Mannitol: instructions for use and reviews

Latin name: Mannitol

ATX code: B05BC01, B05CX04

Active substance: mannitol (mannitol)

Producer: Groteks, LLC (Russia), Medpolimer firm (Russia), Biosintez, PAO (Russia), Farmasintez-Tyumen, OOO (Russia), Medsintez plant (Russia), Biosintez, PAO (Russia)

Description and photo update: 27.08.2019

Diuretic drugs have different structures, but have one thing in common. They increase the amount of fluid removed from the body. Otherwise they are called osmotic diuretics. These medicines are used in the complex therapy of hypertension, pathologies of the cardiovascular system. In addition, their use is justified in any other disorders accompanied by swelling of organs and tissues. Among all, Mannitol is the most popular. It is about him that will be discussed in this article.

"Mannitol" - what is it?

"Mannitol" is a drug with a pronounced diuretic effect. Also, the composition significantly increases the volume of blood circulating in the body. The main indications for its use are status epilepticus, high intracranial pressure, and renal failure.

The active ingredient of the drug is the substance of the same name - mannitol. Among the auxiliary ingredients, the instruction notes sodium chloride, sodium sulfacyl, flavacridine hydrochloride. Pharmaceutical companies produce the drug in the form of a solution for intravenous injection. It goes on sale in glass bottles of different sizes.

Pharmacological properties

Instructions for use "Mannitol" characterizes as a drug with a diuretic effect. The diuretic effect is due to an increase in plasma and a decrease in water reabsorption. The use of the drug for therapeutic purposes promotes the transition of fluid from the tissues into the vessels. This is exactly what patients with high pressure in these organs expect.

The diuretic effect is dose-dependent. An increase in the volume of the drug directly proportionally affects the amount of excreted osmotically free liquid, chlorine and sodium. With azotemia in patients with cirrhosis of the liver or ascites, the use of the drug is inappropriate. Its use can provoke hyponatremia, so self-treatment is unacceptable. During therapy, the physician should constantly monitor the content of sodium / potassium in the blood serum, as well as diuresis and blood pressure.

Indications for appointment

• kidney failure;
• an attack of glaucoma;
• acute liver failure;
• elevated;
• chemical poisoning.

Also, the solution of "Mannitol" is used during surgery with extracorporeal circulation, for the prevention of hemoglobinemia.

Mode of application

The diuretic is administered intravenously by drip or jet. It is recommended to warm it up to body temperature first. The dosage regimen is determined by the doctor, taking into account the patient's condition and his disease. For prophylactic purposes, the drug is prescribed at the rate of 500 mg per kilogram of weight, for therapeutic purposes - 1.5 g per kilogram of weight. The daily dosage should not exceed 180 g.

During surgical intervention using extracorporeal circulation, the patient is injected with 20-40 g of the solution immediately before the operation. For patients with oliguria, the medicine is first slowly dripped over five minutes. The dosage regimen is determined by the doctor. If within three hours after the injection an increase in diuresis up to 45 ml / g is not observed, the drug is canceled.

Contraindications and side effects

What does the instructions for use say about contraindications? "Mannitol" is not recommended for the following pathologies:

• hemorrhagic stroke;
• dehydration of the body;
• insufficiency of the left ventricle;
• pulmonary edema;
• acute tubular necrosis;
• subarachnoid bleeding.

With extreme caution, the drug is prescribed to pregnant and lactating women. The use of the drug is permissible only under the supervision of a physician. The specialist must weigh the ratio of risk to the baby and benefit to the mother.

Information about side effects

Before starting therapy, you should read the annotation to the drug. What does the instructions for use say about side effects? Mannitol, if the allowable dosage is exceeded, can cause dehydration. Therefore, the use of the drug is permissible only under the supervision of a physician. Dyspepsia, thirst, low blood pressure, convulsions - these symptoms indicate a change in the water and electrolyte balance in the body. The drug should be stopped and consult a doctor. The specialist must adjust the treatment regimen or prescribe a synonym for the drug.

