Ethanolamine Oleate (Parenteral-Local)

VA CLASSIFICATION
Primary: CV900

Commonly used brand name(s): Ethamolin.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Sclerosing agent—

Indications

Accepted

Esophageal varices, bleeding (treatment)—Ethanolamine oleate is indicated in the treatment of bleeding esophageal varices, and the prevention of recurrent bleeding in patients whose varices have recently bled.
—Ethanolamine oleate does not correct portal hypertension, the underlying cause of esophageal varices. Recanalization of varices and collateralization may therefore occur, requiring further treatment. ^{{01} {02}}

Acceptance not established
Ethanolamine oleate sclerotherapy has been used to treat cystic lesions including testicular hydroceles, spermatoceles, and renal cysts ^{{03} {04} {05}} . In the case of scrotal lesions, improved results were obtained when treatment was limited to a maximum of 3 cysts ^{03}. In addition, sclerotherapy for the treatment of spermatoceles was not recommended for men in their reproductive years who wish to have children because of the danger of its causing infertility ^{03}. Even though results have generally been good, data is limited and further study is required to define the role of ethanolamine oleate in these conditions.

Unaccepted
Ethanolamine oleate is not indicated for the prophylactic treatment of esophageal varices that have not bled. Trials of prophylactic sclerotherapy have shown mixed results and varied greatly in design; the early favorable results were obtained from poor quality studies. ^{{01} {02} {06} {07}}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    343.55 ^{08}

Mechanism of action/Effect:

Injection of ethanolamine oleate causes an acute, dose-related inflammatory reaction of the intimal endothelium of the vein. This leads to scarring and possible occlusion of the vein. An acute, dose-related extravascular inflammatory reaction also occurs as ethanolamine oleate rapidly diffuses through the venous wall. ^{{01} {02}}

Ethanolamine oleate also causes a transient activation of the coagulation and fibrinolytic systems. The oleic acid component, which is responsible for the inflammatory response, may initiate coagulation by activation of Hageman factor and release of tissue factor. However, the ethanolamine component may inhibit clot formation by chelating calcium, which is necessary for coagulation. Therefore, a procoagulant effect of ethanolamine oleate has not been demonstrated. ^{{01} {09}}

Absorption:

After injection into an esophageal varix, ethanolamine oleate is cleared from the injection site within five minutes via the portal vein ^{01}. Some of the medication also flows into the azygos vein through the periesophageal vein if more than 20 mL is injected ^{01}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients allergic to ethanolamine, oleic acid, or morrhuate sodium ^{27} may be allergic to ethanolamine oleate also ^{{01} {02}}.

Carcinogenicity

There have been a few case reports of esophageal carcinoma following endoscopic injection sclerotherapy for esophageal varices ^{10}. However, an association between sclerotherapy and carcinoma is difficult to determine ^{10}. In the reported cases, various sclerosants were used and other risk factors such as age and alcohol/tobacco abuse were present ^{10}. There were also geographic differences in the sites of sclerosis and the development of carcinoma ^{10}. Present information is insufficient to establish a causal relationship between endoscopic sclerotherapy and development of esophageal carcinoma ^{10}. Further study and observation are required, and periodic long-term follow-up should be performed following endoscopic sclerotherapy ^{10}.

Pregnancy/Reproduction

Pregnancy—
Studies have not been done in humans ^{01}.

Studies have not been done in animals ^{01}.

FDA Pregnancy Category C ^{01}.

Breast-feeding

It is not known whether ethanolamine oleate is distributed into breast milk ^{{01} {02}}.

Pediatrics

Appropriate studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of ethanolamine oleate in children ^{{11} {12} {13} {14}}.


Geriatrics


Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of ethanolamine oleate in the elderly ^{15}.

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:
» Allergy to ethanolamine, oleic acid, ethanolamine oleate^{01}{02} , or morrhuate sodium^{27}

Side/Adverse Effects

Note: Many of these complications are related to injection sclerotherapy in general and are not necessarily a result of ethanolamine oleate therapy specifically.
Portal gastropathy may develop following endoscopic injection sclerotherapy of esophageal varices, with a peak incidence 6 to 9 months after treatment. Its development may be a result of the transmission of pressure to gastric mucosal and submucosal veins and the formation of gastric capillary ectasia with obstruction of the esophageal varices. ^{{16} {17}}
Overdosage of ethanolamine oleate during injection sclerotherapy of esophageal varices can result in severe intramural necrosis of the esophagus. Complications occurring after such an overdose have resulted in death. ^{{01} {02}}

