Introduction
Clobetasol propionate is a ultra-high potency synthetic corticosteroid used topically for its potent anti-inflammatory, antipruritic, and vasoconstrictive properties. As a class I corticosteroid, it represents one of the most potent topical steroids available in clinical practice. This monograph provides comprehensive information about clobetasol's pharmacology, clinical applications, and safety considerations.
Mechanism of Action
Clobetasol exerts its effects through binding to intracellular glucocorticoid receptors, forming complexes that migrate to the cell nucleus. These complexes bind to glucocorticoid response elements in DNA, modulating gene transcription. The drug inhibits the release of inflammatory mediators (including cytokines, histamine, and prostaglandins), suppresses migration of leukocytes, reverses capillary permeability, and prevents fibroblast proliferation. Its vasoconstrictive activity correlates with its clinical potency.
Indications
FDA-approved indications include:
- Short-term treatment of inflammatory and pruritic manifestations of moderate to severe corticosteroid-responsive dermatoses
- Plaque psoriasis
- Atopic dermatitis
- Eczema
- Lichen planus
- Discoid lupus erythematosus
Off-label uses (with specialist supervision):
- Alopecia areata
- Vitiligo (with phototherapy)
- Granuloma annulare
- Keloids and hypertrophic scars
Dosage and Administration
Topical cream/ointment/lotion (0.05%):- Adults: Apply thin film to affected area twice daily
- Maximum duration: 2 consecutive weeks
- Maximum weekly dose: 50g
- Apply to affected scalp areas twice daily
- Pediatric patients: Use only under close supervision; limited to smallest area and shortest duration
- Geriatric patients: Increased risk of skin atrophy; use cautiously
- Hepatic impairment: No specific dosage adjustment recommended
- Renal impairment: No specific dosage adjustment recommended
Pharmacokinetics
Absorption: Systemic absorption varies with formulation, application site, skin integrity, and use of occlusive dressings. Intact skin: 0.5-1%; inflamed skin: 3-5%; occluded skin: up to 25%. Distribution: Highly lipophilic; distributes widely in body tissues. Crosses placenta and excreted in breast milk. Metabolism: Primarily hepatic via CYP3A4 to inactive metabolites. Elimination: Renal excretion of metabolites (60-70%); fecal excretion (10-20%). Half-life: approximately 5-6 hours.Contraindications
- Hypersensitivity to clobetasol or any component of formulation
- Rosacea
- Perioral dermatitis
- Acne vulgaris
- Cutaneous viral infections (herpes simplex, varicella)
- Fungal infections
- Tuberculosis of the skin
- Not for ophthalmic use
Warnings and Precautions
Boxed Warning: Not for ophthalmic use; may cause glaucoma or cataracts Systemic Effects: Prolonged use may cause HPA axis suppression, Cushing's syndrome, hyperglycemia, glucosuria Local Effects: Skin atrophy, striae, telangiectasia, hypopigmentation, contact dermatitis Special Considerations:- Use cautiously on face, groin, axillae
- Avoid occlusive dressings unless medically necessary
- Discontinue if skin irritation develops
- Not recommended for children under 12 years
- Pregnancy Category C: Use only if potential benefit justifies potential risk
Drug Interactions
Significant Interactions:- Increased systemic absorption with other topical corticosteroids
- Enhanced effects with CYP3A4 inhibitors (ketoconazole, erythromycin)
- Reduced effects with CYP3A4 inducers (rifampin, phenytoin)
- May decrease efficacy of hypoglycemic agents
- May enhance potassium-wasting effects of diuretics
Adverse Effects
Common (≥1%):- Burning/stinging at application site
- Pruritus
- Skin dryness
- Erythema
- Folliculitis
- HPA axis suppression
- Cushing's syndrome
- Glaucoma (with periocular use)
- Secondary skin infections
- Allergic contact dermatitis
- Striae and skin atrophy
- Hypopigmentation
Monitoring Parameters
Clinical Monitoring:- Skin response and adverse effects at application site
- Signs of HPA axis suppression (fatigue, weakness, nausea, hypotension)
- Growth velocity in pediatric patients
- Intraocular pressure with periocular use
- Morning plasma cortisol (with prolonged use or large surface area)
- Blood glucose in diabetic patients
- Electrolytes with suspected systemic absorption
Patient Education
Application Instructions:- Wash hands before and after application
- Apply thin layer to clean, dry skin
- Do not cover unless directed by healthcare provider
- Avoid contact with eyes, mouth, and mucous membranes
- Use only as prescribed; do not exceed recommended duration
- Report any signs of skin irritation or infection
- Inform all healthcare providers about clobetasol use
- Do not use on children unless specifically prescribed
- Avoid sunlight exposure; use sunscreen on treated areas
- No improvement after 2 weeks
- Worsening of condition
- Signs of systemic effects (unexplained weight gain, moon face, fatigue)
- Vision changes or eye pain
References
1. FDA Prescribing Information: Clobetasol Propionate Cream/Ointment/Lotion 2. Wolverton SE. Comprehensive Dermatologic Drug Therapy. 4th ed. Elsevier; 2021 3. Bolognia JL, Schaffer JV, Cerroni L. Dermatology. 4th ed. Elsevier; 2018 4. Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I. Treatment of Skin Disease: Comprehensive Therapeutic Strategies. 5th ed. Elsevier; 2018 5. American Academy of Dermatology Guidelines for Topical Corticosteroid Use (2020) 6. British Association of Dermatologists Guidelines for Topical Corticosteroid Use (2017) 7. UpToDate: Clobetasol drug information (2023) 8. Clinical Pharmacology [database online]. Tampa, FL: Elsevier; 2023