Available analogues

Considering the description of the drug "Mannitol" (what it is, how and for what purpose it is prescribed), it is important to pay attention to its analogues. Despite the good tolerability of the drug, it is not suitable for everyone. If during the treatment period the patient develops a headache and vision problems, it should be discontinued. In especially serious cases, the doctor prescribes an examination to exclude complications such as subdural bleeding.

Close in mechanism of action and pharmacological properties of "Mannitol" is a lyophilisate for the preparation of an infusion solution "Urea". Among other analogues of the drug, Mannitol deserved positive reviews. This is a drug used to increase the volume of urine. Pharmaceutical companies produce it in the form of a solution for injection. "Mannitol" and "Mannitol" are identical drugs. Their use is justified with increased intracranial pressure, cerebral edema, glaucoma and other disorders. The only difference is the side effects. The intake of "Mannitol" is sometimes accompanied by a violation of the water-electrolyte balance and the appearance of symptoms characteristic of this condition. Exceeding the recommended dosage of Mannitol during treatment can lead to the development of thrombophlebitis and tachycardia. From a medical point of view, Mannitol is safer.

Price, drug reviews

The opinions of consumers about the drug are met with both positive and negative connotations. An important advantage of a diuretic is its low price. For example, for a bottle (200 ml) you will have to pay only 100 rubles. Reviews of patients confirm that the drug fully performs the functions assigned to it. Side effects are extremely rare.

Negative reviews are most often due to the way the drug "Mannitol" is used. Pills are the preferred treatment option for many. This diuretic is produced only in the form of a solution for injection. Therefore, patients are forced to refuse it, replacing it with analogues.

In conclusion, it should be noted that Mannitol is an effective osmotic diuretic. Still, it's a drug. Therefore, before using it, you must read the instructions. Be healthy!

Formula: C6H14O6, chemical name: 1,2,3,4,5,6-hexanehexol; D-mannitol; D-mannitol.
Pharmacological group: organotropic agents / agents that regulate the function of the organs of the genitourinary system and reproduction / diuretics; organotropic agents / respiratory agents / secretolytics and stimulants of the motor function of the respiratory tract.
Pharmachologic effect: diuretic, decongestant, mucolytic, expectorant.

