The drug mannitol application. Mannitol is an extremely interesting and useful organic substance.

Mannitol (mannitol)

Composition and form of release of the drug

Solution for infusion transparent, colorless.

When administered by inhalation

From the side of metabolism: often - loss of appetite.

From the nervous system: often - headache; infrequently - dizziness.

From the organ of hearing: infrequently - pain in the ears.

From the respiratory system: very often - cough; often - hemoptysis, bronchospasm, wheezing, bronchial asthma, deterioration, pain in the pharyngolaryngeal region, wet cough, discomfort in the chest, infected sputum; infrequently - a positive test for the fungus in the sputum, the syndrome of "bogging" of the respiratory tract, throat irritation, rhinorrhea.

From the digestive system: often - vomiting, posttussive vomiting; infrequently - gastroesophageal reflux disease, glossalgia.

From the skin and subcutaneous tissues: infrequently - acne, itching, rash, cold sweat, acne.

From the musculoskeletal system: infrequently - arthralgia, joint stiffness, musculoskeletal pain in the chest.

From the urinary system: infrequently - urinary incontinence.

Others: infrequently - pain in the area of ​​​​the hernial sac.

drug interaction

With the simultaneous use of mannitol with cardiac glycosides, an increase in their toxic effect associated with hypokalemia is possible.

special instructions

With / in the introduction

Use with caution in patients with severe forms of chronic heart failure, hypovolemia, impaired renal function.

If symptoms such as headache, vomiting, dizziness, visual disturbances appear during the administration of mannitol, the administration should be discontinued and the development of such complications as subdural and subarachnoid bleeding should be excluded.

When using mannitol, it is necessary to control blood pressure, diuresis, the concentration of electrolytes in the blood serum (potassium, sodium).

When administered by inhalation

It is necessary to carefully monitor the condition of patients with bronchial asthma for worsening of symptoms of bronchial asthma after inhalation of the initial dose.

Patients should be monitored for the absence of bronchial hyperresponsiveness to inhaled mannitol when assessed during inhalation of the initial dose prior to the initiation of chronic use at therapeutic doses. If the patient is hyperreactive, inhaled mannitol should not be used. The usual precautions apply when controlling bronchial hyperreactivity.

With inhalation of mannitol, bronchospasm may develop even in patients who have not experienced hyperresponsiveness to inhalation of the initial dose.

The safety and efficacy of inhaled mannitol has not been established in patients with an FEV1 less than 30% of normal.

Patients with a history of hemoptysis should be carefully monitored.

Pediatric use

Pregnancy and lactation

There are no adequate and well-controlled studies in humans.

The use of mannitol during pregnancy and lactation is possible in cases where the intended benefit to the mother outweighs the possible risk to the fetus or infant.

Application in childhood

For impaired renal function

Contraindicated in chronic renal failure, violation of the filtration function of the kidneys.

Use with caution in patients with impaired renal function.

Solution - 1 l:

• Active substance: mannitol 150 g.
• Excipients: sodium chloride - 9 g, water for injection - up to 1 liter.
• Theoretical osmolarity: 1132 mOsm/l.

200 ml - polypropylene bottles (1) - packs of cardboard.

200 ml - polypropylene bottles - cardboard boxes (for hospitals).

Description of the dosage form

Solution for infusion transparent, colorless.

pharmachologic effect

Osmotic diuretic. Increasing the osmotic pressure of plasma and filtration without subsequent tubular reabsorption leads to water retention in the tubules and an increase in urine volume. By increasing the osmolarity of the plasma, it causes the movement of fluid from the tissues (in particular, the eyeball, brain) into the vascular bed. It causes a pronounced diuretic effect, in which a large amount of osmotically free water is excreted, as well as sodium, chlorine, without significant excretion of potassium. Causes an increase in BCC.

Inhaled mannitol (in the appropriate dosage form) is intended to improve pulmonary hygiene by correcting the impaired mucociliary clearance characteristic of cystic fibrosis. Although the exact mechanism of action is not known, inhaled mannitol is thought to alter the viscoelastic properties of sputum, increase hydration of the periciliary fluid layer, and increase mucociliary and cough clearance.

Pharmacokinetics

With intravenous administration of mannitol, Vd corresponds to the volume of extracellular fluid. Mannitol may be slightly metabolized in the liver to form glycogen. Excretion of mannitol is regulated by glomerular filtration without significant tubular reabsorption. T1 / 2 is about 100 minutes. Excreted by the kidneys, when administered intravenously at a dose of 100 g, 80% is determined in the urine within 3 hours. In renal failure, T1 / 2 may increase up to 36 hours.

