Bupivacaine

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Bupivacaine: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Bupivacaine

ATX code: N01BB01

Active ingredient: bupivacaine (Bupivacaine)

Manufacturer: Claris Lifesigns Ltd. (Claris Lifesciences, Ltd.) (India); Velpharm LLC (Russia); Synthesis JSC (Russia); Ozone LLC (Russia); Grotex LLC (Russia)

Description and photo updated: 2019-27-08

Prices in pharmacies: from 511 rubles.

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Bupivacaine is a long-acting local anesthetic.

Release form and composition

Dosage form of release - solution for injection: transparent, colorless (in ampoules or vials of 4, 10, 20 ml, in a cardboard box of 5 or 10 ampoules or vials, or in blisters or cardboard trays of 5 ampoules or vials, in a cardboard pack of 1 or 2 packs or trays; each pack also contains instructions for the use of Bupivacaine).

Composition of 1 ml solution:

active substance: bupivacaine hydrochloride monohydrate - 5 mg;
auxiliary components: sodium chloride - 8 mg, 0.1 M hydrochloric acid solution or 0.1 M sodium hydroxide solution - up to pH 4.0–6.5, water for injection - up to 1 ml.

Pharmacological properties

Pharmacodynamics

Bupivacaine is a long-acting amide-type local anesthetic, four times more effective than lidocaine. Being a weak lipophilic base, it penetrates into the nerve through the lipid sheath, after which (due to the transition to the cationic form due to a lower pH value) it inhibits voltage-dependent sodium channels, thereby reversibly blocking the conduction of nerve fibers. Also, bupivacaine has hypotensive activity and decreases heart rate (heart rate).

Due to intercostal block, postoperative analgesia can be maintained from 7 to 14 hours.

A single epidural administration of Bupivacaine at a concentration of 5 mg / ml provides a clinically significant effect within 2–5 hours, and peripheral nerve block can last up to 12 hours.

In comparison with cerebrospinal fluid, bupivacaine is a weak hyperbaric solution at 20 ° C, at 37 ° C it exhibits the properties of a weak hypobaric solution. Since the distribution in the subarachnoid space of the solution is affected by gravity, it can be considered isobaric.

At a dose of 2.5 mg / ml, the effect of bupivacaine on motor nerves is reduced.

Pharmacokinetics

The pKa index (pH at which 50% of the molecules of the substance are ionized in the solution) of bupivacaine is 8.2; the coefficient of its separation (distribution) at T = 25 ° C in an n-octanol / phosphate buffer solution with a pH of 7.4 - 346.

Bupivacaine is completely absorbed from the epidural space into the blood; from the subarachnoid space it is absorbed in small amounts and slowly. The absorption of the substance is two-phase, the half-lives (T _1/2) for the two phases are 7 and 360 minutes, respectively. Its slow elimination is due to the phase of gradual absorption of the substance in the epidural space, due to a significant excess of the T _1/2 value after epidural injection.

The indicator of the total plasma clearance of bupivacaine is 0.58 l / min; in an equilibrium state Vd (volume of distribution) - 73 l; final T _1/2 ~ 2.7 h; the intermediate level of hepatic extraction after administration is ~ 0.38. Bupivacaine binds to plasma proteins by 96%, mainly with α1-acid glycoproteins. Its clearance is almost entirely determined by metabolism in the liver and depends more on the activity of the hepatic enzyme systems than on liver perfusion. The resulting metabolites are pharmacologically less active than the parent substance.

The maximum plasma concentration (Cmax) depends on the dose and route of administration of Bupivacaine, as well as on vascularization in the area of administration.

The pharmacokinetics of bupivacaine in children from 1 to 7 years of age is similar to that in adult patients.

Bupivacaine crosses the placental barrier and is secreted during lactation. The degree of binding to plasma proteins in the fetus is lower than in the maternal, while the level of the unbound fraction in the fetus and the mother is equivalent.

Bupivacaine is metabolized mainly in the liver to 4-hydroxy-bupivacaine by aromatic hydroxylation and to 2,6-pipecoloxylidine (PPK) by N-dealkylation. Both reactions involve the cytochrome CYP3A4 isoenzyme.

