Edecrin

Frequency Not Defined

Injection site reaction

Hyperuricemia

Gout

Hypotension

Hypokalemia

Electrolyte abnormalities

Hyperglycemia/hypoglycemia

Hyperlipidemia

Ototoxicity

Tinnitus

Photosensitivity

Muscle cramps

Dizziness

Confusion

Headache

Nausea/vomiting

Anorexia

Dysphagia

Diarrhea

Pancreatitis

Agranulocytosis

Neutropenia

Thrombocytopenia

Hematuria

Mechanism of Action

Loop diuretic acting at Na/2Cl reabsorptive pump at ascending loop of Henle and distal renal tubule. Intereference with the chloride-binding cotransport system, causes increased excretion of water, sodium, chlorine, magnesium, and calcium.

Pharmacokinetics

Half-Life: 2-4 hr

Onset

• Initial effect: IV: 5-15 min, PO: 30-60 min
• Max effect: IV: 15 min-3 hr, PO: 2 hr

Other Information

Duration: IV: 2-7 hr, PO: 4-8 hr

Bioavailability: 100%

Protein Bound: 90%

Metabolism: conjugation w/ compounds containing sulfhydryl groups, such as cysteine & N-acetylcysteine in liver

Excretion: urine 66%

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using ethacrynic acid and call your doctor at once if you have any of these serious side effects:

• dry mouth, thirst, nausea, vomiting;
• feeling weak, drowsy, restless, or light-headed;
• fast or uneven heartbeat;
• muscle pain or weakness;
• easy bruising or bleeding, unusual weakness;
• fever, chills, body aches, flu symptoms;
• severe or watery diarrhea;
• blood in your urine or stools;
• coughing up blood or vomit that looks like coffee grounds;
• rapid weight loss;
• hearing loss, feeling of fullness in the ear; or
• jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

• mild diarrhea, stomach pain, loss of appetite;
• trouble swallowing;
• headache; or
• dizziness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Ethacrynic acid is an unsaturated ketone derivative of an aryloxyace -tic acid. It is designated chemically as [2,3-dichloro-4-(2-methylene-1-oxobutyl)phenoxy] acetic acid, and has a molecular weight of 303.14. Ethacrynic acid is a white, or practically white, crystalline powder, very slightly soluble in water, but soluble in most organic solvents such as alcohols, chloroform, and benzene. Its empirical formula is C13H12Cl2O4 and its structural formula is:

Ethacrynate sodium, the sodium salt of ethacrynic acid, is soluble in water at 25°C to the extent of about 7 percent. Solutions of the sodium salt are relatively stable at about pH 7 at room temperature for short periods, but as the pH or temperature increases the solutions are less stable. The molecular weight of ethacrynate sodium is 325.12. Its empirical formula is C13H11Cl2NaO4 and its structural formula is:

EDECRIN is supplied as 25 mg tablets for oral use. The tablets contain the following inactive ingredients: colloidal silicon dioxide, lactose, magnesium stearate, starch and talc. Intravenous SODIUM EDECRIN (Ethacrynate Sodium) is a sterile freeze-dried powder and is supplied in a vial containing:

Ethacrynate sodium equivalent to ethacrynic acid 50.0 mg

Inactive ingredient: Mannitol 62.5 mg

Tablets EDECRIN, 25 mg, are white, capsule shaped, scored tablets, coded VRX 205 on one side and EDECRIN on the other. They are supplied as follows:

NDC 25010-215-15 in bottles of 100.

Intravenous SODIUM EDECRIN is a dry white material either in a plug form or as a powder. It is supplied in vials containing ethacrynate sodium equivalent to 50 mg of ethacrynic acid,

NDC 25010-210-27.

Storage

Store in a tightly closed container at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

Manufactured for: Aton Pharma, Inc. (division of Valeant, Pharmaceuticals North America LLC), Bridgewater, NJ 08807. by: Valeant Pharmaceuticals International, Inc., Steinbach, MB R5G 1Z7. Revised: Mar 2012

Serious side effects can occur including:

• electrolyte imbalance and excessive water loss. This medication may affect electrolytes including sodium and potassium. Your doctor will check these levels using a blood test. Warning signs of electrolyte imbalance include:
  • dry mouth
  • thirst
  • weakness
  • lack of energy
  • drowsiness
  • restlessness
  • muscle pains or cramps
  • muscle fatigue
  • low blood pressure
  • decreased urination
  • fast heart rate
  • nausea and vomiting
• hepatic coma and death. Edecrin should be given with caution to patients with advanced cirrhosis of the liver.
• hearing loss. Deafness, tinnitus, and vertigo have occurred, most frequently in patients with severe kidney disease.
• extremely low blood pressure
• worsening of kidney disease
• worsening of gout

Do not take Edecrin if you:

• are allergic to any ingredient in it
• are not able to produce urine

Stop taking Edecrin if you experience severe, watery diarrhea or if your kidney disease worsens while receiving this medication.

• Take Edecrin exactly as prescribed.
• This medication comes in tablet form and is usually taken once or twice daily.
• Edecrin is best taken with food.
• Because Edecrin increases urination, it is best taken in the morning to avoid having to get up in the night to urinate. If you take it more than once a day, take your last dose by late afternoon.
• If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose.