With inhalation administration (in the appropriate dosage form), the absolute bioavailability of mannitol compared with intravenous administration was 0.59 ± 0.15. The rate and extent of absorption of mannitol after inhalation administration was very similar to the rate and extent of absorption after oral administration. T1 / 2 after inhalation administration is 1.5 ± 0.5 hours. The metabolism of mannitol during inhalation administration has not been studied during pharmacokinetic studies. Pulmonary deposition studies have shown a 24.7% deposition of inhaled mannitol, which confirms its distribution in the target organ. Preclinical toxicological studies show that mannitol entering the lungs is absorbed into the blood; while Cmax in serum is reached within 1 hour. There is no evidence that mannitol accumulates in the body. The cumulative volume of mannitol excreted in the urine over a 24-hour period was similar to the volume excreted in the urine after inhalation (55%) and oral administration (54%) of mannitol. 87% of the dose is excreted in the urine within 24 hours. The average final T1 / 2 in adults from serum was about 4-5 hours, from urine - about 3.6 hours.

Clinical pharmacology

Osmotic diuretic.

Indications for use Mannitol

For intravenous administration (stream or drip)

Edema of the brain. intracranial hypertension. epileptic status. Intraocular hypertension, acute attack of glaucoma.

Oliguria in acute renal failure. To determine the rate of glomerular filtration in acute oliguria.

Acute liver failure. Acute liver failure in patients with preserved filtration capacity of the kidneys and other conditions requiring increased diuresis.

Poisoning with barbiturates, salicylates, bromides, lithium preparations, forced diuresis in other poisonings.

Post-transfusion complications after the introduction of incompatible blood.

For the prevention of hemolysis and hemoglobinemia during transurethral resection of the prostate gland or when performing surgical procedures such as bypass surgery on the cardiopulmonary system, during operations with extracorporeal circulation.

For inhalation administration

Treatment of cystic fibrosis in children over 6 years of age and adults in addition to the use of dornase alfa, and in patients with intolerance or ineffectiveness of dornase alfa.

Contraindications for the use of Mannitol

For intravenous administration: chronic renal failure, violation of the filtration function of the kidneys, left ventricular failure (especially accompanied by pulmonary edema), hemorrhagic stroke, subarachnoid hemorrhage (except for bleeding during craniotomy), severe forms of dehydration, hyponatremia, hypochloremia, hypokalemia, hypersensitivity to mannitol.

For inhalation administration: bronchial hyperreactivity to inhaled mannitol.

Mannitol Use in pregnancy and children

There are no adequate and well-controlled studies in humans.

The use of mannitol during pregnancy and lactation is possible in cases where the intended benefit to the mother outweighs the possible risk to the fetus or infant.

Mannitol side effects

With / in the introduction

From the side of metabolism: violations of the water and electrolyte balance (increased BCC, dilution hyponatremia, hyperkalemia) and their manifestations (muscle weakness, convulsions, dry mouth, thirst, impaired consciousness).

Other: tachycardia, chest pain, thrombophlebitis, skin rash.

When administered by inhalation

From the side of metabolism: often - loss of appetite.

From the nervous system: often - headache; infrequently - dizziness.

On the part of the organ of hearing: infrequently - pain in the ears.

From the respiratory system: very often - cough; often - hemoptysis, bronchospasm, wheezing, bronchial asthma, deterioration, pain in the pharyngolaryngeal region, wet cough, discomfort in the chest, infected sputum; infrequently - a positive test for the fungus in the sputum, the syndrome of "bogging" of the respiratory tract, throat irritation, rhinorrhea.

From the digestive system: often - vomiting, post-cough vomiting; infrequently - gastroesophageal reflux disease, glossalgia.

From the skin and subcutaneous tissues: infrequently - acne, itching, rash, cold sweat, acne.

From the musculoskeletal system: infrequently - arthralgia, joint stiffness, musculoskeletal pain in the chest.

From the urinary system: infrequently - urinary incontinence.

Other: infrequently - pain in the area of ​​the hernial sac.

drug interaction

With the simultaneous use of mannitol with cardiac glycosides, an increase in their toxic effect associated with hypokalemia is possible.

Dosage of Mannitol

Mannitol is administered intravenously or by inhalation in appropriate dosage forms.

When administered intravenously (slowly by stream or drip), the prophylactic dose is 500 mg / kg of body weight, the therapeutic dose is 1-1.5 g / kg. The daily dose should not exceed 140-180 g. In operations with extracorporeal circulation, it is administered at a dose of 20-40 g immediately before the operation.

