(eth a KRIN ik AS id)
Management of edema associated with congestive heart failure; hepatic cirrhosis or renal disease; short-term management of ascites due to malignancy, idiopathic edema, and lymphedema
Hypersensitivity to ethacrynic acid or any component of the formulation; anuria; history of severe watery diarrhea caused by this product; infants
Note: Dose equivalency for patients with normal renal function (approximate): Ethacrynic acid 50 mg = bumetanide 1 mg = furosemide 40 mg = torsemide 20 mg
Edema:
Oral: 50-200 mg/day in 1-2 divided doses; may increase in increments of 25-50 mg at intervals of several days to a maximum of 400 mg/24 hours.
IV: 0.5-1 mg/kg/dose (maximum: 100 mg/dose); repeat doses not routinely recommended; however, if indicated, repeat doses every 8-12 hours.
Oral: Initial: 25-50 mg/day
Edema: Oral: Children: 1 mg/kg/dose once daily; increase at intervals of 2-3 days as needed, to a maximum of 3 mg/kg/day.
CrCl <10 mL/minute: Avoid use.
Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.
No dosage adjustment provided in manufacturers labeling, use with caution.
IV formulation should be diluted in D5W or NS (1 mg/mL) and infused over several minutes.
Injection should not be given SubQ or IM due to local pain and irritation. Single IV doses should not exceed 100 mg. Administer each 10 mg over a minute. If a second dose is needed, it is recommended to use a new injection site to avoid possible thrombophlebitis.
This product may cause a potassium loss. Your healthcare provider may prescribe a potassium supplement, another medication to help prevent the potassium loss, or recommend that you eat foods high in potassium, especially citrus fruits. Do not change your diet on your own while taking this medication, especially if you are taking potassium supplements or medications to reduce potassium loss. Too much potassium can be as harmful as too little.
Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Discard unused reconstituted solution after 24 hours.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous, as ethacrynate sodium:
Sodium Edecrin: 50 mg (1 ea)
Generic: 50 mg (1 ea)
Tablet, Oral:
Edecrin: 25 mg [DSC]
Edecrin: 25 mg [scored]
Generic: 25 mg
A 1 mg/mL oral suspension may be made with ethacrynic acid powder. Dissolve 120 mg ethacrynic acid powder in a small amount of 10% alcohol. Add a small amount of 50% sorbitol solution and stir. Adjust pH to 7 with 0.1N sodium hydroxide solution. Add sufficient quantity of 50% sorbitol solution to make a final volume of 120 mL. Add methylparaben 6 mg and propylparaben 2.4 mg as preservatives. Stable for 220 days at room temperature.
Das Gupta V, Gibbs CW Jr, and Ghanekar AG, Stability of Pediatric Liquid Dosage Forms of Ethacrynic Acid, Indomethacin, Methyldopate Hydrochloride, Prednisone and Spironolactone," Am J Hosp Pharm, 1978, 35(11):1382-5.[PMID: 568384]Handbook on Extemporaneous Formulations, Bethesda, MD: American Society of Hospital Pharmacists, 1987.Stable in D5LR, D5NS, D5W, LR, NS.
Incompatible with whole blood or its derivatives.
Y-site administration: Incompatible with nesiritide.
