Professional Drug Information > Ureaphil

Urea (Parenteral-Local)

VA CLASSIFICATION
Primary: GU600

Commonly used brand name(s): Ureaphil.

Another commonly used name is
carbamide .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Abortifacient—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

[Abortion, elective]— Urea, when administered by transabdominal intra-amniotic injection as a hypertonic solution, is used for aborting second trimester pregnancy beyond the sixteenth week of gestation. ^{{04} {07} {08} {12} {13}} The use of hypertonic urea solution for abortion has generally been replaced by dilation and evacuation, though it may be useful in selected patients ^{{15} {16}}. Urea is used in combination with oxytocin or prostaglandins ^{{07} {08} {12}}. Use between the 12th and 16th weeks is difficult because of the small amount of amniotic fluid present and results in an increased failure rate. ^{04}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    60.06

Mechanism of action/Effect:

The mechanism by which urea causes fetal death and abortion has not been elucidated but may be related to damage of decidual cells by hypertonic urea and subsequent release of prostaglandins, which induce uterine contractions ^{{03} {04} {07}}. Hypertonic urea induces fetal death ^{07}.

Time to peak effect:


Mean abortion time:

Urea with dinoprost: 16 to 17 hours ^{07}.

Urea with oxytocin: 18 to 30 hours. ^{{04} {08}}


Elimination:
    Renal. ^{{04} {12}}


Precautions to Consider


Adolescents

No published information is available on the use of intra-amniotic urea in adolescent females. However, no adolescent-specific problems have been documented to date.


Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

» Oxytocin or other oxytocics    (concurrent use with urea may result in uterine hypertonus, possibly causing uterine rupture or cervical laceration, especially in the absence of adequate cervical dilation; although combinations are sometimes used for therapeutic advantage, patient should be closely monitored during concurrent use ^{04})


Aspirin    (In one study, aspirin, in doses of 600 mg given with and once every 6 hours after instilling urea intra-amniotically, increased the normal intra-amniotic urea induction-to-abortion time in primigravida patients. ^{04})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Blood urea nitrogen (BUN) concentrations ^{{03} {04}}    (may be increased following administration but usually return to acceptable levels within 24 hours ^{{03} {04}})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Absolute contraindications to labor
» Ruptured membranes
Risk-benefit should be considered when the following medical problems exist
Allergy to urea
Cervical stenosis or
Uterine fibroids    (risk of uterine rupture)


» Dehydration or ^{{03} {04} {05}}
» Renal function impairment, severe ^{{03} {04} {05}}    (risk of electrolyte imbalance and impaired clearance)


» Diabetes mellitus or ^{{03} {04}}
» Sickle cell disease ^{{03} {04}}    (risk of intravascular hemolysis or thrombosis)


» Hepatic function impairment, severe ^{{03} {04} {05}}    (blood ammonia concentrations may be elevated)


» Intracranial bleeding, active ^{{03} {04} {05}}    (unless use of urea is followed promptly by surgical intervention to control hemorrhage, since urea may increase bleeding)


» Relative contraindications to labor ^{{03} {04}}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Contractions, frequency, duration, and force of and
Temperature, pulse, and blood pressure determinations and
Uterine tone, resting    (recommended at frequent intervals during abortion procedure)


Fluid intake and output monitoring ^{07}    (especially when used with oxytocin ^{07})


Electrolytes ^{{04} {07} {12}}    (measurement of serum concentrations is recommended at regular intervals, especially when used with oxytocin ^{07})


Vaginal examination ^{08}    (recommended postabortion to check for signs of cervical trauma ^{08})




Side/Adverse Effects

Note: Urea may cause uterine hypertonicity with spasm and tetanic contraction that can lead to posterior cervical perforations, cervical lacerations, uterine rupture, and hemorrhage, especially when given with oxytocics ^{{07} {13}}.
Intra-amniotic administration of hypertonic urea has been associated with disseminated intravascular coagulation. ^{{03} {04} {07} {10} {12}}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible cause in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Inadvertent intravascular, myometrial, or intraperitoneal administration ^{04}(pain in lower abdomen or weakness)

Note: Inadvertent intravascular, myometrial, or intraperitoneal administration may lead to myometrial necrosis and/or dehydration with resulting vomiting, hyponatremia ^{05}, and hypokalemia ^{05} or hyperkalemia. Instillation should be discontinued immediately.


Incidence rare
    
Electrolyte imbalance ^{12}(confusion; irregular heartbeat ; muscle cramps or pain; numbness, tingling, pain, or weakness in hands or feet; unusual tiredness or weakness; weakness or heaviness of legs)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Nausea or vomiting ^{{03} {04} {05} {08}}

Incidence less frequent or rare
    
Headache ^{{03} {04} {05}}
    
diarrhea ^{04}



Those indicating possible postabortion complications and the need for medical attention if they occur after medication is discontinued
    
Endometritis (chills; shivering; fever; foul-smelling vaginal discharge; pain in lower abdomen)
    
increase in uterine bleeding




Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Urea (Intra-amniotic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to urea
Other medications, especially oxytocin or other oxytocics
Other medical problems, especially renal function impairment, diabetes mellitus, sickle cell disease, or hepatic function impairment

Proper use of this medication
Importance of taking oral fluids during procedure ^{{03} {04}}

» Proper dosing


Side/adverse effects
Signs of potential side effects, especially pain in lower abdomen, weakness, electrolyte imbalance


General Dosing Information
It is recommended that intra-amniotic urea be administered in a hospital setting.