You should not use ethacrynic acid if you are allergic to it, or if:

• you are unable to urinate; or

• you have recently had severe watery diarrhea.

To make sure ethacrynic acid is safe for you, tell your doctor if you have:

• cirrhosis or other liver disease;

• heart disease;

• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood);

• kidney disease;

• gout; or

• if you are on a low-salt diet.

Ethacrynic acid is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether ethacrynic acid passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Ethacrynic acid is not approved for use by anyone younger than 18 years old.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Take this medicine after a meal, unless your doctor tells you otherwise.

Ethacrynic acid will make you urinate more often and you may get dehydrated easily. Follow your doctor's instructions about using potassium supplements or getting enough salt and potassium in your diet.

While using ethacrynic acid, you may need frequent blood tests and weight checks.

Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

Avoid becoming dehydrated. Follow your doctor's instructions about the type and amount of liquids you should drink while you are taking ethacrynic acid.

It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects. You may also need to weigh yourself daily and record your weight .

This medicine may cause you to lose more potassium from your body than normal. Your doctor will monitor the potassium in your blood while you are taking this medicine. To prevent the loss of too much water and potassium, tell your doctor if you become sick with severe or continuing nausea, vomiting, or diarrhea. Check with your doctor right away if you have one or more of these symptoms: dry mouth; increased thirst; muscle cramps; or nausea or vomiting .

This medicine may cause changes in your blood sugar levels. If you notice a change in the results of your blood or urine sugar tests, or if you have any questions, check with your doctor .

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• 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

• 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

Get emergency help immediately if any of the following symptoms of overdose occur:

• 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 side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• 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

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Tell all of your health care providers that you take Edecrin. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• Have your blood pressure checked often. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Talk with your doctor before you drink alcohol.
• This medicine is a strong fluid-lowering drug (diuretic). Sometimes too much water and major elements (potassium) in the blood may be lost. This can lead to serious health problems. Your doctor will follow you closely to change the dose to match your body's needs.
• If you are on a low-salt or salt-free diet, talk with your doctor.
• You may need extra potassium. Talk with your doctor.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking Edecrin with your other drugs.
• If you are taking this medicine and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• Watch for gout attacks.
• If you are 65 or older, use Edecrin with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

Use Edecrin as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take after meals.
• This medicine may cause you to pass urine more often. To keep from having sleep problems, try to take before 6 pm.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Edecrin (Ethacrynic Acid) is a potent diuretic which, if given in excessive amounts, may lead to profound diuresis with water and electrolyte depletion. Therefore, careful medical supervision is required, and dose and dose schedule must be adjusted to the individual patient's needs (see DOSAGE AND ADMINISTRATION).

The effects of Edecrin on electrolytes are related to its renal pharmacologic activity and are dose dependent. The possibility of profound electrolyte and water loss may be avoided by weighing the patient throughout the treatment period, by careful adjustment of dosage, by initiating treatment with small doses, and by using the drug on an intermittent schedule when possible. When excessive diuresis occurs, the drug should be withdrawn until homeostasis is restored. When excessive electrolyte loss occurs, the dosage should be reduced or the drug temporarily withdrawn.

Initiation of diuretic therapy with Edecrin in the cirrhotic patient with ascites is best carried out in the hospital. When maintenance therapy has been established, the individual can be satisfactorily followed as an outpatient. Edecrin should be given with caution to patients with advanced cirrhosis of the liver, particularly those with a history of previous episodes of electrolyte imbalance or hepatic encephalopathy. Like other diuretics it may precipitate hepatic coma and death.

Too vigorous a diuresis, as evidenced by rapid and excessive weight loss, may induce an acute hypotensive episode. In elderly cardiac patients, rapid contraction of plasma volume and the resultant hemoconcentration should be avoided to prevent the development of thromboembolic episodes, such as cerebral vascular thromboses and pulmonary emboli which may be fatal. Excessive loss of potassium in patients receiving digitalis glycosides may precipitate digitalis toxicity. Care should also be exercised in patients receiving potassium-depleting steroids.

A number of possibly drug-related deaths have occurred in critically ill patients refractory to other diuretics. These generally have fallen into two categories: (1) patients with severe myocardial disease who have been receiving digitalis and presumably developed acute hypokalemia with fatal arrhythmia; (2) patients with severely decompensated hepatic cirrhosis with ascites, with or without accompanying encephalopathy, who were in electrolyte imbalance and died because of intensification of the electrolyte defect.

Deafness, tinnitus, and vertigo with a sense of fullness in the ears have occurred, most frequently in patients with severe impairment of renal function. These symptoms have been associated most often with intravenous administration and with doses in excess of those recommended. The deafness has usually been reversible and of short duration (one to 24 hours). However, in some patients the hearing loss has been permanent. A number of these patients were also receiving drugs known to be ototoxic. Edecrin may increase the ototoxic potential of other drugs (see PRECAUTIONS, Drug Interactions).

Lithium generally should not be given with diuretics (see PRECAUTIONS, Drug Interactions).

Rx only

NDC 25010-215-15

Edecrin®
(Ethacrynic Acid)

25 mg

VALEANT
Pharmaceuticals North America LLC

100 Tablets