Urea

Urea is an Keratolytic Agent belonging to pharmacology class of Emollients.

Urea can be used in the treatment of Syndrome of inappropriate antidiuretic hormone secretion–associated hyponatremia, treatment and/or maintenance therapy and Hyperkeratotic conditions.

Urea is Rapidly absorbed from the GI tract and get Distributed in extracellular and intracellular fluids (e.g. lymph, bile, CSF and blood). It crosses the placenta and penetrates the eye which gets excreted in the form of Urine (unchanged).

The common side effects associated with Urea include Venous thrombosis or phlebitis at inj site; haemolysis; sloughing or necrosis due to extravasation

Urea is available in the form of Powder, cream, gel, foam, solution, lotion, ointment, suspension.

The molecule is available in India, USA, Japan, Germany.

Urea softens hyperkeratotic areas by dissolving the intracellular matrix, resulting in loosening the horny layer of the skin, or softening and debridement of the nail plate

Onset of action: Treatment of hyperkeratotic areas: 1 to 2 weeks; full resolution may take >4 to 6 weeks.

Urea is available in Powder, cream, gel, foam, solution, lotion, ointment, suspension.

Urea can be used in the treatment of Syndrome of inappropriate antidiuretic hormone secretion–associated hyponatremia, treatment and/or maintenance therapy and Hyperkeratotic conditions.

Urea normalizes serum sodium levels by inducing osmotic excretion of free water. Urea also ameliorates hyponatremia in syndrome of inappropriate antidiuretic hormone secretion by a more specific effect, diminishing the natriuresis in association with increased medullary urea content.

Urea is approved for use in the following clinical indications

Syndrome of inappropriate antidiuretic hormone secretion–associated hyponatremia, treatment and/or maintenance therapy: A medical food for the management of hyponatremia (euvolemic and hypervolemic).

Hyperkeratotic conditions: Debridement and promotion of normal healing of hyperkeratotic surface lesions, particularly where healing is retarded by local infection, necrotic tissue, fibrinous or purulent debris, or eschar; treatment of hyperkeratotic conditions, such as dry, rough skin; skin cracks and fissures; dermatitis; psoriasis; xerosis; ichthyosis; eczema; keratosis; keratoderma; corns and calluses; damaged, ingrown, and devitalized nails.

Syndrome of inappropriate antidiuretic hormone secretion–associated hyponatremia, treatment and/or maintenance therapy:

Note: May consider in patients who do not respond to fluid restriction or are unable to be fluid restricted, or to maintain serum sodium level after successful treatment of symptomatic hyponatremia. Goal of initial therapy is to achieve a 24-hour increase in serum sodium concentration by 4 to 6 mEq/L (maximum serum sodium increase: 8 mEq/L in any 24-hour period), which is sufficient to improve most symptoms of hyponatremia. However, if patient is symptomatic (acute or chronic hyponatremia), it is recommended to increase serum sodium by 4 to 6 mEq/L within the first 6 hours, then maintain serum sodium at a constant level for the remainder of the 24-hour period. In chronic severe hyponatremia, overcorrection or too rapid correction increases the risk of iatrogenic osmotic demyelination syndrome.

Oral: Initial: 15 to 30 g daily in 1 or 2 divided doses; titrate dose based on clinical response in increments of 15 g at weekly intervals; maximum daily dose: 60 g/day. For treatment goals, refer to "Note."

Hyperkeratotic conditions: Topical: Apply 1 to 3 times daily.

Powder, cream, gel, foam, solution, lotion, ointment, suspension.

• 15g, 10%, 20%, 25%, 30%, 35%, 40%, 41%, 42%, 45%, 50%

Powder, cream, gel, foam, solution, lotion, ointment, suspension.

Urea may be contraindicated in the following conditions:

Severely impaired renal function, marked dehydration, frank liver failure. Pulmonary congestion or pulmonary oedema, active intracranial bleeding, heart failure. Sickle cell disease with signs and symptoms of CNS involvement.

Concerns related to adverse effects:

• Skin reactions: Some products may cause photosensitivity. Use skin protection and limit sun exposure during therapy and for one week after.

Other warnings/precautions:

• Appropriate use: Avoid contact with eyes, lips, and mucous membranes. Discontinue use if redness, discomfort, or irritation occurs.

There is no sufficient scientific evidence traceable regarding use and safety of Urea in concurrent use with alcohol.

It is not known if urea is found in breast milk.

The adverse reactions related to Urea can be categorized as

Common Adverse effects:

Venous thrombosis or phlebitis at inj site; Haemolysis; Sloughing or Necrosis due to Extravasation

Less Common Adverse effects:

Fluid and Electrolyte Imbalance; Hypersensitivity Reactions; Pulmonary Oedema.

Rare Adverse effects:

Headache, nausea, vomiting, syncope, disorientation, dizziness, agitation, mental confusion, nervousness, hypotension, tachycardia, cardiotoxicity, hyperthermia.

The clinically relevant drug interactions of Urea is briefly summarized here

Increased excretion of lithium.

The most common side effects of Urea includes:

Venous thrombosis or phlebitis at inj site; Hemolysis; Sloughing or Necrosis due to Extravasation.

Pharmacodynamics:

Urea is an osmotic diuretic similar to mannitol but more irritant. It induces diuresis by increasing osmotic pressure of the glomerular filtrate and increasing excretion of sodium, potassium and chloride ions. Its osmotic effect also draws water from cells e.g. brain, CSF and anterior chamber of the eye, thereby decreasing intracranial or intraocular pressure. Unlike mannitol, urea penetrates the eye and causes a rebound increase in intraocular pressure if the plasma concentration of the drug is less than that in the vitreous humour. Applied topically, urea promotes hydration of keratin and mild keratolysis in dry skin. It increases water uptake by the stratum corneum and has an antipruritic effect.

Pharmacokinetics:

Absorption: Rapidly absorbed from the GI tract.

Distribution: Distributed in extracellular and intracellular fluids (e.g. lymph, bile, CSF and blood). It crosses the placenta and penetrates the eye.

Excretion: Urine (unchanged).

1. https://www.uptodate.com/contents/Urea -drug-information?search=Urea &source=panel_search_result&selectedTitle=1~148&usage_type=panel&kp_tab=drug_general&display_rank=1#F154338
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022352s017lbl.pdf
3. https://www.medicaid.nv.gov/Downloads/provider/Urea _2015-1215.pdf
4. https://www.mims.com/india/drug/info/Urea ?type=full&mtype=generic#mechanism-of-action