Furosemid-Darnitsa, solution for and 1% 2 ml No. 10

General characteristics. Structure:

Active ingredient: furasemide; 1 ml of solution contains furosemide in recalculation for 100% dry matter of 10 mg;

excipients: sodium chloride, 1 M hydroxide sodium solution, water for injections.

Pharmacological properties:

Pharmacodynamics. Causes quickly coming, severe and short-term diuresis. Has natriuretic and hloruretichesky effects, increases removal of K+, Ca2+, Mg2+. Getting into a gleam of a renal tubule in a thick segment of the ascending Henle's loop knee, blocks Na reabsorption + and Cl–. Owing to increase in allocation of Na + there is secondary (mediated by osmotically connected water) a strengthened removal of water and increase in secretion of K+ in a distal part of a renal tubule. At the same time removal of Ca2 + and Mg2+ increases. Has the secondary effects caused by release of intra renal mediators and redistribution of an intra renal blood-groove. Against the background of course treatment there is no easing of effect.

At heart failure quickly leads to decrease in preload of heart by means of expansion of large veins. Has hypotensive effect owing to increase in removal of NaCl and decrease in reaction of smooth muscles of vessels to vasopressor influences and as a result of reduction of volume of the circulating blood. Effect of furosemide after intravenous administration comes in 5–10 min.; after intake – in 30–60 min.; an action maximum – in 1–2 h; effect duration – 2–3 h (at reduced function of kidneys – to 8 h). During action removal of Na + considerably increases, however after its termination the speed of removal decreases below the initial level (a syndrome of a ricochet or cancellation). The phenomenon is caused by sharp activation renin-angiotensin-aldosteronovoy of system and other anti-natriuretic neurohumoral links of regulation in response to a massive diuresis; arginine-vazopressivnuyu and sympathetic stimulates systems. Reduces the level of an atrial natriuretic factor in plasma, causes vasoconstriction. Owing to a ricochet phenomenon at reception of 1 times a day also arterial pressure can not have significant effect on daily removal of Na +.

Pharmacokinetics. Absorption – high, TCmax at intake – 1–2 h, at intravenous administration – 30 min. Other pharmacokinetic parameters at intravenous administration and intake match. Bioavailability – 60–70%. The relative volume of distribution – 0,2 l/kg. Communication with proteins of plasma – 98%. Gets through a placental barrier, it is allocated with breast milk. It is metabolized in a liver with formation of 4-chlorine-5-sulfamoylanthranilic acid. Cosecretes in a gleam of renal tubules through the system of transport of anions existing in proximal department of nephron. T1/2 is 0,5–1 h. It is removed preferential by kidneys (88%) in not changed look both in the form of metabolites and with a stake (12%). Clearance – 1,5–3 ml/min.

 

Pharmaceutical characteristics.

main physical and chemical properties: transparent, colourless or slightly yellowish liquid.

Incompatibility. Intravenously entered furosemide has slightly alkali reaction therefore it cannot be mixed with medicines with pH <5,5.

Indications to use:

Hypostases at chronic heart failure, cirrhosis, diseases of kidneys, an acute heart failure (fluid lungs), brain hypostasis, hypertensive crisis, arterial hypertension, a hypercalcemia; carrying out an artificial diuresis at poisonings, an eclampsia.

Route of administration and doses:

The mode of dosing is set by the doctor individually, depending on expressiveness of disturbances of water and electrolytic balance, size of glomerular filtering, weight of a condition of the patient. In the course of use of drug it is necessary to adjust indicators of water and electrolytic balance taking into account a diuresis and dynamics of the general condition of the patient.

Furosemide is appointed intravenously only in that case when uses inside is inexpedient or inefficient (for example, at disturbance of absorption in intestines) or in case of need bystry effect. In case of use of intravenous therapy whenever possible faster transition to therapy by medicine for internal use is recommended.

For achievement of optimum efficiency and oppression of counter regulation in general is preferred as continuous infusion of furosemide in comparison with repeated bolyusny injections.

When continuous infusion of furosemide is inexpedient for further treatment after introduction of one or several bolyusny doses, is preferred as the further scheme of treatment with purpose of low doses which are entered through short time intervals (about 4 hours), in comparison with high bolyusny doses which are entered through wide intervals of time.

For adults the recommended maximum daily dose of furosemide makes  1500 mg.

For children the recommended furosemide dose for parenteral introduction makes   1 mg/kg body scales, but the maximum daily dose should not exceed 20 mg.

Special recommendations concerning dosing.

Dosing for adults, generally, is based on the following recommendations.

Hypostases at chronic congestive heart failure. The recommended initial dose for use inside makes from 20 mg to 50 mg a day. In case of need it is possible to regulate a dose according to the therapeutic answer of the patient. It is recommended to accept the day dose divided into two or three receptions.

Hypostases at acute congestive heart failure. The recommended initial dose makes from 20 to 40 mg and is appointed in the form of a bolyusny injection. In case of need it is possible to regulate a dose according to the therapeutic answer of the patient.

