H-Trimazole

Approved Indications:

• Treatment of inflammatory fungal skin infections caused by dermatophytes and yeasts, where both antifungal and anti-inflammatory effects are required.
• Commonly prescribed for tinea corporis, tinea cruris, and tinea pedis with associated inflammation and itching.
• Cutaneous candidiasis with inflammation.
• Seborrheic dermatitis with secondary fungal involvement.

Clinically Accepted Off-label Uses:

• Inflammatory fungal infections resistant to antifungal monotherapy.
• Combination therapy for fungal intertrigo with significant erythema and pruritus.

Note: This combination is generally used for superficial fungal infections accompanied by significant inflammation.

• Topical Application: Apply a thin layer to the affected skin area twice daily (morning and evening).
• Duration: Usually 1 to 2 weeks; prolonged use beyond 2 weeks is generally not recommended due to corticosteroid component.
• Pediatrics: Use with caution; not generally recommended for children under 12 years without medical supervision.
• Elderly: No specific dose adjustment; caution advised due to thinner skin and potential steroid side effects.
• Special Populations: Avoid use on large body surface areas, broken skin, or under occlusive dressings to reduce systemic absorption risks.
• Administration Route: Topical dermatological application only; avoid contact with eyes, mucous membranes, and open wounds.

Clotrimazole acts as an antifungal by inhibiting the enzyme 14-α-demethylase, a cytochrome P450-dependent enzyme critical in ergosterol synthesis. This inhibition disrupts fungal cell membrane integrity, causing increased permeability and cell death. Hydrocortisone, a mild corticosteroid, exerts anti-inflammatory, antipruritic, and vasoconstrictive effects by modulating inflammatory gene expression, decreasing cytokine production, and stabilizing lysosomal membranes, thereby reducing inflammation and itching associated with fungal infections. The combination offers synergistic benefits—targeting fungal pathogens while alleviating inflammation.

• Absorption: Minimal systemic absorption of both clotrimazole and hydrocortisone through intact skin; absorption may increase with prolonged use, occlusion, or damaged skin.
• Distribution: Primarily remains localized in the epidermis and upper dermis.
• Metabolism: Any systemically absorbed hydrocortisone is metabolized hepatically via reduction and conjugation. Clotrimazole undergoes hepatic metabolism when systemically absorbed, primarily by CYP3A4 enzymes.
• Elimination: Metabolites are excreted mainly via urine and feces.
• Onset of Action: Antifungal effects appear within days; anti-inflammatory effects are typically evident within hours to days.
• Half-life: Not clinically significant for topical formulations due to local action.

• Pregnancy:
• Topical hydrocortisone is categorized as FDA Pregnancy Category C; animal studies show risk at high doses, but limited human data. Use only if benefits outweigh risks.
• Clotrimazole topical and vaginal use is Category B; no demonstrated fetal risk in animal studies.
• Combination products should be used cautiously during pregnancy, avoiding extensive or prolonged application.
• Lactation:
• Minimal systemic absorption reduces risk during breastfeeding.
• Use cautiously; avoid applying to breast area to prevent infant exposure.

• Primary Class: Antifungal + Corticosteroid Combination
• Subclass: Imidazole Antifungal + Topical Glucocorticoid

• Known hypersensitivity to clotrimazole, hydrocortisone, or any excipients in the formulation
• Viral skin infections (e.g., herpes simplex, varicella)
• Acne vulgaris or rosacea affected areas
• Tuberculous or syphilitic skin infections
• Fungal infections without inflammation (monotherapy with antifungal preferred)

• Avoid prolonged or extensive use to prevent steroid-related adverse effects such as skin atrophy or systemic absorption.
• Use caution in patients with diabetes, as corticosteroids may affect glucose control.
• Discontinue if signs of worsening fungal infection or secondary infection occur.
• Avoid application near eyes; risk of glaucoma or cataracts with inadvertent ocular exposure to steroids.
• Not recommended for use on broken or ulcerated skin.
• High-risk groups include elderly, children, and patients with impaired skin barrier function.

Common:

• Local burning, itching, or irritation at the application site
• Dryness or peeling of skin
• Mild erythema or rash

Serious (Rare):

• Skin atrophy, striae, telangiectasia with prolonged use
• Secondary bacterial or fungal superinfection
• Hypersensitivity reactions, including contact dermatitis
• Systemic corticosteroid effects (rare with topical use), such as adrenal suppression

Severity: Usually mild and transient; serious effects are dose- and duration-dependent.

• Minimal systemic absorption limits drug interactions.
• Potential increased risk of systemic corticosteroid effects when used with other corticosteroids or CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) that may increase hydrocortisone levels if systemic absorption occurs.
• Use caution with other topical products to avoid additive irritation.

• Clinical guidelines recommend limiting combination antifungal-steroid use to short durations (usually ≤2 weeks) to reduce corticosteroid-related adverse effects.
• Recent dermatology consensus emphasizes reserving combination therapy for inflammatory fungal infections not responding adequately to antifungal monotherapy.
• No changes in approved indications; continued caution advised regarding potential steroid misuse in fungal infections.

• Store at controlled room temperature, preferably 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Keep tube tightly closed when not in use.
• Do not freeze.
• Use within the expiration date printed on the package.