Pharmacological properties

Mannitol is an osmotic diuretic. Mannitol is a lyophilized mass of light yellow color. Mannitol is soluble in water, very easily soluble in hot water. The use of mannitol leads to the retention of water in the renal tubules and an increase in urine volume due to an increase in the osmotic pressure of blood serum and filtration in the glomeruli of the kidneys without further reabsorption in the renal tubules (mannitol undergoes little tubular reabsorption). Basically, mannitol has an effect in the proximal tubule, but the effect remains to a small extent in the descending loop of the nephron, as well as in the collecting ducts. Mannitol does not penetrate tissue barriers (for example, the blood-brain barrier) and cell membranes, and does not increase the concentration of residual nitrogen in the blood serum. Mannitol causes the movement of fluid from the tissues (in particular, the brain, the eyeball) into the vascular bed, increasing the osmolarity of the blood serum. Diuresis from the use of mannitol is accompanied by a moderate increase in sodium excretion without a significant effect on potassium excretion. Mannitol 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. The diuretic effect of mannitol is the higher, the greater its concentration (dose). Mannitol is ineffective for impaired filtration function of the kidneys, as well as for azotemia in patients with ascites and cirrhosis of the liver. Mannitol causes an increase in circulating blood volume.
Spray-dried mannitol can be administered by inhalation using a special inhalation device. Mannitol inhalation is intended to improve pulmonary hygiene by correcting the impaired mucociliary clearance that is characteristic of cystic fibrosis. The exact mechanism of action of mannitol by inhalation is not known, but inhaled mannitol is thought to alter the viscoelastic properties of sputum, increase hydration of the periciliary fluid layer, and increase cough and mucociliary clearance.
The volume of distribution of mannitol when administered intravenously corresponds to the volume of extracellular fluid, since the drug is distributed only in the extracellular sector. Mannitol when administered intravenously does not penetrate cell membranes and tissue barriers (for example, placental and blood-brain barriers). Mannitol, when administered intravenously, may be slightly metabolized in the liver with the formation of glycogen and carbon dioxide. The half-life of mannitol after intravenous administration is approximately 100 minutes. Mannitol when administered intravenously is excreted by the kidneys. Excretion of mannitol is regulated by glomerular filtration, with no significant involvement of secretion and reabsorption in the renal tubules. With intravenous administration of 100 g of mannitol, 80% of the drug is determined in the urine within three hours. In patients with renal insufficiency, the half-life of mannitol when administered intravenously may increase up to 36 hours.
In a study in 18 healthy adult male volunteers, the absolute bioavailability of mannitol by inhalation versus intravenous administration was 0.44 to 0.74. The extent and rate of absorption of mannitol by inhalation was very similar to the extent and rate of absorption after oral administration. The maximum concentration of mannitol in the blood serum after the inhalation route of administration was reached after 1-2 hours. In a study in 9 patients with cystic fibrosis (3 adolescents, 6 adults) given inhaled mannitol 400 mg as a single dose (Day 1), then twice daily for one week (Days 2 to 7), mannitol PK parameters were similar for adolescents and adults, except for a longer average apparent terminal half-life in adolescents (on the first day - 7.29 hours, on the seventh day - 6.52 hours) when compared with adults (on the first day - 6.10 hours, in seventh day - 5.42 hours). Overall, comparison of the area under the pharmacokinetic concentration-time curve of inhaled mannitol between day 1 and day 7 showed that the pharmacokinetics were independent of time, showing linearity at the dose level administered in this study. Mannitol is metabolized by the intestinal microflora when taken orally, but after intravenous administration of any significant metabolism is not observed. A small percentage of systemically absorbed mannitol undergoes hepatic metabolism to form carbon dioxide and glycogen. Studies that have been conducted on mice, rats, and humans have shown that mannitol does not have toxic metabolites. The metabolism of mannitol by inhalation has not been studied in pharmacokinetic studies. Pulmonary sedimentation studies showed a 24.7% sedimentation of inhaled mannitol, indicating distribution in the target organ. Preclinical toxicological studies have shown that mannitol entering the lungs is absorbed into the blood, while the maximum plasma concentration of the drug is reached within one hour. In pharmacokinetic studies of mannitol in 18 healthy adult volunteers, after intravenous administration of 500 mg of mannitol, its volume of distribution ranged from 20.5 to 48.1 liters. There is no evidence that mannitol accumulates in the body, so the distribution of inhaled mannitol has not been evaluated in pharmacokinetic studies. The total volume of mannitol that was excreted in the urine during the day was close to the volume that was excreted in the urine after inhalation (55%) and oral (54%) mannitol. When administered intravenously, mannitol is excreted almost unchanged by glomerular filtration. With urine during the day, 87% of the dose of mannitol is excreted. The mean terminal half-life of mannitol in adults was approximately 4 to 5 hours in plasma and approximately 3.6 hours in urine.

Indications

For intravenous administration: intracranial hypertension (with hepatic and/or renal insufficiency); swelling of the brain; epileptic status; acute attack of glaucoma; intraocular hypertension (with the ineffectiveness of other drugs that reduce intraocular pressure); acute liver failure; acute liver failure in patients with preserved filtration function of the kidneys (as part of combined treatment); other conditions that require increased diuresis; oliguria in acute renal failure; to determine the rate of glomerular filtration in acute oliguria; post-transfusion complications after the introduction of incompatible blood; forced diuresis in case of poisoning with salicylates, barbiturates, lithium preparations, bromides, other drugs, medicines, chemical and toxic substances; prevention of hemolysis and hemoglobinemia when performing surgical procedures such as shunting on the cardiopulmonary system or during transurethral resection of the prostate, as well as during surgical interventions using extracorporeal circulation to prevent renal ischemia and associated acute renal failure.
For inhalation use: cystic fibrosis in patients over 6 years of age in addition to the use of dornase alfa, and in patients who are intolerant to dornase alfa or have not responded positively to its use.

