Uregyt^® (Tablets) Instructions for Use

Marketing Authorization Holder

Egis Pharmaceuticals PLC (Hungary)

ATC Code

C03CC01 (Etacrynic acid)

Active Substance

Etacrynic acid (Rec.INN registered by WHO)

Dosage Form

Uregyt®

Tablets 50 mg: 20 pcs.

Dosage Form, Packaging, and Composition

Tablets are white or greyish-white, round, flat, with a bevel, with a score on one side and the engraving “UREGYT” on the other side, practically odorless.

Excipients: gelatin – 6.8 mg, lactose monohydrate – 75 mg, magnesium stearate – 4 mg, potato starch – 58.2 mg, talc – 6 mg.

10 pcs. – blisters (2) – carton packs.

Clinical-Pharmacological Group

Diuretic

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

Etacrynic acid is a fast-acting diuretic that functions at the level of the ascending limb of the loop of Henle, and the proximal and distal renal tubules. Etacrynic acid inhibits the active transport of chloride ions and, consequently, sodium. The effect develops rapidly and is independent of the acid-base balance.

Etacrynic acid promotes increased excretion of potassium, so therapy with this diuretic should be accompanied by appropriate correction of plasma potassium levels.

The diuretic effect is dose-dependent and related to the degree of fluid retention. When using etacrynic acid, water and electrolytes are excreted from the body several times more intensively than with thiazide diuretic therapy, because Etacrynic acid significantly more strongly suppresses sodium reabsorption. This is why Etacrynic acid is effective in severe renal failure. The drug has almost no effect on glomerular filtration and renal blood flow, except in cases where there is a marked decrease in plasma volume associated with increased diuresis. Electrolyte excretion during therapy with etacrynic acid occurs differently than with the use of thiazide diuretics. The primary excretion of sodium and chloride ions is accompanied by a significant loss of chloride ions compared to sodium ions.

With long-term use of the drug, the excretion of chloride ions decreases, while the excretion of potassium and hydrogen ions may increase. Etacrynic acid is effective in both acidosis and alkalosis.

Pharmacokinetics

After oral administration, Etacrynic acid is rapidly and completely absorbed from the gastrointestinal tract. Bioavailability is 100%. The diuretic effect begins 30 minutes after taking the drug, the maximum diuretic effect is reached after 2 hours, and the effect lasts from 6 to 8 hours.

Plasma protein binding is 90%.

Metabolism occurs in the liver by conjugation.

The drug is predominantly excreted by the kidneys (60%), and 40% is excreted through the intestines, partly (20%) unchanged, partly in the form of conjugates.

Etacrynic acid does not cross the blood-brain barrier. It is poorly removed by hemodialysis.

Indications

• Edema of cardiac, renal, post-thrombotic type, edema against the background of portal hypertension;
• When therapy with other diuretic drugs is ineffective.

ICD codes

Dosage Regimen

The initial daily dose of the drug is 50 mg (1 tablet). Subsequently, the dose can be gradually increased until the desired effect is achieved, but not more than 200 mg (4 tablets). The drug acts for 8 to 10 hours, so it is recommended to take the entire daily dose in the morning after breakfast.

For a gradual diuretic effect, the minimum dose of the drug (25 mg) is sufficient.

In adult patients, the desired diuretic effect can be achieved with a dose of 50-100 mg. During therapy, it is necessary to regularly monitor diuresis.

The usual maintenance dose is 25 – 200 mg per day.

Maintenance therapy can be carried out with the omission of individual doses to maintain the effectiveness of the drug. The drug can be given every other day or every two days, or at intervals of 2-3 days.

Elderly patients sometimes require lower doses.

Combination therapy: etacrynic acid can be effectively used in combination with other diuretics.

Adverse Reactions

Adverse effects are presented in accordance with the following frequency grouping criteria: common (from >1/100 to <1/10), uncommon (from >1/1000 to <1/100), rare (from >1/10000 to <1/1000), very rare (<1/10000) adverse reactions, with unknown frequency (frequency cannot be determined from the available clinical data).

From the hematopoietic and lymphatic system agranulocytosis and severe neutropenia were observed in several critically ill patients who were prescribed the drug to provide a diuretic effect. Rarely: development of thrombocytopenia.

From the CNS common: headache, increased fatigue; rare: anxiety, impaired consciousness.

From the organs of vision and hearing blurred vision, reversible deafness, ringing in the ears, dizziness with a feeling of stuffiness in the ears. Deafness can also be irreversible, especially in patients receiving concomitant therapy with other ototoxic drugs.

From the gastrointestinal tract common: abdominal discomfort and pain, dysphagia, nausea, vomiting and diarrhea; very rare: profuse diarrhea, gastrointestinal bleeding; acute pancreatitis. In rare cases, jaundice and increased activity of “liver” enzymes in the serum of patients who were simultaneously receiving several drugs, including etacrynic acid, were noted.

From the urinary system hematuria.

From the skin rare: Henoch-Schönlein purpura, rash.

From metabolism anorexia, hyperuricemia, gout attack, hypoglycemia, hyperglycemia.

Laboratory parameters decreased levels of blood glucose, blood urea nitrogen, uric acid, potassium, calcium, chlorides, magnesium and sodium.

Other fever, chills.

Contraindications

• Anuria;
• Severe disorders of water-electrolyte balance and acid-base state;
• Hepatic coma;
• Pregnancy and breastfeeding;
• Lactose intolerance;
• Lactase deficiency and glucose-galactose malabsorption
  (tablets contain lactose monohydrate);
• Children under 18 years of age (lack of sufficient clinical data);
• Hypersensitivity to the active substance or any other component of the drug.