Patients with oliguria should be given a test dose of mannitol (200 mg/kg) intravenously over 3-5 minutes. If after that within 2-3 hours there is no increase in the rate of diuresis to 30-50 ml / g, then further administration of mannitol should be refrained.

Inhalation of the initial dose (400 mg) is carried out under the supervision of an experienced physician or other medical professional who has received appropriate training and equipment to monitor hemoglobin oxygen saturation, conduct spirometry and relieve acute bronchospasm. 5-15 minutes before inhalation of the initial dose (but after measuring baseline FEV1 and monitoring hemoglobin oxygen saturation), the patient should receive a bronchodilator. All measurements of FEV1 and monitoring of hemoglobin oxygen saturation are carried out 60 seconds after inhalation.

Precautionary measures

With / in the introduction

Use with caution in patients with severe forms of chronic heart failure, hypovolemia, impaired renal function.

If symptoms such as headache, vomiting, dizziness, visual disturbances appear during the administration of mannitol, the administration should be discontinued and the development of such complications as subdural and subarachnoid bleeding should be excluded.

When using mannitol, it is necessary to control blood pressure, diuresis, the concentration of electrolytes in the blood serum (potassium, sodium).

When administered by inhalation

It is necessary to carefully monitor the condition of patients with bronchial asthma for worsening of symptoms of bronchial asthma after inhalation of the initial dose.

Patients should be monitored for the absence of bronchial hyperresponsiveness to inhaled mannitol when assessed during inhalation of the initial dose prior to the initiation of chronic use at therapeutic doses. If the patient is hyperreactive, inhaled mannitol should not be used. The usual precautions apply when controlling bronchial hyperreactivity.

With inhalation of mannitol, bronchospasm may develop even in patients who have not experienced hyperresponsiveness to inhalation of the initial dose.

The safety and efficacy of the inhaler mannitel has not been established in patients with an FEV1 less than 30% of normal.

Patients with a history of hemoptysis should be carefully monitored.

Mannitol

International non-proprietary name

Mannitol

Dosage form

Solution for infusion 15% 200 ml, 400 ml

Compound

1 liter of the drug contains

Aactive substance - mannitol 150.0 g,

Excipients: sodium chloride, water for injection.

Description

Clear, colorless solution, odorless.

Pharmacotherapeutic group

Plasma substituting and perfusion solutions.

Solutions for intravenous administration.

Osmodiuretics. Mannitol.

ATX code B05BC01

Pharmacological properties

Pharmacokinetics

Mannitol is a hexavalent alcohol that is poorly absorbed when taken orally due to the high polarity of its molecule, which leads to the only possible route of administration - parenteral administration (IV). The volume of distribution of mannitol corresponds to the volume of extracellular fluid, since it is distributed only in the extracellular sector. The drug does not penetrate cell membranes and tissue barriers (eg, blood-brain, placental). Mannitol may be slightly metabolized in the liver to form glycogen.

The half-life of mannitol is about 100 minutes. The drug is excreted by the kidneys. Excretion of mannitol is regulated by glomerular filtration without significant involvement of tubular reabsorption and secretion. If you enter intravenously 100 g of mannitol, then 80% of it is determined in the urine within 3 hours.

In patients with renal insufficiency, the half-life of mannitol may increase up to 36 hours.

Pharmacodynamics

Mannitol increases plasma osmolarity, causing the movement of fluid from tissues into the vascular bed. Mannitol has a strong diuretic effect. The principle of the diuretic action of mannitol is that it is well filtered in the renal glomeruli, creates a high osmotic pressure in the lumen of the renal tubules (mannitol is little reabsorbed) and reduces water reabsorption. It acts mainly in the proximal tubules, although the effect is preserved to some extent in the descending loop of the nephron and in the collecting ducts. Unlike other osmotic diuretics, mannitol is able to excrete large amounts of free water. Diuresis is accompanied by a significant release of sodium and chlorine without a significant effect on the excretion of potassium. It should be borne in mind that the natriuresis that occurs when prescribing mannitol is less than water, which sometimes leads to hypernatremia. Mannitol does not significantly affect the acid-base state.

The diuretic effect of mannitol depends on the amount of the drug filtered through the kidneys. The effect is all the more pronounced, the higher the concentration of the drug and the rate of its administration. If the filtration function of the renal glomeruli is impaired, the diuretic effect of the mannitol solution may be absent.