Method of administration of mannitol and dosage

Mannitol is administered intravenously (slow jet or drip), used by inhalation.
The dose of intravenously administered mannitol depends on the weight, age, condition of the patient and concomitant treatment. Before intravenous administration, the drug must be heated (possibly in a water bath) to 37 degrees Celsius.
Preventive intravenous dose of mannitol is 0.5 g/kg of body weight, therapeutic - 1.0 - 1.5 g/kg; The daily dose of mannitol should not exceed 140-180 g.
In acute renal failure, the daily dose of mannitol for adults is 50-180 g of mannitol. In many cases, an adequate therapeutic effect is achieved with a dose of 50 to 100 g per day. The maximum rate of intravenous administration, during the first five minutes, can be 200 mg / kg, then the rate of intravenous administration of the drug should be adjusted to maintain urine output at 30 - 50 ml / h. If necessary, repeated intravenous administration of mannitol at the same dose is possible after 4-8 hours with a maximum daily dose of 180 g.
Patients with suspected renal failure or oliguria should receive a test dose of mannitol (approximately 200 mg/kg body weight) intravenously over 3 to 5 minutes. The response to the test dose is considered sufficient if the urine output in the next 2 to 3 hours is 30 to 50 ml/h. In the absence of an adequate response, repeated intravenous administration of the test dose is possible, but if the effect is not achieved even with repeated intravenous administration, then mannitol therapy should be discontinued.
With cerebral edema, increased intracranial pressure, the intravenous dose of mannitol is from 1.5 to 2 g / kg of body weight, which is administered over 30 - 60 minutes; also, the clinical effect was achieved when using a dose of the drug 0.25 - 0.5 g / kg, which was administered no more than every 6 - 8 hours.
To reduce elevated intraocular pressure, the dose of mannitol is 1.5 - 2 g / kg of body weight, which is administered over 0.5 - 1 hour. When preparing a patient for an ophthalmic operation, in order to achieve the maximum effect, mannitol is administered 1–1.5 hours before the operation at a dose of 1.5–2 g/kg of body weight.
For the prevention of intraoperative and postoperative ischemia and associated acute renal failure, mannitol is administered intravenously at a dose of 50-100 g during or immediately after surgery.
To ensure forced diuresis in case of post-infusion complications, poisoning with salicylates, barbiturates, lithium preparations, bromides, other drugs, medicines, chemical and toxic substances, the dose of mannitol should be adjusted to maintain diuresis at the level of 100 ml / hour. The initial loading dose may be approximately 25 g.
When preparing a patient for surgery, mannitol should be administered intravenously 1 to 1.5 hours before surgery to achieve maximum effect. When carrying out operations with cardiopulmonary bypass, immediately before the start of perfusion, 20-40 g of mannitol are injected into the apparatus.
Before starting therapy with inhaled mannitol, all patients should be assessed for increased bronchial reactivity to inhaled mannitol at the initial dose. Patients in whom spirometry is contraindicated and who therefore cannot be assessed for increased bronchial reactivity at the initial dose of inhaled mannitol should not receive the drug. The patient should use the initial dose of mannitol for inhalation use (400 mg) under the supervision and supervision of an experienced physician or other healthcare professional who has been appropriately trained and equipped to monitor hemoglobin oxygen saturation, perform spirometry and relieve an acute attack of bronchospasm. The patient should receive a bronchodilator 5 to 15 minutes prior to the initial dose of mannitol for inhalation use (but after measuring the initial forced expiratory volume in the first second and oxygen saturation of hemoglobin). All measurements of forced expiratory volume in the first second and monitoring of hemoglobin oxygen saturation are taken one minute after inhalation of a dose of mannitol for inhalation use. Evaluation when using the initial dose of mannitol for inhalation use is carried out in stages. At the first stage, the initial forced expiratory volume in the first second and the saturation of hemoglobin with oxygen of the patient are measured before taking the initial dose of mannitol for inhalation use. At the second stage, the patient inhales 40 mg of the drug, after which hemoglobin saturation with oxygen is monitored. At the third stage, the patient inhales 80 mg of the drug, after which hemoglobin saturation with oxygen is monitored. At the fourth stage, the patient inhales 120 mg of the drug, after which the forced expiratory volume is measured in the first second and hemoglobin oxygen saturation is monitored. At the fifth stage, the patient inhales 160 mg of the drug, after which the forced expiratory volume is measured in the first second and hemoglobin oxygen saturation is monitored. At the sixth stage, the forced expiratory volume is measured in the first second of the patient 15 minutes after taking the initial dose.
