Clotrimazole, an imidazole derivative, is a synthetic azole antifungal agent.100, 101, 125
Clotrimazole lozenges are used orally for the topical treatment of oropharyngeal candidiasis, which has been confirmed by potassium hydroxide smear and/or culture.6, 125 Clotrimazole lozenges are also used prophylactically to reduce the incidence of oropharyngeal candidiasis in patients who are immunocompromised as the result of immunosuppressive therapy (e.g., corticosteroids, antineoplastic agents, radiation therapy) for the treatment of leukemia, solid tumor, or renal transplantation; the manufacturer states that safety and efficacy of oral clotrimazole troches for prophylaxis of oropharyngeal candidiasis in patients immunocompromised as the result of primary immunodeficiency or other causes have not been determined.7, 125 Clotrimazole lozenges are not indicated for the treatment of systemic fungal infections, including systemic candidiasis.125
Oropharyngeal candidiasis can occur in association with HIV infection, diabetes, malignancies, steroid use, radiation therapy, antimicrobial therapy, and denture use, and is typically a sign of immune suppression.5, 8, 127 Such infections are largely caused by Candida albicans , either alone or in mixed infections.5, 127 The Infectious Diseases Society of America (IDSA) published guidelines for the treatment of oropharyngeal candidiasis in 2021.5 These guidelines recommend the use of clotrimazole lozenges (10 mg 5 times daily) or miconazole mucoadhesive buccal tablet 50 mg applied to the mucosal surface over the canine fossa once daily for 7-14 days for mild oropharyngeal candidiasis; oral fluconazole is recommended for moderate to severe disease.5 The US Department of Health and Human Services (HHS) Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV has provided recommendations for the treatment of oropharyngeal candidiasis in persons with HIV.127 These experts recommend systemic therapy with oral fluconazole as the preferred antifungal treatment of choice for oropharyngeal candidiasis, except during pregnancy; oral fluconazole has been shown to have superior or similar efficacy to topical agents, is more convenient than topical agents, and is usually better tolerated.127 Topical therapy with clotrimazole lozenge is recommended by the HHS Panel as one of several alternative treatment options to oral fluconazole.127 In pregnant patients, topical treatments are preferred.127 Topical oral therapy with clotrimazole is ineffective for the treatment of esophageal candidiasis in HIV-infected patients; if used, a systemic antifungal should also be given.127
Although oral clotrimazole has been used for prophylaxis against oropharyngeal candidiasis in HIV-infected individuals†, the HHS Panel states that routine primary prophylaxis is not recommended because mucosal disease is associated with low morbidity and mortality, acute therapy is highly effective, and antifungal prophylaxis in these situations can cause drug-resistant strains of Candida to develop.8, 127
Dermatophytoses and Cutaneous Candidiasis
Clotrimazole is used topically for the treatment of dermatophytosis and cutaneous candidiasis.100, 101, 102, 103 Various topical clotrimazole products are commercially available.100, 101, 102, 103 Clotrimazole 1% cream and solution are FDA-labeled for the topical treatment of candidiasis due to Candida albicans .100, 101 Clotrimazole is also available in over-the-counter (OTC) topical preparations for the treatment of tinea pedis (athlete's foot), tinea cruris (jock itch), and tinea corporis (ringworm of the body) caused by Trichophyton rubrum , T. mentagrophytes , Epidermophyton floccosum , or Microsporum canis .100, 101, 102, 103 Clotrimazole is also available in combination with betamethasone dipropionate as a cream or lotion that is used topically for the treatment of tinea pedis, tinea cruris, and tinea corporis caused by T. rubrum , T. mentagrophytes , or E. floccosum in adults.156, 157
Tinea pedis, tinea cruris, and tinea corporis usually can be treated with nonprescription antifungal medications; however, systemic therapy may be required for severe, chronic, or refractory cases.104, 105, 106, 107 Clotrimazole 1% cream or solution is considered one of several first-line therapies for the treatment of tinea pedis, tinea corporis, and tinea cruris.105, 106, 107
