VA Class:CV600
Morrhuate sodium is a sclerosing agent.
Morrhuate sodium is used for the obliteration of primary varicose veins that consist of simple dilation with competent valves. Sclerotherapy should not be used in patients with significant valvular or deep vein incompetence. (See Cautions: Precautions and Contraindications.) Although morrhuate sodium has been used as a sclerosing agent for the treatment of internal hemorrhoids, there is no substantial evidence that the drug is effective for this use.
Most patients with symptomatic primary varicose veins should be treated initially with compression stockings. If this treatment is inadequate, surgery may be required. Sclerosing agents may be useful as a supplement to venous ligation to obliterate residual varicose veins or in patients who have conditions which increase the risk of surgery. However, many clinicians consider sclerotherapy to be of limited value because the effects are not permanent and the potential success of surgery may be decreased if sclerotherapy is ineffective.
Morrhuate sodium has been used effectively for endoscopic sclerotherapy in the management of bleeding esophageal varices†.100, 101, 102, 103, 104, 105, 108, 112, 113 Morrhuate sodium 5% solutions or diluted (in dextrose injection) solutions of the drug have been administered by intravariceal or paravariceal injection using a flexible fiberoptic endoscope.100, 101, 102, 103, 104, 105, 108, 112, 113 Endoscopic sclerotherapy has been used for control of acute hemorrhage100, 101, 102, 104, 105, 107, 108, 109, 113 or prevention of initial or recurrent bleeding100, 101, 103, 105, 107, 108, 109, 113, 115 associated with esophageal varices. When endoscopic sclerotherapy is used in the management of an acute bleeding episode, the patient generally is stabilized using appropriate measures as necessary, including vasopressin therapy, balloon tamponade, management of encephalopathy, and correction of hypovolemia, anemia, and coagulation disorders, prior to initiation of sclerotherapy.103, 107, 108, 115 Endoscopic sclerotherapy has been used as an alternative or adjunct to surgery,100, 108, 109, 113 but the precise role of sclerotherapy in the management of bleeding esophageal varices, particularly regarding long-term efficacy, has not been fully elucidated.102, 103, 107, 108, 109, 112, 113 In one study in a limited number of patients with severe liver cirrhosis (Child class C) in whom acute variceal hemorrhage was treated with endoscopic sclerotherapy or portocaval shunt, variceal rebleeding, duration of rehospitalization for hemorrhage, and transfusions during long-term (averaging 530 days) follow-up were greater for patients initially treated with sclerotherapy (which included long-term, repeated, outpatient sclerotherapy as necessary for variceal obliteration); long-term survival was similar in both groups, but 40% of surviving sclerotherapy-treated patients subsequently required surgical treatment of bleeding varices following discharge.100 Additional study of the relative efficacy and safety of this and other sclerosing agents in the management of this condition is necessary.102, 106, 108, 109, 112 Complications (e.g., mucosal lesions, bacteremia, esophageal stenosis/ stricture or perforation, dysphagia and other esophageal dysfunction, chest pain, pleural effusions, mediastinitis, respiratory failure, fever) associated with esophageal sclerotherapy are variable depending on the technique employed, skill and experience of the endoscopist, cause of the underlying liver disease associated with the varices, and clinical condition of the patient, but the possibility that complications can be severe and potentially fatal should be considered.101, 102, 103, 104, 105, 108, 109, 110, 111, 112, 114
Morrhuate sodium is administered only by IV injection. Care must be taken to avoid extravasation. (See Cautions: Adverse Effects.) Specialized references should be consulted for specific procedures and techniques of administration. When small veins are injected, when the ampul is cold, or when the ampul contains solid matter, the injection should be warmed by immersing in hot water. The injection should become clear on warming; only a clear solution should be used. Because the injection froths easily, a large bore needle should be used to fill the syringe. However, a smaller bore needle should be used for injection.
To determine possible sensitivity to the drug, some clinicians recommend injection of 0.25-1 mL of 5% morrhuate sodium injection into a varicosity 24 hours before administration of a larger dose. The drug also has been administered by intravariceal or paravariceal† injection using specialized techniques via a flexible fiberoptic endoscope for the management of bleeding esophageal varices†.100, 101, 102, 103, 104, 105 (See Uses.)
Dosage of morrhuate sodium depends on the size and degree of varicosity. The usual adult dose for obliteration of small or medium veins is 50-100 mg (1-2 mL of the 5% injection). For large veins, 150-250 mg (3-5 mL of the 5% injection) is used. The drug may be given as multiple injections at one time or in single doses. Therapy may be repeated at 5- to 7-day intervals, according to the patient's response. Following injection of morrhuate sodium, the vein promptly becomes hard and swollen for 2-4 inches, depending on the size and response of the vein. After 24 hours, the vein is hard and slightly tender to touch (with little or no periphlebitis). The skin around the injected vein becomes light-bronze; this color usually disappears shortly. An aching sensation and feeling of stiffness usually occur and last approximately 48 hours.
Local reactions to morrhuate sodium consist of burning or cramping sensations, or urticaria at the site of injection. Sloughing and necrosis of tissue may occur following extravasation of the drug. Headache and drowsiness may occur rarely. Pulmonary embolism has been reported.
Rarely, patients may have or may develop hypersensitivity to morrhuate sodium, characterized by dizziness, weakness, vascular collapse, asthma, respiratory depression, GI disturbances (e.g., nausea, vomiting), and urticaria. Anaphylactic reactions may occur within a few minutes after injection of the drug and are most likely to occur when therapy is reinstituted after an interval of several weeks.
