Bupivacaine Grindex - instructions for use, dose, side effects, contraindications

Excipients: sodium chloride - 8.0 mg, 0.1 M sodium hydroxide solution or 0.1 M hydrochloric acid solution to pH 4.0-6.5, water for injection up to 1 ml.

Description:

A clear, colorless liquid.

Pharmacotherapeutic group:Local anesthetic

ATX: & nbsp

N.01.B.B.01 Bupivacaine

Pharmacodynamics:

The local anesthetic is a long-acting amide type, 4 times stronger than lidocaine. Reversibly blocks the impulse through the nerve fiber due to the effect on the sodium channels. Has hypotensive effect, slows heart rate. Postoperative analgesia is maintained for 7-14 hours with intercostal blockade. After a single epidural injection, the duration of the effect using a concentration of 5 mg / ml is from 2 to 5 hours, and up to 12 hours - with peripheral nerve block.

The use of solutions at a concentration of 2.5 mg / ml has less effect on the motor nerves.

Pharmacokinetics:

The pKa value of bupivacaine is 8.2, the partition coefficient is 346 (at 25 ° C in n-octanol / phosphate buffer pH 7.4).

The rate of absorption depends on the dose, route of administration and blood supply at the injection site. With intercostal blockade due to rapid absorption, the maximum plasma concentration is 4 mg / l (with 400 mg), with subcutaneous injections in the abdomen, plasma concentrations are lower.

In children with caudal blockade, there is rapid absorption and a high plasma concentration is achieved - about 1-1.5 mg / l (with 3 mg / kg body weight).

Bupivacaine is completely absorbed into the blood from the epidural space; the absorption is biphasic, the half-life for the two phases is 7 minutes and 6 hours, respectively. Slow absorption limits the rate of elimination of bupivacaine, which explains the longer half-life after introduction into the epidural space than with intravenous administration.

The equilibrium volume of bupivacaine distribution is 73 liters, the hepatic extraction coefficient is 0.4, the total plasma clearance is 0.58 liters per minute, and the half-life of plasma is 2.7 hours. The half-life of newborns in comparison with adults may be longer - up to 8 hours. In children older than three months, the half-life is equal to that of adults.

The pharmacokinetics of bupivacaine in children is similar to its pharmacokinetics in adults.

The connection with plasma proteins is 96%, mainly with α1-acid plasma glycoproteins. After major operations, the concentration of this protein can be increased, which may lead to a higher overall concentration of bupivacaine in the plasma. The free fraction of bupivacaine does not change.Therefore, the potentially toxic plasma concentration is well tolerated.

Bupivacaine is almost completely metabolized in the liver, mainly by aromatic hydroxylation to 4-hydroxybupivacaine and N-dealkylation to 2,6-pipecyloxylidine (RRK), both reactions are catalyzed by the cytochrome isoenzyme CYP3A4. Thus, the clearance depends on the hepatic blood flow and the activity of the metabolizing enzymes.

Bupivacaine penetrates the placenta, the concentration of unbound bupivacaine in the fetus is equal to the maternal. In view of the lower association with plasma proteins in the fetus, the total plasma concentration is lower.

Indications:

Surgical anesthesia in adults and children over 12 years.

Acute pain in adults and children over 1 year.

Infiltration anesthesia, when a long-term anesthetic effect is required, for example, in post-operative pain.

Conductive anesthesia with a prolonged effect or epidural anesthesia in cases where the addition of epinephrine is contraindicated and undesirable significant relaxation of the muscles.

Anesthesia in obstetrics.

Contraindications:

- Hypersensitivity to any of the components of the drug or to other local anesthetics of the amide type;

- severe arterial hypotension (cardiogenic or hypovolemic shock);

- Children's age: up to 12 years with surgical anesthesia, up to 1 year: with all indications for use;

- intravenous regional anesthesia (Bira blockade) (accidental penetration of bupivacaine into the bloodstream can cause the development of acute systemic toxic reactions);

- Paracervical blockade in obstetrics.

Conditions that are contraindications to epidural anesthesia:

- diseases of the central nervous system (CNS) (eg, meningitis, tumors, poliomyelitis, intracranial hemorrhage);

- purulent skin infections at or near the lumbar puncture;

- spinal stenosis, active diseases (eg, spondylitis, tumors, tuberculosis) or trauma (for example, fracture) of the spine;

- sepsis, subacute combined degeneration of the spinal cord due to pernicious anemia and tumors of the brain and spinal cord;

- cardiogenic or hypovolemic shock;

- a clotting disorder or active anticoagulant therapy.

Carefully:

Cardiovascular failure (possibly progression), heart block, inflammatory diseases or infection of the injection site (with infiltration anesthesia), cholinesterase deficiency, kidney failure, advanced age (over 65 years), late pregnancy (III (for example, chronic heart failure, liver diseases), simultaneous administration of antiarrhythmic agents (including beta-blockers ), children's age (1-12 years).

Bupivacaine should be used with caution in patients receiving other local anesthetics or preparations structurally similar to local anesthetic agents of the amide type, such as antiarrhythmics (eg, lidocaine, mexiletine).