After administration for 24 hours, about 1% of bupivacaine is excreted unchanged by the kidneys, and about 5% as PPK. In relation to the administered dose, the plasma concentration of PPK and 4-hydroxy-bupivacaine during administration and after prolonged administration is low.

With liver disease, especially in patients with severe hepatic impairment, the risk of toxic reactions increases with the use of local amide-type anesthetics.

In elderly patients, the maximum analgesic / anesthetic effect of Bupivacaine occurs faster than in younger patients. In addition, in old age, there is a higher maximum plasma level of bupivacaine, and their total plasma clearance is reduced.

Indications for use

acute pain in patients from 1 year old;
surgical anesthesia in patients over 12 years old;
infiltration anesthesia in cases where a long-term anesthetic effect is required, for example, to reduce the severity of postoperative pain;
long-lasting conduction anesthesia or epidural anesthesia in patients for whom the addition of epinephrine is contraindicated, as well as in cases where significant muscle relaxation is undesirable;
anesthesia in obstetrics;
spinal anesthesia during surgical operations on the lower extremities, including operations on the hip joint lasting 3-4 hours, which do not require a pronounced motor block - intrathecal administration.

Contraindications

Absolute:

arterial hypotension in severe course (hypovolemic / cardiogenic shock);
intravenous regional anesthesia (Beer blockade), since in case of accidental penetration of Bupivacaine into the bloodstream, the development of systemic toxic reactions in the acute course can be observed;
paracervical blockade in obstetrics;
age: with surgical anesthesia - up to 12 years; for all indications for use, except for intrathecal anesthesia (in this case, Bupivacaine can be used from birth) - up to 1 year;
individual intolerance to the components of the drug, as well as other local anesthetics of the amide type.

Additional contraindications for epidural / intrathecal anesthesia:

diseases of the central nervous system, including intracranial hemorrhage, poliomyelitis, meningitis, tumors;
spinal stenosis, active diseases / injuries of the spine, including tumors, spondylitis, tuberculosis, fractures;
purulent skin infections at or near the site of the lumbar puncture;
sepsis, subacute combined degeneration of the spinal cord associated with pernicious anemia and spinal / brain tumors;
hypovolemic / cardiogenic shock;
active anticoagulant therapy or blood clotting disorders.

Relative (the appointment of Bupivacaine requires caution in the presence of the following diseases / conditions):

decreased hepatic blood flow (for example, against the background of chronic heart failure, liver disease);
cardiovascular failure (due to the likelihood of progression);
heart block;
inflammatory diseases or infection of the injection site (during infiltration anesthesia);
renal failure;
cholinesterase deficiency;
combined use with local anesthetics or drugs with a similar structure, antiarrhythmic drugs (including beta-blockers);
general serious condition;
III trimester of pregnancy;
age 1-12 years and from 65 years.

Bupivacaine, instructions for use: method and dosage

The use of Bupivacaine is possible only by a physician with experience in local anesthesia, or under his supervision. In order to achieve the required degree of anesthesia, the lowest possible dose should be administered.

Intravascular administration of the solution is unacceptable. Before / during the use of Bupivacaine, it is recommended to conduct an aspiration test. The drug should be administered slowly, fractionally, or at a rate of 25-50 mg / min, while maintaining continuous verbal contact with the patient and monitoring the heart rate. During epidural administration, a dose of 3 to 5 ml of Bupivacaine in combination with epinephrine must be administered. Accidental intravascular injection can lead to a short-term increase in heart rate, intrathecal - spinal block. With the development of toxic signs, the administration of the solution should be stopped immediately.

