foam, hold the can containing the foam upright and spray a small amount into the cap of the can or other cool surface.¹⁰⁶ Do not dispense foam directly onto affected areas or onto hands since the foam will begin to melt immediately on contact with warm skin.¹⁰⁶ If fingers are warm, rinse them in cold water and dry before handling the foam.¹⁰⁶ Using the fingertips, gently massage small amounts of foam onto affected areas until the foam disappears and entire affected area has been treated.¹⁰⁶

When using the 2% gel, do not apply sunscreen or cosmetics to the affected area until at least 20 minutes after application of the gel.¹⁰⁵ Do not wash the affected area for at least 3 hours after application of the gel.¹⁰⁵

Avoid fire, flame, and/or smoking during and immediately after application of 2% foam or gel.^{105 106} (See Flammability under Cautions.)

Dosage

Pediatric Patients

Topical Seborrheic Dermatitis in Children ≥12 Years of Age

2% gel: Apply to affected areas once daily for 2 weeks.^{105 107 108}

2% foam: Apply to affected areas twice daily for 4 weeks.^{106 109}

Dandruff in Children ≥12 Years of Age

Topical

1% shampoo: For self-medication, apply to wet hair, lather, and rinse thoroughly; then repeat application, lathering, and rinsing.¹⁰⁴ Use every 3 or 4 days for up to 8 weeks as needed or as directed by a clinician.¹⁰⁴ Thereafter, use as needed to control dandruff.¹⁰⁴

Adults

Dermatophytoses

Tinea Corporis or Tinea Cruris

Topical

2% cream: Apply and rub gently into affected and surrounding area of skin once or twice daily for 2 weeks.^{1 2 25 58 59 62 110} There is some evidence that twice-daily regimen may occasionally be more effective than once-daily regimen.^{25 62} If clinical improvement does not occur after treatment, reevaluate diagnosis.^{1 110}

Tinea Pedis

Topical

2% cream: Apply and rub gently into affected and surrounding area of skin once or twice daily for 6 weeks.^{1 2 60 66 79 110} If clinical improvement does not occur after treatment, reevaluate diagnosis.^{1 110}

Moccasin-type (dry-type) tinea pedis may require more prolonged therapy.^{66 79}

Cutaneous Candidiasis

Topical

2% cream: Apply and rub gently into affected and surrounding area of skin once or twice daily for 2 weeks.^{1 2 25 58 59 110} If clinical improvement does not occur after treatment, reevaluate diagnosis.^{1 110}

Pityriasis (Tinea) Versicolor

Topical

2% cream: Apply and rub gently into affected and surrounding area of skin once daily for 2 weeks.^{1 110} If clinical improvement does not occur after treatment, reevaluate diagnosis.^{1 110}

2% shampoo: Apply to damp skin of the affected area and a wide margin surrounding this area and lather; after 5 minutes, rinse with water.⁷² A single application should be sufficient,^{72 97} although once-daily application for 3 days also has been used.⁹⁷

Seborrheic Dermatitis

Topical

2% cream: Apply and rub gently into affected areas twice daily^{1 12 42 43 44 67 71} for 4 weeks or until clinical clearing.^{1 12 42 43 44 71}

2% foam: Apply and gently massage into affected areas twice daily for 4 weeks.^{106 109}

2% gel: Apply to affected areas once daily for 2 weeks.^{105 107 108}

2% shampoo: For seborrheic dermatitis of the scalp†, has been used to wash the hair and scalp 2 or 3 times weekly for 2–4 weeks.^{76 98 99 101} After a response was obtained, has been used once weekly every other week to prevent relapse.⁹⁸

Dandruff

Topical

1% shampoo: For self-medication to control flaking, scaling, and itching associated with dandruff, apply to thoroughly wet hair, lather and rinse thoroughly; then repeat application, lathering, and rinsing.¹⁰⁴ Use every 3 or 4 days for up to 8 weeks as needed or as directed by a clinician.¹⁰⁴ Thereafter, use as needed to control dandruff.¹⁰⁴

2% shampoo: For treatment of dandruff†, has been used to wash the hair and scalp 2 or 3 times weekly for 2–4 weeks.^{76 98 99 101} After a response was obtained, has been used once weekly every other week to prevent relapse.⁹⁸

