Urea

(rINN)
Urea Chemical formula
Synonyms: Carbamida; Carbamide; E927b; Karbamid; Karbamidi; Močovina; Mocznik; Üre; Urée; Ureia; Ure˙ja; Ureum. Carbonic acid diamide.
Cyrillic synonym: Карбамид; Мочевина.

💊 Chemical information

Chemical formula: NH2.CO.NH2 = 60.06.
CAS — 57-13-6.
ATC — B05BC02; D02AE01.
ATC Vet — QB05BC02; QD02AE01.

Pharmacopoeias.

In Chin., Eur., Jpn, and US.

Ph. Eur. 6.2

(Urea). Transparent, slightly hygroscopic, crystals or a white or almost white, crystalline powder. Very soluble in water; soluble in alcohol; practically insoluble in dichloromethane. Store in airtight containers.

USP 31

(Urea). Colourless or white, practically odourless, prismatic crystals, or white crystalline powder or pellets. May gradually develop a slight odour of ammonia on prolonged standing. Soluble 1 in 1.5 of water, 1 in 10 of alcohol, and 1 in 1 of boiling alcohol; practically insoluble in chloroform and in ether. Solutions are neutral to litmus. Store at a temperature of 25°, excursions permitted between 15° and 30°.

Incompatibility.

Urea can cause haemolysis when mixed with blood and should never be added to whole blood for transfusion or given through the same set by which blood is being infused.

💊 Adverse Effects and Precautions

As for Mannitol. Urea should also be used with caution in liver impairment as blood-ammonia concentrations can rise, and should be avoided in liver failure. Urea is reported to be more irritant than mannitol, and intravenous use may cause venous thrombosis or phlebitis at the site of injection; extravasation may cause sloughing or necrosis. Only large veins should be used for infusion, and urea should not be infused into veins of the lower limbs of elderly patients. Extreme care is essential to prevent accidental extravasation of urea infusions. Rapid intravenous injection of solutions of urea can cause haemolysis; the risk is reduced by using glucose or invert sugar solutions as diluent. Urea should not be mixed with whole blood. Topical applications may be irritant to sensitive skin.

Infants and neonates.

High plasma-urea concentrations have been reported1,2 in neonates after topical application of emollient creams containing urea. Since there was no evidence of dehydration2,3 absorption of urea through the skin was the likely cause. Raised plasma-urea concentrations have been reported4 in infants with erythematous skin conditions who had not been treated with urea cream and this was attributed to dehydration due to increased insensible water loss through the damaged skin.
1. Beverley DW, Wheeler D. High plasma urea concentrations in collodion babies. Arch Dis Child 1986; 61: 696–8
2. Oudesluys-Murphy AM, van Leeuwen M. High plasma urea concentrations in collodion babies. Arch Dis Child 1987; 62: 212
3. Beverley DW, Wheeler D. High plasma urea concentration in babies with lamellar ichthyosis. Arch Dis Child 1986; 61: 1245–6
4. Garty BZ. High plasma urea concentration in babies with lamellar ichthyosis. Arch Dis Child 1986; 61: 1245.

Pregnancy.

There have been reports of women suffering coagulopathy associated with urea treatment given for termination of pregnancy.1,2
1. Grundy MFB, Craven ER. Consumption coagulopathy after intra-amniotic urea. BMJ 1976; 2: 677–8
2. Burkman RT, et al. Coagulopathy with midtrimester induced abortion: association with hyperosmolar urea administration. Am J Obstet Gynecol 1977; 127: 533–6.

💊 Pharmacokinetics

Urea is fairly rapidly absorbed from the gastrointestinal tract but causes gastrointestinal irritation. Urea is distributed into extracellular and intracellular fluids including lymph, bile, CSF, and blood. It is reported to cross the placenta, and penetrate the eye. It is excreted unchanged in the urine.