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

Those indicating need for medical attention
Incidence less frequent
    
Esophageal stricture
    
pneumonia, including
aspiration pneumonia
    
portal vein thrombosis
^{{01}{02}{16}{18}{19}}
Incidence rare
    
Allergic reactions, including
anaphylaxis
urticaria
and generalized skin reactions
    
CNS infection, including
brain abscess
and meningitis
    
disseminated intravascular coagulation
    
esophageal perforation
    
renal failure, acute
    
spinal cord paralysis ^{{01}{02}{16}{18}{20}{21}{22}{23}{24}}
Note: A case of fatal anaphylactic shock occurred in a patient who had a known allergic disposition and received a larger than normal volume of ethanolamine oleate ^{01}.





Those indicating need for medical attention only if they continue or are bothersome

Note: The following adverse effects are generally transient, self-limiting, and inconsequential ^{{16} {18}}. In the case of fever and bacteremia, antibiotic therapy is not indicated unless fever is high, has erratic swings, persists beyond 48 hours, or is associated with other signs of infection ^{16}.

Incidence more frequent
    
Chest pain
    
dysphagia
    
fever
^{{01}{02}{16}{18}}
Incidence less frequent
    
Bacteremia^{{01}{02}{16}{18}}



Those not indicating need for medical attention
Incidence more frequent
    
Abnormal chest x-rays, including
pulmonary infiltrates
and pleural effusions
    
esophageal ulceration
^{{01}{02}{16}{18}{25}}




General Dosing Information
Ethanolamine oleate should be administered only by physicians who are experienced with the use of an acceptable injection technique ^{{01} {02}}.

For treatment of esophageal varices ^{{01} {02}}
Careful monitoring and reduction of the total dose per session is recommended in patients with concomitant cardiorespiratory or significant liver disease (Child Class C).

Esophageal ulceration following ethanolamine oleate sclerotherapy is more common in patients in Child Class C.

Esophageal ulceration, necrosis, and delayed perforation appear to occur more often when the medication is injected submucosally. This route of administration is not recommended.

Because fatal aspiration pneumonia has occurred following ethanolamine oleate sclerotherapy, precautions should be taken to prevent its occurrence, particularly in the elderly and critically ill patients.

Antibiotic prophylaxis is recommended for immunosuppressed patients or for patients with valvular heart disease or prosthetic graft material because of the potential for bacteremia associated with endoscopy ^{18}. Staphylococcus aureus and alpha hemolytic streptococci are the most commonly identified organisms associated with bacteremia following upper gastrointestinal endoscopy ^{18}.

Safety considerations for handling this medication
The physician should wear protective eye gear during procedures to prevent eye damage by spattered sclerosant ^{16}.

For treatment of adverse effects
Serious anaphylactic reactions require emergency treatment, which consists of the following ^{{01} {02} {26}}

   • 0.25 mL of a 1:1,000 intravenous solution of epinephrine (0.25 mg).
   • Oxygen.
   • Parenteral antihistamines.
   • Intravenous corticosteroids.
   • Airway management (including intubation).


Parenteral Dosage Forms

ETHANOLAMINE OLEATE INJECTION

Usual adult dose
Esophageal varices, bleeding
Intravenous, 1.5 to 5 mL per varix, up to a maximum dose of 20 mL per treatment session.

To obliterate the varix, injections may be given at the time of the acute bleeding episode and then one week, six weeks, three months, and six months later as indicated. ^{{01} {02}}


Usual adult prescribing limits
20 mL per treatment session ^{{01} {02}}.

Usual pediatric dose
Esophageal varices, bleeding
Intravenous, 2 to 3 mL per varix, up to a maximum dose of 10 to 20 mL per treatment session ^{14}.


Usual pediatric prescribing limits
10 to 20 mL per treatment session ^{14}.

Strength(s) usually available
U.S.—


5% (50 mg [approximate] per mL) (Rx) [Ethamolin (benzyl alcohol, 2% by volume)]

Canada—


5% (50 mg [approximate] per mL) (Rx) [Ethamolin (benzyl alcohol, 2% by volume)]

Packaging and storage:
Store at controlled room temperature, between 15 and 30 °C (59 and 86 °F). Protect from light. ^{{01} {02}}

Note: Injection should be inspected visually for particulate matter and discoloration prior to administration ^{01}.