Cautions for Ketoconazole

Contraindications

• 
  

  Hypersensitivity to ketoconazole or any ingredient in the formulation.^{1 72 105 110}

  
  

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Contact dermatitis reported following topical application of ketoconazole or other imidazole-derivative azole antifungals.^{61 89 90 91 92 93 94 110}

If a reaction suggesting sensitivity or chemical irritation occurs (e.g., rash), discontinue the drug.^{1 72 104 105 106 110}

Possible cross-sensitization among the imidazole derivatives.^{89 90 91 92 93 94}

Sulfite Sensitivity

Some formulations of the 2% cream contain sodium sulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.¹¹⁰ Overall prevalence of sulfite sensitivity in the general population is unknown, but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.¹¹⁰

General Precautions

Systemic Adverse Effects

Although hepatotoxicity, decreased testosterone concentrations, and decreased ACTH-induced corticosteroid concentrations have been reported with oral ketoconazole,^{32 105 110} these adverse effects have not been reported with topical ketoconazole^{105 110} and are unlikely since the drug does not appear to be appreciably absorbed following topical application to skin.^{2 56 57}

Flammability

2% foam and gel are flammable.^{105 106} Avoid fire, flame, and/or smoking during and immediately after application of foam or gel.^{105 106} (See Storage under Stability.)

Specific Populations

Pregnancy

Category C.^{1 72 105 106 110}

2% cream, foam, gel, or shampoo: Use during pregnancy only when potential benefits justify possible risks to the fetus.^{1 72 105 106 110}

1% shampoo: Pregnant women considering self-medication should consult a clinician before using the preparation.¹⁰⁴

Lactation

Not known whether ketoconazole distributed into milk following topical application.^{1 105 106 110}

2% cream: Discontinue nursing or the cream.^{1 110}

2% foam, gel, or shampoo: Use with caution.^{72 105 106}

1% shampoo: Nursing women considering self-medication should consult clinician before using the preparation.¹⁰⁴

Pediatric Use

2% cream: Safety and efficacy not established in children;^{1 110} has been used without unusual adverse effect in children 2 days to 12 years of age.^{15 17}

2% foam: Safety and efficacy not established in children <12 years of age.¹⁰⁶

2% gel: Safety and efficacy not established in children <12 years of age.¹⁰⁵

1% shampoo: Safety and efficacy for self-medication not established in children <12 years of age.¹⁰⁴

2% shampoo: Safety and efficacy not established in children.⁷²

Common Adverse Effects

2% cream: Local reactions at application site (severe irritation, pruritus, stinging).^{1 2 25 26 58 59 60 61 110}

2% foam: Application site reactions (e.g., burning).^{106 109}

2% gel: Application site reactions (e.g., burning), headache.^{105 107 108}

2% shampoo: When applied to the skin, pruritus, application site reaction, dry skin.⁷² When applied to scalp, increased hair loss, irritation, abnormal hair texture, loss of hair curl in patients with permanently waved (“permed”) hair, scalp pustules, dry skin, pruritus, oiliness or dryness of the hair and scalp.⁷²

Interactions for Ketoconazole

No formal drug interaction studies to date.¹⁰⁵

Ketoconazole Pharmacokinetics

Absorption

Bioavailability

Ketoconazole does not appear to be appreciably absorbed systemically following topical application to skin or scalp.^{1 2 24 25 56 63 72 105 106 110}

2% cream: Topical application to chest, back, and arms of healthy adults with intact skin does not result in detectable blood concentrations.^{1 2 24 110} Following topical application in vitro in a skin model, ketoconazole was retained in the stratum corneum and the boundary of the stratum corneum and stratum granulosum for up to 16 hours.^{56 63}

2% foam: Topical application of 3 g twice daily for 4 weeks in patients with moderate to severe seborrheic dermatitis resulted in plasma ketoconazole concentrations <6 ng/mL in 75% of patients; maximum plasma concentration was 11 ng/mL.¹⁰⁶

2% gel: Topical application once daily for 2 weeks (0.05-3.47 g daily) in patients with severe seborrheic dermatitis (1–14% of body surface area) resulted in mean peak plasma concentrations of 1.35 ng/mL on day 7 and 0.8 ng/mL on day 14.¹⁰⁵

2% shampoo: Chronic use of 2% shampoo (4–10 times weekly for 6 months, 2–3 times weekly for 3–26 months) did not result in detectable plasma concentrations.⁷²

Small amounts of ketoconazole are absorbed systemically when the drug is administered intravaginally.²⁴

Distribution

Extent

Not known whether ketoconazole distributed into milk following topical application of 2% cream, foam, gel, or shampoo.^{1 105 106 110}

Stability

Storage

Topical

2% Cream

20–25°C¹¹⁰ or 15–30°C,¹ depending on manufacturer.

