Furosemide (Tablets, Solution) Instructions for Use

ATC Code

C03CA01 (Furosemide)

Active Substance

Furosemide (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Diuretic

Pharmacotherapeutic Group

Diuretic agent

Pharmacological Action

A “loop” diuretic; it causes a rapidly occurring, strong, and short-term diuresis. It blocks the reabsorption of sodium and chloride ions both in the proximal and distal parts of the renal tubules and in the thick segment of the ascending limb of the loop of Henle. Furosemide has a pronounced diuretic, natriuretic, and chloruretic effect.

Due to the increased excretion of sodium ions, a secondary (mediated by osmotically bound water) enhanced excretion of water and an increase in the secretion of potassium ions in the distal part of the renal tubule occur. Simultaneously, the excretion of calcium and magnesium ions increases. It has secondary effects due to the release of intrarenal mediators and the redistribution of intrarenal blood flow. During course treatment, the effect does not weaken.

In heart failure, Furosemide rapidly reduces preload (due to venous dilation), reduces pressure in the pulmonary artery and left ventricular filling pressure. It has an antihypertensive effect due to increased excretion of sodium chloride and a reduced response of vascular smooth muscle to vasoconstrictor influences, and as a result of a decrease in circulating blood volume.

After oral administration of 40 mg of furosemide, the diuretic effect begins within 60 minutes and lasts about 3-6 hours (with reduced kidney function – up to 8 hours). During the period of action, the excretion of sodium ions increases significantly; however, after its cessation, the excretion rate decreases below the initial level ( “rebound” or “withdrawal” syndrome).

The phenomenon is due to a sharp activation of the renin-angiotensin-aldosterone system and other antinatriuretic neurohumoral regulatory links in response to massive diuresis; it stimulates the arginine-vasopressive and sympathetic systems. It reduces the level of atrial natriuretic factor in the blood plasma and causes vasoconstriction. Due to the “rebound” syndrome, when taken once a day, it may not have a significant effect on the daily excretion of sodium ions and blood pressure.

Pharmacokinetics

Absorption is high, C_max is noted in blood plasma when taken orally after 1 hour. Bioavailability is 60-70%. Relative V_d is 0.2 l/kg. Binding to plasma proteins is 98%. It penetrates the placental barrier and is excreted in breast milk. It is metabolized in the liver to form 4-chloro-5-sulfamoylanthranilic acid. It is secreted into the lumen of the renal tubules via the anion transport system existing in the proximal part of the nephron. It is excreted predominantly (88%) by the kidneys unchanged and in the form of metabolites; the remainder is excreted by the intestines. T_1/2 is 1-1.5 hours.

Pharmacokinetics in special patient groups

In renal failure, the excretion of furosemide slows down, and T_1/2 increases; in severe renal failure, the terminal T_1/2 can increase to 24 hours.

In nephrotic syndrome, a decrease in plasma protein concentrations leads to an increase in the concentrations of unbound furosemide (its free fraction), which increases the risk of ototoxic action. On the other hand, the diuretic effect of furosemide in these patients may be reduced due to the binding of furosemide to albumin in the tubules and a decrease in the tubular secretion of furosemide.

During hemodialysis, peritoneal dialysis, and continuous ambulatory peritoneal dialysis, Furosemide is excreted insignificantly.

In hepatic insufficiency, the T_1/2 of furosemide increases by 30-90%, mainly due to an increase in the relative volume of distribution. Pharmacokinetic parameters in this category of patients can vary greatly.

In heart failure, severe arterial hypertension, and in elderly patients, the excretion of furosemide is slowed due to reduced renal function.

Indications

Edematous syndrome

• In chronic heart failure;
• In chronic renal failure;
• In nephrotic syndrome (in nephrotic syndrome, treatment of the underlying disease is paramount);
• In liver diseases;
• Arterial hypertension.

ICD codes

Dosage Regimen

Tablets

Take orally, on an empty stomach. If it is necessary to use furosemide, it is recommended to use its smallest doses sufficient to achieve the required effect. The maximum daily dose for adults is 1500 mg. The initial single dose for children is determined at the rate of 1-2 mg/kg of body weight/day with a possible increase in the dose to a maximum of 6 mg/kg/day, provided the drug is taken no more often than every 6 hours. The duration of treatment is determined by the doctor individually depending on the indications.

Adults

Edematous syndrome in chronic heart failure

The initial dose is 20-80 mg/day. The required dose is selected depending on the diuretic response. It is recommended to divide the daily dose into 2-3 doses.

Edematous syndrome in chronic renal failure

In patients with chronic renal failure, careful dose selection is required by gradually increasing it so that fluid loss occurs gradually (at the beginning of treatment, fluid loss of approximately up to 2 kg of body weight/day is possible). The recommended initial dose is 40-80 mg/day. The required dose is selected depending on the diuretic response. The entire daily dose should be taken once or divided into two doses. In patients on hemodialysis, the usual maintenance dose is 250-1500 mg/day.

