Medicine use mannitol. Mannitol is an extremely interesting and useful organic substance

Mannitol

Composition and release form 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.

On the part of the hearing organ: 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 fungus in the sputum, “swamping” syndrome of the respiratory tract, throat irritation, rhinorrhea.

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

For the skin and subcutaneous tissues: uncommon - acne, itching, rash, cold sweat, acne.

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

From the urinary system: infrequently - urinary incontinence.

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

Drug interactions

With the simultaneous use of mannitol with cardiac glycosides, their toxic effect associated with hypokalemia may increase.

special instructions

With intravenous administration

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

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

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

When administered by inhalation

Patients with bronchial asthma should be carefully monitored for worsening asthma symptoms after inhalation of the initial dose.

Patients should be monitored for bronchial hyperresponsiveness to inhaled mannitol when assessed during the initial inhalation dose before initiating chronic use at therapeutic doses. If the patient exhibits hyperresponsiveness, inhaled mannitol should not be used. Usual precautions apply when controlling bronchial hyperresponsiveness.

With inhalation of mannitol, bronchospasm may develop even in patients who did not experience hyperreactivity to inhalation of the initial dose.

The safety and effectiveness of inhaled mannitol have not been established in patients with FEV1 less than 30% of normal.

Patients with a history of hemoptysis should be carefully monitored.

Use in pediatrics

Pregnancy and lactation

Adequate and strictly controlled studies in humans have not been conducted.

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

Use in childhood

For impaired renal function

Contraindicated in chronic renal failure, impaired renal filtration function.

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 l.
• Theoretical osmolarity: 1132 mOsm/L.

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

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

Description of the dosage form

The solution for infusion is transparent, colorless.

pharmachologic effect

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

Inhaled mannitol (in an appropriate dosage form) is intended to improve pulmonary hygiene by correcting impaired mucociliary clearance characteristic of cystic fibrosis. Although the exact mechanism of action is unknown, it is believed that inhaled mannitol changes the viscoelastic properties of sputum, increases hydration of the periciliary fluid layer, and increases mucociliary and cough clearance.

Pharmacokinetics

With intravenous administration of mannitol, Vd corresponds to the volume of extracellular fluid. Mannitol may undergo minor metabolism in the liver to form glycogen. The excretion of mannitol is regulated by glomerular filtration without significant tubular reabsorption. T1/2 is about 100 min. Excreted by the kidneys, with intravenous administration in a dose of 100 g, 80% is determined in the urine within 3 hours. In case of renal failure, T1/2 can increase to 36 hours.

When administered by inhalation (in the appropriate dosage form), the absolute bioavailability of mannitol compared to 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 demonstrated a 24.7% deposition rate for inhaled mannitol, confirming its target organ distribution. Preclinical toxicology studies show that mannitol that enters the lungs is absorbed into the blood; in this case, Cmax in serum is achieved 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)

Brain swelling. Intracranial hypertension. Status epilepticus. 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 renal filtration capacity and other conditions requiring increased diuresis.

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

Post-transfusion complications after administration 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, as well as in patients intolerant or ineffective to dornase alfa.

Contraindications to the use of Mannitol

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

For inhaled administration: bronchial hyperreactivity to inhaled mannitol.

Mannitol Use in pregnancy and children

Adequate and strictly controlled studies in humans have not been conducted.

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

Mannitol Side Effects

With intravenous administration

Metabolism: disturbances in water and electrolyte balance (increased blood volume, dilution hyponatremia, hyperkalemia) and their manifestations (muscle weakness, cramps, dry mouth, thirst, impaired consciousness).

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

When administered by inhalation

Metabolism: often - loss of appetite.

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

On the part of the hearing organ: 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 fungus in the sputum, “swamping” syndrome 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: uncommon - arthralgia, joint stiffness, musculoskeletal pain in the chest area.

From the urinary system: infrequently - urinary incontinence.

Other: infrequently - pain in the hernial sac.

Drug interactions

With the simultaneous use of mannitol with cardiac glycosides, their toxic effect associated with hypokalemia may increase.

Mannitol dosage

Mannitol is administered intravenously or inhaled in appropriate dosage forms.

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

Patients with oliguria should first administer a test dose of mannitol (200 mg/kg) intravenously over 3-5 minutes. If after this, within 2-3 hours there is no increase in the diuresis rate 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 health care professional who has undergone appropriate training and has equipment to monitor hemoglobin oxygen saturation, perform spirometry and relieve acute bronchospasm. 5-15 minutes before inhalation of the initial dose (but after measuring the initial FEV1 and monitoring hemoglobin oxygen saturation), the patient should receive a bronchodilator. All FEV1 measurements and monitoring of hemoglobin oxygen saturation are carried out 60 seconds after inhalation.

Precautionary measures

With intravenous administration

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

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

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

When administered by inhalation

Patients with bronchial asthma should be carefully monitored for worsening asthma symptoms after inhalation of the initial dose.

Patients should be monitored for bronchial hyperresponsiveness to inhaled mannitol when assessed during the initial inhalation dose before initiating chronic use at therapeutic doses. If the patient exhibits hyperresponsiveness, inhaled mannitol should not be used. Usual precautions apply when controlling bronchial hyperresponsiveness.