ACE Inhibitors: Loop Diuretics may enhance the hypotensive effect of ACE Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Allopurinol: Loop Diuretics may enhance the adverse/toxic effect of Allopurinol. Loop Diuretics may increase the serum concentration of Allopurinol. Specifically, Loop Diuretics may increase the concentration of Oxypurinol, an active metabolite of Allopurinol. Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Aminoglycosides: Loop Diuretics may enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Monitor therapy
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Analgesics (Opioid): May enhance the adverse/toxic effect of Diuretics. Analgesics (Opioid) may diminish the therapeutic effect of Diuretics. Monitor therapy
Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Beta2-Agonists: May enhance the hypokalemic effect of Loop Diuretics. Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Loop Diuretics. Consider therapy modification
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Canagliflozin: May enhance the hypotensive effect of Loop Diuretics. Management: If canagliflozin is combined with a loop diuretic, monitor for symptoms of intravascular volume depletion and hypotension. Canadian product labeling recommends avoiding the combination of canagliflozin and loop diuretics. Consider therapy modification
Cardiac Glycosides: Loop Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of loop diuretics. Monitor therapy
Cefazedone: May enhance the nephrotoxic effect of Loop Diuretics. Monitor therapy
Cefotiam: Loop Diuretics may enhance the nephrotoxic effect of Cefotiam. Monitor therapy
Ceftizoxime: Loop Diuretics may enhance the nephrotoxic effect of Ceftizoxime. Monitor therapy
Cephalothin: Loop Diuretics may enhance the nephrotoxic effect of Cephalothin. Monitor therapy
Cephradine: May enhance the nephrotoxic effect of Loop Diuretics. Monitor therapy
CISplatin: Loop Diuretics may enhance the nephrotoxic effect of CISplatin. Loop Diuretics may enhance the ototoxic effect of CISplatin. Monitor therapy
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Loop Diuretics. Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Loop Diuretics. Monitor therapy
CycloSPORINE (Systemic): May enhance the adverse/toxic effect of Loop Diuretics. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Dofetilide: Loop Diuretics may enhance the QTc-prolonging effect of Dofetilide. Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Empagliflozin: May enhance the hypotensive effect of Loop Diuretics. Monitor therapy
Foscarnet: Loop Diuretics may increase the serum concentration of Foscarnet. Consider therapy modification
Fosphenytoin: May diminish the diuretic effect of Loop Diuretics. Monitor therapy
Furosemide: May enhance the ototoxic effect of Ethacrynic Acid. Avoid combination
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Ivabradine: Loop Diuretics may enhance the arrhythmogenic effect of Ivabradine. Monitor therapy
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Levosulpiride: Loop Diuretics may enhance the adverse/toxic effect of Levosulpiride. Avoid combination
Licorice: May enhance the hypokalemic effect of Loop Diuretics. Monitor therapy
Lithium: Loop Diuretics may decrease the serum concentration of Lithium. Loop Diuretics may increase the serum concentration of Lithium. Monitor therapy
Methotrexate: May diminish the therapeutic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Methotrexate. Methotrexate may increase the serum concentration of Loop Diuretics. Management: Monitor for increased methotrexate and/or loop diuretic levels/toxicity with concomitant use of these agents and monitor for decreased therapeutic effects of loop diuretics. Methotrexate and/or loop diuretic dose reductions may be necessary. Consider therapy modification
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Neuromuscular-Blocking Agents: Loop Diuretics may diminish the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Loop Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the diuretic effect of Loop Diuretics. Loop Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Management: Monitor for evidence of kidney injury or decreased therapeutic effects of loop diuretics with concurrent use of an NSAID. Consider avoiding concurrent use in CHF or cirrhosis. Concomitant use of bumetanide with indomethacin is not recommended. Consider therapy modification
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Phenytoin: May diminish the diuretic effect of Loop Diuretics. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Probenecid: May enhance the adverse/toxic effect of Loop Diuretics. Probenecid may diminish the diuretic effect of Loop Diuretics. Probenecid may increase the serum concentration of Loop Diuretics. Management: Monitor for decreased diuretic effects or increased adverse effects of loop diuretics with concomitant use of probenecid. Bumetanide prescribing information recommends against concomitant use of probenecid. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Reboxetine: May enhance the hypokalemic effect of Loop Diuretics. Monitor therapy
RisperiDONE: Loop Diuretics may enhance the adverse/toxic effect of RisperiDONE. Management: Consider alternative diuretic therapy (e.g., thiazides) to more potent diuretics (e.g., furosemide) in elderly patients receiving risperidone. Patients who require use of more potent diuretic therapy should be closely monitored and adequately hydrated. Consider therapy modification
Salicylates: May diminish the diuretic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Monitor therapy
Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with diuretics, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, hydrate adequately and monitor fluid and renal status. Consider therapy modification
Tobramycin (Oral Inhalation): Loop Diuretics may enhance the nephrotoxic effect of Tobramycin (Oral Inhalation). Loop Diuretics may enhance the ototoxic effect of Tobramycin (Oral Inhalation). Monitor therapy
Topiramate: Loop Diuretics may enhance the hypokalemic effect of Topiramate. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Ethacrynic Acid may increase the serum concentration of Vitamin K Antagonists. Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Blood pressure, renal function, serum electrolytes, and fluid status closely, including weight and I & O daily; hearing
Frequency not defined.