Edema in nephrotic syndrome

The initial dose is 40-80 mg/day. The required dose is selected depending on the diuretic response. The daily dose can be taken in one dose or divided into several doses.

Edematous syndrome in liver diseases

Furosemide is used in addition to treatment with aldosterone antagonists in case of their insufficient effectiveness. To prevent the development of complications, such as impaired orthostatic regulation of circulation or disturbances in electrolyte or acid-base status, careful dose selection is required so that fluid loss occurs gradually (at the beginning of treatment, fluid loss of approximately up to 0.5 kg of body weight/day is possible). The initial dose is 20-80 mg/day.

Arterial hypertension

Furosemide can be used as monotherapy or in combination with other antihypertensive agents. The usual maintenance dose is 20-40 mg/day. When adding furosemide to already prescribed medications, their dose should be reduced by half. For arterial hypertension combined with chronic renal failure, the use of furosemide in higher doses may be required.

Solution

It is set individually, depending on the indications, clinical situation, and patient’s age. During treatment, the dosage regimen is adjusted depending on the magnitude of the diuretic response and the dynamics of the patient’s condition.

When taken orally, the initial dose for adults is 20-80 mg/day, then if necessary, the dose is gradually increased to 600 mg/day. For children, a single dose is 1-2 mg/kg.

The maximum dose when taken orally for children is 6 mg/kg.

With IV (bolus) or IM administration, the dose for adults is 20-40 mg once a day, in some cases – 2 times a day. For children, the initial daily dose for parenteral administration is 1 mg/kg.

Adverse Reactions

From the cardiovascular system pronounced decrease in blood pressure, collapse, tachycardia, arrhythmias, tendency to thrombosis, decrease in circulating blood volume.

From the central nervous system: dizziness, headache, muscle weakness, calf muscle cramps (tetany), paresthesia, apathy, adynamia, weakness, lethargy, drowsiness, confusion.

From the sensory organs visual and hearing impairment, tinnitus.

From the digestive system anorexia, dryness of the oral mucosa, thirst, nausea, vomiting, diarrhea, constipation, cholestatic jaundice, pancreatitis (exacerbation), hepatic encephalopathy.

From the genitourinary system oliguria, acute urinary retention (in patients with benign prostatic hyperplasia), interstitial nephritis, hematuria, decreased potency.

From the endocrine system decreased glucose tolerance, manifestation of latent diabetes mellitus.

Allergic reactions purpura, urticaria, exfoliative dermatitis, multiforme exudative erythema, vasculitis, necrotizing angiitis, skin itching, chills, fever, photosensitivity, anaphylactic shock, Stevens-Johnson syndrome, bullous pemphigoid, toxic epidermal necrolysis.

From the hematopoietic organs leukopenia, thrombocytopenia, agranulocytosis, aplastic anemia, eosinophilia.

From water-electrolyte metabolism hypovolemia, dehydration (risk of thrombosis and thromboembolism), hypokalemia, hyponatremia, hypochloremia, hypocalcemia, hypomagnesemia, metabolic alkalosis.

Laboratory parameters: hyperglycemia, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, glucosuria, hypercalciuria, increased activity of liver transaminases, eosinophilia.

Contraindications

• Acute renal failure with anuria;
• Severe hepatic failure, hepatic coma and precoma;
• Acute glomerulonephritis, severely expressed disturbances of urine outflow of any etiology (including unilateral damage to the urinary tract), hyperuricemia;
• Decompensated mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, increased central venous pressure (over 10 mm Hg);
• Disturbance of water-electrolyte metabolism (hypovolemia, pronounced hyponatremia and hypokalemia, hypochloremia, hypocalcemia, hypomagnesemia);
• Digitalis intoxication;
• Pregnancy;
• Breastfeeding period;
• Age under 3 years (solid dosage form);
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (due to the presence of lactose monohydrate in the drug composition);
• Wheat allergy (not celiac disease);
• Hypersensitivity to furosemide and to any of the components of the drug used.

Patients with allergies to sulfonamides (sulfonamide antimicrobial agents or sulfonylurea drugs) may have cross-allergy to Furosemide.

With caution

Arterial hypotension, conditions in which an excessive decrease in blood pressure is particularly dangerous (stenosing lesions of the coronary and/or cerebral arteries), in acute myocardial infarction (increases the risk of cardiogenic shock), in latent or manifest diabetes mellitus (decreased glucose tolerance), gout, in hepatorenal syndrome, in hypoproteinemia (risk of ototoxicity), in impaired urine outflow (benign prostatic hyperplasia, urethral stricture or hydronephrosis), in hearing loss, pancreatitis, diarrhea, in history of ventricular arrhythmia, in systemic lupus erythematosus.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and during breastfeeding.

Use in Hepatic Impairment

Used according to the dosage regimen for edematous syndrome in liver diseases.

Use in Renal Impairment

Used according to the dosage regimen for edematous syndrome in chronic renal failure, for edema in nephrotic syndrome.

Pediatric Use

Contraindicated for use in children under 3 years of age in solid dosage form.

Geriatric Use

Used in elderly patients according to indications.