Approximate dose range (can be adjusted depending on the patient's condition and the depth of anesthesia):

infiltration anesthesia: at a concentration of 2.5 mg / ml - 5-60 ml; at a concentration of 5 mg / ml - 5–30 ml;
therapeutic / diagnostic blockade: at a concentration of 2.5 mg / ml - 1–40 ml, for example, in cases of blockade of the trigeminal nerve –1–5 ml, cervicothoracic node of the sympathetic trunk - 10–20 ml;
intercostal block: at a concentration of 5 mg / ml - 2-3 ml per nerve, maximum - 10 nerves;
large blockade (eg, brachial / sacral plexus block, epidural block): at a concentration of 5 mg / ml - 15-30 ml;
anesthesia in obstetrics (for example, caudal / epidural anesthesia during vaginal delivery): at a concentration of 2.5 mg / ml - 6-10 ml; at a concentration of 5 mg / ml - 6-10 ml. Re-introduction of Bupivacaine in the initial dose is allowed every 2–3 hours;
epidural anesthesia for caesarean section: at a concentration of 5 mg / ml - 15-30 ml;
epidural analgesia in the form of intermittent bolus injection: the initial dose is 20 ml at a concentration of 2.5 mg / ml, then the drug is administered every 4-6 hours (depending on the patient's age and the number of damaged segments) in 6-16 ml at the same concentration.

The recommended regimen for using Bupivacaine for epidural analgesia in the form of a continuous infusion, for example, for postoperative pain (type of blockade: the volume of the bolus / infusion solution at a concentration of 2.5 mg / ml; bolus doses are indicated in cases where the solution was bolus during the previous hour was not introduced):

chest level: 5-10 ml / 2.5-5 ml / h;
lumbar level: 5-10 ml / 5-7.5 ml / h;
natural childbirth: 6-10 ml / 2-5 ml / h.

During surgical interventions, additional administration of the drug is possible.

With the combined use of narcotic analgesics, the dose of Bupivacaine is reduced.

With prolonged administration of the drug, it is necessary to regularly monitor the following parameters: blood pressure, heart rate and other signs of potential toxicity (in cases of toxic effects, the administration of the Bupivacaine solution is immediately stopped).

The recommended maximum single dose is 2 mg / kg body weight, for adults, on average, 150 mg for 4 hours (equivalent to 60 ml at a concentration of 2.5 mg / ml or 30 ml at a concentration of 5 mg / ml).

The maximum daily dose is 400 mg (you need to take into account the patient's age, physique and other significant conditions).

In children 1–12 years of age, regional anesthesia should be performed by a physician with experience working with children and knowledge of the appropriate injection technique.

The doses given below are indicative and may vary depending on the individual characteristics of the patients. Typically, high-birth-weight children need to taper the dose based on the ideal weight.

It is recommended to use the minimum dose necessary to achieve sufficient anesthesia.

For caudal, lumbar and thoracic epidural anesthesia, a solution at a concentration of 2.5 mg / ml with a volume of 0.6–0.8 ml / kg (dose - 1.5–2 mg / kg) is used. The drug begins to act in 20-30 minutes, the duration of anesthesia is from 2 to 6 hours. With thoracic epidural anesthesia, bupivacaine is given in increasing doses until the desired level of pain relief is achieved.

For regional blockade (for example, blockade and infiltration of small nerves) and blockade of peripheral nerves (for example, blockade of the ilio-inguinal / ilio-hypogastric nerves), Bupivacaine is prescribed at a dose of 0.5-2 mg / kg at a concentration of 2.5 or 5 mg / ml.

For children, the dose is calculated on the basis of 2 mg / kg.

In order to prevent the ingress of Bupivacaine into the vascular bed, an aspiration test must be performed before and during the administration of the main dose. The solution is administered slowly, the total dose is divided into several injections, especially with lumbar and thoracic epidural anesthesia. It is necessary to ensure continuous monitoring of the indicators of vital organs.

The recommended regimen of Bupivacaine use in children for other indications:

peritonsillar infiltration anesthesia (from 2 years): at a concentration of 2.5 mg / ml, 7.5 and 12.5 mg per amygdala;
blockade of the penis: at a concentration of 5 mg / ml, 0.2–0.5 ml / kg (equivalent to 1–2.5 mg / kg);
blockade of the ilio-inguinal / ilio-hypogastric nerves (from 1 year): at a concentration of 2.5 mg / ml, 0.1–0.5 ml / kg (equivalent to 0.25–1.25 mg / kg); children from 5 years old can use the drug at a concentration of 5 mg / ml.

Information on epidural (continuous / bolus) anesthesia in children is insufficient.

If it is necessary to obtain a solution at a concentration of 2.5 mg / ml, the drug with a concentration of 5 mg / ml can be diluted with compatible solvents (for example, 0.9% sodium chloride solution for injection).