During the assessment when using the initial dose of the drug, it is important to educate the patient on the correct technique for using the inhaler. Each mannitol inhalation capsule is inserted into the device separately. The contents of the capsule are inhaled using an inhaler in one or two breaths. After inhalation, the empty capsule is discarded and the next capsule is inserted into the inhaler.
A patient diagnosed with increased bronchial reactivity to inhaled mannitol should not receive therapeutic doses if any of the following conditions occur: a 10 percent or greater drop in hemoglobin oxygen saturation at any point during the assessment; a drop in forced expiratory volume in the first second by 20% or more with a total dose of 240 mg; a drop in forced expiratory volume in the first second of 20% or more (when compared to baseline) at the end of the assessment and no recovery to less than 20% of baseline within 15 minutes.
A therapeutic dose regimen for inhaled mannitol should not be initiated prior to evaluation at the initial dose.
The recommended dosage of mannitol for inhalation use is 400 mg twice a day in the morning and evening 2 to 3 hours before bedtime.
When using mannitol for inhalation use, the inhaler should be replaced after one week of use. If the inhaler requires cleaning, then first make sure that it does not contain a capsule, then rinse it in warm water and allow it to dry completely in the air before the next use.
The patient should receive a bronchodilator drug 5 to 15 minutes before using mannitol for inhalation use. Recommended course of action: administer bronchodilator drug, administer inhaled mannitol, physiotherapy or exercise, then administer dornase alfa (if used).
To eliminate the phase of increasing the volume of circulating blood, including in heart failure, it is necessary to combine the administration of mannitol together with "loop" diuretics.
Due to the risk of developing pulmonary edema in left ventricular heart failure, it is necessary to combine the use of mannitol with fast-acting "loop" diuretics.
During the use of mannitol, it is necessary to monitor the indicators of central hemodynamics, blood pressure, diuresis, electrolyte levels in blood plasma (chlorine, potassium, sodium).
If headache, dizziness, vomiting, visual disturbances occur during the administration of mannitol, it is necessary to stop the administration of the drug and exclude the development of complications such as subarachnoid and subdural bleeding.
During the use of mannitol, in case of signs of dehydration, the introduction of fluids into the body is necessary.
It is possible to use mannitol in heart failure (but only in conjunction with "loop" diuretics) and in hypertensive crisis with encephalopathy.
Repeated administration of mannitol should be carried out under the control of indicators of the water-electrolyte state of the blood serum.
The introduction of mannitol in anuria, which is caused by organic kidney disease, can lead to the development of pulmonary edema.
Due to the risk of pseudo-agglutination, mannitol should not be co-administered with blood transfusions through the same infusion set.
When co-administering mannitol with other medicinal products, to control pharmaceutical compatibility, it is necessary to check their solubility and stability in a solution of mannitol.
There may be cases of crystallization of the drug when stored at temperatures below 20 degrees Celsius. If crystals precipitate, the drug must be heated in a water bath at a temperature of 50 to 70 degrees Celsius until the crystals disappear. The drug is suitable for use if the solution remains clear and the crystals do not fall out again when it is cooled to a temperature of 36 degrees Celsius.
Patients with asthma should be closely monitored for worsening of asthma symptoms and signs following an initial dose of inhaled mannitol. Patients should be instructed to tell their healthcare provider about worsening symptoms and signs of asthma.
When assessed during an initial dose of inhaled mannitol, patients should be monitored for increased bronchial reactivity to inhaled mannitol prior to initiation of therapeutic doses of the medicinal product. If the patient exhibits increased bronchial reactivity, then mannitol for inhalation use in therapeutic doses should not be prescribed. The usual precautions are used in the control of increased bronchial reactivity. Mannitol for inhalation use can cause bronchospasm requiring therapy even in patients who did not show increased bronchial reactivity to the initial dose of inhaled mannitol.
