Edecrin Side Effects

Generic Name: ethacrynic acid

Note: This page contains information about the side effects of ethacrynic acid. Some of the dosage forms included on this document may not apply to the brand name Edecrin.

Not all side effects for Edecrin may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to ethacrynic acid: oral tablet

In addition to its needed effects, some unwanted effects may be caused by ethacrynic acid (the active ingredient contained in Edecrin). In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking ethacrynic acid:

Rare
  • Bleeding gums
  • bloating
  • clay-colored stools
  • constipation
  • darkened urine
  • indigestion
  • itching
  • large, flat, blue or purplish patches in the skin
  • loss of appetite
  • nausea
  • painful knees and ankles
  • pains in stomach, side, or abdomen, possibly radiating to the back
  • pinpoint red spots on skin
  • raised red swellings on the skin, the buttocks, legs, or ankles
  • skin rash
  • unpleasant breath odor
  • vomiting of blood
  • yellow eyes or skin
Incidence not determined
  • Anxiety
  • black, tarry stools
  • blood in urine
  • blurred vision
  • cold sweats
  • coma
  • confusion
  • convulsions (seizures)
  • cool, pale skin
  • cough or hoarseness
  • depression
  • dizziness
  • dry mouth
  • fast heartbeat
  • fever with or without chills
  • flushed, dry skin
  • fruit-like breath odor
  • general feeling of tiredness or weakness
  • headache
  • increased hunger
  • increased thirst
  • increased urination
  • joint pain, stiffness, or swelling
  • lower back, side, or stomach pain
  • nausea
  • nervousness
  • nightmares
  • painful or difficult urination
  • pale skin
  • shakiness
  • shortness of breath
  • slurred speech
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • sweating
  • swelling of the feet or lower legs
  • troubled breathing
  • unexplained weight loss
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • vomiting
  • watery and severe diarrhea

If any of the following symptoms of overdose occur while taking ethacrynic acid, get emergency help immediately:

Symptoms of overdose
  • Confusion
  • decreased urination
  • dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
  • increase in heart rate
  • irregular heartbeat
  • muscle cramps or pain
  • numbness, tingling, pain, or weakness in the hands or feet
  • rapid breathing
  • sunken eyes
  • thirst
  • trembling
  • weakness and heaviness of the legs
  • wrinkled skin

Some of the side effects that can occur with ethacrynic acid may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Incidence not determined
  • Continuing ringing or buzzing or other unexplained noise in ears
  • difficulty swallowing
  • fear
  • feeling of constant movement of self or surroundings
  • feeling of fullness in the ears
  • general feeling of discomfort or illness
  • hearing loss
  • mild diarrhea
  • sensation of spinning
  • stomach soreness or discomfort
  • weight loss

For Healthcare Professionals

Applies to ethacrynic acid: intravenous powder for injection, oral tablet

Nervous system

A cooperative study by the Boston Collaborative Drug Surveillance Program evaluated 32 of 11,526 patients who developed deafness while in the hospital. The incidence of deafness associated with intravenous ethacrynic acid (the active ingredient contained in Edecrin) in this study was 0.7%. No hearing impairment developed in 118 patients who had received the drug by oral administration.

The actual mechanism of ototoxicity is not known, but is believed to be due to inhibition of enzymes that are involved in the endolymph sodium-potassium membrane concentration gradient or to direct effects on the cochlear hair cells. Light microscopic findings in affected cochlea include rupture of endothelial layers and edematous changes of the marginal cells of the stria vascularis.[Ref]

Nervous system side effects have been associated with ethacrynic acid. Temporary or permanent deafness has been reported in rare cases after intravenous administration of ethacrynic acid. Deafness has been reported even after a single, standard intravenous dose. Ototoxicity is extremely rare after oral administration. Most cases are reported in patients with renal insufficiency.[Ref]

Renal

Renal side effects including renal loss of urinary sodium, potassium, chloride, and magnesium may develop leading to significant hypokalemic, hypochloremic metabolic alkalosis. Alkalosis can develop in the absence of hypokalemia due to inhibition of bicarbonate secretion and excessive urinary chloride loss.[Ref]