Hypostases at a chronic renal failure. The natriuretic effect of furosemide depends on a certain quantity of factors, including severity of a renal failure and balance of sodium. Thus, it is impossible to provide efficiency of a dose precisely. For patients with a chronic renal failure it is necessary to titrate carefully a dose for ensuring gradual initial loss of liquid. It means introduction of such dose which leads to a daily degrowth of a body approximately on 2 kg (about 280 mmol of Na+) for adult patients.

In case of intravenous administration the dose of furosemide can be defined as follows – treatment begin with continuous intravenous infusion 0,1 mg for a minute, then rate of administering of infusion increases everyone half an hour depending on the answer of the patient.

At an acute renal failure. Before beginning furosemide use, it is necessary to compensate a hypovolemia, hypotension and an essential electrolytic and acid-base imbalance.

It is recommended to carry out as soon as possible transition from intravenous administration to oral administration.

The recommended initial dose makes 40 mg and is appointed in the form of an intravenous injection. If purpose of this dose does not lead to desirable increase in a conclusion of liquid, it is possible to appoint furosemide in the form of continuous intravenous infusion, since introduction from 50 mg to 100 mg of medicine an hour.

Hypostases at liver diseases. Furosemide is appointed as addition of therapy by antagonists of Aldosteronum when use only of antagonists of Aldosteronum is insufficient. For prevention of complications, such as orthostatic hypotension or disturbance of electrolytic and acid-base balance, the dose needs to be titrated carefully to provide gradual initial loss of liquid. It means introduction of such dose which leads to a day degrowth of a body approximately on 0,5 kg for adult patients.

If intravenous administration is absolutely necessary, the initial single dose makes 20 – 40 mg.

Hypertensive crisis. The recommended initial dose from 20 mg to 40 mg is appointed in the form of an intravenous bolyusny injection. In case of need it is possible to regulate a dose depending on the therapeutic answer of the patient.

Support of an artificial diuresis in case of poisoning. Furosemide is appointed intravenously in addition to introduction of infusion of electrolytic solutions. The dose depends on the therapeutic answer to furosemide. Loss of liquid and electrolytes has to be regulated to initiation and during treatment. In case of poisoning with acid or alkaline substances a conclusion of liquid can be accelerated by alkalization or urine oxidation respectively.

The recommended initial dose makes from 20 mg to 40 mg and is appointed intravenously.

Children. As diuretic means – intramusculary or intravenously, in the beginning 1 mg/kg once, then increase a dose by 1 mg/kg not earlier than in 2 h before achievement of desirable effect.

If necessary the dose can be raised to maximum – 6 mg/kg of body weight. An interval between repeated introductions – 6–12 h.

Special recommendations concerning use. It is necessary to appoint furosemide in the form of a slow injection or infusion, with a speed no more than 4 mg in a minute. For patients with strongly affected function of a liver (blood serum creatinine> of 5 mg/dl) the recommended speed of infusion makes no more than 2,5 mg in a minute.

Intramuscular injection: it is necessary to appoint in the form of an intramuscular injection only in exceptional cases when are inexpedient use inside and intravenous administration. It is necessary to take into account that the way of administration of remedy in the form of an intramuscular injection is not shown for treatment of acute states, such as a fluid lungs.

Furosemide cannot be mixed with other medicines in one syringe!

Solution of Furosemide cannot be entered together with other medicines!

Furosemide represents solution with level рН about 9, has no buffer capacity. Thus, active ingredient can drop out in a deposit at values рН lower than 7. In case of cultivation of this solution, it is necessary to provide that рН weak solution was ranging from poorly alkaline to neutral.

Normal normal (salt) saline solution approaches as solvent. It is recommended to apply weak solutions as soon as possible.

Features of use:

Use during pregnancy or feeding by a breast. It is allocated with milk of women during feeding by a breast in this connection, it is necessary to stop feeding during treatment. At pregnancy (especially the first half) drug is accepted according to vital indications after careful assessment of a ratio of advantage for mother/risk for a fruit.

Children. For children the dose needs to be reduced according to body weight.

Against the background of course treatment it is necessary to control periodically the arterial pressure, concentration of electrolytes in plasma (including Na+, Ca2+, K+, Mg2+), an acid-base condition, residual nitrogen, creatinine, uric acid, functions of a liver and to carry out if necessary the corresponding correction of treatment (with bigger frequency rate at patients with frequent vomiting and against the background of parenterally entered liquids). Patients with hypersensitivity to streptocides and derivatives of sulphonylurea can have cross sensitivity to furosemide. To the patient receiving high doses of furosemide in order to avoid development of a hyponatremia and a metabolic alkalosis it is inexpedient to limit consumption of table salt. For prevention of a hypopotassemia co-administration of the drugs K+ and kaliysberegayushchy diuretics is recommended (first of all Spironolactonum), and also to adhere to the diet rich in K+. The increased risk of development of disturbances of water and electrolytic balance is observed at patients with a renal failure. Selection of the mode of dosing by the patient with ascites against the background of cirrhosis should be carried out in stationary conditions (disturbances of water and electrolytic balance can entail development of a hepatic coma). Regular control of electrolytes in plasma is shown to this category of patients. At emergence or strengthening of an azotemia and oliguria in patients with the serious progressing illness of kidneys it is recommended to suspend treatment. At patients with a diabetes mellitus or with reduced tolerance to glucose periodic control of concentration of glucose in blood and urine is necessary. At patients, in unconsciousness, with a prostatauxe, narrowing of ureters or a hydronephrosis control of urination in connection with a possibility of an acute ischuria is necessary.