Hypertonic urea should not be administered if a bloody amniotic tap is obtained.

Withdrawal of 100 to 200 mL of amniotic fluid is recommended prior to instillation of hypertonic urea to prevent sudden increases in intra-amniotic pressure and to ensure adequate concentrations of urea.

Extra-amniotic injection of urea should be avoided. ^{{03} {04}}

To aid urea excretion and prevent dehydration, it is recommended that patients take oral fluids freely during the procedure ^{04}; intravenous fluids may also be required. ^{03} Intake of fluids should not exceed output by 1500 mL in each 24 hours.

Concurrent intravenous administration of a dilute solution of oxytocin is usually begun within 1 to 2 hours after urea instillation to shorten the induction-to-abortion time ^{03} and reduce the failure rate, although the rate of incomplete abortion is 30 to 40% even with oxytocin. ^{{03} {04}}

Instillation of hypertonic urea may be followed immediately by intra-amniotic administration of the equivalent of 5 to 10 mg of dinoprost.

Some clinicians recommend using a dose of 80 grams of urea as a 59.7% solution in combination with 5 mg of dinoprost tromethamine (prostaglandin F ₂ tromethamine).

If urea is not effective, it is recommended that alternative methods such as oxytocin or dinoprost not be used until the uterus has stopped contracting.


Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.


UREA STERILE USP

Usual adult and adolescent dose
[Abortion]
Intra-amniotic, after transabdominal tap of the amniotic sac, a volume of 40 to 60% urea solution (in 5% dextrose injection) equal to the volume of amniotic fluid removed, up to a maximum of 200 to 250 mL (usually 80 grams of urea) administered slowly while observing for adverse reactions. ^{{03} {04}}


Note: The instillation may be repeated 48 hours after the initial dose if the abortion process is not established or clinically imminent, provided the membranes are still intact. ^{{03} {04}}


Size(s) usually available:
U.S.—


40 grams (Rx) [Ureaphil^{05}]

Packaging and storage:
Prior to reconstitution, store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.

Preparation of dosage form:
To prepare a 40, 50, or 60% injection, add 5% Dextrose Injection USP to 80 grams (2 vials) of urea to make a final volume of 200, 150, or 135 mL, respectively. ^{{03} {04}}

Reconstitution time may be prolonged by the endothermic reaction that occurs and can be shortened by warming the diluent to 60 °C in a water bath immediately before reconstitution. The resulting solution should be at body temperature for administration. ^{04}

One gram of urea is equivalent to approximately 16.7 mOsm (calculated on basis of urea being reconstituted with water for injection; equals 666 mOsm per liter ^{05}).

The osmolarity of urea infusion when prepared in the specified diluent is as follows:

Urea (%)	Diluent	Total mOsm/liter
40 {04}	5% Dextrose Injection USP	6920
50 {04}	5% Dextrose Injection USP	8586

Stability:
Sterile Urea USP should be freshly reconstituted for each patient. The solution should be used within 24 hours. ^{{03} {05}} Discard any unused portion. ^{05}

Urea solutions cannot be heat-sterilized because of instability.

Note: Reconstituted solution should be at body temperature for instillation.

Revised: 02/22/2000

References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

1. Not used
   

2. Not used
   

3. Sterile Urea USP for Reconstitution to a 40 to 50% solution for Transabdominal Intra-amniotic Injection (Abbott Labs). Package Insert 3/82. Rec. 9/27/82.
   

4. ASHP. American Hospital Formulary Service. Bethesda: 2000. Urea 40–50% Injection monograph:2941-2942.
   

5. Product Information: Ureaphil®, sterile urea, USP. Abbott Labs, North Chicago, IL, (PI revised 3/95), reviewed 2/2000.
   

6. Kastrup, EK, et al. (editors). Facts and comparisons: drug information service. St. Louis: J.B. Lippincott Co. Facts and comparisons division. 1988.
   

7. Castadot RG. Pregnancy termination: techniques, risks, and complications and their management. Fertil Steril 1986; 45(1): 5-17.
   

8. Craft I. Induction of abortion by combined intra-amniotic urea and prostaglandin E2 or prostaglandin E2 alone. Lancet 1973; June 16; 1344-6.
   

9. Craft I. Intra-amniotic prostaglandins and urea for abortion. Lancet 1973; July 28: 207.
   

10. Lawson HW, Atrash HK, Franks AL. Fatal pulmonary embolism during legal induced abortion in the United States from 1972 to 1985. Am J Obstet Gynecol 1990; 162(4): 986-90.
    

11. Shuster J, et al. Ovarian pregnancy diagnosed after a failed midtrimester therapeutic abortion: a case report. J Reprod Med 1990; 35(2): 187-90.
    

12. Reynolds JEF (editor). Martindale, the extra pharmacopeia. 29th ed. London: The Pharmaceutical Press, 1989: 1005-6.
    

13. Pernoll ML, Benson RC (editors). Current obstetric and gynecologic diagnosis and management. 6th ed. Norwalk, CT: Appleton & Lange, 1987: 604-9.
    

14. Scott JR, DiSaia PJ, Hammond CB, Spellacy WN. Danforth"s obstetrics and gynecology. 6th ed. Philadelphia: J.B. Lippincott Co., 1990.
    

15. Obstetrics and Gynecology Meeting, November 18, 1991.
    

16. Panel consensus, panel survey date 4/6/92.
    

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