With inhalation of mannitol, bronchospasm may develop even in patients who did not experience hyperreactivity to inhalation of the initial dose.

The safety and effectiveness of inhaled mannitel have not been established in patients with FEV1 less than 30% of normal.

Patients with a history of hemoptysis should be carefully monitored.

Mannitol

International nonproprietary 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

Transparent, colorless solution, odorless.

Pharmacotherapeutic group

Plasma replacement 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 determines 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 (for example, blood-brain, placental). Mannitol may undergo minor metabolism in the liver to form glycogen.

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

In patients with renal impairment, the half-life of mannitol may be prolonged to 36 hours.

Pharmacodynamics

Mannitol increases plasma osmolarity and causes fluid to move 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 high osmotic pressure in the lumen of the renal tubules (mannitol is poorly reabsorbed) and reduces water reabsorption. It acts mainly in the proximal tubules, although the effect persists to some extent in the descending loop of the nephron and in the collecting ducts. Unlike other osmotic diuretics, mannitol is capable of removing 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 mannitol is prescribed is less than water natriuresis, 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 more pronounced, the higher the concentration of the drug and the speed of its administration. If the filtration function of the renal glomeruli is impaired, the diuretic effect of mannitol solution may be absent.

Indications for use

Cerebral edema, intracranial hypertension

Acute attack of glaucoma

Oliguria in acute renal or renal-hepatic failure 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 administration of incompatible blood

Directions for use and doses

Mannitol is administered intravenously in a slow 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 ensures 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. For 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 weakened patients, a dose of 500 mg/kg is sufficient. In case of poisoning in children, an intravenous infusion of up to 2 g/kg body weight or 60 g per 1 m2 of body surface is administered.

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

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

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

In patients with oliguria, in order to determine the response to osmotic diuretics, before starting a continuous infusion, a test dose (200 mg/kg) of mannitol should be administered intravenously over 3-5 minutes. Mannitol is not effective if the diuresis rate does not increase to 50 ml/hour within 3 hours. If a response to the test dose is obtained, then the administration of mannitol solution (12.5-25 g) should be repeated after 1-2 hours to maintain the diuresis rate above 100 ml/hour.

Side effects

Often

Headache

Dry mouth

Nausea and vomiting

Dry skin

Rarely

Chest pain

Tachycardia

Skin rash

Thrombophlebitis

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

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

With rapid intravenous administration

Headache

Nausea and vomiting

Fever

Chest pain

Breathing problems

Contraindications

- hypersensitivity to the components of the drug

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

Hemorrhagic stroke, subarachnoid hemorrhage (except bleeding during craniotomy)

Pulmonary edema due to acute left ventricular failure

Decompensated cardiovascular failure

Severe dehydration

Hypokalemia, hyponatremia, hypochloremia

Post-traumatic increase in intracranial pressure with risk of hemorrhage

Drug interactions

Concomitant 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 diuretics. Simultaneous use with other diuretics enhances their effect. When used with neomycin, the risk of developing oto- and nephrotoxicity increases.

special instructions

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

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

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

Concomitant 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 when storing the drug at temperatures 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 administration - cool to body temperature 36 °C.

Use in pediatrics

The drug is prescribed to children and adolescents 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 expected benefit to the mother outweighs the possible risk to the fetus or infant.

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

The drug is used in hospital settings, where activities such as driving a car or working with equipment are not required.

Overdose

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

Treatment: stop administering 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 along with instructions for medical use in the state and Russian languages ​​in a quantity 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. Soluble in water (very easily - in hot water).

Pharmacology

pharmachologic effect- decongestant, diuretic.

Increases the osmotic pressure of plasma, promotes the transition of fluid from tissues to the vascular bed, and increases the bcc. Filtered by the kidneys without subsequent tubular reabsorption, it increases the osmotic pressure in the tubules and interferes with the reabsorption of water, 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 higher the dose, the higher the diuretic effect. Approximately 80% of the administered intravenous dose is found in the urine within 3 hours. It is not effective in cases of impaired filtration function of the kidneys, as well as in azotemia in patients with liver cirrhosis and ascites.

May undergo minor hepatic metabolism.

Use of the substance Mannitol

Brain edema, increased intracranial pressure in renal or renal-hepatic failure, status epilepticus, acute attack of glaucoma, operations with extracorporeal circulation, acute renal (with preserved renal filtration function) 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, impaired renal filtration function, congestive heart failure, hemorrhagic stroke, subarachnoid hemorrhage (except bleeding during craniotomy), severe forms of dehydration, hyponatremia, hypochloremia, hypokalemia, acute tubular necrosis.

Restrictions on use

Pregnancy, lactation period.

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

There may be an increase in the toxic effect of cardiac glycosides (hypokalemia).

Routes of administration

Precautions for the substance Mannitol

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

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

Administration of mannitol for anuria caused by organic kidney diseases 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, to dissolve which it is necessary to heat the bottle in hot water or in an autoclave, shaking occasionally. Cool to body temperature or below before use.

Interactions with other active ingredients

Trade names

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