Bupivacaine solution is for single use only.

For adults during surgical operations on the lower extremities, including operations on the hip joint, for intrathecal administration, Bupivacaine is prescribed 2-4 ml (10-20 mg), the onset of action - after 5-8 minutes, the duration of anesthesia - from 1.5 to 4 hours. There is no experience with higher doses. Elderly patients and patients in late pregnancy reduce the dose. Only experienced doctors can administer the drug. The recommended injection site is at the L3 level.

Bupivacaine is administered only after confirmation that the solution has entered the subarachnoid space. One of the reasons for the lack of effect from the use of the drug may be its poor distribution in the subarachnoid space (corrected by changing the position of the patient).

In children weighing up to 40 kg, it is allowed to use Bupivacaine at a concentration of 5 mg / ml.

The volume of cerebrospinal fluid in newborns and infants is larger, so they need a relatively high dose per kilogram of body weight to achieve the same degree of blockage as in adults, compared to adults.

The recommended regimen for using the drug in children (depending on weight):

up to 5 kg: 0.4–0.5 mg / kg;
5-15 kg: 0.3-0.4 mg / kg;
15-40 kg: 0.25-0.3 mg / kg.

Side effects

Violations caused by the use of Bupivacaine are difficult to distinguish from the physiological manifestations of nerve blockade, reactions that are directly or indirectly caused by the administration of the solution, and reactions caused by leakage of cerebrospinal fluid.

Neurological disorders are a rare but well-known adverse reaction associated with local anesthesia, especially with intrathecal and epidural administration of bupivacaine.

Possible side effects (> 10% - very common;> 1% and 0.1% and 0.01% and <0.1% - rarely; <0.01% - very rare):

gastrointestinal tract: very often - nausea; often - vomiting;
cardiovascular system: very often - lowering blood pressure; often - bradycardia, increased blood pressure; rarely - arrhythmia, cardiac arrest;
immune system: rarely - anaphylactic shock, allergic reactions;
urinary tract and kidneys: often - urinary retention;
nervous system: often - dizziness, paresthesia; infrequently - signs of toxicity of the central nervous system (in the form of seizures, paresthesia in the mouth, numbness of the tongue, hyperacusis, visual impairment, loss of consciousness, tremor, dizziness, tinnitus, dysarthria); rarely - damage to peripheral nerves, neuropathy, paresis, arachnoiditis, paraplegia;
organ of vision: rarely - diplopia;
respiratory, mediastinal and chest organs: rarely - respiratory depression.

Disturbances arising from intrathecal administration:

immune system: rarely - anaphylactic shock, allergic reactions;
cardiovascular system: very often - lowering blood pressure, bradycardia; rarely - cardiac arrest;
respiratory organs: rarely - respiratory depression;
gastrointestinal tract: very often - nausea; often - vomiting;
nervous system: often - headache that occurs after puncture of the dura mater; infrequently - paresis, paresthesia, dysesthesia; rarely - neuropathy, complete unintentional spinal block, paralysis, paraplegia, arachnoiditis;
skeletal muscle, connective tissue and bones: infrequently - back pain, muscle weakness;
urinary tract and kidney: often - urinary incontinence / retention.

Side effects in children are similar to those in adults, but in children, early signs of toxicity are more difficult to recognize when the block is given under anesthesia or sedation.

Overdose

Possible types of bupivacaine overdose:

accidental intravascular injection: the manifestation of a toxic reaction occurs within 1-3 minutes;
the introduction of high doses that significantly exceed the recommended ones: the time to reach the maximum plasma concentrations of bupivacaine depends on the injection site and can be from 20 to 30 minutes, while signs of intoxication appear slowly.