The safety and efficacy of inhaled mannitol has not yet been demonstrated in patients with a forced expiratory volume in the first second of less than 30% predicted.
Formal studies of mannitol for inhaled use in patients with impaired renal and/or hepatic function have not been conducted. There are no specific dose recommendations for these patient groups.
Patients with a history of significant episodes of hemoptysis (greater than 60 ml) during the use of inhaled mannitol should be carefully monitored. Formal studies of inhaled mannitol in patients with episodes of hemoptysis within the previous six months have not been conducted.
A study on the effect of inhaled mannitol on fertility has not been conducted.
Mannitol for inhalation is not recommended for use in children under 6 years of age due to insufficient data on efficacy and safety.
In the phase 2 and 3 studies, the mean age of patients was approximately 20 years. The oldest patient in the Phase 2 study was 56 years of age. There are no specific dose recommendations for the use of inhaled mannitol in the elderly.
Adverse reactions of mannitol for inhalation use were evaluated in the DPM-CF-301 study, in which participants took study drug from 1 to 218 days with a mean duration of exposure of 135.5 (70.09) days. The duration of drug exposure in the pediatric and adolescent subgroups was 136.2 (69.24) and 145.7 (64.58) days, respectively. A total of 822 adverse reactions were reported in 154 (87%) patients in the mannitol group and 541 adverse reactions in 109 (92.4%) patients in the control group. Treatment-related adverse reactions were reported by 72 (40.7%) patients who received mannitol and 26 (22%) patients in the control group. Hemoptysis, pharyngolaryngeal pain, cough, toothache, diarrhea, and vomiting were more commonly reported in patients treated with mannitol. In this study, 28 (15.8%) patients who received mannitol and 10 (8.5%) patients in the control group withdrew from the study due to adverse reactions. The most frequently reported adverse reactions that led to the withdrawal of patients from the study were hemoptysis, deterioration, cough.
Cough was the most commonly observed adverse reaction associated with inhaled mannitol during initial dose evaluation. Bronchospasm is the most important side effect associated with inhaled mannitol in the evaluation using the initial dose of the drug. It is expected that the majority of patients who take mannitol for inhalation use in the therapeutic dose regimen may develop adverse reactions. The most commonly observed adverse reaction associated with the use of inhaled mannitol in the therapeutic dose regimen is cough. Clinically, the most important adverse reaction associated with the use of inhaled mannitol in the therapeutic dose regimen is hemoptysis.
Due to hemoptysis, 5 study participants in the mannitol group withdrew from the study. None of the study participants in the control group withdrew from the study due to hemoptysis. Hemoptysis was more common as a serious side effect in the mannitol group (6 (3.4%) patients in the study compared to 2 (1.7%) patients in the control group). However, the proportion of patients who reported hemoptysis as a side effect or hemoptysis during an exacerbation of the disease was 15.8% in the mannitol group and 15.3% in the control group.
Cough is an extremely common side effect when using inhaled mannitol. Although a wet cough has been reported as a common side effect, it is helpful in clearing phlegm.
There was no evidence of carcinogenicity when studied in rats and mice for two years with the introduction of mannitol (5% or less) in food. Carcinogenicity studies have not been conducted with inhaled mannitol. No clastogenic or mutagenic effects were found in the analysis of mannitol in the standard genetic toxicity test series. The effect of inhaled mannitol on hematological parameters, biochemical indicator of the functional state of the liver, parameters of blood serum urea and electrolyte levels was not observed.
There are no data on the effect of mannitol for intravenous administration on the ability to perform potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions (including driving vehicles, mechanisms), since the drug is used exclusively in a hospital setting. When using mannitol for inhalation, there was no negative effect on the ability to perform potentially hazardous activities that require increased concentration and speed of psychomotor reactions. At the time of the use of mannitol, it is necessary to refuse to perform potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions (including driving vehicles, mechanisms).

