Furosemide, tablets 40 mg 56 pcs

Pharmacotherapeutic group: Diuretic.

ATC code: C03CA01

Pharmacological properties

Pharmacodynamics

Furosemide is a fast-acting diuretic that is a sulfonamide derivative. Furosemide blocks the transport system of sodium, potassium, chlorine ions in the thick segment of ascending knee of Genle loop, due to which its diuretic action depends on entering the drug into renal tubules lumen (due to mechanism of anion transport). Diuretic effect of Furosemide is associated with inhibition of sodium chloride reabsorption in this part of the Genle loop. Secondary effects to the increase in sodium excretion are: increase in the amount of excreted urine (due to osmotically bound water) and increased potassium secretion in the distal part of the renal tubule. At the same time the excretion of calcium and magnesium ions increases.

If tubular secretion is decreased or if furosemide binds to albumin in the tubular lumen (e.g., in nephrotic syndrome), the effect of furosemide is reduced.

Furosemide does not decrease diuretic activity when administered as a course because furosemide interrupts the tubule-glomerular feedback in Macula densa (a tubular structure closely associated with the juxtaglomerular complex). Furosemide causes dose-dependent stimulation of the renin-angiotensin-aldosterone system.

In heart failure, furosemide rapidly reduces preload (through vein dilation), reduces pulmonary artery pressure and left ventricular filling pressure. This rapidly developing effect appears to be mediated through the effects of prostaglandins, and therefore a condition for its development is the absence of disturbances in prostaglandin synthesis, in addition to which sufficient preservation of renal function is also required to realize this effect.

Furosemide has hypotensive effect due to increase in sodium excretion, decrease in circulating blood volume and decrease in vascular smooth muscle response to vasoconstrictor stimuli (due to the natriuretic effect furosemide reduces vascular response to catecholamines which concentration is increased in patients with arterial hypertension).

After oral administration of 40 mg of Furosemide, the diuretic effect develops within 60 minutes and lasts about 3-6 hours. When increasing the dosage of Furosemide from 10 to 100 mg, a dose-dependent increase in diuresis and natriuresis is observed.

Pharmacokinetics

Intake

Furosemide is rapidly absorbed in the gastrointestinal tract. The time to reach maximum blood concentration (T_max) is 1 to 1.5 hours. Bioavailability of furosemide in healthy volunteers is approximately 50-70%. In patients, the bioavailability of furosemide may decrease up to 30%, as it may be affected by various factors, including the underlying disease.

Distribution

The volume of distribution of furosemide is 0.1-0.2 L/kg body weight. Furosemide binds to plasma proteins (more than 98%), mainly to albumin.

Metabolism/Exhaustion

Furosemide is excreted predominantly unchanged and mainly by secretion in the proximal tubules. Glucuronized metabolites of furosemide account for 10-20% of the drug excreted by the kidneys. The remaining dose is excreted through the intestine, apparently by biliary secretion. Final elimination half-life of furosemide is approximately 1-1.5 hours. Furosemide penetrates the placental barrier and is excreted in the mother’s milk. Its concentrations in the fetus and the newborn are the same as in the mother.

Peculiarities of pharmacokinetics in selected groups of patients

In renal failure elimination of furosemide is delayed and the elimination half-life is prolonged; in severe renal insufficiency, the final elimination half-life may be prolonged up to 24 hours.

In nephrotic syndrome, decreased plasma protein concentrations lead to increased concentrations of unbound furosemide (its free fraction), thereby increasing the risk of ototoxic effects. 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 decreased tubular secretion of furosemide.

In hemodialysis and peritoneal dialysis, and continuous ambulatory peritoneal dialysis, furosemide is marginally excreted.

In hepatic insufficiency, the half-life of furosemide is increased by 30-90%, mainly due to increased volume of distribution. Pharmacokinetic parameters in this category of patients may vary significantly.