The main toxic reactions characteristic of an overdose of Bupivacaine:

from the side of the central nervous system (central nervous system): gradually manifested intoxication in the form of symptoms of dysfunction of the central nervous system with an increasing degree of severity. The initial signs, as a rule, are paresthesias around the mouth, slight dizziness, numbness of the tongue, pathologically increased perception of sounds, tinnitus. Further, visual impairment and tremors are possible, more serious signs preceding the development of generalized seizures, which should not be regarded as symptoms of neurotic behavior. After that, loss of consciousness and the development of large convulsive seizures lasting from several seconds to several minutes are possible. As a result of increased muscle activity and a deficiency of gas exchange in the lungs, with convulsions, rapid development of oxygen deficiency and hypercapnia is possible, and in especially severe cases, apnea. Acidosis increases the toxicity of local anesthetics. These reactions take place due to the redistribution of bupivacaine from the central nervous system and a fairly high rate of its metabolism. The relief of the toxic effect of the drug can occur quickly, unless it is administered in very high doses;
from the CVS (cardiovascular system): a toxic effect on CVS is observed in more severe cases, as a rule, it is preceded by negative side effects from the central nervous system. With the introduction of patients in a state of deep sedation or general anesthesia, prodromal neurological symptoms may be absent. Against the background of high concentrations of bupivacaine in blood plasma, it is possible to develop hypotension, impaired conduction of the heart muscle, decrease in cardiac output, atrioventricular (AV) blockade, bradycardia, ventricular arrhythmia (up to sudden cardiac arrest). Occasionally, cardiac arrest without prodromal neurological reactions is noted. If the blockade is performed under general anesthesia in children, it is difficult to notice the early signs of toxic effects of the anesthetic.

If signs of general intoxication are found, it is required to immediately stop the injection of the drug and start taking therapeutic measures aimed at maintaining ventilation of the lungs, blood circulation and relief of seizures. It is recommended to use oxygen and, if necessary, ventilate the lungs with a mask and oxygen bag.

When the convulsions do not go away on their own within 15–20 seconds, anticonvulsant drugs should be administered intravenously. For example, sodium thiopental at a dose of 100–150 mg, which quickly relieves seizures, or the slower acting diazepam at a dose of 5–10 mg. Soon the muscle relaxant Suxamethonium removes the seizure activity, but when it is administered, it is necessary to intubate the trachea and carry out artificial ventilation of the lungs, which significantly limits the possibility of using the drug by specialists who do not know these methods.

With a clear inhibition of cardiovascular function (drop in blood pressure, bradycardia), ephedrine is injected intravenously at a dose of 5–10 mg, if necessary, a second injection is performed after 2–3 minutes. In case of cardiac arrest, cardiopulmonary resuscitation is initiated immediately. Optimization of oxygenation, maintenance of ventilation and circulation, together with correction of acidosis, are vital measures, as acidosis and hypoxia will potentiate the systemic toxic effects of bupivacaine. Epinephrine should be administered intravenously / intracardiacally as soon as possible at a dose of 0.1–0.2 mg, if necessary, the administration should be repeated. Cardiac arrest may require prolonged resuscitation.

special instructions

Bupivacaine should be administered in an appropriately equipped room where the equipment and drugs necessary for cardiac monitoring and resuscitation are available for immediate use. Personnel performing anesthesia must be suitably qualified.

There is evidence of cardiac arrest / death when using the drug for peripheral blockade or epidural anesthesia.

With a high concentration of Bupivacaine in the blood, the likelihood of acute toxic reactions from the cardiovascular and central nervous systems increases.

Some types of local anesthesia can cause serious adverse reactions:

retrobulbar injection: the possibility of penetration of the solution into the cranial subarachnoid space, which can lead to temporary blindness, apnea, seizures, collapse and other undesirable reactions (immediate relief of these disorders is required);
retrobulbar and peribulbar administration: the likelihood of developing persistent dysfunction of the eye muscles;
epidural anesthesia, especially against the background of hypovolemia: suppression of the cardiovascular system (caution is required when prescribing to patients with diseases of the cardiovascular system);
Inadvertent intravascular injection of Bupivacaine into the neck / head area: the likelihood of developing cerebral symptoms.

When carrying out epidural anesthesia, it is possible to develop a decrease in blood pressure and bradycardia. It is possible to reduce the likelihood of these disorders by the preliminary introduction of colloidal and crystalloid solutions. In cases of a decrease in blood pressure, sympathomimetics (for example, ephedrine at a dose of 5-10 mg) should be immediately administered intravenously.