2% Foam

20–25°C; do not refrigerate or freeze.¹⁰⁶

Flammable; do not store in direct sunlight and do not expose to heat or temperatures >49°C.¹⁰⁶ Do not puncture and/or incinerate container.¹⁰⁶

2% Gel

25°C (may be exposed to 15–30°C).¹⁰⁵

1% Shampoo

2–30°C; protect from light and freezing.¹⁰⁴

2% Shampoo

≤25°C; protect from light.⁷²

Actions and SpectrumActions

• 
  

  Imidazole-derivative azole antifungal.^{1 3 4 5 6 11 23 32 72 105 106 110}

  
  


• 
  

  Structurally related to other imidazole-derivative azole antifungals (e.g., butoconazole, clotrimazole, econazole, miconazole, oxiconazole, sulconazole, tioconazole).^{3 4 5 6 11 23}

  
  


• 
  

  Usually fungistatic; may be fungicidal at high concentrations after prolonged incubation or against very susceptible organisms.^{3 5 21 34 48 49 50 52 53 54 55}

  
  


• 
  

  Presumably exerts its antifungal activity by altering cellular membranes, resulting in increased membrane permeability, secondary metabolic effects, and growth inhibition.^{1 21 23 32 48 49 50 51 52 55 105 106 110} Fungistatic activity may result from interference with ergosterol synthesis.^{1 21 34 49 50 51 55 105 106 110} Fungicidal activity at high concentrations may result from a direct physiochemical effect on the fungal cell membrane.^{3 55}

  
  


• 
  

  Mechanism(s) of action in the treatment of dandruff not fully determined.⁷²

  
  


• 
  

  Spectrum of antifungal activity includes many fungi, including yeasts and dermatophytes.^{1 2 3 10 22 32 40 72 110}

  
  


• 
  

  Dermatophytes: Active against Epidermophyton floccosum,^{1 4 6 10 22 32 40 72 110} Microsporum audouini,^{1 10 22 32 40 72 110} M. canis,^{1 4 10 22 32 40 72 110} M. gypseum,^{1 4 10 22 32 40 72 110} Trichophyton mentagrophytes,^{1 4 10 22 32 40 72 110} T. rubrum,^{1 4 10 22 32 40 72 110} and T. tonsurans.^{1 4 10 22 32 40 72 110}

  
  


• 
  

  Other fungi: Active against Candida albicans,^{4 5 6 7 8 10 22 32 36 40 72 110} C. tropicalis,^{72 110} and Malassezia furfur (Pityrosporum orbiculare, P. ovale).^{1 39 40 45 72 105 106 110}

  
  

Advice to Patients

• 
  

  Importance of using the medication for the full, prescribed treatment period, even if symptoms improve; importance of consulting with clinician if the skin condition does not improve after a full course of therapy.^{56 57 104 106}

  
  


• 
  

  Importance of discontinuing use^{1 72 104 105 110} and contacting clinician if signs or symptoms of irritation or sensitization occur.^{56 57 104 105 106}

  
  


• 
  

  Importance of not applying 2% cream, foam, or gel to eyes^{1 105 106} or intravaginally.^{56 57 105 106}

  
  


• 
  

  If using 2% foam or gel, importance of avoiding fire, flame, and/or smoking during and immediately following application.^{105 106} Importance of not throwing foam container into a fire, even if can is empty.¹⁰⁶

  
  


• 
  

  If using shampoo, importance of avoiding contact with eyes;^{72 104} if contact with eyes occurs, rinse thoroughly with water.¹⁰⁴

  
  


• 
  

  Importance of not using the 1% shampoo for self-medication of dandruff if the scalp is broken or inflamed.¹⁰⁴ Importance of discontinuing use and contacting a clinician if rash occurs or the condition worsens or does not improve within 2–4 weeks.¹⁰⁴

  
  