It is recommended that treated patients be monitored for signs and symptoms of sodium or potassium depletion. These may include weakness, lassitude, muscle hypotonicity, orthostasis, syncope, rising BUN, and signs of "hemoconcentration," such as a rising hematocrit. In some cases, addition of a carbonic anhydrase inhibitor may decrease the risk of metabolic alkalosis and accentuate diuresis. Concomitant potassium therapy is usually needed. A potassium-sparing agent may be coadministered, if indicated, to attenuate urinary potassium losses.[Ref]

Cardiovascular

Cardiovascular problems may arise from profound ethacrynic acid-induced intravascular volume depletion. Dizziness, orthostasis, or syncope indicate the need to reduce the amount or frequency of the dose. Ethacrynic acid-induced hypokalemia is almost expected, and can predispose some patients to cardiac arrhythmias.[Ref]

Gastrointestinal

Gastrointestinal side effects are rare. Nausea, vomiting, diarrhea, and epigastric pain are usually mild and short-lived. A drug surveillance study has found an association between gastrointestinal bleeding and the intravenous administration of ethacrynic acid (the active ingredient contained in Edecrin) A single case each of acute and fatal gastric ulceration, abdominal pain, and pancreatitis has been associated with ethacrynic acid.[Ref]

An association between the administration of ethacrynic acid (EA) and the occurrence of gastrointestinal (GI) bleeding was found during a routine computer monitoring of data in a drug surveillance program. Even after adjustments for diagnosis, age, sex, BUN levels, and heparin therapy, the frequency of GI bleeding among patients receiving EA was higher than in those who received other diuretics.[Ref]

Metabolic

Metabolic changes associated with loop diuretics including hyperuricemia, mild glucose intolerance, and hypocalcemia have been reported rarely during ethacrynic acid (the active ingredient contained in Edecrin) therapy. The metabolic and hemodynamic changes associated with ethacrynic acid can induce or exacerbate hepatic encephalopathy, which may be important in patients with significant liver disease.[Ref]

Hepatic

A 25-year-old man with rheumatic heart disease, bacterial endocarditis, and congestive heart failure (CHF) developed elevated serum transaminases and jaundice within two weeks after starting digoxin, ethacrynic acid (the active ingredient contained in Edecrin) (EA), and antibiotics. EA alone was discontinued, and the jaundice resolved over the next two weeks. These signs recurred upon rechallenge, and resolved upon discontinuation of the drug. Due to recurrent edema, EA was restarted again. Within seven days the patient developed jaundice, hepatic encephalopathy, and eventually died with CHF. Beside passive venous congestion, the liver, at autopsy, revealed cholestasis and hepatocellular damage.[Ref]

Hepatic side effects including rare cases of cholestatic jaundice, agranulocytosis, and thrombocytopenia have been reported.[Ref]

Dermatologic

Dermatologic problems are rare. Rashes and two cases of Henoch-Schoenlein purpura have been associated with ethacrynic acid (the active ingredient contained in Edecrin) [Ref]

Of 50 patients with congestive heart failure who were given ethacrynic acid in one study, two developed a necrotizing hemorrhagic lesion of the Henoch-Schonlein type. In both cases, the lesions appeared on the lower extremities two to three weeks after beginning therapy. Histology in one revealed vasculitis involving the arterioles and capillaries. There were no accompanying changes in the platelet count, bleeding time, or clotting times. Each patient was also taking other medications.[Ref]

Hematologic

Hematologic side effects including rare cases of fatal agranulocytosis, sometimes with thrombocytopenia, have been associated with ethacrynic acid (the active ingredient contained in Edecrin) Other factors, such as underlying diseases and concomitant medications, make implication of ethacrynic acid difficult in these cases.[Ref]

A 54-year-old woman with liver cirrhosis, ascites, and hepatic encephalopathy developed a fever and abdominal discomfort associated with a peripheral white blood cell count of 2,200/mm3 and a bone marrow examination consistent with agranulocytosis. The patient's serum did not show leukocyte agglutinins either in the presence or absence of the drug. The patient died of sepsis. Autopsy revealed postnecrotic cirrhosis and ascites. There was no evidence of malignancy or tuberculosis. The patient was also receiving antibiotics, and had previously received thiazide diuretics.[Ref]

