Furosemide, 10 mg/ml 2 ml 10 pcs

“Loop” diuretic. Disrupts reabsorption of sodium, chlorine ions in the thick segment of the ascending part of the loop of Genle. Due to the increased excretion of sodium ions, there is a secondary (mediated by osmotically bound water) enhanced excretion of water and increased secretion of potassium ions in the distal part of the renal tubule. At the same time, the excretion of calcium and magnesium ions increases.

It has secondary effects due to release of intrarenal mediators and redistribution of intrarenal blood flow. There is no attenuation of the effect during the course of treatment.

In case of heart failure, it quickly leads to reduction of the preload on the heart by expanding the large veins. It has a hypotensive effect due to increased excretion of sodium chloride and due to decreased reaction of vascular smooth muscle to vasoconstrictor effects and due to reduction of the blood circulation volume. The action of furosemide after intravenous injection occurs after 5-10 min, after oral administration – after 30-60 min, maximum action – after 1-2 hours, the duration of effect – 2-3 hours (with reduced renal function – up to 8 hours). During the period of action, excretion of sodium ions increases significantly, but after its cessation the excretion rate decreases below the initial level (the syndrome of “ricochet” or “withdrawal”). The phenomenon is due to a sharp activation of renin-angiotensin and other antinatriuretic neurohumoral regulatory links in response to massive diuresis; it stimulates the arginine-vasopressive and sympathetic systems. Reduces the level of atrial natriuretic factor in plasma, causes vasoconstriction.

Owing to the “ricochet” phenomenon, once daily administration may have no significant effect on the daily excretion of sodium ions and BP. When administered intravenously, it causes dilatation of peripheral veins, reduces preload, decreases left ventricular filling pressure and pulmonary artery pressure as well as systemic BP.

The diuretic effect develops 3-4 min after IV administration and lasts 1-2 h; after oral administration, it takes 20-30 min and lasts up to 4 h.

Pharmacokinetics

After oral administration absorption is 60-70%. In severe kidney disease or chronic heart failure the degree of absorption decreases.

The Vd is 0.1 l/kg. Binding with plasma proteins (mainly with albumin) is 95-99%. Metabolized in liver. Excreted by kidneys – 88%, with bile – 12%. T1/2 in patients with normal renal and hepatic function is 0.5-1.5 hours. In anuria T1/2 may be increased up to 1.5-2.5 hours, in concomitant renal and hepatic failure – up to 11-20 hours.

Indications

Oedema syndrome of various genesis, including chronic heart failure stage II-III, liver cirrhosis (portal hypertension syndrome), nephrotic syndrome. Pulmonary edema, cardiac asthma, cerebral edema, eclampsia, performing forced diuresis, severe arterial hypertension, some forms of hypertensive crisis, hypercalcemia.

Active ingredient

Composition

Solution for injection 1%

1 ml 1 ampoule

Furosemide 10 mg 20 mg

How to take, the dosage

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

In case of oral administration the initial dose for adults is 20-80 mg/day, then if necessary the dose is gradually increased up to 600 mg/day. In children the single dose is 1-2 mg/kg.

The maximum oral dose in children is 6 mg/kg.

When administered intravenously (by jet) or intramural administration, the dose for adults is 20-40 mg 1 time/day, in some cases 2 times/day. In children the initial daily dose for parenteral use is 1 mg/kg.

Interaction

Concomitant use with antibiotics of the group of aminoglycosides (including gentamicin, tobramycin) may increase nephro- and ototoxic effects.

Furosemide decreases clearance of gentamicin and increases plasma concentrations of gentamicin as well as tobramycin.

When used concomitantly with antibiotics of the group of cephalosporins that may cause renal dysfunction, there is a risk of increased nephrotoxicity.

Concomitant use with beta-adrenomimetics (including fenoterol, terbutaline, salbutamol) and with GCS may increase hypokalemia.

In concomitant use with hypoglycemic agents, insulin, the effectiveness of hypoglycemic agents and insulin may decrease, because furosemide has the ability to increase plasma glucose content.

In concomitant use with ACE inhibitors the antihypertensive effect is increased. Significant arterial hypotension is possible, especially after the first dose of furosemide, apparently due to hypovolemia, which leads to transient enhancement of the hypotensive effect of ACE inhibitors. The risk of renal dysfunction increases and development of hypokalemia is not excluded.

Concomitant use with furosemide increases the effects of nondepolarizing myorelaxants.

In concomitant use with indomethacin, other NSAIDs may decrease diuretic effect, probably due to inhibition of prostaglandin synthesis in kidneys and retention of sodium in the body caused by indomethacin, which is a non-specific COX inhibitor; decrease of antihypertensive effect.