Precautions and Contraindications
Since severe adverse local effects may occur following extravasation of morrhuate sodium, the drug should be administered only by a physician familiar with a proper injection technique. Morrhuate sodium should only be administered when adequate facilities, drugs (e.g., epinephrine, antihistamines, corticosteroids), and personnel are available for the treatment of anaphylactic reactions. Morrhuate sodium is contraindicated in patients who have shown a previous hypersensitivity reaction to the drug or to the fatty acids of cod liver oil. Continued administration of the drug is contraindicated when an unusual local reaction at the injection site or a systemic reaction occurs.
Thrombosis induced by morrhuate sodium may extend into the deep venous system in patients with significant valvular incompetency. Therefore, valvular competency, deep vein patency, and deep vein competency should be determined by angiography and/or by tests such as the Trendelenburg's and Perthes' tests before injection of sclerosing agents. The drug is contraindicated for obliteration of superficial veins in patients with persistent occlusion of deep veins. Morrhuate sodium is also contraindicated in patients with acute superficial thrombophlebitis; underlying arterial disease; varicosities caused by abdominal and pelvic tumors, uncontrolled diabetes mellitus, thyrotoxicosis, tuberculosis, neoplasms, asthma, sepsis, blood dyscrasias, acute respiratory or skin diseases; and in bedridden patients. Treatment with morrhuate sodium should be delayed in patients with acute local or systemic infections (including infected ulcers). Extensive therapy with the drug is inadvisable in patients who are severely debilitated or senile.
Animal reproduction studies have not been performed with morrhuate sodium; it also is not known whether morrhuate sodium can cause fetal harm when administered to pregnant women. Morrhuate sodium should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
It is not known whether morrhuate sodium can affect reproduction capacity in humans.
When injected into a vein, morrhuate sodium causes inflammation of the intima and formation of a thrombus. This blood clot occludes the injected vein and fibrous tissue develops, resulting in obliteration of the vein.
Morrhuate sodium is a mixture of the sodium salts of the saturated and unsaturated fatty acids of cod liver oil prepared by saponification of cod liver oil. Morrhuate sodium occurs as a pale-yellowish, granular powder with a slight fishy odor and is soluble in water and in alcohol. The commercially available injection varies from light or medium yellow to light brown. The pH of the commercially available injection is adjusted to 6.9-9.6 with sodium hydroxide, hydrochloric acid, and/or morrhuic acid.
Morrhuate sodium injections should be stored at 15-30°C; injections should be protected from freezing. Morrhuate sodium oxidizes and becomes discolored in air. Solid matter may separate from morrhuate sodium injection on standing, and the injection should not be used if the solid does not dissolve completely on warming.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IV use only | 50 mg/mL* | Morrhuate Sodium Injection | |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
100. Cello JP, Grendell JH, Crass RA et al. Endoscopic sclerotherapy versus portacaval shunt in patients with severe cirrhosis and acute variceal hemorrhage: long-term follow-up. N Engl J Med . 1987; 316:11-5. [PubMed 3491317]
101. Sanowski RA. Endoscopic injection sclerotherapy for esophageal varices. Resident Staff Phys . 1985; 31:25-30.
102. Ayres SJ, Goff JS, Warren GH. Endoscopic sclerotherapy for bleeding esophageal varices: effects and complications. Ann Intern Med . 1983; 98:900-3. [PubMed 6602573]
103. Tihansky DP, Reilly JJ, Schade RR et al. The esophagus after injection sclerotherapy of varices: immediate postoperative changes. Radiology . 1984; 153:43-7. [PubMed 6332339]
104. Agha FP. The esophagus after endoscopic injection sclerotherapy: acute and chronic changes. Radiology . 1984; 153:37-42. [PubMed 6332338]
105. Reilly JJ Jr, Schade RR, Van Thiel DS. Esophageal function after injection sclerotherapy: pathogenesis of esophageal stricture. Am J Surg . 1984; 147:85-8. [PubMed 6606991]
106. Gordon RS Jr. Endoscopic sclerotherapy for esophageal variceal hemorrhage. N Engl J Med . 1985; 312:989. [PubMed 3871912]
107. The Copenhagen Esophageal Varices Sclerotherapy Project. Sclerotherapy after first variceal hemorrhage in cirrhosis: a randomized multicenter trial. N Engl J Med . 1984; 311:1594-600. [PubMed 6390203]
108. American College of Physicians Health and Public Policy Committee. Endoscopic sclerotherapy for esophageal varices. Ann Intern Med . 1984; 100:608-10. [PubMed 6608304]
109. Allison JG. The role of injection sclerotherapy in the emergency and definitive management of bleeding esophageal varices. JAMA . 1983; 249:1484-7. [PubMed 6600796]
110. Monroe P, Morrow CF Jr, Millen JE et al. Acute respiratory failure after sodium morrhuate esophageal sclerotherapy. Gastroenterology . 1983; 85:693-9. [PubMed 6603387]
111. Musso R, Giustolisi R, Cacciola E. Acute respiratory distress during sclerotherapy for esophageal varices. Ann Intern Med . 1987; 106:640. [PubMed 3826974]
112. The ACG Committee on FDA Related Matters. Variceal sclerosing agents. Am J Gastroenterol . 1984; 79:424-8. [PubMed 6609635]
113. Cello JP, Grendell JH, Crass RA et al. Endoscopic sclerotherapy versus portacaval shunt in patients with severe cirrhosis and variceal hemorrhage. N Engl J Med . 1984; 311:1589-94. [PubMed 6334234]
114. Snady H, Korsten MA, Waye JD. The relationship of bacteremia to the length of injection needle in endoscopic variceal sclerotherapy. Gastrointest Endosc . 1985; 31:243-6. [PubMed 4029571]
115. Larson AW, Cohen H, Zweiban B et al. Acute esophageal variceal sclerotherapy: results of a prospective randomized controlled trial. JAMA . 1986; 255:497-500. [PubMed 3510333]