Patients of advanced age can be more sensitive to action of a usual dose for adults.

Ability to influence speed of response at control of motor transport or other mechanisms. During treatment it is necessary to avoid occupations potentially dangerous types of activity requiring special attention and speed of psychomotor reactions.

Side effects:

From cardiovascular system: a lowering of arterial pressure, orthostatic hypotension, a collapse, tachycardia, arrhythmias, decrease in volume of the circulating blood.

From a nervous system: dizziness, headache, myasthenia, spasms of gastrocnemius muscles (tetany), paresthesias, apathy, adynamia, weakness, slackness, drowsiness, confusion of consciousness.

From sense bodys: vision disorder and hearing.

From the alimentary system: a loss of appetite, dryness in a mouth, thirst, nausea, vomiting, locks or diarrhea, cholestatic jaundice, pancreatitis (aggravation). From urinogenital system: an oliguria, an acute ischuria (at patients with a prostatauxe), intersticial nephrite, a hamaturia, decrease in a potentiality.

At a hypercalcuria furosemide can cause a nephrocalcinosis or a nephrolithiasis.

Allergic reactions: purpura, urticaria, exfoliative dermatitis, multiformny exudative erythema, vasculitis, necrotizing angiitis, skin itch, fever, fever, photosensitization, acute anaphylaxis.

From bodies of a hemopoiesis: leukopenia, thrombocytopenia, agranulocytosis, aplastic anemia.

From water and electrolytic exchange: hypovolemia, dehydration (risk of development of thrombosis and thromboembolism), hypopotassemia, hyponatremia, hypochloraemia, hypocalcemia, hypomagnesiemia, metabolic alkalosis.

Laboratory indicators: hyperglycemia, hypercholesterolemia, hyperuricemia, glucosuria, hypercalcuria.

Interaction with other medicines:

Increases concentration and risk of development nefro-and ototoksichesky effect of cephalosporins, aminoglycosides, chloramphenicol, Acidum etacrynicum, Cisplatinum, Amphotericinum In (owing to competitive renal removal). Increases efficiency of diazoxide and theophylline, reduces efficiency of hypoglycemic medicines, Allopyrinolum.

Reduces renal clearance of the drugs Li + and increases probability of development of intoxication. Strengthens hypotensive effect of hypotensive medicines, the neuromuscular blockade caused by the depolarizing muscle relaxants (succinylcholine) and (tubocurarine) weakens action of not depolarizing muscle relaxants. Pressor amines and furosemide mutually reduce efficiency.

The medicines blocking canalicular secretion increase concentration of furosemide in blood serum.

At simultaneous use of glucocorticosteroids, Amphotericinum In the risk of development of a hypopotassemia increases, with cardiac glycosides the risk of development of digitalis intoxication owing to a hypopotassemia (for highly - and low-polar cardiac glycosides) and lengthenings of T1/2 increases (for low-polar). Non-steroidal anti-inflammatory drugs, сукральфат reduce diuretic effect, owing to inhibition of synthesis of Pg, change of concentration of a renin in plasma and allocation of Aldosteronum. Reception of salicylates in high doses against the background of therapy by furosemide increases risk of manifestation of their toxicity (owing to competitive renal removal). Intravenously entered furosemide has slightly alkali reaction therefore it cannot be mixed with medicines with pH <5,5.

Contraindications:

Hypersensitivity to drug (including to streptocides), an acute renal failure with an anury (the size of glomerular filtering less than 3-5 ml/min.), a heavy liver failure, a hepatic coma and a prekoma, an urethra stenosis, an acute glomerulonephritis, obstruction of urinary tract a stone, prekomatozny states, a hyper glycemic coma, a hyperuricemia, gout, a dekompensirovanny mitral or aortal stenosis, a hypertrophic subaortic stenosis, increase in the central venous pressure, arterial hypotension, an acute myocardial infarction, pancreatitis, disturbance of introduction and electrolytic exchange (a hypovolemia, a hyponatremia, a hypopotassemia, a hypochloraemia, a hypocalcemia, a hypomagnesiemia), digitalis intoxication.

Overdose:

Symptoms. A lowering of arterial pressure, a collapse, shock, a hypovolemia, dehydration, haemo concentration, arrhythmias (including AV blockade, fibrillation of ventricles), an acute renal failure with an anury, thrombosis, a thrombembolia, drowsiness, confusion of consciousness, sluggish paralysis, apathy.

Treatment. Correction of water-salt balance and an acid-base state, completion of volume of the circulating blood, a symptomatic treatment. There is no specific antidote.

Storage conditions:

Period of validity. 3 years. To store in the place, unavailable to children, in original packaging, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 2 ml in an ampoule and on 10 ampoules in cardboard packaging.