• 
  

  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, or any concomitant illnesses.^{1 105}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 72 104 105 106 110}

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Ketoconazole

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Topical	Cream	2%*	Ketoconazole Cream
	Foam	2%	Extina	Stiefel
	Gel	2%	Xolegel	Barrier Therapeutics
	Shampoo	1%	Nizoral A-D	McNeil
		2%*	Ketoconazole Shampoo,
			Nizoral	Ortho-McNeil

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Ketoconazole 2% Cream (FOUGERA): 15/$19.99 or 45/$49.97

Ketoconazole 2% Cream (FOUGERA): 30/$27.99 or 90/$76.97

Ketoconazole 2% Cream (FOUGERA): 60/$35.99 or 180/$99.98

Ketoconazole 2% Shampoo (PERRIGO PHARMACEUTICALS): 120/$27.99 or 240/$49.97

Kuric 2% Cream (JSJ PHARMACEUTICALS): 75/$113.65 or 225/$311.47

Nizoral 2% Shampoo (JANSSEN): 120/$49.99 or 240/$92.98

Xolegel 2% Gel (AQUA PHARMACEUTICALS): 45/$355.99 or 135/$1024.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Taro Pharmaceuticals. Ketoconazole cream, 2% prescribing information. Brampton, Ontario; 2002 Nov.

2. Cauwenbergh GF, Degreef H, Verhoeve LS. Topical ketoconazole in dermatology: a pharmacological and clinical review. Mykosen. 1984; 27:395-401. [PubMed 6090895]

3. Van den Bossche H, Ruysschaert JM, Defrise-Quertain F et al. The interaction of miconazole and ketoconazole with lipids. Biochem Pharmacol. 1982; 31:2609-17. [PubMed 6291539]

4. Shadomy S, Espinel-Ingroff A, Kerkering TM. In-vitro studies with four new antifungal agents: BAY n 7133, bifonazole (BAY h 4502), ICI 153,066 and Ro 14-4767/002. Sabouraudia. 1984; 22:7-15. [PubMed 6322364]

5. Lefler E, Stevens DA. Inhibition and killing of Candida albicans in vitro by five imidazoles in clinical use. Antimicrob Agents Chemother. 1984; 25:450-4. [IDIS 184277] [PubMed 6375555]

6. Espinel-Ingroff A, Shadomy S, Gebhart RJ. In vitro studies with R 51,211 (itraconazole). Antimicrob Agents Chemother. 1984; 26:5-9. [IDIS 187623] [PubMed 6089654]

7. Bergan T, Vangdal M. In vitro activity of antifungal agents against yeast species. Chemotherapy. 1983; 29:104-10. [IDIS 169053] [PubMed 6301773]

8. Gebhart RJ, Espinel-Ingroff A, Shadomy S. In vitro susceptibility studies with oxiconazole (Ro 13-8996). Chemotherapy. 1984; 30:244-7. [IDIS 187989] [PubMed 6086246]

9. Cohen J. Antifungal chemotherapy. Lancet. 1982; 2:532-7. [IDIS 155949] [PubMed 6125688]

10. Dixon D, Shadomy S, Shadomy HJ et al. Comparison of the in vitro antifungal activities of miconazole and a new imidazole, R41,400. J Infect Dis. 1978; 138:245-8. [PubMed 681800]

11. Graybill JR, Craven PC. Antifungal agents used in systemic mycoses: activity and therapeutic use. Drugs. 1983; 25:41-62. [IDIS 165275] [PubMed 6297871]

12. Farr PM, Shuster S. Treatment of seborrhoeic dermatitis with topical ketoconazole. Lancet. 1984; 2:1271-2. [IDIS 193282] [PubMed 6150296]

13. Donadini A. The combination of an anti-inflammatory steroid, an antibacterial agent, and an antifungal in the treatment of outpatients with skin diseases of uncertain aetiology. Curr Ther Res Clin Exp. 1985; 37:478-84.

14. Cristiani T. Experience with the combination of an anti-inflammatory steroid, an antibacterial agent and an antimycotic agent in the topical treatment of skin diseases of various origins. Curr Ther Res Clin Exp. 1985; 37:225-31.

15. Minak G, Beverini S. Treatment of forms of infantile dermatitis with a multi-purpose drug combination. Curr Ther Res Clin Exp. 1984; 36:1198-1202.