Indications for use

Cerebral edema, intracranial hypertension

Acute attack of glaucoma

Oliguria in acute renal or renal-hepatic insufficiency with preserved filtration capacity of the kidneys (as part of combination therapy)

Forced diuresis in case of poisoning with barbiturates and salicylates

Prevention of hemolysis during operations with extracorporeal circulation in order to prevent renal ischemia and associated acute renal failure.

Post-transfusion complications after the introduction of incompatible blood

Dosage and administration

Mannitol is administered intravenously slowly by stream or drip. The therapeutic dose of a 15% mannitol solution is 1.0-1.5 g/kg. The daily dose of mannitol should not exceed 140-180 g.

Adults are administered 50-100 g of the drug at a rate that provides a diuresis level of at least 30-50 ml / h.

The usual pediatric dose is 0.25 - 0.5 g / kg, which is administered over 2-6 hours. The maximum daily dose for children is 2.0 g / kg or 60 g per 1 m2 of body surface. The dose and rate of administration of mannitol for children are selected individually, depending on the severity of the patient's condition. With cerebral edema, increased intracranial pressure or glaucoma - 1-2 g / kg or 30-60 g per 1 m2 of body surface for 30-60 minutes. In children with low body weight or exhausted patients, a dose of 500 mg / kg is sufficient. In case of poisoning in children, intravenous infusion is carried out up to 2 g / kg of body weight or 60 g per 1 m2 of body surface.

In case of poisoning in adults, 50-200 g is administered at an infusion rate that maintains diuresis at a level of 100-500 ml / hour. The maximum dose for adults is up to 6 g / kg of body weight for 24 hours.

For the prevention of hemolysis and hemoglobinemia during transurethral resection of the prostate gland, when performing bypass surgery on the cardiopulmonary system or during operations with extracorporeal circulation, the dose (dry powder) is 500 mg / kg of body weight.

In operations using extracorporeal circulation, Mannitol is administered at a dose of 20-40 g immediately before the start of perfusion.

In patients with oliguria, in order to detect a reaction to osmotic diuretics, before starting a continuous infusion, a test dose (200 mg / kg) of mannitol should be injected intravenously over 3-5 minutes. Mannitol is not effective if the diuresis rate has not increased to 50 ml/hour within 3 hours. If a response to a trial dose is obtained, then the introduction of a solution of mannitol (12.5-25 g) should be repeated after 1-2 hours to maintain the urine output at a level above 100 ml/hour.

Side effects

Often

Headache

Dry mouth

Nausea and vomiting

Dry skin

Rarely

Pain behind the sternum

Tachycardia

Skin rash

Thrombophlebitis

Muscle weakness, cramps, hallucinations, low blood pressure due to dehydration

Violations of water and electrolyte metabolism (increased blood volume, hyponatremia, hyperkalemia)

With rapid intravenous administration

Headache

Nausea and vomiting

Fever

Chest pain

Respiratory failure

Contraindications

- hypersensitivity to drug components

Severe renal failure with impaired filtration process, with anuria for more than 12 hours

Hemorrhagic stroke, subarachnoid hemorrhage (except for bleeding during craniotomy)

Pulmonary edema on the background of acute left ventricular failure

Decompensated cardiovascular insufficiency

Severe degree of dehydration

Hypokalemia, hyponatremia, hypochloremia

Post-traumatic increase in intracranial pressure with a risk of hemorrhage

Drug Interactions

Simultaneous use of the drug with cardiac glycosides may increase their toxic effect due to hypokalemia. The drug potentiates the diuretic effect of saluretics, carbonic anhydrase inhibitors and other diuretic drugs. Simultaneous use with other diuretics enhances their effect. When used with neomycin, the risk of developing oto- and nephrotoxicity increases.

special instructions

In heart failure, especially in left ventricular failure (due to the risk of pulmonary edema), Mannitol should be combined with fast-acting "loop" diuretics. Perhaps the use of heart failure (only in combination with "loop" diuretics) and hypertensive crisis with encephalopathy. During the infusion, it is necessary to monitor renal function, as well as control diuresis to avoid accumulation of mannitol. It is necessary to control blood pressure, the concentration of electrolytes (potassium ions, sodium ions) and sugar in the blood serum. Repeated administration of the drug should be carried out under the control of indicators of water and electrolyte balance of the blood.

Mannitol is not effective for azotemia in patients with cirrhosis of the liver and ascites. It should be borne in mind that initially with the introduction of a solution of mannitol, the volume of extracellular fluid increases and hyponatremia develops.