💊 Uses and Administration

Urea promotes hydration and is mainly applied topically in the treatment of ichthyosis and hyperkeratotic skin disorders. Used intravenously it has osmotic diuretic properties similar to mannitol and has been used in the treatment of acute increases in intracranial pressure, due to cerebral oedema, and to decrease intra-ocular pressure in acute glaucoma, but has been largely superseded by mannitol. Urea has also been given intra-amniotically for the termination of pregnancy. When applied topically urea has hydrating and keratolytic properties. In the management of ichthyosis and other dry skin disorders it is applied in creams or lotions containing 5 to 25% urea; higher concentrations of 30% and 40% have also been used in severe cases. A preparation containing 40% may be used for nail destruction. For the reduction of raised intracranial or intra-ocular pressure, urea is given intravenously, as an infusion of a 30% solution in glucose 5 or 10% or invert sugar 10%, at a rate not exceeding 4 mL/minute, in a dose of 0.5 to 1.5 g/kg to a maximum of 120 g daily. Doses used in children are based on the same regimen, but see also below. Rebound increases in intracranial and intra-ocular pressure may occur after about 12 hours. Solutions of urea 40 to 50% have been given by intraamniotic injection for the termination of pregnancy. Urea labelled with carbon-13 is used in the in vivo diagnosis of Helicobacter pylori infection. The test involves collecting a breath sample before and after oral ingestion of a single dose of 13 C-urea. H. pylori produces urease which hydrolyses the urea to carbon dioxide and ammonia; therefore, an excess of carbon-13-labelled carbon dioxide in the sample, compared with a baseline sample, indicates infection. Doses of 13 C-urea include 50 mg, 75 mg, or 100 mg depending on the kit being used. Urea labelled with the radionuclide carbon-14 is also used in a urea breath test for H. pylori detection.

Administration in children.

For the reduction of raised intracranial or intra-ocular pressure in children, urea is given intravenously in dosage regimens similar to those used in adults (see above). However, for children under 2 years of age, a dose of 100 mg/kg may be adequate. Breath test kits containing13C-urea for the diagnosis of Helicobacter pylori infection are available for children. However, the BNFC states that the appropriateness of testing in children has not been established, and that endoscopy with biopsy is more accurate than in vivo breath testing, which is frequently unreliable in children.

💊 Preparations

BP 2008: Urea Cream; USP 31: Urea for Injection.

