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Medication Safety Issues
Sound-alike/look-alike issues:
Edecrin® may be confused with Eulexin®, Ecotrin®
Pronunciation
(eth a KRIN ik AS id)
U.S. Brand Names
Index Terms
Generic Available
No
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
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
Pregnancy Risk Factor
B
Pregnancy Considerations
No data available. Generally, use of diuretics during pregnancy is avoided due to risk of decreased placental perfusion.
Lactation
Contraindicated
Contraindications
Hypersensitivity to ethacrynic acid or any component of the formulation; anuria; history of severe watery diarrhea caused by this product; infants
Warnings/Precautions
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.
• 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 I.V. 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.
Adverse Reactions
Frequency not defined.
Central nervous system: Headache, fatigue, apprehension, confusion, fever, chills, encephalopathy (patients with pre-existing liver disease); vertigo
Dermatologic: Skin rash, Henoch-Schönlein purpura (in patient with rheumatic heart disease)
Endocrine & metabolic: Hyponatremia, hyperglycemia, variations in phosphorus, CO2 content, bicarbonate, and calcium; reversible hyperuricemia, gout, hyperglycemia, hypoglycemia (occurred in two uremic patients who received doses above those recommended)
Gastrointestinal: Anorexia, malaise, abdominal discomfort or pain, dysphagia, nausea, vomiting, and diarrhea, gastrointestinal bleeding, acute pancreatitis (rare)
Genitourinary: Hematuria
Hepatic: Jaundice, abnormal liver function tests
Hematology: Agranulocytosis, severe neutropenia, thrombocytopenia
Local: Thrombophlebitis (with intravenous use), local irritation and pain
Ocular: Blurred vision
Otic: Tinnitus, temporary or permanent deafness
Renal: Serum creatinine increased
Drug Interactions
ACE Inhibitors: Loop Diuretics may enhance the hypotensive effect of ACE Inhibitors. Specifically, postural hypotension which can accompany ACE Inhibitor initiation. Loop Diuretics may enhance the nephrotoxic effect of ACE Inhibitors. Risk C: 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 Oxypurinolol, an active metabolite of Allopurinol. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Aminoglycosides: Loop Diuretics may enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Bile Acid Sequestrants: May decrease the absorption of Loop Diuretics. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
Corticosteroids (Systemic): May enhance the hypokalemic effect of Loop Diuretics. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Dofetilide: Loop Diuretics may enhance the QTc-prolonging effect of Dofetilide. Risk C: Monitor therapy
Furosemide: May enhance the ototoxic effect of Ethacrynic Acid. Risk X: Avoid combination
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Lithium: Loop Diuretics may decrease the serum concentration of Lithium. Loop Diuretics may increase the serum concentration of Lithium. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: 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. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phenytoin: May diminish the diuretic effect of Loop Diuretics. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Salicylates: May diminish the diuretic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Compatibility
Stable in D5NS, D5W, LR, NS.
Incompatible with whole blood or its derivatives.
Y-site administration: Compatible: Heparin with hydrocortisone sodium succinate, potassium chloride, vitamin B complex with C.
Compatibility when admixed: Compatible: Chlorpromazine, cimetidine, prochlorperazine, promazine. Incompatible: Hydralazine, procainamide, ranitidine, tolazoline, triflupromazine.
Mechanism of Action
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
Pharmacodynamics/Kinetics
Onset of action: Diuresis: Oral: ~30 minutes; I.V.: 5 minutes
Peak effect: Oral: 2 hours; I.V.: 30 minutes
Duration: Oral: 12 hours; I.V.: 2 hours
Absorption: Oral: Rapid
Protein binding: >90%
Metabolism: Hepatic (35% to 40%) to active cysteine conjugate
Half-life elimination: Normal renal function: 2-4 hours
Excretion: Feces and urine (30% to 60% as unchanged drug)
Dosage
I.V. formulation should be diluted in D5W or NS (1 mg/mL) and infused over several minutes.
Children: Oral: 1 mg/kg/dose once daily; increase at intervals of 2-3 days as needed, to a maximum of 3 mg/kg/day.
Adults:
Oral: 50-200 mg/day in 1-2 divided doses; may increase in increments of 25-50 mg at intervals of several days; doses up to 200 mg twice daily may be required with severe, refractory edema.