Developed: 08/10/1995

References

1. Ethamolin package insert (Reed & Carnrick—US), Rev 8/92, Rec 2/95.
   

2. Ethamolin package insert (Reed & Carnrick—Canada), Rev 1993, Rec 3/95.
   

3. Tammela TLJ, Hellström PA, Mattila SI, et al. Ethanolamine oleate sclerotherapy for hydroceles and spermatoceles: a survey of 158 patients with ultrasound followup. J Urol 1992; 147: 1551-3.
   

4. Hellström P, Tammela T, Kontturi M, et al. Ethanolamine oleate as a sclerosant for testicular hydroceles and epididymal cysts. Br J Urol 1988; 62: 445-8.
   

5. Brown B, Sharifi R, Lee M. Ethanolamine sclerotherapy of a renal cyst. J Urol 1995; 153: 385-6.
   

6. Bornman PC, Krige JEJ, Terblanche J. Management of oesophageal varices. Lancet 1994; 343: 1079-84.
   

7. Lopes GM, Grace ND. Gastroesophageal varices: prevention of bleeding and rebleeding. Gastroenterol Clin North Am 1993; 22: 801-20.
   

8. Fleeger CA, editor. USP dictionary of USAN and international drug names 1995. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1994: 264.
   

9. Kang JH, Kambayashi J, Sakon M, et al. Mechanism of the haemostatic effect of ethanolamine oleate in the injection sclerotherapy for oesophageal varices. Br J Surg 1987; 74: 50-3.
   

10. Kokudo N, Sanjo K, Umekita N, et al. Squamous cell carcinoma after endoscopic injection sclerotherapy for esophageal varices. Am J Gastroenterol 1990; 85: 861-4.
    

11. Stringer MD, Howard ER. Longterm outcome after injection sclerotherapy for oesophageal varices in children with extrahepatic portal hypertension. Gut 1994; 35: 257-9.
    

12. Hill ID, Bowie MD. Endoscopic sclerotherapy for control of bleeding varices in children. Am J Gastroenterol 1991; 86: 472-6.
    

13. Maksoud JG, Gonçalves MEP, Porta G. The endoscopic and surgical management of portal hypertension in children: analysis of 123 cases. J Pediatr Surg 1991; 26: 178-81.
    

14. Howard ER, Stringer MD, Mowat AP. Assessment of injection sclerotherapy in the management of 152 children with oesophageal varices. Br J Surg 1988; 75: 404-8.
    

15. Ohta M, Hashizume M, Kamakura T, et al. Endoscopic injection sclerotherapy for esophageal varices in the elderly. World J Surg 1994; 18: 764-8.
    

16. Truesdale RA, Wong RKH. Complications of esophageal variceal sclerotherapy. Gastroenterol Clin North Am 1991; 20: 859-70.
    

17. Tanoue K, Hashizume M, Wada H, et al. Effects of endoscopic injection sclerotherapy on portal hypertensive gastropathy: a prospective study. Gastrointest Endosc 1992; 38: 582-5.
    

18. Heaton ND, Howard ER. Complications and limitations of injection sclerotherapy in portal hypertension. Gut 1993; 34: 7-10.
    

19. Kochhar R, Goenka MK, Mehta SK. Esophageal strictures following endoscopic variceal sclerotherapy. Antecedents, clinical profile, and management. Dig Dis Sci 1992; 37: 347-52.
    

20. Bordas JM, Feu F, Vilella A, et al. Anaphylactic reaction to ethanolamine oleate injection in sclerotherapy of esophageal varices. Endoscopy 1989; 21: 50.
    

21. Maling TJB, Cretney MJ. Ethanolamine oleate and acute renal failure. N Z Med J 1975; 82: 269-70.
    

22. Ng EKW, Chung SCS, Leong HT, et al. Perforation after endoscopic injection sclerotherapy for bleeding gastric varices. Surg Endosc 1994; 8: 1221-2.
    

23. Toyoda K, Saku Y, Sadoshima S, et al. Purulent meningitis after endoscopic injection sclerotherapy for esophageal varices. Intern Med 1994; 33: 706-9.
    

24. Bellary SV, Isaacs P. Disseminated intravascular coagulation (DIC) after endoscopic injection sclerotherapy with ethanolamine oleate [letter]. Endoscopy 1990; 22: 151.
    

25. Zeller FA, Cannan CR, Prakash UBS. Thoracic manifestations after esophageal variceal sclerotherapy. Mayo Clin Proc 1991; 66: 727-32.
    

26. Rakel RE, editor. Conn's current therapy 1995. Philadelphia: W.B. Saunders Company, 1995: 676-7.
    

27. Reviewer comment, 7/95.