Proprietary Preparations

Arg.: Hidroplus; Keratopic; Lociherp; Nutralcon; Optiwhite†; Ureadin; Urecrem; Uremol; Xerobase; Austral.: Aquacare; Hamilton Skin Therapy; Nutraplus; Urecare; Urederm; Austria: Nubral; Braz.: Emoderm; Hidrapel Plus; Nutraplus; Ureadin; Canad.: Dermaflex; Ultra Mide; Uree; Uremol; Urisec; Chile: Ayr con urea; Ayr-5; Hyderm; Nutraplus†; Uramol; Ureadin 10 and 20; Cz.: Elacutan; Excipial U; Linola Urea; Fin.: Fenuril; Fr.: AntiDessechement; Charlieu Topic†; Ictyoderm†; Nutraplus; Sedagel; Ger.: Balisa; Basodexan; Elacutan; Eucerin Salbe†; Hyanit N; Linola Urea; Nubral; Onychomal; Sebexol cum urea; Ureotop; Hong Kong: Balneum Intensiv; Carmol; Caruderma; Euderm; Nutraplus†; Urecare; Urederm; Hung.: Linola Urea; Indon.: Calmuderm; Carmed; Moisderm; Soft U Derm; Urederm; Irl.: Aquadrate; Nutraplus; Ital.: Dermal Care; Jpn: Keratinamin; Malaysia: Balneum Intensiv; Euderm†; Nutraplus; UO; Urecare†; Mex.: Derma-Keri; Dermoplast; Karmosan; Nutraplus; Uramol; NZ: Aquacare; Nutraplus; Philipp.: Nutraplus; Port.: Eucerin Pele Seca†; Rebladerm†; Ureadin 10 and 20; Singapore: Aqurea; Balneum Intensiv; Euderm†; Excipial U; Nutraplus; UO; Urecare†; Spain: Nutraplus†; Swed.: Calmuril; Canoderm; Caress; Fenuril; Karbaderm†; Karbasal; Monilen; Switz.: Carbamide Emulsion; Eucerin peau seche; Excipial U; Linola Uree; Nutraplus; Vita-Merfen Soins dermatologiques†; Thai.: Balneum Intensiv†; Nutraplus; Turk.: Excipial; Nutraplus; Urederm; UK: Aquadrate; Nutraplus; USA: Aquacare; Carmol; Gormel; Hydro 40; Kerafoam; Keralac; Kerol; Lanaphilic; Nutraplus; Rinnovi; Ultra Mide; Umecta; Ureacin; Ureaphil; Vanamide; Venez.: Aquaphar; Dermisol; Uricrim. Multi-ingredient: Arg.: Acilac; Akerat; Aloebel; Cremisona†; Cremsor N; Hidrolac; Lactiderm; Lactiderm HC†; Lactocrem; Masivol Urea; Onixol†; Oxidermos; Sadeltan F†; Turgent Colageno; Turgent Emulsion; Ureadin Facial; Urecrem Hidro; Vansame; Austral.: Aussie Tan Skin Moisturiser; Calmurid; Curaderm†; Dermadrate; Psor-Asist; SP Cream†; Austria: Aleot; Calmurid; Calmurid HC; Canesten Bifonazol comp; Fungiderm comp†; Ichth-Oestren; Keratosis; Keratosis forte; Mirfulan; Optiderm; Belg.: Calmurid†; Braz.: Donnagel; Oticerim; Oto-Biotic†; Tricolpex; Tricomax; Vagi Biotic; Vagi-Sulfa; Canad.: Amino-Cerv; Hydrophil; Kerasal; Uremol-HC; Chile: Akerat; Mycosporan Onycoset†; Ureadin 30; Ureadin Facial; Ureadin Forte; Ureadin Pediatrics; Ureadin Rx DB; Ureadin Rx PS; Ureadin Rx RD; Cz.: Betacorton U; Kerasal; Mycospor Sada na Nehty; Fin.: Calmuril; Wicaran; Wicarba; Wicnecarb; Wicnevit; Fr.: Akerat; Amycor Onychoset; Body Peel; Charlieu Topicrem; Day Peel; Liperol; Night Peel; Pedi-Relax Anti-callosites†; Provictol†; PSO; Topic 10; Ger.: Balisa VAS; Brand- u. Wundgel-Medice N; Calmurid†; Canesten Extra Nagelset; Carbamid + VAS; Fungidexan; Hydrodexan; Kelofibrase†; Mirfulan; Mycospor Nagelset†; Nubral 4†; Nubral Forte†; Oestrugol N†; Optiderm; Psoradexan; Psorigerb N†; Remederm; Ureata S†; Ureotop + VAS; Gr.: Lyoderm; Urecortin; Hong Kong: Balneum Intensiv Plus; Dermadrate; Hung.: ReseptylUrea; Squa-med; India: Cotaryl; Indon.: Foothy; Irl.: Alphaderm; Calmurid; Calmurid HC; Israel: Agispor Onychoset; Calmurid; Calmurid HC†; Derma-Care; Keratospor; U-Lactin Foot Cream; U-Lactin Forte; Ital.: Altadrine; Eudermico†; Ipso Urea; Keraflex; Optiderm; Verunec; Xerial; Malaysia: Balneum Intensiv Plus; Ucort; Mex.: Eucerin Piel Seca/Reseca†; Hidribet 5†; Hidribet†; Lowila; Mycospor Onicoset; Suavene; Urader Lactato; Ureaderm Lactato; Neth.: Calmurid; Calmurid HC; Symbial; NZ: Calmurid†; Dermadrate; Philipp.: Remederm; Pol.: Hasceral; Keratolit; Mycospor Onychoset; Optiderm; SolcoKerasal; Sterovag; Port.: Calmurid; Carmitol; Creme Laser Hidrante; Hidratoderme†; Mycospor†; U Lactin; Ureadin; Ureadin 10 Plus; Ureadin Facial; Ureadin Forte; Ureadin Maos; Rus.: Mycospor (Микоспор); S.Afr.: Calmurid HC†; Covancaine; Mycospor Onycho-set; Singapore: Balneum Intensiv Plus; Dermadrate; Topicrem; U-Lactin; Spain: Cortisdin Urea; Kanapomada; Mycospor Onicoset; Swed.: Fenuril-Hydrokortison; Switz.: Acne Gel; Antikeloides Creme; Betacortone; Calmurid; Calmurid HC†; Carbamide + VAS; Carbamide Creme; Kerasal; Klyx Magnum; Optiderm; Sebo Creme; Sebo-Psor; Turexan Capilla; Turexan Lotion; Thai.: Balneum Intensiv Plus†; Gynestin; Turk.: Betacorton; Kerasal; Mycospor; Ureacort; UK: Alphaderm; Antipeol; Balneum Plus; Calmurid; Calmurid HC; Cymex; E45 Itch Relief; St James Balm; Vesagex Heelbalm; USA: Accuzyme; AllanEnzyme; AllanfillEnzyme; Amino-Cerv; Ethezyme; Gladase; Gladase-C; Hydrocerin Plus; Kovia; Panafil; Panafil-White; Pap-Urea; Rosula; Rosula NS; Ziox; Zoderm; Venez.: Akerat; Caduril; Hidribet; Hidribet 5/5; Mycospor Onicoset; Pantonic; Pelset Plus; Ureaderm Lactato; Urimet†; Urisalic†.
Published January 24, 2019.