I.V.: 0.5-1 mg/kg/dose (maximum: 100 mg/dose); repeat doses not routinely recommended; however, if indicated, repeat doses every 8-12 hours.
Dosing adjustment/comments in renal impairment: Clcr <10 mL/minute: Avoid use.
Dialysis: Not removed by hemo- or peritoneal dialysis; supplemental dose is not necessary.
Administration: I.V.
Injection should not be given SubQ or I.M. due to local pain and irritation. Single I.V. doses should not exceed 100 mg. Administer each 10 mg over a minute.
Administration: I.V. Detail
If a second dose is needed, it is recommended to use a new injection site to avoid possible thrombophlebitis.
pH: 6.3-7.7
Monitoring Parameters
Blood pressure, renal function, serum electrolytes, and fluid status closely, including weight and I & O daily; hearing
Dietary Considerations
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.
Patient Education
Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy without consulting prescriber. Take prescribed dose with food early in day. Include orange juice or bananas (or other potassium-rich foods) in your diet, but do not take potassium supplements without consulting prescriber. If you have diabetes, monitor serum glucose closely (this medication may alter glucose levels). May cause postural hypotension (use caution when rising from lying or sitting position, when climbing stairs, or when driving); lightheadedness, dizziness, or drowsiness (use caution driving or when engaging in hazardous activities); diarrhea; or decreased accommodation to heat (avoid excessive exercise in hot weather). Report hearing changes (ringing in ears); persistent headache; unusual confusion or nervousness; abdominal pain or blood stool (black stool); palpitations, chest pain, rapid heartbeat; flu-like symptoms; skin rash or itching; blurred vision; swelling of ankles or feet; weight changes of more than 3 lb/day; increased fatigue; or joint/muscle swelling, pain, cramping, or trembling. Breast-feeding precaution: Do not breast-feed.
Geriatric Considerations
Ethacrynic acid is rarely used because of its increased incidence of ototoxicity as compared to the other loop diuretics.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: Ethacrynic acid has limited use over other loop diuretics because of increased risk of ototoxicity. If given the morning of surgery, it may render the patient volume depleted and blood pressure may be labile during general anesthesia.
Cardiovascular Considerations
Limited use over other loop diuretics because of increased risk of ototoxicity. Hypotensive effect of ethacrynic acid may be more pronounced in patients previously on a diuretic therapy or who have volume depletion.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause dizziness; may rarely cause drowsiness, nervousness, or confusion
Mental Health: Effects on Psychiatric Treatment
Rare reports of agranulocytosis; use caution with clozapine and carbamazepine; may increase serum lithium levels, however, more likely with thiazide diuretic
Nursing: Physical Assessment/Monitoring
Assess potential for interactions with other pharmacological agents or herbal products patient may be taking (especially anything that would impact blood pressure or add to risk of ototoxicity). Infusion: See Administration. Assess results of laboratory tests, therapeutic effectiveness (according to purpose for use), and adverse response (eg, dehydration, electrolyte imbalance, CNS changes) on a regular basis during therapy. Caution patients with diabetes to monitor glucose levels closely (may cause hyper/hypoglycemia). Teach patient appropriate use, possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as ethacrynate sodium:
Sodium Edecrin®: 50 mg
Tablet:
Edecrin®: 25 mg [scored]
Pricing: U.S. (www.drugstore.com)
Tablets (Edecrin)
25 mg (100): $112.49
Extemporaneously Prepared
To make a 1 mg/mL suspension: 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 50% sorbitol solution to make a final volume of 120 mL. (Methylparaben 6 mg and propylparaben 2.4 mg are added as preservatives.) Stable 220 days at room temperature.
Handbook on Extemporaneous Formulations, Bethesda, MD: American Society of Hospital Pharmacists, 1987.
References
Cowley AJ and Elkeles RS, “Diabetes and Therapy With Potent Diuretics,” Lancet, 1978, 1(8056):154.
Gomolin IH and Garschick E, “Ethacrynic Acid-Induced Deafness Accompanied by Nystagmus,” N Engl J Med, 1980, 303(12):702.
Lant A, “Diuretics: Clinical Pharmacology and Therapeutic Use,” Drugs, 1985, 29(1):57-87.
International Brand Names
Lexi-Comp.com
Last full review/revision July 2009
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