Introduction
Urea is a naturally occurring compound that serves as the primary end product of protein metabolism in humans. As a pharmaceutical agent, urea has been used for decades as a topical dermatological preparation and, in specific formulations, as a systemic osmotic diuretic. Its hygroscopic properties make it particularly valuable in dermatology for moisturizing and keratolytic effects.
Mechanism of Action
Topical Application: Urea exerts its effects through several mechanisms:- Keratolytic action: Breaks down the protein matrix of the stratum corneum by disrupting hydrogen bonds
- Hydration: Acts as a humectant, drawing water into the stratum corneum from deeper epidermal layers
- Proteolytic effect: Enhances desquamation by solubilizing fibrin
- Osmotic diuresis: Increases plasma osmolality, drawing water from tissues into plasma and promoting renal excretion
- Reduces intracranial and intraocular pressure: Creates an osmotic gradient across the blood-brain and blood-aqueous humor barriers
Indications
FDA-Approved Indications:- Topical: Dry, rough skin conditions (xerosis), ichthyosis, hyperkeratotic disorders, onychomycosis (as adjunctive therapy)
- Systemic: Reduction of intracranial pressure, reduction of intraocular pressure, promotion of diuresis in cerebral edema
- Nail debridement, wound debridement, pruritus relief
Dosage and Administration
Topical Preparations:- Creams/lotions: 10-50% concentrations applied 1-3 times daily
- Ointments: Typically 10-40% strength
- Higher concentrations (40-50%) reserved for severe hyperkeratosis
- Intravenous: 30% solution infused at 1-1.5 g/kg over 1-2.5 hours
- Maximum dose: 120 g/24 hours in adults
- Renal dose adjustment required for impaired renal function
- Pediatrics: Safety established for topical use; systemic use requires careful monitoring
- Geriatrics: No specific dosage adjustment needed for topical use
- Hepatic impairment: No dosage adjustment required
- Renal impairment: Contraindicated for systemic use in severe renal impairment
Pharmacokinetics
Absorption: Minimal systemic absorption from intact skin; rapidly absorbed following intravenous administration Distribution: Distributed throughout total body water; crosses blood-brain barrier and placenta Metabolism: Hepatic metabolism via urease to ammonia and carbon dioxide Elimination: Primarily renal excretion (50-70% within 24 hours); clearance correlates with glomerular filtration rate Half-life: Approximately 1.5 hoursContraindications
- Hypersensitivity to urea or any component of the formulation
- Severe renal impairment (for systemic use)
- Active intracranial bleeding (unless during craniotomy)
- Dehydration
- Hepatic impairment with elevated blood ammonia levels
Warnings and Precautions
Systemic Use:- Risk of hemolysis with rapid infusion
- Electrolyte imbalances possible
- Extravasation may cause tissue necrosis
- Monitor for ammonia toxicity in patients with hepatic impairment
- May cause stinging or irritation on broken skin
- Avoid contact with eyes and mucous membranes
- Caution in patients with known skin sensitivity
- Pregnancy Category C: Use only if potential benefit justifies potential risk
- Lactation: Unknown if excreted in human milk; use caution
Drug Interactions
Significant Interactions:- Lithium: Increased renal clearance may reduce lithium efficacy
- Nephrotoxic drugs: Increased risk of renal impairment
- Other osmotic agents: Additive effects may cause excessive dehydration
- Topical corticosteroids: May enhance penetration of corticosteroids
Adverse Effects
Common (Topical):- Transient stinging or burning (10-20%)
- Pruritus (5-15%)
- Local irritation (5-10%)
- Erythema (3-8%)
- Electrolyte imbalances (hypernatremia, hypokalemia)
- Dehydration
- Thrombophlebitis at injection site
- Hemolysis
- Ammonia toxicity (confusion, tremor, coma)
- Intracranial hemorrhage rebound
Monitoring Parameters
Systemic Therapy:- Serum electrolytes (sodium, potassium)
- Renal function (BUN, creatinine)
- Fluid balance (intake/output)
- Neurological status
- Intracranial pressure (if applicable)
- Intraocular pressure (if applicable)
- Skin response and tolerance
- Signs of irritation or hypersensitivity
- Clinical improvement of skin condition
Patient Education
Topical Application:- Apply to clean, dry skin unless directed otherwise
- Wash hands before and after application
- Use sparingly on broken or irritated skin
- May increase sensitivity to sunlight; use sun protection
- Report severe irritation, rash, or worsening of condition
- Store at room temperature away from moisture
- Keep out of reach of children
- Do not use beyond expiration date
- Follow prescribed concentration and frequency
- Severe skin reactions
- Signs of infection
- Systemic symptoms (if using high concentrations on large areas)
References
1. FDA prescribing information for urea preparations 2. Wolverton SE. Comprehensive Dermatologic Drug Therapy. 4th ed. Elsevier; 2021 3. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics. 13th ed. McGraw-Hill; 2017 4. Lexicomp Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.; 2023 5. ClinicalTrials.gov: Urea topical and systemic studies 6. Journal of the American Academy of Dermatology: Urea in dermatotherapy 7. New England Journal of Medicine: Osmotic diuretics in clinical practice 8. Cochrane Database of Systematic Reviews: Urea for dry skin conditions