Contraindications for use

For intravenous administration: hypersensitivity (including to the auxiliary components of the drug); left ventricular heart failure (especially left ventricular heart failure, accompanied by pulmonary edema); pulmonary edema; anuria against the background of acute necrosis of the tubules of the kidneys in severe lesions; acute tubular necrosis; organic kidney damage; violation of the filtration function of the kidneys; subarachnoid hemorrhage (with the exception of bleeding during craniotomy); hemorrhagic stroke; violation of the permeability of the blood-brain barrier; hyponatremia; severe dehydration; hypokalemia; hypochloremia; chronic heart failure III - IV functional class according to the classification of the New York Association of Cardiology; breastfeeding period; age up to 18 years (safety and effectiveness of use have not been established).
For inhalation use: hypersensitivity (including to the auxiliary components of the drug); bronchial hyperreactivity to inhaled mannitol; breastfeeding period; age up to 6 years (safety and effectiveness of use have not been established).

Application restrictions

For intravenous administration: severe violations of the functional state of the kidneys; chronic heart failure; hypovolemia; elderly age; pregnancy.
For inhalation use: asthma; impaired lung function with a forced expiratory volume in the first second of less than 30%; pregnancy.

Use during pregnancy and lactation

Strictly controlled and adequate studies of the safety of the use of mannitol in women during pregnancy and lactation have not been conducted. There are no clinical data on the effect of mannitol on pregnancy. Animal reproduction studies with inhaled mannitol have not been conducted. However, studies with oral administration of mannitol indicate no teratogenic effects in rats and mice at daily doses up to 1.6 g/kg and in hamsters at daily doses of 1.2 g/kg. Since the consequences of a possible hyperreactivity reaction on the mother and / or fetus are unknown, special care should be taken when prescribing mannitol to women during pregnancy. The use of mannitol during pregnancy is possible on prescription in cases where the expected benefit of treatment for the mother outweighs the possible risk to the fetus. There are no data on the excretion of mannitol in the breast milk of women. Excretion of mannitol into milk in animals has not been studied. If it is necessary to use mannitol during lactation, breastfeeding should be discontinued (it is not known whether mannitol is excreted in breast milk). The decision to continue/discontinue breastfeeding or continue/discontinue inhalation mannitol therapy should be made taking into account the benefits of breastfeeding for the baby and the benefits of therapy for the mother.

side effects of mannitol

Interaction of mannitol with other substances

With the combined use of mannitol and cardiac glycosides, it is possible to increase the toxic effect of cardiac glycosides against the background of hypokalemia.
With the combined use of mannitol and other diuretic drugs, the diuretic effect of the latter is enhanced.
With the combined use of mannitol and neomycin (as well as all other aminoglycosides), the risk of developing ototoxicity and nephrotoxicity increases.
With the combined use of mannitol (in high doses) and anticancer drugs (lomustine (CCNU), methotrexate, cisplatin), a short-term (no more than 5-7 minutes) increase in the permeability of the blood-brain barrier for anticancer drugs is possible.
Co-administration of mannitol and lithium medicinal products increases the excretion of lithium by the kidneys, so dose adjustment may be required.
With the combined use of mannitol and atracurium besilate (as well as other n-anticholinergics (muscle relaxants)) may increase neuromuscular blockade.
With the combined use of mannitol and cyclosporine, the risk of developing nephrotoxicity increases, so regular monitoring of the functional state of the kidneys is necessary.
With the combined use of mannitol and oral anticoagulants, the effectiveness of the latter may decrease due to an increase in the concentration of blood clotting factors secondary to dehydration.
Mannitol is pharmaceutically incompatible with cefepime, filgrastim, imipenem/cilastatin solutions. When sodium chloride and potassium chloride are added to a mannitol solution, precipitation of mannitol may occur. When co-administering mannitol with other drugs, to control pharmaceutical compatibility, it is necessary to test for their solubility and stability in a solution of mannitol.
Mannitol for inhalation has been used safely and effectively in clinical trials with standard CF drugs such as antibiotics, mucolytics, bronchodilators, vitamins, pancreatic enzymes, systemic and inhaled glucocorticosteroids, and analgesics. However, formal interaction studies of mannitol for inhalation use with other medicinal products have not been conducted.

