Introduction
Clotrimazole is a broad-spectrum synthetic antifungal medication belonging to the imidazole class. First developed in the 1960s, it remains a widely used topical and mucosal antifungal agent for treating various superficial fungal infections. It is available in multiple formulations including creams, lotions, solutions, troches, and vaginal tablets.
Mechanism of Action
Clotrimazole exerts its antifungal effect by inhibiting the synthesis of ergosterol, an essential component of fungal cell membranes. It binds to cytochrome P450-dependent 14α-demethylase, which converts lanosterol to ergosterol. This disruption of ergosterol synthesis increases membrane permeability, causing leakage of intracellular contents and ultimately fungal cell death. Clotrimazole demonstrates fungistatic activity at low concentrations and fungicidal activity at higher concentrations against susceptible organisms.
Indications
FDA-approved indications include:
- Topical treatment of tinea pedis, tinea cruris, tinea corporis, and tinea versicolor caused by susceptible dermatophytes
- Oropharyngeal candidiasis (using troche formulation)
- Vulvovaginal candidiasis (using vaginal tablets/cream)
- Cutaneous candidiasis
Off-label uses may include:
- Prophylaxis against oropharyngeal candidiasis in immunocompromised patients
- Superficial fungal infections of the ear (otic solution)
Dosage and Administration
Topical formulations (cream, lotion, solution):- Apply thin layer to affected area twice daily (morning and evening)
- Duration: 2-4 weeks for dermatophyte infections; 2 weeks for cutaneous candidiasis
- 1% cream: 5g intravaginally daily for 7-14 days
- 2% cream: 5g intravaginally daily for 3 days
- 100mg vaginal tablet: 1 tablet daily for 7 days
- 500mg vaginal tablet: single dose
- 10mg dissolved slowly in mouth 5 times daily for 14 days
- For prophylaxis: 10mg troche 3 times daily
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Pediatrics: Safety established for children >3 years (topical); >5 years (troches)
- Geriatrics: No specific dosage adjustments
Pharmacokinetics
Absorption: Minimal systemic absorption following topical application (<0.5% of applied dose). Vaginal administration results in approximately 3% absorption. Oral troches have negligible systemic absorption due to poor gastrointestinal absorption. Distribution: When absorbed, widely distributed in body tissues. Protein binding approximately 90%. Metabolism: Extensively metabolized in the liver via cytochrome P450 enzymes to inactive metabolites. Elimination: Primarily excreted in feces (∼50%) and urine (∼30%) as metabolites. Elimination half-life is approximately 2-4 hours following systemic absorption.Contraindications
- Hypersensitivity to clotrimazole or any component of the formulation
- Hypersensitivity to other imidazole antifungal agents
- First trimester of pregnancy (for vaginal formulations - relative contraindication)
Warnings and Precautions
- For external use only (topical formulations)
- Avoid contact with eyes, nose, and mouth
- Discontinue if irritation or sensitivity develops
- Vaginal formulations may damage latex condoms and diaphragms
- Use with caution in patients with hepatic impairment (though systemic absorption is minimal)
- Superinfections may occur with prolonged use
- Not for ophthalmic use
Drug Interactions
- Minimal systemic interactions due to poor absorption
- Potential interaction with other drugs metabolized by CYP450 enzymes if significant systemic absorption occurs
- Vaginal formulations may interact with latex contraceptives (condoms, diaphragms)
- No clinically significant interactions with warfarin or oral contraceptives reported
Adverse Effects
Topical formulations:- Common: Local irritation, burning, itching, erythema
- Rare: Blistering, peeling, edema, urticaria
- Common: Local irritation, burning, itching
- Uncommon: Lower abdominal cramps, vaginal discharge
- Rare: Dysuria, frequency, headache
- Common: Nausea, vomiting, unpleasant mouth sensations
- Uncommon: Abnormal liver function tests
- Rare: Anaphylaxis (extremely rare)
Monitoring Parameters
- Clinical response to therapy
- Signs of local irritation or hypersensitivity reactions
- For prolonged use: liver function tests (though rarely indicated)
- Signs of superinfection
- Compliance with full treatment course
Patient Education
- Complete full course of therapy even if symptoms improve
- For topical use: Clean and dry area before application; wash hands after application
- For vaginal products: Use even during menstruation; complete full course
- For troches: Allow to dissolve slowly in mouth; do not chew or swallow whole
- Avoid tight-fitting clothing over affected areas
- Report any signs of worsening infection or irritation
- Vaginal products may stain clothing (use sanitary napkin)
- Inform healthcare provider if pregnant or breastfeeding
- Store at room temperature away from moisture
References
1. Lexicomp Online. Clotrimazole: Drug Information. Wolters Kluwer Clinical Drug Information, Inc. 2023. 2. Micromedex Solutions. Clotrimazole. IBM Watson Health. 2023. 3. 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-e50. 4. Gupta AK, Skinner AR. Management of tinea corporis, tinea cruris, and tinea pedis: A comprehensive review. Indian Dermatol Online J. 2016;7(2):77-86. 5. FDA Prescribing Information: Lotrimin (clotrimazole) Cream. Bayer HealthCare Pharmaceuticals Inc. 2022. 6. Sobel JD. Vulvovaginal candidosis. Lancet. 2007;369(9577):1961-1971.