Ultravate - Drug Monograph

Introduction

Ultravate (halobetasol propionate) is a high-potency topical corticosteroid indicated for the short-term treatment of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. It is classified as a Class I super-high potency corticosteroid according to the Vasoconstrictor Assay classification system.

Mechanism of Action

Halobetasol propionate exerts its anti-inflammatory, antipruritic, and vasoconstrictive effects through binding to intracellular glucocorticoid receptors. This binding initiates complex reactions that ultimately lead to:

• Inhibition of inflammatory cytokine production
• Prevention of inflammatory cell migration
• Reduction of edema and erythema
• Decreased capillary permeability
• Suppression of the immune response in the skin

The drug also induces phospholipase A2 inhibitory proteins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes.

Indications

FDA-approved indications:

• Short-term treatment of moderate to severe corticosteroid-responsive dermatoses including:

- Psoriasis (plaque type) - Eczema - Atopic dermatitis - Lichen planus - Lichen simplex chronicus

Off-label uses (based on clinical evidence):

• Discoid lupus erythematosus
• Alopecia areata
• Granuloma annulare

Dosage and Administration

• Apply a thin film to affected areas twice daily (morning and evening)
• Treatment duration should not exceed 2 consecutive weeks
• Total weekly dosage should not exceed 50 grams

• Pediatric patients: Use should be limited and under close supervision. Not recommended for children under 12 years.
• Geriatric patients: May require more frequent monitoring for adverse effects
• Hepatic impairment: Use with caution; consider reduced frequency of application
• Renal impairment: No specific dosage adjustments required

• Gently cleanse and dry affected area before application
• Use the smallest amount necessary to cover affected areas
• Do not use occlusive dressings unless directed by physician
• Avoid application to face, groin, or axillae

Pharmacokinetics

• Systemic absorption depends on application site, skin integrity, and use of occlusive dressings
• Greater absorption occurs through inflamed skin, denuded skin, or with occlusive dressing use
• Approximately 2.6-6.6% systemic absorption through intact skin

• Extensive protein binding (approximately 91%)
• Distributed throughout body tissues
• Crosses placental barrier

• Primarily hepatic metabolism via CYP3A4
• Forms inactive metabolites

• Renal excretion of metabolites (40-60%)
• Biliary excretion (approximately 20%)
• Elimination half-life: 12-16 hours

Contraindications

• Hypersensitivity to halobetasol propionate or any component of the formulation
• Viral skin infections (herpes simplex, varicella)
• Fungal skin infections
• Bacterial skin infections
• Tuberculosis of the skin
• Perioral dermatitis
• Acne rosacea
• Use on children under 12 years of age

Warnings and Precautions

• Reversible HPA axis suppression may occur with prolonged use
• Potential for hyperglycemia, glucosuria, Cushing's syndrome
• Increased risk in patients with liver dysfunction

• Skin atrophy, striae, telangiectasia
• Contact dermatitis
• Hypopigmentation
• Perioral dermatitis
• Miliraria

• Use with caution in patients with cirrhosis or hepatic impairment
• Avoid use in patients with impaired skin integrity
• Discontinue if irritation develops
• Not for ophthalmic use
• Pregnancy Category C: Use only if potential benefit justifies potential risk
• Excretion in breast milk: Use caution in nursing mothers

Drug Interactions

• Other topical corticosteroids: Increased risk of systemic effects
• CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin): May increase systemic corticosteroid levels
• Live vaccines: Immunosuppression may enhance replication of vaccine virus

• Drugs that induce CYP3A4 (rifampin, carbamazepine, phenytoin): May reduce efficacy

Adverse Effects

• Burning sensation at application site (10-15%)
• Pruritus (5-8%)
• Skin dryness (3-5%)
• Erythema (2-4%)
• Skin irritation (2-3%)

• Folliculitis
• Acneiform eruptions
• Hypopigmentation
• Hypertrichosis
• Allergic contact dermatitis

• HPA axis suppression
• Cushing's syndrome
• Glaucoma (with periocular use)
• Secondary infections
• Vision changes

Monitoring Parameters

• Baseline assessment of skin condition
• Documentation of affected body surface area
• Assessment of contraindications

• Weekly evaluation of treatment response
• Monitoring for local adverse effects
• Assessment for signs of systemic absorption (especially with prolonged use or large surface area)
• In long-term use: periodic evaluation of HPA axis function

• Evaluation for rebound flare of dermatosis
• Assessment for persistent skin changes

Patient Education

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

• Do not use on face, groin, or underarms unless specifically directed
• Limit treatment to 2 weeks unless advised otherwise
• Report any signs of skin irritation, infection, or lack of improvement
• Avoid contact with eyes and mucous membranes

• Severe skin reactions
• Signs of infection (pus, increased redness, swelling)
• Symptoms of systemic absorption (unusual weight gain, fatigue, muscle weakness)
• Vision changes
• No improvement after 2 weeks of treatment

• Store at room temperature (20-25°C)
• Keep tube tightly closed
• Do not freeze
• Keep out of reach of children

References

1. FDA Prescribing Information: Ultravate (halobetasol propionate) Cream and Ointment. Revised 2022. 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. 6th ed. Elsevier; 2022. 5. Katzung BG, Vanderah TW. Basic & Clinical Pharmacology. 15th ed. McGraw Hill; 2021. 6. ClinicalTrials.gov. Studies involving halobetasol propionate. Accessed January 2024. 7. UpToDate. Halobetasol propionate: Drug information. Wolters Kluwer. Updated December 2023. 8. Journal of the American Academy of Dermatology. 2016;74(5):AB67. Clinical efficacy study of halobetasol propionate. 9. British Journal of Dermatology. 2019;180(5):1057-1064. Long-term safety profile of super-potent topical corticosteroids. 10. Pharmacotherapy: A Pathophysiologic Approach. 12th ed. McGraw Hill; 2023.