Clotrimazole is used topically as a 1% cream or solution for the treatment of tinea versicolor due to Malassezia furfur .100, 101 Uncomplicated cases of pityriasis (tinea) versicolor generally can be treated with topical agents such as clotrimazole cream, selenium sulfide shampoo or lotion, or other topical azole antifungals (e.g., econazole, ketoconazole, miconazole, oxiconazole), an allylamine antifungal (e.g., terbinafine), ciclopirox, or zinc pyrithione shampoo.99 Systemic therapies are reserved for more extensive or resistant infections.99
Clotrimazole vaginal cream is used for the treatment of vulvovaginal candidiasis; only nonprescription (OTC) 1% and 2% vaginal cream preparations are currently available for this use.4, 108, 109 Prior to use of clotrimazole in a patient who has signs and symptoms of uncomplicated vulvovaginal candidiasis, the diagnosis should be confirmed either by demonstrating yeast or pseudohyphae with direct microscopic examination of vaginal discharge (e.g., saline or 10% potassium hydroxide [KOH] wet mounts) or by culture; identifying Candida by culture in the absence of symptoms is not an indication for antifungal treatment since approximately 10-20% of females harbor Candida or other yeasts in the vagina.4 Treatment guidelines from the Centers for Disease Control and Prevention (CDC) and the Infectious Diseases Society of America (IDSA) recommend a topical (i.e., intravaginal) azole antifungal in a single-dose or short-course (generally 1-3 days) regimen or a single dose of oral fluconazole for the treatment of uncomplicated vulvovaginal candidiasis.4, 5 These agents are effective for the relief of symptoms and result in negative cultures in 80-90% of treated non-pregnant patients with sporadic or infrequent infections with mild-to-moderate symptoms that are likely to be caused by Candida albicans .4 For recurrent vulvovaginal candidiasis, prolonged courses of treatment are recommended, typically with 7-14 days of topical azole antifungal therapy or oral fluconazole administered every 3 days for a total of 3 doses, followed by a maintenance antifungal regimen.4, 5 In most people with HIV, vulvovaginal candidiasis is uncomplicated and responds well to a short course of oral or topical treatment with either oral fluconazole, topical azoles (including clotrimazole), or oral ibrexafungerp.127 Severe or recurrent episodes should be treated with a longer duration of therapy (at least 7 days).127
Clotrimazole is administered topically to the oropharyngeal area as an oral lozenge, to the skin as a cream or solution, or intravaginally as a vaginal cream.100, 101, 108, 109, 125
The topical cream and solution are not intended for ophthalmic use.100, 101
Clotrimazole also is available in fixed combination with betamethasone dipropionate as a cream or lotion; see prescribing information for the combination product for additional details.156, 157
Store clotrimazole oral lozenges, topical cream, and topical solution at 20—25°C.100, 101, 125 Avoid freezing oral lozenges.125
Dissolve oral lozenges slowly in mouth over approximately 30 minutes.125
Apply cream or solution twice daily (in the morning and evening); massage gently into affected area and surrounding skin.100, 101
Clotrimazole lozenges are administered orally and dissolved slowly in the mouth over approximately 30 minutes.125 For the topical treatment of oropharyngeal candidiasis in adults and pediatric patients older than 3 years of age, the usual dosage of oral clotrimazole is one 10-mg lozenge 5 times daily for 14 consecutive days.125 Because limited data are available on the safety and effectiveness of prolonged therapy with clotrimazole lozenges, therapy should be limited to short-term use, if possible.125
For prophylaxis to reduce the incidence of oropharyngeal candidiasis in adults who are immunocompromised as the result of immunosuppressive therapy (e.g., corticosteroids, antineoplastic agents, radiation therapy) used for the treatment of leukemia, solid tumor, or renal transplantation, the usual dosage of oral clotrimazole is one 10-mg lozenge 3 times daily for the duration of chemotherapy or until corticosteroid therapy is reduced to maintenance levels.125 The safety and efficacy of clotrimazole lozenges for prophylactic use in pediatric patients have not been established.125