Local

Local intravenous site pain and thrombophlebitis are common. If more than one injection is needed, a new intravenous site or use of a central venous catheter is recommended.[Ref]

References

1. Matz GJ, Beal DD, Krames L "Ototoxicity of ethacrynic acid. Demonstrated in a human temporal bone." Arch Otolaryngol 90 (1969): 152-5

2. "Ethacrynic Acid." Med Lett Drugs Ther 9 (1967): 53-5

3. Ng PS, Conley CE, Ing TS "Deafness after ethacrynic acid." Lancet 1 (1969): 673-4

4. Matz GJ "The ototoxic effects of ethacrynic acid in man and animals." Laryngoscope 86 (1976): 1065-86

5. Chaffee WG Jr "Hazards of ethacrynic acid." JAMA 212 (1970): 159

6. Sheffield PA, Turner JS Jr "Ototoxic drugs: a review of clinical aspects, histopathologic changes and mechanisms of action." South Med J 64 (1971): 359-63

7. Ajodhia JM, Dix MR "Drug-induced deafness and its treatment." Practitioner 216 (1976): 561-70

8. Cooperman LB, Rubin IL "Toxicity of ethacrynic acid and furosemide." Am Heart J 85 (1973): 831-4

9. Boston Collaborative Drug Surveillance Program "Drug-induced deafness." JAMA 224 (1973): 515-6

10. Meriwether WD, Mangi RJ, Serpick AA "Deafness following standard intravenous dose of ethacrynic acid." JAMA 216 (1971): 795-8

11. Homer MJ "Deafness after ethacrynic acid." N Engl J Med 285 (1971): 1152

12. Rybak LP "Ototoxicity of loop diuretics." Otolaryngol Clin North Am 26 (1993): 829-44

13. Schwartz AB "Diuretic-induced hypokalemia." Am Fam Physician 11 (1975): 101-4

14. Arnold W, Nadol JB Jr, Weidauer H "Ultrastructural histopathology in a case of human ototoxicity due to loop diuretics." Acta Otolaryngol (Stockh) 91 (1981): 399-414

15. Merrill JP "Hazards of ethacrynic acid." JAMA 212 (1970): 159

16. Matz GJ, Naunton RF "Ototoxic drugs and poor renal function." JAMA 206 (1968): 2119

17. Gomolin IH, Garschick E "Ethacrynic acid-induced deafness accompanied by nystagmus." N Engl J Med 303 (1980): 702

18. Hybels RL "Drug toxicity of the inner ear." Med Clin North Am 63 (1979): 309-19

19. Marlowe FI "Ototoxic agents." Otolaryngol Clin North Am 11 (1978): 791-800

20. David DS, Hitzig P "Diuretics and ototoxicity." N Engl J Med 284 (1971): 1328-9

21. Schwartz FD, Pillay VK, Kark RM "Ethacrynic acid: its usefulness and untoward effects." Am Heart J 79 (1970): 427-8

22. Schneider WJ, Becker EL "Acute transient hearing loss after ethacrynic acid therapy." Arch Intern Med 117 (1966): 715-7

23. Beauchamp GD, Crouch TC "Deafness. Review of intravenous ethacrynic acid." J Kans Med Soc 76 (1975): 166-8,180

24. Ballantyne J "Ototoxicity: a clinical review." Audiology 12 (1973): 325-36

25. Quick CA, Duvall AJ 3d "Early changes in the cochlear duct from ethacrynic acid: an electronmicroscopie evaluation." Laryngoscope 80 (1970): 954-65

26. Rybak LP "Ototoxicity of ethacrynic acid (a persistent clinical problem)." J Laryngol Otol 102 (1988): 518-20

27. Council by Merck Sharp & Dohme "Evaluation of a new oral diuretic agent." JAMA 208 (1969): 2327-9

28. Pillay VK, Schwartz FD, Aimi K, Kark RM "Transient and permanent deafness following treatment with ethacrynic acid in renal failure." Lancet 1 (1969): 77-9