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

Indications

Active ingredient

Composition

Active ingredient: Furosemide 40.00 mg

Excipients:

Potato starch 56.88 mg

Lactose monohydrate 53.00 mg

Pregelatinized corn starch 7.00 mg

talt 2.40 mg

silica colloidal silica (aerosil) 0.40 mg

magnesium stearate 0.32 mg

How to take, the dosage

General recommendations

The tablets should be taken on an empty stomach, without chewing and with plenty of water.

When Furosemide is prescribed, it is recommended that it be taken in the lowest dose sufficient to have the desired therapeutic effect.

The recommended maximum daily dose for adults is 1500 mg, and in children it is 40 mg.

The duration of treatment is determined by the physician individually depending on the indications.

Special dosing recommendations

Children

In children, the recommended daily dose for oral administration is 2 mg/kg body weight (but no more than 40 mg per day).

Adults

. The natriuretic response to furosemide depends on several factors, including the severity of renal failure and blood sodium content, so the effect of the dose cannot be accurately predicted. In patients with chronic renal failure, careful dose selection is required, by gradually increasing the dose so that fluid loss occurs gradually (at the beginning of treatment, fluid loss of up to approximately 2 liters/day, approximately 280 mmol of sodium per day is possible).

The recommended starting dose is 40-80 mg/day. The required dose is adjusted according to the diuretic response. The entire daily dose should be taken once or divided into 2 doses. In patients on hemodialysis, the maintenance oral dose is usually 250-1500 mg/day.

. Before treatment with Furosemide, hypovolemia, arterial hypotension and significant disorders of the water-electrolyte balance and/or acid-base balance should be eliminated. Treatment begins with intravenous administration of Furosemide. The recommended initial dose is 40 mg intravenously. If the necessary diuretic effect is not achieved, Furosemide may be administered as a continuous intravenous infusion, starting at a rate of 50-100 mg/hour.

It is recommended that the patient be switched as soon as possible from intravenous infusion to tablet administration of Furosemide (the dose of tablets depends on the selected intravenous dose).

The recommended starting dose is 40-80 mg/day. The required dose is adjusted depending on the diuretic response. The daily dose may be taken once or divided into several doses (see sections “Pharmacokinetics” and “Precautions”).

The recommended starting dose is 20-80 mg/day. The required dose is adjusted depending on the diuretic response. It is recommended that the daily dose be divided into 2-3 doses.

The drug Furosemide may be used in monotherapy or in combination with other hypotensive agents. The usual maintenance dose is a dose of 20-40 mg/day. In arterial hypertension combined with chronic renal insufficiency, higher doses of Furosemide may be required.

Interaction

Unrecommended combinations

Combinations in which caution should be exercised

Interactions to consider

In patients with hypovolemia and dehydration (including those taking Furosemide), NSAIDs may cause acute renal failure. Furosemide may increase the toxicity of salicylates.

Special Instructions

Symptomatic arterial hypotension leading to dizziness, fainting or loss of consciousness may occur in patients receiving furosemide, especially: in elderly patients; in patients taking other drugs that may lead to arterial hypotension; and in patients with other diseases that carry the risk of developing arterial hypotension. Caution should be exercised when treating such patients, and/or they may need to reduce the dose of furosemide.

Before starting treatment with Furosemide, the presence of severe urinary outflow disorders, including unilateral ones, should be excluded. Patients with partial urine outflow disorder require close monitoring, especially at the beginning of treatment with Furosemide.

With Furosemide treatment it is necessary to perform regular monitoring of sodium, potassium and creatinine concentration in serum; especially careful monitoring should be conducted in patients with high risk of electrolyte and fluid disturbances in cases of additional fluid and electrolyte losses (e.g., due to vomiting, diarrhea or heavy perspiration).

Before and during treatment with Furosemide, hypovolemia or dehydration as well as clinically significant electrolyte-water balance and/or acid-base balance disorders should be monitored and, if they occur, treatment with Furosemide may need to be discontinued for short periods.