If headache, vomiting, dizziness, visual disturbances occur during the administration of the drug, the administration should be stopped and the development of such complications as subdural and subarachnoid bleeding should be excluded.

Simultaneous use with cardiac glycosides may increase the risk of digitalis poisoning and hypokalemia.

Simultaneous use with other diuretics enhances their effect.

There may be cases of crystallization during storage of the drug at a temperature below 20 ° C, in case of crystallization, the solution should be slightly heated in a water bath at a temperature of 50 ° C up to 70 ° C until the crystals disappear, and immediately before the introduction - cool to a body temperature of 36 ° C.

Application in pediatrics

For children and adolescents, the drug is prescribed only for health reasons. There are no data on contraindications for the use of the drug in children and adolescents.

Pregnancy and lactation

There are no data on contraindications for the use of the drug during pregnancy and lactation. The use of the drug during pregnancy and lactation is possible with caution in cases where the intended benefit to the mother outweighs the possible risk to the fetus or infant.

Features of the influence of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

The drug is used in stationary conditions, where the performance of such an activity as driving a car or working with machinery is not provided.

Overdose

Symptoms: signs of dehydration (nausea, vomiting, hallucinations), muscle weakness, convulsions, loss of consciousness.

Treatment: stop the administration of the drug. Carrying out symptomatic therapy.

Release form and packaging

200 ml and 400 ml of the drug in a polypropylene container with one or two ports.

Containers are packed in a cardboard box together with instructions for medical use in the state and Russian languages ​​in an amount equal to the number of containers.

Storage conditions

Gross formula

C6H14O6

Pharmacological group of the substance Mannitol

Nosological classification (ICD-10)

CAS code

69-65-8

Characteristics of the substance Mannitol

Osmotic diuretic.

Lyophilized mass of light yellow color. Let's dissolve in water (very easily — in hot).

Pharmacology

pharmachologic effect- decongestant, diuretic.

Increases the osmotic pressure of the plasma, promotes the transition of fluid from the tissues into the vascular bed, increases the bcc. It is filtered by the kidneys without subsequent tubular reabsorption, increases the osmotic pressure in the tubules and prevents water reabsorption, which leads to water retention in the tubules and an increase in urine volume. At the same time, natriuresis increases significantly without a significant increase in kaliuresis. The diuretic effect is higher, the higher the dose. Approximately 80% of the administered intravenous dose is found in the urine within 3 hours. It is not effective in violation of the filtration function of the kidneys, as well as in azotemia in patients with cirrhosis of the liver and ascites.

May be slightly metabolized in the liver.

Application of the substance Mannitol

Cerebral edema, increased intracranial pressure in renal or renal-hepatic insufficiency, status epilepticus, acute attack of glaucoma, operations with extracorporeal circulation, acute renal (with preserved filtration function of the kidneys) and liver failure, post-transfusion complications caused by the introduction of incompatible blood, acute barbiturate poisoning and other substances (forced diuresis).

Contraindications

Hypersensitivity, organic kidney damage, violation of the filtration function of the kidneys, congestive heart failure, hemorrhagic stroke, subarachnoid hemorrhage (except for bleeding during craniotomy), severe forms of dehydration, hyponatremia, hypochloremia, hypokalemia, acute tubular necrosis.

Application restrictions

Pregnancy, lactation.

Side effects of Mannitol

Dehydration (dry skin, dyspepsia, myasthenia gravis, convulsions, dry mouth, thirst, hallucinations, decreased blood pressure), electrolyte imbalance, tachycardia, chest pain, thrombophlebitis, skin rash.

Interaction

An increase in the toxic effect of cardiac glycosides (hypokalemia) is possible.

Routes of administration

Precautions Substance Mannitol

To eliminate the phase of increasing BCC, incl. in heart failure, should be combined with loop diuretics.

Therapy should be carried out under the control of water and electrolyte balance and central hemodynamics. If headache, vomiting, dizziness, visual disturbances occur during administration, the administration should be stopped and the development of such complications as subdural and subarachnoid bleeding should be excluded.

The introduction of mannitol in anuria caused by organic kidney disease can lead to the development of pulmonary edema.

special instructions

A 10% solution can be prepared at room temperature, 15% and 20% solutions can be prepared by heating in a water bath to 37 °C. In a 20% solution of mannitol, especially when it is cooled, crystals may form, for the dissolution of which it is necessary to heat the vial in hot water or in an autoclave, shaking occasionally. Cool to body temperature or below before use.

Interactions with other active substances

Trade names

Name	The value of the Wyshkovsky Index ®