Long-term intra-articular administration of bupivacaine is not approved due to the likelihood of chondrolysis.

The solution does not contain preservatives, and therefore it should be administered immediately after opening the ampoule or vial.

When following a diet with limited salt intake, the sodium content in the preparation must be taken into account.

Spinal anesthesia can lead to severe blockages and paralysis of the intercostal muscles and diaphragm, especially during pregnancy.

In rare cases, there is a serious adverse reaction to spinal anesthesia in the form of high or complete spinal block, which leads to respiratory and cardiovascular depression. Possible negative consequences: arterial hypotension, bradycardia, cardiac arrest.

Neurological complications are rare consequences of spinal anesthesia. They can lead to anesthesia, paresthesia, paralysis, and muscle weakness. Sometimes these complications are permanent. Caution is required in patients with hemiplegia, multiple sclerosis, neuromuscular disorders, and paraplegia. Before prescribing a drug, the expected benefit must be weighed against the possible risk.

Influence on the ability to drive vehicles and complex mechanisms

When driving motor vehicles, it should be borne in mind that Bupivacaine can have a transient effect on motor coordination and motor function.

Application during pregnancy and lactation

Bupivacaine has been used as an anesthetic in a large number of women of reproductive age and pregnant women. Until now, there have been no specific changes in reproductive function and an increase in the incidence of fetal defects.

The addition of epinephrine to bupivacaine can cause a decrease in blood flow in the uterus and a weakening of its contractility, especially if the solution accidentally gets into the mother's vessels. Paracervical blockade can cause severe disturbances in the fetus from the CVS, since the anesthetic reaches the fetus in high doses.

In connection with the above, during pregnancy, the use of Bupivacaine is permissible only if the intended benefit to the mother exceeds the potential risk to the fetus.

Bupivacaine, like other anesthetics, passes into breast milk in small doses that do not pose a risk to the development of the baby. Despite this, breastfeeding should be interrupted while using the drug.

Pediatric use

In pediatric practice, for intrathecal (spinal) anesthesia, Bupivacaine can be used from the neonatal period.

For other indications, the drug is contraindicated in children under 1 year of age, at the age of 1 to 12 years, it is prescribed with caution.

The age limit for surgical anesthesia is children under 12 years of age.

With impaired renal function

Bupivacaine is used with caution for anesthesia in patients with renal failure.

For violations of liver function

Bupivacaine is used with caution for anesthesia in patients with reduced hepatic blood flow, for example, with liver disease.

Use in the elderly

For elderly patients over 65 years of age, the drug is administered with caution.

Drug interactions

With the combined use of Bupivacaine with certain drugs / substances, the following effects may develop (combinations require caution):

other local anesthetics or class Ib antiarrhythmic drugs: mutual enhancement of toxic effects;
class III antiarrhythmic drugs: mutual enhancement of cardiovascular toxic effects.

When preparing for the introduction of Bupivacaine, it is necessary to avoid its prolonged contact with metal objects, since metal ions at the injection site can cause reactions manifested by edema and pain.

Analogs

Bupivacaine analogues are: Markain Spinal, Maksikain, Ancain, Buvanestin, Omnikain, Markain Spinal Heavy, BlokkoS, Bupivacaine hydrochloride, Bupivacaine-Binergia, Bupivacain-M, Bupivacain-Grindeks Spinal, Bupivacaine-Grindex

Terms and conditions of storage

Store in a dark place at temperatures up to 25 ° C. The solution cannot be frozen. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Bupivacaine

Both patients and practitioners leave mostly favorable reviews about Bupivacaine. The latter note the convenient packaging of the drug, long-term anesthetic effect, good depth of anesthesia and distribution of the substance in the tissues, sufficient to achieve the desired effect. It is emphasized that this anesthetic should always be present in the practice of an outpatient surgeon.

The price of Bupivacaine in pharmacies

The approximate price of Bupivacaine injection solution 5 mg / ml, 10 ml in an ampoule, for 5 ampoules in a package is 526–666 rubles.

Bupivacaine: prices in online pharmacies

Drug name

Price

Pharmacy

Bupivacaine 5 mg / ml solution for injection 4 ml 5 pcs.

RUB 511

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Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!