When treating with Furosemide it is always advisable to eat food rich in potassium (lean meat, potatoes, bananas, tomatoes, cauliflower, spinach, dried fruits and so on). In some cases, the intake of potassium or the use of potassium-saving drugs may be indicated.

In patients with hypoproteinemia, such as that associated with nephrotic syndrome, the effectiveness of furosemide may be impaired and its ototoxicity increased. Caution is required to increase the dose.

A higher rate of death has been observed in elderly patients with dementia treated concomitantly with risperidone and furosemide compared with patients receiving either furosemide alone or risperidone alone. The pharmacophysiological mechanism of this effect has not been established. Concomitant use of risperidone with other diuretics (mainly low-dose thiazide diuretics) has not been associated with increased mortality in elderly patients with dementia. In elderly patients with dementia, furosemide and risperidone should be used with caution, carefully weighing the benefit-risk ratio. Because dehydration is a common risk factor for increased mortality, patient dehydration should be avoided when deciding to use this combination in elderly patients with dementia.

There is a possibility of worsening the course or exacerbation of systemic lupus erythematosus.

The dosing regimen of patients with ascites in cirrhosis should be chosen in hospital (impaired water-electrolyte balance can lead to hepatic coma).

Impact on driving, operating machinery

Some side effects (e.g., significant decrease in blood pressure) may impair ability to concentrate and decrease psychomotor reactions, which may be dangerous when driving vehicles or engaging in other potentially dangerous activities. This especially refers to the period of starting treatment or increasing the dose of the drug, as well as in cases of simultaneous intake of hypotensive drugs or alcohol. In such cases, it is not recommended to drive vehicles or engage in potentially dangerous activities.

Synopsis

Contraindications

Hypersensitivity to the active ingredient or any of the excipients of the drug;

Side effects

The following are the adverse reactions (ARs) that have been identified in clinical trials as well as in the use of furosemide in clinical practice.

The following criteria were used to assess the frequency of NRs: “very common” (≥ 1/10); “common” (≥ 1/100, < 1/10); “infrequent” (≥ 1/1000, < 1/100); “rare” (≥ 1/10000, < 1/1000); “very rare” (< 1/10000). NRs are grouped according to the system-organ classes of the MedDRA Medical Regulatory Dictionary, within each class NRs are listed in descending order of frequency of occurrence, within each group allocated by frequency of occurrence, NRs are categorized in decreasing order of importance.

Blood and lymphatic system disorders

Frequently:

Infrequent:

Rarely:

Very rare:

Disorders of the immune system

Rarely:

Frequency unknown:

Metabolic and nutritional disorders

Very common:

Overdose

If an overdose is suspected, you should always consult a physician, as certain treatment measures may be necessary in case of an overdose.

Symptoms:The clinical picture of acute or chronic overdose of the drug depends mainly on the degree and consequences of fluid and electrolyte loss. Overdose can manifest itself as hypovolemia, dehydration, hemoconcentration, cardiac rhythm and conduction disorders (including atrioventricular blockade and ventricular fibrillation). Symptoms of these disorders are a pronounced decrease in blood pressure, progressing up to the development of shock, acute renal failure, thrombosis, delirium, flaccid paralysis, apathy and confusion.

Treatment:There is no specific antidote. If little time has elapsed after ingestion, to reduce absorption of furosemide from the gastrointestinal tract, attempt to induce vomiting or gastric lavage and then take activated charcoal orally.

The treatment is aimed at correction of clinically significant disorders of electrolyte-water balance and acid-base status with monitoring of serum electrolytes, acid-base status, hematocrit, and the prevention or therapy of possible severe complications arising from these disorders.

Pregnancy use

Pregnancy

Furosemide penetrates the placental barrier, therefore the drug should not be prescribed during pregnancy. Furosemide should only be taken if the anticipated benefit to the mother exceeds the potential risk to the fetus, in which case the fetus should be closely monitored.

Period of breastfeeding

The drug is contraindicated during lactation because furosemide may be excreted with breast milk and suppress lactation. Women taking furosemide should stop breastfeeding.