Dermatophytoses and Cutaneous Candidiasis
For dermatologic use in adults and pediatric patients, a sufficient amount of clotrimazole 1% cream or 1% solution should be massaged gently into the affected and surrounding areas of skin twice daily (in the morning and evening).100, 101 Clinical improvement and relief of pruritus usually occur within 1 week; if clinical improvement does not occur after 4 weeks of treatment, the diagnosis should be reevaluated.100, 101
If the fixed-combination cream or lotion containing clotrimazole 1% and betamethasone 0.05% is used for the treatment of tinea corporis or tinea cruris in adult patients, a thin film of the cream or sufficient amount of lotion should be applied twice a day for 1 week; do not use more than 45 g of cream or 45 mL of lotion per week and do not use with occlusive dressing.156, 157 If clinical improvement does not occur within 1 week of treatment, reevaluate the diagnosis. Do not use for longer than 2 weeks.156, 157
If the fixed-combination cream containing clotrimazole 1% and betamethasone 0.05% is used for the treatment of tinea pedis in adult patients, a sufficient amount of the cream or lotion should be massaged into affected skin areas twice a day for 2 weeks; do not use more than 45 g of cream or 45 mL of lotion per week and do not use with occlusive dressing.156, 157 If clinical improvement does not occur within 2 weeks of treatment, reevaluate the diagnosis.156, 157 Do not use for longer than 4 weeks.156, 157
For the treatment of pityriasis (tinea) versicolor in adults and pediatric patients, a sufficient amount of clotrimazole 1% cream or 1% solution should be gently massaged into the affected area and surrounding skin twice daily (in the morning and evening).100, 101 If clinical improvement does not occur after 4 weeks of treatment, the diagnosis should be reevaluated.100, 101
If 1% clotrimazole vaginal cream is used for self-medication of vulvovaginal candidiasis in adults and children 12 years of age or older, one applicatorful of the cream may be inserted intravaginally once daily (preferably at bedtime) for 7-14 consecutive days.4, 108 If the 2% clotrimazole vaginal cream is used for self-medication of vulvovaginal candidiasis, one applicatorful of the 2% cream should be inserted intravaginally once daily at bedtime for 3 consecutive days.4, 109
Clotrimazole topical solution and cream are not for ophthalmic use.100, 101
Clotrimazole lozenges are not indicated for the treatment of systemic mycoses, including systemic candidiasis.125 To achieve maximum therapeutic effect of clotrimazole when the drug is administered orally as a lozenge, the lozenge must be dissolved slowly in the mouth; therefore, patients receiving clotrimazole lozenges must be of such age and physical and/or mental condition that they can comprehend and follow administration instructions.125
If irritation or sensitization occurs, discontinue the drug.100, 101
Possible abnormal liver function test results (e.g., increased serum AST) reported in patients receiving clotrimazole lozenges.125 Liver function tests should be conducted periodically during oral therapy with clotrimazole lozenges, especially in patients with preexisting hepatic impairment.125
If there is a lack of response to clotrimazole, appropriate microbiological studies should be repeated to confirm the diagnosis and rule out other pathogens before instituting another course of antifungal therapy.100, 101
When clotrimazole is used in fixed combination with betamethasone dipropionate, the cautions, precautions, contraindications, and interactions associated with betamethasone must be considered in addition to those associated with clotrimazole.156, 157
There are no adequate and controlled studies of clotrimazole lozenges in pregnant women; the drug should be used during pregnancy only if the potential benefits justify the potential risks to the fetus.125 In clinical trials, use of intravaginal clotrimazole in pregnant women in the second and third trimester was not associated with adverse effects; there are no adequate and well-controlled studies in pregnant women in the first trimester.100, 101 .