16. Berardesca E. Combination treatment of skin diseases of mixed aetiology with an anti-inflammatory steroid, an antibacterial agent, and an antifunal. Curr Ther Res Clin Exp. 1985; 37:791-6.

17. Trabacco M. Treatment of dermatological manifestations in infants with a multivalent combination. Curr Ther Res Clin Exp. 1985; 37:784-9.

18. Pazzaglia A. Clinical results obtained with a combination of an anti-inflammatory steroid, an antibacterial agent and an antifungal in dermatological outpatient practice. Int J Clin Pharmacol Ther Toxicol. 1985; 23:367-72. [PubMed 4030166]

19. Gini M. Use of a combination of an anti-inflammatory corticosteroid, an antibacterial agent and an antifungal in the local post-operative treatment of cutaneo-mucosal diseases following cryosurgery. Int J Clin Pharmacol Ther Toxicol. 1985; 23:373-5. [PubMed 4030167]

20. Pellerano S. Use of a combination of an anti-inflammatory steroid, an antibacterial agent and an antifungal in dermatological practice. Int J Clin Pharmacol Ther Toxicol. 1985; 23:215-8. [PubMed 3888858]

21. Borgers M, Van den Bossche H, De Brabander M. The mechanism of action of the new antimycotic ketoconazole. Am J Med. 1983; 74(Suppl 1B):2-8. [IDIS 165048] [PubMed 6295147]

22. Heel RC. In vitro and in vivo activity. In: Levine HB, ed. Ketoconazole in the management of fungal disease. New York: Adis Press; 1982:57-66.

23. Janssen Pharmaceutica. Product information form for ketoconazole. Piscataway, NJ; 1986 Feb.

24. Rawlins M. Systemic absorption of ketoconazole 2% cream. Janssen clinical research report N 31403. Piscataway, NJ; 1982 Sep.

25. Janssen Pharmaceutica. Ketoconazole 2% cream: systemic absorption, skin irritancy, and therapeutic effectiveness in animals and man. A review of the available data up to April 1983. Research report No. N 31597. Piscataway, NJ; 1983 Apr.

26. Savin RC. Double-blind comparison of 2% ketoconazole cream (R 41,400) and placebo in the treatment of tinea versicolor: Janssen Pharmaceutica clinical research report N 31513. Piscataway, NJ; 1983 Mar.

27. Taplin D, Carmargo G. Double-blind comparison of 2% ketoconazole cream (R 41,400) and placebo in the treatment of tinea corporis and tinea cruris. Janssen Pharmaceutica clinical research report No. N 31514. Piscataway, NJ; 1983 Mar.

28. Taplin D, Carmargo G. Double-blind comparison of 2% ketoconazole cream (R 41,400/98) and placebo in the treatment of fungal infections of the feet. Janssen Pharmaceutica clinical research report No. N 31511. Piscataway, NJ; 1983 Mar.

29. Torres MA, Mohamed J, Cavazos-Adame H et al. Topical ketoconazole for fungal keratitis. Am J Ophthalmol. 1985; 100:293-8. [IDIS 204217] [PubMed 4025470]

30. Komadina TG, Wilkes DI, Shock JP et al. Treatment of Aspergillus fumigatus keratitis in rabbits with oral and topical ketoconazole. Am J Ophthalmol. 1985; 99:476-9. [PubMed 3872596]

31. O’Day DM, Ray WA, Head WS et al. Influence of the corneal epithelium on the efficacy of topical antifungal agents. Invest Ophthalmol Vis Sci. 1984; 25:855-9. [PubMed 6329991]

32. Teva Pharmaceuticals. Ketoconazole tablets prescribing information. Sellersville, PA; 2003 Nov.

34. Pye GW, Marriott MS. Inhibition of sterol C14 demethylation by imidazole-containing antifungals. Sabouraudia. 1982; 20:325-9. [PubMed 6760419]

35. Odds FC, Webster CE, Abbott AB. Antifungal relative inhibition factors: BAY 1-9139, bifonazole, butoconazole, isoconazole, itraconazole (R 51211), oxiconazole, Ro 14-4767/002, sulconazole, terconazole and vibunazole (BAY n-7133) compared in vitro with nine established antifungal agents. J Antimicrob Chemother. 1984; 14:105-14. [PubMed 6094418]