Cardiovascular: Thrombophlebitis (with intravenous use)
Central nervous system: Apprehension, brain disease (patients with preexisting liver disease), chills, confusion, fatigue, headache, vertigo
Dermatologic: IgA vasculitis (in patient with rheumatic heart disease), skin rash
Endocrine & metabolic: Abnormal phosphorus levels (variations), abnormal serum calcium (variations), gout, hyperglycemia, hyperuricemia (reversible), hypoglycemia (occurred in two uremic patients who received doses above those recommended), hyponatremia, variations in bicarbonate, variations in CO2 content
Gastrointestinal: Abdominal distress, abdominal pain, anorexia, diarrhea, dysphagia, gastrointestinal hemorrhage, malaise, nausea, vomiting, acute pancreatitis (rare)
Genitourinary: Hematuria
Hematologic & oncologic: Agranulocytosis, severe neutropenia, thrombocytopenia
Hepatic: Abnormal hepatic function tests, jaundice
Local: Local irritation, local pain
Ophthalmic: Blurred vision
Otic: Deafness (temporary or permanent), tinnitus
Renal: Increased serum creatinine
Miscellaneous: Fever
Concerns related to adverse effects:
- Fluid/electrolyte loss: Loop diuretics are potent diuretics; excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation are required. Watch for and correct electrolyte disturbances; adjust dose to avoid dehydration. In contrast to thiazide diuretics, a loop diuretic can also lower serum calcium concentrations. Electrolyte disturbances can predispose a patient to serious cardiac arrhythmias.
- Hypersensitivity reactions: Can rarely occur, however, ethacrynic acid has no cross-reactivity to sulfonamides or sulfonylureas.
- Nephrotoxicity: Monitor fluid status and renal function in an attempt to prevent oliguria, azotemia, and reversible increases in BUN and creatinine; close medical supervision of aggressive diuresis required.
- Ototoxicity: Rapid IV administration, renal impairment, excessive doses, and concurrent use of other ototoxins is associated with ototoxicity; has been associated with a higher incidence of ototoxicity than other loop diuretics.
Disease-related concerns:
- Cirrhosis: In cirrhosis, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.
Concurrent drug therapy issues:
- Antihypertensives: Coadministration of antihypertensives may increase the risk of hypotension.
Special populations:
- Surgical patients: If given the morning of surgery, ethacrynic acid may render the patient volume depleted and blood pressure may be labile during general anesthesia.
Other warnings and precautions:
- Diuretic resistance: For some patients, despite higher doses of loop diuretic treatment, an adequate diuretic response cannot be attained. Diuretic resistance can usually be overcome by intravenous administration, the use of two diuretics together (eg, furosemide and chlorothiazide), or the use of a diuretic with a positive inotropic agent. When such combinations are used, serum electrolytes need to be monitored even more closely (Cody, 1994; ACC/AHA [Yancy, 2013]; HFSA, 2010).
B
Adverse events have not been observed in animal reproduction studies.
Inhibits reabsorption of sodium and chloride in the ascending loop of Henle and distal renal tubule, interfering with the chloride-binding cotransport system, thus causing increased excretion of water, sodium, chloride, magnesium, and calcium
Oral: Rapid
Hepatic (35% to 40%) to active cysteine conjugate
Feces and urine (30% to 60% as unchanged drug)
Diuresis: Oral: ~30 minutes; IV: 5 minutes; Peak effect: Oral: 2 hours; IV: 30 minutes
Oral: 12 hours; IV: 2 hours
Normal renal function: 2-4 hours
>90%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience loss of strength and energy, headache, lack of appetite, vomiting, or nausea. Have patient report immediately to prescriber signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or nausea or vomiting), signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), severe dizziness, passing out, hearing impairment, tinnitus, vision changes, severe joint pain, bruising, bleeding, jaundice, or severe diarrhea (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.