Special Precautions

Before starting therapy with furosemide, the presence of severe disturbances in urine outflow should be excluded; patients with partial impairment of urine outflow require careful monitoring. During course treatment, it is necessary to periodically monitor blood pressure, plasma electrolyte levels (including sodium, calcium, potassium, magnesium ions), acid-base status, residual nitrogen, creatinine, uric acid, liver function and, if necessary, make appropriate corrections to the treatment.

The use of furosemide slows down the excretion of uric acid, which can provoke an exacerbation of gout.

Patients with hypersensitivity to sulfonamides and sulfonylurea derivatives may have cross-sensitivity to furosemide.

For patients receiving high doses of furosemide, to avoid the development of hyponatremia and metabolic alkalosis, it is not advisable to restrict salt intake. To prevent hypokalemia, the simultaneous administration of potassium preparations and potassium-sparing diuretics is recommended, as well as adherence to a diet rich in potassium. The selection of the dosage regimen for patients with ascites due to liver cirrhosis should be carried out in a hospital setting (disturbances in water-electrolyte balance can lead to the development of hepatic coma). This category of patients is indicated for regular monitoring of plasma electrolyte levels.

If azotemia and oliguria appear or intensify in patients with severe progressive kidney diseases, it is recommended to suspend treatment.

In patients with diabetes mellitus or reduced glucose tolerance, periodic monitoring of blood and urine glucose levels is required.

In unconscious patients, with benign prostatic hyperplasia, ureteral strictures, or hydronephrosis, control of urination is necessary due to the possibility of acute urinary retention.

Effect on ability to drive vehicles and mechanisms

During the treatment period, one should avoid engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with phenobarbital and phenytoin, the effect of furosemide is reduced.

It increases the concentration and risk of nephro- and ototoxic action of cephalosporins, chloramphenicol, ethacrynic acid, cisplatin, amphotericin B (due to competitive renal excretion).

With simultaneous use of aminoglycosides with furosemide, the excretion of aminoglycosides slows down and the risk of their ototoxic and nephrotoxic action increases. For this reason, the use of this combination of drugs should be avoided except in cases where it is necessary for vital indications, and in this case, correction (reduction) of the maintenance doses of aminoglycosides is required.

It increases the effectiveness of diazoxide and theophylline, reduces the effectiveness of hypoglycemic agents, allopurinol.

Drugs that block tubular secretion increase the concentration of furosemide in the blood serum. Drugs with nephrotoxic action – when combined with furosemide, the risk of their nephrotoxic action increases.

Corticosteroids and carbenoxolone, when combined with furosemide, increase the risk of hypokalemia.

With simultaneous use with cardiac glycosides, the risk of digitalis intoxication increases against the background of water-electrolyte disturbances (hypokalemia or hypomagnesemia).

It enhances the neuromuscular blockade of depolarizing muscle relaxants (suxamethonium) and weakens the effect of non-depolarizing muscle relaxants (tubocurarine).

NSAIDs (including indomethacin and acetylsalicylic acid) in combination with furosemide can cause a temporary decrease in creatinine clearance and an increase in serum potassium levels and reduce the diuretic and antihypertensive effect of furosemide. In patients with hypovolemia and dehydration (including against the background of furosemide intake), NSAIDs can cause the development of acute renal failure. Furosemide can enhance the toxic effect of salicylates (due to competitive renal excretion).

Sucralfate reduces the absorption of furosemide and weakens its effect (these drugs should be taken at least 2 hours apart).

Combined use with carbamazepine may increase the risk of hyponatremia.

Antihypertensive agents, diuretics, or other agents capable of reducing blood pressure, when combined with furosemide, can lead to a more pronounced antihypertensive effect.

Prescribing ACE inhibitors to patients previously treated with furosemide can lead to an excessive decrease in blood pressure with deterioration of kidney function, and in some cases to the development of acute renal failure, therefore, three days before starting treatment with ACE inhibitors or increasing their dose, it is recommended to discontinue furosemide or reduce its dose.

Probenecid, methotrexate, and other drugs that, like Furosemide, are secreted in the renal tubules, can reduce the effect of furosemide (the same pathway of renal secretion); on the other hand, Furosemide can lead to a decrease in the renal excretion of these drugs.

Lithium salts – under the influence of furosemide, the excretion of lithium decreases, thereby increasing the serum concentration of lithium and increasing the risk of toxic effects of lithium, including its damaging effects on the heart and nervous system. Therefore, when using this combination, monitoring of serum lithium concentrations is required.

Simultaneous intake of cyclosporine A and furosemide increases the risk of gouty arthritis due to hyperuricemia caused by furosemide and impaired renal excretion of urates by cyclosporine.

Pressor amines (epinephrine, norepinephrine) and Furosemide mutually reduce effectiveness.

Radiocontrast agents – in patients at high risk of developing nephropathy upon administration of radiocontrast drugs who received Furosemide, a higher frequency of impaired renal function was observed compared to patients at high risk of developing nephropathy upon administration of radiocontrast drugs who received only intravenous hydration before the administration of the radiocontrast agent.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.