Clotrimazole

Approved Indications:
A. Dermatological and Mucocutaneous Fungal Infections:

• Tinea corporis (ringworm of the body)
• Tinea cruris (jock itch)
• Tinea pedis (athlete’s foot)
• Tinea versicolor (pityriasis versicolor)
• Cutaneous candidiasis (including intertrigo and diaper rash)
• Candidal balanitis
• Vaginal candidiasis (vaginal yeast infection)

B. Oropharyngeal Infections:

• Oropharyngeal candidiasis (thrush)

C. Off-label (Clinically Accepted) Uses:

• Prophylaxis and treatment of oropharyngeal candidiasis in immunocompromised patients (e.g., HIV, cancer)
• Fungal otitis externa (as part of combination preparations)
• Treatment of superficial fungal infections in diabetic patients under monitoring

Topical (Cream, Lotion, Solution, Powder):

• Apply to affected area twice daily (morning and evening), gently rubbed into the skin.
• Duration:
• Tinea corporis/cruris: 2–4 weeks
• Tinea pedis: Up to 4 weeks
• Cutaneous candidiasis: 2 weeks
• Tinea versicolor: 1–2 weeks

Vaginal (Tablet/Pessary or Cream):

• 100 mg vaginal tablet: One tablet intravaginally once daily for 7 days
• 200 mg vaginal tablet: One tablet intravaginally once daily for 3 days
• 500 mg vaginal tablet: Single-dose therapy
• Vaginal cream (2%): 5 g intravaginally once daily for 3–7 days

Oral (Lozenge/Troche):

• 10 mg lozenge: Slowly dissolved in mouth five times daily for 14 days
• Do not chew or swallow; allow to dissolve slowly

Pediatrics:

• Oral and topical formulations may be used with caution under medical supervision
• For oral thrush: 10 mg troche, 3–5 times daily in children over 3 years

Special Populations:

• Elderly: No specific dose adjustment needed
• Renal/Hepatic Impairment: Not systemically absorbed; no adjustment necessary

Clotrimazole is an imidazole antifungal agent that works by inhibiting the synthesis of ergosterol, a key component of fungal cell membranes. Specifically, it inhibits the cytochrome P450-dependent enzyme 14-α-demethylase, which prevents the conversion of lanosterol to ergosterol. This leads to increased membrane permeability, leakage of essential intracellular contents, and ultimately fungal cell death. Its fungistatic or fungicidal activity depends on the concentration and the fungal species.

• Absorption:
• Topical/vaginal: Minimal systemic absorption
• Oral lozenge: Localized effect in oral cavity with minimal systemic levels
• Distribution: Confined to the stratum corneum and local mucosa
• Metabolism: If absorbed, extensively metabolized in the liver
• Elimination: Predominantly fecal excretion
• Half-life: Not clinically significant due to local action
• Bioavailability: Negligible systemic bioavailability with topical/vaginal use
• Onset of Action: Symptom improvement usually begins within a few days

• Pregnancy:
• Category B (topical/vaginal): Animal studies have not shown risk; human studies are limited but no known harm reported
• Avoid intravaginal formulations during the first trimester unless necessary
• Lactation:
• Safe during breastfeeding when used topically or vaginally
• Avoid application to the nipple or breast area to prevent infant ingestion
• Not excreted in significant amounts into breast milk

• Primary Class: Antifungal Agent
• Subclass: Imidazole Derivative (Topical Antifungal)

• Known hypersensitivity to clotrimazole or any of its excipients
• Use in the eyes (not for ophthalmic use)
• Severe systemic fungal infections (not effective via topical or local use)

• High-risk groups: Immunocompromised individuals may require systemic antifungal therapy
• Allergic reactions: Rarely, may cause hypersensitivity or contact dermatitis
• Prolonged use: Avoid extended use beyond recommended duration
• Oropharyngeal use: Not for use in children under 3 years without medical advice due to choking risk
• Pregnancy precautions: Use intravaginally only if clearly needed during the first trimester
• Avoid tight-fitting or non-breathable clothing in affected areas (e.g., groin, feet)

Common:

• Skin (Topical use): Mild burning, stinging, itching, redness, irritation
• Vaginal: Vulvovaginal burning or itching, pelvic cramps, discharge
• Oral: Unpleasant taste, mild nausea (with lozenges)

Serious (Rare):

• Allergic contact dermatitis
• Urticaria
• Anaphylactic reaction (extremely rare)
• Oral mucosal irritation (from lozenges)

Severity: Typically mild and self-limiting
Onset: Usually within the first few applications

• Topical/Vaginal/Oral (local): Minimal systemic absorption; clinically significant interactions are rare
• Systemic Absorption (rare): May theoretically inhibit CYP3A4; caution advised with drugs like tacrolimus or sirolimus if significant absorption occurs
• Vaginal use: May reduce the effectiveness of latex condoms and diaphragms; advise alternative contraceptive methods during use
• Alcohol: No known interaction

• CDC and WHO Guidelines: Continue to recommend clotrimazole as first-line topical antifungal for dermatophyte and Candida infections
• New Formulations: Development of newer clotrimazole-combination preparations with corticosteroids (e.g., betamethasone + clotrimazole) for inflammatory fungal dermatoses
• Updated Recommendations (2023): Vaginal clotrimazole still preferred as a first-line option for uncomplicated vulvovaginal candidiasis in pregnancy (second and third trimesters)

• Topical Cream/Ointment/Lotion:
• Store below 25°C (77°F)
• Protect from direct light and moisture
• Do not freeze
• Vaginal Tablet/Cream:
• Store at 15°C to 30°C (59°F to 86°F)
• Protect from humidity; use applicators as directed
• Do not refrigerate unless specified by manufacturer
• Oral Troches/Lozenges:
• Store at room temperature (20°C to 25°C)
• Keep in original packaging to protect from moisture
• Do not chew or swallow whole