29. Martinez-Maldonado M "Electrolyte disturbances resulting from diuretic therapy." Tex Med 69 (1973): 83-7

30. Walker WG "The clinical use of furosemide and ethacrynic acid." Med Clin North Am 51 (1967): 1277-83

31. Sousa RC de, Jenny M "Clinical study of a new diuretic--ethacrynic acid." Helv Med Acta 33 (1967): 424-36

32. Plumb VJ, James TN "Clinical hazards of powerful diuretics. Furosemide and ethacrynic acid." Mod Concepts Cardiovasc Dis 47 (1978): 91-4

33. Frohlich ED "Editorial: Use and abuse of diuretics." Am Heart J 89 (1975): 1-3

34. Bar-On H, Eisenberg S, Eliakim M "Clinical experience with ethacrynic acid with reference to a possible complication of the Schoenlein-Henoch type." Isr J Med Sci 3 (1967): 113-8

35. DeRubertis FR, Michelis MF, Beck N, Davis BB "Complications of diuretic therapy: severe alkalosis and syndrome resembling inappropriate secretion of antidiuretic hormone." Metabolism 19 (1970): 709-19

36. Lieberman FL, Reynolds TB "The use of ethacrynic acid in patients with cirrhosis and ascites." Gastroenterology 49 (1965): 531-8

37. Laudignon N, Ciampi A, Coupal L, Chemtob S, Aranda JV "Furosemide and ethacrynic acid: risk factors for the occurrence of serum electrolyte abnormalities and metabolic alkalosis in newborns and infants." Acta Paediatr Scand 78 (1989): 133-5

38. White SJ, Williamson K "What to watch for when you give loop diuretics." RN 42 (1979): 25-7

39. Sullivan RC, Freemon FR, Caranasos GJ "Complications from diuretic therapy with ethacrynic acid and furosemide." South Med J 64 (1971): 869-72

40. Schmidt P, Friedman IS "Adverse effects of ethacrynic acid." N Y State J Med 67 (1967): 1438-42

41. Gaillard R, Vallotton B, Muller F "Letter: Hypotension after angiotensin-II infusion and hypovolaemia induced by diuretic." Lancet 1 (1974): 1349

42. Kounis NG "Diuretics and renal pain." Br Med J 3 (1973): 641

43. Jick H, Porter J "Drug-induced gastrointestinal bleeding. Report from the Boston Collaborative Drug Surveillance Program, Boston University Medical Center." Lancet 2 (1978): 87-9

44. Pain AK "Acute gastric ulceration associated with drug therapy." Br Med J 1 (1967): 634

45. Slone D, Jick H, Lewis GP, Shapiro S, Miettinen OS "Intravenously given ethacrynic acid and gastrointestinal bleeding. A finding resulting from comprehensive drug surveillance." JAMA 209 (1969): 1668-71

46. Gray GM "Drugs, malnutrition, and carbohydrate absorption." Am J Clin Nutr 26 (1973): 121-4

47. Coni NK, Gordon PW, Mukherjee AP, Read PR "The effect of frusemide and ethacrynic acid on carbohydrate metabolism." Age Ageing 3 (1974): 85-90

48. Domenet JG "Diabetogenic effect of oral diuretics." Br Med J 3 (1968): 188

49. Pickkers P, Schachter M, Hughes AD, Feher MD, Sever PS "Thiazide-induced hyperglycaemia: a role for calcium-activated potassium channels?" Diabetologia 39 (1996): 861-4

50. Hutchison JC "Ethacrynic acid. A non-diabetogenic diuretic." Pa Med 72 (1969): 65-7

51. Andersen OO, Persson I "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J 2 (1968): 798-801

52. Datey KK, Deshmukh SN, Dalvi CP, Purandare NM "Hepatocellular damage with ethacrynic acid." Br Med J 3 (1967): 152-3

53. Walker JG "Fatal agranulocytosis complicating treatment with ethacrynic acid. Report of a case." Ann Intern Med 64 (1966): 1303-5

54. Da Costa AJ, Cash JD "Haemolysis with ethacrynic acid." Lancet 2 (1971): 1039

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