With caution elderly age, liver cirrhosis with and without ascites, hypokalemia, hypomagnesemia, water-electrolyte balance disorders, primary hyperaldosteronism, connective tissue diseases (systemic lupus erythematosus).

Use in Pregnancy and Lactation

Controlled trials of the drug during pregnancy have not been conducted. The use of the drug Uregyt^® is contraindicated in pregnant women, because, like other diuretic agents, it can cause hypovolemia with increased blood viscosity, which reduces placental blood flow.

It is currently unknown whether Etacrynic acid can pass into breast milk, so if it is necessary to take this drug, the patient should stop breastfeeding.

Use in Hepatic Impairment

Use with caution in liver cirrhosis. Contraindicated in hepatic coma.

Use in Renal Impairment

Contraindicated in anuria.

Pediatric Use

Contraindicated in children under 18 years of age.

Geriatric Use

Use with caution in the elderly.

Special Precautions

Treatment should be started with low doses, which should be increased gradually to avoid dehydration. The patient’s body weight should be monitored.

During treatment, it is necessary to regularly monitor the electrolyte content in the blood plasma, consume foods rich in potassium, and, if necessary, prescribe potassium preparations simultaneously.

Uregyt^® can be used in combination with other diuretics, the effects of which are additive.

Additional potassium supplementation is not required for many patients receiving diuretics. However, the administration of potassium chloride or the use of potassium-sparing diuretics is recommended in patients with cirrhosis, nephrotic syndrome, or those receiving digitalis preparations. Patients with normal renal function can be prescribed potassium preparations (with regular monitoring of plasma potassium levels), since excess potassium is excreted from the body. In renal failure, potassium should not be administered. Indications for potassium administration are always established depending on the plasma potassium level.

If the patient develops diarrhea with large fluid losses, therapy should be discontinued. During therapy, systematic monitoring of plasma electrolyte levels is recommended. Etacrynic acid may potentiate concomitant antihypertensive therapy. In this case, there is a risk of developing orthostatic collapse.

In case of excessive diuresis, the drug should be discontinued until the water-electrolyte status stabilizes. In case of large electrolyte losses, the dose of the drug can be reduced or therapy can be temporarily stopped.

The drug should be given to patients with liver cirrhosis with great caution, because diuretics increase the risk of hepatic coma, which can be fatal.

In case of high risk of metabolic alkalosis (cirrhosis with ascites), the use of potassium-sparing diuretics or the administration of potassium chloride may reduce or prevent hypokalemia.

Loop diuretics reduce the level of magnesium ions in the blood.

Excessive fluid loss with urine (rapid and significant weight loss) can lead to the development of severe hypotension. In elderly patients with cardiac pathology, excessive diuresis may be accompanied by a decrease in circulating plasma volume and an increased risk of thromboembolic complications. Caution should be exercised when prescribing the drug to patients predisposed to hypokalemia (some cases of diarrhea, chronic heart failure, use of digitalis preparations, history of ventricular arrhythmias, kidney diseases with potassium loss, hyperaldosteronism with normal renal function, history of systemic lupus erythematosus).

The effects of cardiac glycosides may be enhanced against the background of hypokalemia caused by diuretics.

With concomitant therapy with hormonal drugs that induce potassium loss (corticosteroids), laboratory monitoring is required.

In renal edema, the effectiveness of this diuretic may be reduced by hypoproteinemia.

The risk of developing orthostatic hypotension may be increased with concomitant use of alcohol, barbiturates and diazepam.

During therapy with etacrynic acid, alcoholic beverages should not be consumed. Athletes should be aware that false-positive doping control results may be obtained during therapy with etacrynic acid.

Due to the lack of sufficient clinical data, Uregyt^® is not recommended for children.

Each tablet of Uregyt^® contains 75 mg of lactose, therefore, this drug should not be taken by patients with rare hereditary galactose intolerance, lactase deficiency, and glucose-galactose malabsorption syndrome.

Effect on ability to drive vehicles and operate machinery

In the initial individually determined period of treatment, it is necessary to refrain from potentially hazardous activities that require quick mental and motor reactions. In the course of further treatment, the degree of restrictions is determined depending on the individual tolerance of the drug.

Overdose

Symptoms decreased blood pressure, excessive diuresis, electrolyte loss and dehydration.

Treatment symptomatic and supportive. Vomiting should be induced or gastric lavage performed. If necessary, dehydration, electrolyte disturbances and hepatic coma should be corrected. In case of respiratory failure, oxygen should be inhaled and artificial ventilation of the lungs should be established.

The active substance is poorly removed from the bloodstream by hemodialysis. There is no specific antidote.

Drug Interactions

Antihypertensive agents and ethanol (possible enhancement of the hypotensive and/or diuretic effect). In the initial period of therapy with angiotensin-converting enzyme (ACE) inhibitors, the diuretic should be discontinued or the dose of the ACE inhibitor should be reduced to avoid pronounced arterial hypotension.

Oral hypoglycemic agents – a decrease in their effectiveness may be observed.

Anticoagulants (warfarin, coumarin): Etacrynic acid displaces them from complexes with plasma proteins, which may enhance the anticoagulant effect. The dose of the anticoagulant should be adjusted or a switch to furosemide should be made.

Etacrynic acid may enhance the ototoxicity of aminoglycosides and cephalosporins. The simultaneous use of these drugs should be avoided.

Non-steroidal anti-inflammatory drugs may weaken the diuretic or antihypertensive effect.

Lithium (increased lithium levels may cause symptoms of intoxication).

Corticosteroids: the risk of hypokalemia and gastrointestinal bleeding may increase.

Storage Conditions

Store at a temperature from 15 to 25°C (77°F). Keep out of reach of children.

Shelf Life

The shelf life is 5 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.