Overdose

Symptoms. With an overdose of mannitol when administered intravenously, the side effects of the drug increase. With rapid intravenous administration of mannitol, especially with reduced glomerular filtration, an increase in intracranial pressure, an increase in intraocular pressure, and hypervolemia may develop. Cases of overdose of mannitol during inhalation use in clinical studies were not observed. In susceptible patients, an overdose of inhaled mannitol may cause bronchospasm, excessive coughing, which should be treated with a beta2-adrenergic agonist and, if necessary, oxygen. In case of an overdose of mannitol, symptomatic and supportive treatment is necessary.

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 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 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

Mannitol - an organic compound, a polyhydric (sugar) alcohol with six carbon atoms - a saturated aliphatic hexaatomic alcohol with the formula CH 2 OH-(CHOH) 4 -CH 2 OH or C 6 H 14 O 6, or C 6 H 8 (OH) 6 . Synonym - mannitol.

It was first isolated from manna, a lichen growing in the southern steppes. Manna (referred to in the Bible as "manna from heaven") is also called the sweet dried juice of tamarisk trees and shrubs. Later, this substance was found in other plants, for example, manno ash and round-leaved ash, asparagus, beets, onions, lilacs, camel thorns, figs, celery, jasmine, cauliflower, olives, mushrooms, seaweed (kelp).

Industrially, mannitol is obtained by processing natural raw materials, most often sea brown algae (seaweed), or by reducing fructose. There are ways to obtain mannitol by chemical synthesis.

Properties

The substance is a crystalline non-hygroscopic powder, colorless and odorless, sweetish in taste. It is readily soluble in water, aniline, alcohol, insoluble in ethers, hydrocarbons.

Possesses weak acidic and basic properties. Forms esters by reacting with acids, such as the hexanitrogen ester nitromannite, which explodes on impact. With careful oxidation, it passes into glucose. Forms anhydrides.

Mannitol has the same chemical formula as dulcite and sorbitol. They differ as optical stereoisomers. Mannitol has an axis of symmetry, occurs in the form of d- and l-isomers that rotate the plane of polarization in different directions, as well as a mixture of these modifications, which does not have optical activity.

It is non-toxic, does not cause allergies, does not contribute to the development of caries, even children and pregnant women can eat it. The EU Commission has confirmed that at the recommended doses, mannitol can be used as a long-term sweetener, as it raises blood glucose levels much less than sucrose. In addition, it is almost half as high in calories as sorbitol and xylitol.

Application of mannitol

In medicine, it is used as a mild laxative, for the preparation saline, diuretic, choleretic agents; for the removal of toxins, barbiturates, salicylates, bromides, lithium and other substances in case of poisoning. It is used to diagnose kidney function.
- In pharmaceuticals: for the production of drugs to lower intracranial and intraocular pressure; drugs for intensive care at the time of the surgical intervention; drugs used in renal and hepatic insufficiency; to relieve convulsive syndrome; for the treatment of the gastrointestinal tract. Popular as a tablet filler with a pleasant fresh and sweet taste, especially lozenges.
- Food additive E421, viscosity stabilizer, confectionery baking powder - in the food industry. It is added to dairy and some other products so that lumps do not form in them and they do not cake. Due to its low hygroscopicity, mannitol is used to make strong icings for sweets, ice cream and chewing gums. E421 enhances the cooling effect of mints and chewing gums. It is used as a sweetener for products for diabetics, for dietary nutrition.
- For the production of drying oils, resins, varnishes, paints, surface-active substances (surfactants); as a raw material for complex organic syntheses in the chemical industry.
- In analytical chemistry, a mannitol solution is used for the titrimetric detection of boron and germanium.
- For the production of cosmetic and perfumery products.
- In microbiology for the preparation of culture media.
- To create a background in electrochemical methods of substance analysis (in polarography).
- As an indicator for the control of technological processes in metallurgy, textile, chemical, food industries and agriculture.

In the store of chemicals and equipment "PrimeChemicalsGroup" you can buy mannitol with delivery, at a good price. Discounts are provided to wholesale buyers.