In animal reproductive studies, clotrimazole demonstrated embryotoxic effects, but was not teratogenic when given in doses significantly higher than the recommended human dose.125
It is not known whether clotrimazole is excreted in human milk, caution should be exercised when the drug is used in nursing woman.100, 101
Safety and efficacy of clotrimazole lozenges have not been established in children <3 years of age.125 Safety and efficacy of prophylactic therapy with clotrimazole lozenges have not been established in children.125
Clotrimazole topical cream or solution is not recommended for self-medication in children <3 years of age.100, 101
Clotrimazole vaginal cream is not recommended for self-medication in children <12 years of age.108, 109
Preparations containing clotrimazole in fixed combination with betamethasone dipropionate are not recommended for use in children <17 years of age or for diaper dermatitis.156, 157
There were an insufficient number of patients ≥65 years of age in clinical studies of clotrimazole lozenges to determine whether geriatric patients respond differently from younger patients; other reported experience did not find any differences in response between these patients.125
Lozenge: nausea, vomiting, unpleasant mouth sensations, and pruritus.125
Topical cream or solution: blistering, erythema, edema, pruritus, burning, stinging, peeling, urticaria, and general irritation of skin.100, 101
Clotrimazole is a broad-spectrum antifungal agent that exerts its antifungal activity by interfering with the biosynthesis of ergosterol, a major component of the fungal cell membrane.9, 100, 101 As a result, cell membrane permeability is altered, causing loss of potassium and other cellular constituents.9, 100, 101 Ergosterol also plays a role in directly stimulating the growth of fungal cells.9 The combined effects of these actions result in a dose- and time-dependent inhibition of fungal growth.9
Clotrimazole is generally considered to be fungistatic, but exhibits fungicidal effects at higher concentrations.9, 100, 101, 125 In vitro, clotrimazole exhibits fungistatic and fungicidal activity against most strains of Trichophyton rubrum, T. mentagrophytes, Epidermophyton floccosum, and Microsporum canis, and Candida species including Candida albicans .100, 101, 125 In general, the in vitro activity of clotrimazole corresponds to that of tolnaftate and griseofulvin against the mycelia of dermatophytes ( Trichophyton , Microsporum , and Epidermophyton ), and to that of the polyenes (amphotericin B and nystatin) against Candida .100, 101 Resistance to clotrimazole has been observed in some Candida isolates, particularly in immunocompromised patients, and has been linked to overexpression of efflux pump genes.9 Cross resistance can occur among the azole antifungals (e.g., clotrimazole, ketoconazole, miconazole).160
Following oral administration of a lozenge containing 10 mg of clotrimazole and dissolution of the lozenge in the mouth (which takes approximately 30 minutes), concentrations of clotrimazole sufficient to inhibit most species of Candida are present in saliva for up to 3 hours.125 Administration of a 10-mg clotrimazole lozenge every 3 hours reportedly maintains salivary concentrations of clotrimazole greater than the MIC of the drug for most species of Candida .125 The long-term effective concentration of clotrimazole in saliva appears to be related to slow release of the drug from the oral mucosa to which the drug is apparently bound.125 The total amount of clotrimazole absorbed following dissolution in the mouth of a lozenge containing the drug has not been determined to date.125
Following topical and vaginal administration, clotrimazole appears to be minimally absorbed.100, 101 Following application to the skin, the highest concentrations of clotrimazole are present in the stratum corneum; lower drug concentrations occur in the stratum spinosum and the papillary and reticular dermis.100, 101
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral (Topical Use Only) | Lozenges | 10 mg* | Clotrimazole Lozenge | |
Topical | Cream | 1%* | Clotrimazole Topical Cream | |
Solution | 1%* | Clotrimazole Topical Solution |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Topical | Cream | 1% with Betamethasone Dipropionate 0.05% (of betamethasone)* | Clotrimazole with Betamethasone Dipropionate Topical Cream | |
Lotion | 1% with Betamethasone Dipropionate 0.05% (of betamethasone)* | Clotrimazole with Betamethasone Dipropionate Topical Lotion |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
