Clodan - Drug Monograph

Introduction

Clodan (clobetasol propionate) is a super-high potency topical corticosteroid used primarily in dermatology for its potent anti-inflammatory, antipruritic, and vasoconstrictive properties. As a class I corticosteroid, it represents one of the most potent topical steroids available for clinical use, making it an important therapeutic option for severe inflammatory skin conditions that are unresponsive to less potent agents.

Mechanism of Action

Clodan exerts its therapeutic effects through binding to intracellular glucocorticoid receptors, forming complexes that migrate to the cell nucleus. These complexes bind to glucocorticoid response elements in DNA, resulting in:

• Downregulation of pro-inflammatory genes encoding cytokines (IL-1, TNF-α, IL-2)
• Inhibition of phospholipase A2, reducing prostaglandin and leukotriene synthesis
• Vasoconstriction of superficial blood vessels
• Reduction in inflammatory cell migration and activity
• Suppression of epidermal proliferation

The drug's exceptional potency is attributed to its chemical structure, which enhances receptor binding affinity and prolongs receptor residence time.

Indications

FDA-approved indications:

• Short-term treatment of inflammatory and pruritic manifestations of moderate to severe corticosteroid-responsive dermatoses
• Plaque psoriasis
• Atopic dermatitis
• Lichen planus
• Discoid lupus erythematosus
• Other eczematous dermatoses unresponsive to less potent steroids

Off-label uses (with clinical caution):

• Alopecia areata
• Vitiligo (as adjunctive therapy)
• Keloids and hypertrophic scars

Dosage and Administration

• Apply a thin film to affected areas twice daily
• Maximum weekly dose: 50g (adults) or 25g (children)
• Duration: Generally limited to 2 consecutive weeks
• Occlusive dressings: May be used for resistant plaques but increase systemic absorption risk

• Pediatric patients (≥12 years): Use smallest effective amount, limit duration
• Geriatric patients: Increased risk of skin atrophy; use cautiously
• Hepatic impairment: No specific dosing recommendations
• Renal impairment: No specific dosing recommendations

• Clean and dry affected area before application
• Use fingertip unit method for appropriate dosing (1 FTU = ~0.5g)
• Avoid use on face, groin, axillae, or other intertriginous areas

Pharmacokinetics

• Percutaneous absorption varies by skin integrity (2-6% through intact skin, up to 40% through damaged skin)
• Enhanced by occlusion, inflammation, and thinner skin sites

• Extensive tissue binding
• Crosses placental barrier
• excreted in breast milk

• Primarily hepatic via CYP3A4
• Extensive first-pass metabolism

• Renal excretion of metabolites (40-60%)
• Biliary excretion (remainder)
• Elimination half-life: ~8-12 hours

Contraindications

• Hypersensitivity to clobetasol propionate or any component of the formulation
• Rosacea
• Perioral dermatitis
• Viral skin infections (herpes simplex, varicella)
• Fungal infections without appropriate antifungal therapy
• Tuberculosis of the skin
• Vaccination sites

Warnings and Precautions

• High-potency corticosteroids can cause reversible HPA axis suppression with the potential for glucocorticosteroid insufficiency
• May cause Cushing's syndrome, hyperglycemia, and glucosuria

• Systemic absorption: Can occur, especially with prolonged use, large surface area, occlusion, or impaired skin barrier
• Skin atrophy: Striae, telangiectasia, skin thinning may occur
• Contact dermatitis: Potential for allergic reactions to vehicle components
• Pediatric patients: Higher risk of systemic effects due to larger surface area to body mass ratio
• Ocular exposure: May cause glaucoma or cataracts
• Pregnancy: Category C - use only if potential benefit justifies potential risk
• Lactation: Systemically absorbed corticosteroids may be excreted in breast milk

Drug Interactions

• Other topical therapies: Increased absorption and potential irritation when combined with other topical medications
• CYP3A4 inhibitors (ketoconazole, erythromycin): May decrease clobetasol metabolism
• Live vaccines: Immunosuppression may enhance vaccine replication risk

• Hypokalemic agents: Enhanced hypokalemia risk
• Diuretics: Potential additive hypokalemic effects

Adverse Effects

• Burning/stinging at application site (15-20%)
• Pruritus (5-10%)
• Skin dryness (3-8%)
• Erythema (2-5%)
• Folliculitis (1-3%)

• HPA axis suppression (dose-dependent)
• Cushing's syndrome
• Glaucoma (with periocular use)
• Secondary skin infections
• Striae atrophicae
• Contact dermatitis
• Hypothalamic-pituitary-adrenal (HPA) axis suppression
• Hyperglycemia

Monitoring Parameters

• Assessment of skin condition severity
• Documentation of treatment area and extent
• Consideration of HPA axis function in high-risk patients

• Clinical response evaluation at 2-week intervals
• Signs of skin atrophy, striae, or telangiectasia
• Symptoms of systemic absorption (edema, weight gain, hypertension)
• Development of secondary infections

• Periodic evaluation for HPA axis suppression if prolonged use necessary
• Growth monitoring in pediatric patients
• Intraocular pressure if used near eyes

• Assessment for rebound flare or steroid addiction
• Evaluation for persistent HPA axis suppression

Patient Education

• Use only as directed by healthcare provider
• Apply thin layer to affected areas only
• Wash hands after application (unless hands are treatment area)
• Do not cover with tight dressings unless instructed

• Limit use to prescribed duration (typically ≤2 weeks)
• Avoid use on face, underarms, or groin unless specifically directed
• Report any signs of skin infection (increased redness, pus, pain)
• Notify provider if condition worsens or doesn't improve after 2 weeks
• Avoid excessive sun exposure; use sunscreen on treated areas

• Do not use on children unless specifically prescribed
• Inform all healthcare providers about Clodan use
• Store at room temperature, away from moisture and heat
• Keep out of reach of children

References

1. FDA Prescribing Information: Clobetasol Propionate Cream and Ointment 2. Wolverton SE. Comprehensive Dermatologic Drug Therapy. 4th ed. Elsevier; 2021 3. Bolognia JL, Jorizzo JL, Schaffer JV. 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. Katzung BG, Vanderah TW. Basic & Clinical Pharmacology. 15th ed. McGraw-Hill; 2021 6. Clinical guidelines from American Academy of Dermatology on topical corticosteroid use 7. Systematic review data from Cochrane Database on high-potency topical corticosteroids 8. Pharmacokinetic studies published in Journal of Drugs in Dermatology and British Journal of Dermatology