36. Odds FC. Laboratory evaluation of antifungal agents: a comparative study of five imidazole derivatives of clinical importance. J Antimicrob Chemother. 1980; 6:749-61. [PubMed 7440468]

37. Clissold SP, Heel RC. Tioconazole: a review of its antimicrobial activity and therapeutic use in superficial mycoses. Drugs. 1986; 31:29-51. [IDIS 210402] [PubMed 3510114]

38. Pottage JC Jr, Kessler HA, Goodrich JM et al. In vitro activity of ketoconazole against herpes simplex virus. Antimicrob Agents Chemother. 1986; 30:215-9. [IDIS 220405] [PubMed 3021048]

39. Ford GP, Ive FA, Midgley G. Pityrosporum folliculitis and ketoconazole. Br J Dermatol. 1982; 107:691-5. [IDIS 161628] [PubMed 6293529]

40. Van Cutsem J. The antifungal activity of ketoconazole. Am J Med. 1982; 74(Suppl 1B):9-15.

41. Anon. Boxed warning added to ketoconazole label. FDA Drug Bull. 1983; 13:15-6. [PubMed 6311655]

42. Skinner RB Jr, Zanolli MD, Noah PW et al. Seborrheic dermatitis and acquired immunodeficiency syndrome. J Am Acad Dermatol. 1986; 14:147-8. [PubMed 2936769]

43. Skinner RB Jr, Noah PW, Taylor RM et al. Double-blind treatment of seborrheic dermatitis with 2% ketoconazole cream. J Am Acad Dermatol. 1985; 12(15 Part 1):852-6. [PubMed 3159759]

44. Skinner RB Jr, Noah PW, Zanolli MD et al. The pathogenic role of microbes in seborrheic dermatitis. Arch Dermatol. 1986; 122:16-7. [PubMed 2935085]

45. Faergemann J. In vitro and in vivo activities of ketoconazole and itraconazole against Pityrosporum orbiculare. Antimicrob Agents Chemother. 1984; 26:773-4.

46. Ryley JF, Wilson RG, Barrett-Bee KJ. Azole resistance in Candida albicans. Sabouraudia. 1984; 22:53-63. [PubMed 6322363]

47. Tavitian A, Raufman JP, Rosenthal LE et al. Ketoconazole-resistant Candida esophagitis in patients with acquired immunodeficiency syndrome. Gastroenterology. 1986; 90:443-5. [IDIS 210426] [PubMed 3510145]

48. Thomas AH. Suggested mechanisms for the antimycotic activity of the polyene antibiotics and the N-substituted imidazoles. J Antimicrob Chemother. 1986; 17:269-79. [PubMed 3516967]

49. Beggs WH, Andrews FA, Sarosi GA. Minireview: action of imidazole-containing antifungal drugs. Life Sci. 1981; 28:111-8. [PubMed 7019609]

50. Borgers M. Mechanism of action of antifungal drugs, with special reference to the imidazole derivatives. Rev Infect Dis. 1980; 2:520-34. [IDIS 124096] [PubMed 7003674]

51. Sud IJ, Feingold DS. Mechanisms of action of the antimycotic imidazoles. J Invest Dermatol. 1981; 76:438-41. [IDIS 133194] [PubMed 7017013]

52. Beggs WH. Growth phase in relation to ketoconazole and miconazole susceptibilities of Candida albicans. Antimicrob Agents Chemother. 1984; 25:316-8.

53. Beggs WH. Influence of growth phase on the susceptibility of Candida albicans to butoconazole, oxiconazole, and sulconazole. J Antimicrob Chemother. 1985; 16:397-9. [PubMed 3902762]

54. Minagawa H, Kitaura K, Nakamizo N. Effects of pH on the activity of ketoconazole against Candida albicans. Antimicrob Agents Chemother. 1983; 23:105-7.

55. Sud IJ, Feingold DS. Heterogeneity of action among antimycotic imidazoles. Antimicrob Agents Chemother. 1981; 20:71-4. [IDIS 135352] [PubMed 6269485]

56. Janssen Pharmaceutica, Titusville, NJ: Personal communication.

57. Reviewers’ comments (personal observations); 1986 Sep.

58. Meisel C. Single-blind, side-to-side comparison of ketoconazole 2% cream and clotrimazole 1% cream in 8 patients w