4. Workowski KA, Bachmann LH, Chan PA et al. Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep. 2021; 70(4): 1-187.
5. Pappas PG, Kauffman CA, Andes DR et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016; 62(4): e1-50.
6. Yap BS, Bodey GP. Oropharyngeal candidiasis treated with a troche form of clotrimazole. Arch Intern Med. 1979 Jun;139(6):656-7. PMID: 375858
7. Yeo E, Alvarado T, Fainstein V, Bodey GP. Prophylaxis of oropharyngeal candidiasis with clotrimazole. J Clin Oncol. 1985 Dec;3(12):1668-71. doi: 10.1200/JCO.1985.3.12.1668. PMID: 4067613..
8. Pienaar ED, Young T, Holmes H. Interventions for the prevention and management of oropharyngeal candidiasis associated with HIV infection in adults and children. Cochrane Database Syst Rev. 2010 Nov 10;2010(11):CD003940. doi: 10.1002/14651858.CD003940.pub3. PMID: 21069679; PMCID: PMC7156835.
9. Crowley PD, Gallagher HC. Clotrimazole as a pharmaceutical: past, present and future. J Appl Microbiol. 2014 Sep;117(3):611-7. doi: 10.1111/jam.12554. Epub 2014 Jun 30. PMID: 24863842.
99. American Academy of Pediatrics. Red Book: 2024-2027 Report of the Committee on Infectious Diseases: Pityriasis Versicolor.
100. Akorn Pharma Inc. Clotrimazole topical solution 1% prescribing information. Fairfield, NJ; 2024 Oct.
101. Taro Pharmaceuticals USA Inc. Clotrimazole cream 1% prescribing information. Hawthorne, NY; 2024 Dec.
102. Padagis Israel Pharmaceuticals Ltd. Clotrimazole cream USP 1% Drug Facts. 2024 Sep.
103. Akron Pharma Inc. Clotrimazole topical solution USP 1% Drug Facts. 2024 Sep.
104. Centers for Disease Control and Prevention (CDC). Ringworm and fungal nail infections (April 2024). http://www.cdc.gov/ringworm/treatment/index.html (accessed 2025 Mar 6).
105. American Academy of Pediatrics. Red Book: 2024-2027 Report of the Committee on Infectious Diseases: Tinea Pedis and Tinea Unguium (Onychomycosis) (Athlete's Foot, Ringworm of the Feet).
106. American Academy of Pediatrics. Red Book: 2024-2027 Report of the Committee on Infectious Diseases: Tinea Cruris (Jock Itch)
107. American Academy of Pediatrics. Red Book: 2024-2027 Report of the Committee on Infectious Diseases: Tinea Corporis (Ringworm of the Body)
108. Strategic Sourcing Services LLC. Clotrimazole vaginal cream USP 1% Drug Facts. 2024 Nov.
109. Taro Pharmaceuticals USA Inc. Clotrimazole USP 2% vaginal cream Drug Facts. 2016 Oct.
115. Cuttner J, Troy KM, Funaro L et al. Clotrimazole treatment for prevention of oral candidiasis in patients with acute leukemia undergoing chemotherapy: results of a double-blind study. Am J Med . 1986; 81:771-4. [PubMed 3535491]
125. Padagis. Clotrimazole lozenge for topical oral administration prescribing information. Minneapolis, MN; 2022 May.
127. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. National Institutes of Health, HIV Medicine Association, and Infectious Diseases Society of America (Updated Oct 29, 2024). From website. [Web]
156. Actavis Pharma Inc. Clotrimazole and betamethasone dipropionate cream prescribing information. Parsipanny, NY; 2024 Aug,
157. Taro Pharmaceuticals USA Inc. Clotrimazole and betamethasone dipropionate lotion prescribing information. Hawthorne, NY; 2016 May
160. Holt RJ, Azmi A. Miconazole-resistant Candida . Lancet . 1978; 1:50-1. [PubMed 74535]