Furosemide is believed to interact similarly with other NSAIDs.

In concomitant use with NSAIDs, which are COX-2 selective inhibitors, this interaction is significantly less pronounced or almost absent.

Concomitant use with astemizole increases the risk of arrhythmia.

Concomitant use with vancomycin may increase ototoxicity and nephrotoxicity.

Concomitant use with digoxin, digitoxin may increase the toxicity of cardiac glycosides associated with the risk of hypokalemia with furosemide.

There have been reports of the development of hyponatremia when concomitant use with carbamazepine.

Concomitant use with colestiramine, colestipol decreases absorption and diuretic effect of furosemide.

Concomitant use with lithium carbonate may increase the effects of lithium due to its increased plasma concentration.

Concomitant use with probenecid decreases renal clearance of furosemide.

Concomitant use with sotalol may cause hypokalemia and development of ventricular pirouette arrhythmia.

Concomitant use with theophylline may change the plasma concentration of theophylline.

Concomitant use with phenytoin significantly reduces the diuretic effect of furosemide.

After IV administration of furosemide with chloral hydrate therapy, increased sweating, fever, BP instability, tachycardia may occur.

Concomitant use with cisapride may increase hypokalemia.

It has been suggested that furosemide may decrease the nephrotoxic effects of cyclosporine.

Concomitant use with cisplatin may increase ototoxic effects.

Special Instructions

With caution use in prostatic hyperplasia, SLE, hypoproteinemia (risk of ototoxicity), diabetes mellitus (reduced glucose tolerance), stenotic atherosclerosis of cerebral arteries, against continuous therapy with cardiac glycosides, in elderly patients with significant atherosclerosis, pregnancy (especially the first half), lactation period.

Electrolyte disturbances should be compensated prior to treatment. During furosemide treatment it is necessary to monitor BP, serum electrolyte and glucose levels, liver and kidney function.

To prevent hypokalemia, it is reasonable to combine furosemide with potassium-saving diuretics. In concomitant use of furosemide and hypoglycemic agents, correction of the dose of the latter may be required.

It is not recommended to mix furosemide solution in the same syringe with any other drugs.

Impact on driving and operating machinery

When using furosemide, one cannot rule out the possibility of decreased ability to concentrate, which is important for persons driving vehicles and operating machinery.

Contraindications

Acute glomerulonephritis, urinary stenosis, urinary tract obstruction by stone, acute renal failure with anuria, hypokalemia, alkalosis, precoma, severe hepatic failure, hepatic coma and precoma, diabetic coma, precoma, hyperglycemic coma, hyperuricemia, gout, decompensated mitral or aortic stenosis, hypertrophic obstructive cardiomyopathy, increased central venous pressure (over 10 mm Hg).

), arterial hypotension, acute myocardial infarction, pancreatitis, disorder of the water-electrolyte exchange (hypovolemia, hyponatremia, hypokalemia, hypochloremia, hypocalcemia, hypomagnesemia), digitalis intoxication, hypersensitivity to furosemide.

Side effects

Cardiovascular system disorders: decreased BP, orthostatic hypotension, collapse, tachycardia, arrhythmias, decreased blood circulation.

CNS and peripheral nervous system disorders: dizziness, headache, myasthenia, cramps of the calves (tetany), paresthesias, apathy, adynamia, weakness, drowsiness, somnolence, confusion.

Sensory organs: visual and hearing disorders.

Digestive system disorders: decreased appetite, dry mouth, thirst, nausea, vomiting, constipation or diarrhea, cholestatic jaundice, pancreatitis (exacerbation).

Urogenital system disorders: oliguria, acute urinary retention (in patients with prostatic hypertrophy), interstitial nephritis, hematuria, decreased potency.

Hematopoietic system disorders: leukopenia, thrombocytopenia, agranulocytosis, aplastic anemia.

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

Metabolism disorders: hypovolemia, hypokalemia, hyponatremia, hypochloremia, hypokalemic metabolic alkalosis (arterial hypotension, dizziness, dry mouth, thirst, arrhythmia, muscle weakness, seizures as a consequence of these disorders), hyperuricemia (with possible aggravation of gout), hyperglycemia.

Allergic reactions: purpura, urticaria, exfoliative dermatitis, erythema multiforme, vasculitis, necrotizing angiitis, skin itching, chills, fever, photosensitization, anaphylactic shock.

Other: when administered intravenously (additionally) – thrombophlebitis, calcification of the kidneys in premature infants.