Pregnancy and lactation:

The use of bupivacine to achieve paracervical blockade in obstetrics can cause severe cardiovascular disorders in the fetus, such as bradycardia / tachycardia.The use of bupivacaine as a means for paracervical blockade is contraindicated (see section "Contraindications"). The use of the drug according to the declared indications for use is possible if the expected benefit for the mother exceeds the possible risk to the fetus.

Bupivacaine penetrates into breast milk, but when applied in therapeutic doses, the effect on the baby is negligible.

Dosing and Administration:

Use bupivacaine can only doctors who have experience in conducting local anesthesia or under their supervision. To achieve the required degree of anesthesia, the minimum possible dose should be administered.

Under no circumstances should you allow accidental intravascular drug administration. It is recommended to perform an aspirate test before and during the administration of the drug. The drug should be administered slowly, at a rate of 25-50 mg / min or fractional, maintaining continuous verbal contact with the patient and controlling the heart rate. During epidural administration, a dose of 3-5 ml of bupivacaine with epinephrine is preset. With a random intravascular injection, there is a short-term increase in the heart rate, with a random intrathecal injection, a spinal block appears.If there are toxic signs, the administration is immediately stopped.

Below are the estimated doses that need to be corrected depending on the depth of anesthesia and the patient's condition.

Infiltration anesthesia: 5-60 ml of the drug at a concentration of 2.5 mg / ml (12.5-150 mg bupivacaine) or 5-30 ml of the drug at a concentration of 5 mg / ml (25-150 mg bupivacaine).

Diagnostic and therapeutic blockade: 1 -40 ml of the drug at a concentration of 2.5 mg / ml (2.5-100 mg of bupivacaine), for example, trigeminal blockade of 1-5 ml of the drug (2.5-12.5 mg of bupivacaine) and the cervical and thoracic sympathetic node a trunk of 10-20 ml (25-50 mg of bupivacaine).

Intercostal blockade: 2-3 ml of the drug at a concentration of 5 mg / ml (10-15 mg of bupivacaine) per nerve, not exceeding the total amount - 10 nerves.

Major blockades (eg, epidural block, sacral or brachial plexus blockade): 15-30 ml of the drug at a concentration of 5 mg / ml (75-150 mg bupivacaine).

Anesthesia in Obstetrics (eg epidural and caudal anesthesia for natural delivery): 6-10 ml of the drug at a concentration of 2.5 mg / ml (15-25 mg of bupivacaine) or 6-10 ml of the drug at a concentration of 5 mg / ml (30-50 mg bupivacaine ).

After every 2-3 hours, repeated administration of the drug in the initial dose is allowed.

Epidural anesthesia in cesarean section: 15-30 ml of the drug in a concentration of 5 mg / ml (75-150 mg of bupivacaine).

Epidural analgesia in the form of intermittent bolus injection: initially inject 20 ml of the drug at a concentration of 2.5 mg / ml (50 mg bupivacaine), then every 4-6 hours, depending on the number of damaged segments and the patient's age, 6-16 ml of the drug at a concentration of 2.5 mg / ml (15 -40 mg of bupivacaine).

Epidural analgesia in the form of continuous infusion (for example, postoperative pain):

Type of blockade	Concentration	Scope	Dose
Epidural introduction (at the lumbar level)
Bolus *	2.5 mg / ml	5-10 ml	12.5-25 mg
Infusion	2.5 mg / ml	5-7.5 ml / hr	12.5-18.75 mg **
Epidural introduction (at the thoracic level)
Bolus *	2.5 mg / ml	5-10 ml	12.5-25 mg
Infusion	2.5 mg / ml	2.5-5 ml / h	6.25-12.5 mg
Epidural introduction (natural childbirth)
Bolus *	2.5 mg / ml	6-10 ml	15-25 mg
Infusion	2.5 mg / ml	2-5 ml / hr	5-12.5 mg

* If during the previous hour the drug was not administered bolus.

** Do not exceed the maximum recommended daily dose (see below).

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

With the simultaneous use of narcotic analgesics, the dose of bupivacaine should be reduced.

With prolonged administration of the drug, the patient should regularly monitor blood pressure, heart rate and other signs of potential toxicity. If toxic effects occur, the drug should be discontinued immediately.

Recommended maximum doses

The maximum recommended single dose, calculated at 2 mg / kg body weight, is 150 mg for adults for four hours. This is equivalent to 60 ml of the drug at a concentration of 2.5 mg / ml (150 mg bupivacaine) and 30 ml drug at a concentration of 5 mg / ml (150 mg bupivacaine).

The maximum recommended daily dose is 400 mg. However, when calculating the total daily dose, it is necessary to take into account the patient's age, physique and other significant conditions.

Children aged 1-12 years

Regional anesthesia should be performed by a doctor who has experience working with children and who has the appropriate technique of administration.

Doses in children, given in the table, are indicative. Variability is possible. Children with high body weight, as a rule, need to reduce the dose, based on the ideal body weight. In determining the methods of anesthesia and taking into account the individual characteristics of patients should use the generally accepted guidelines for anesthesia.

It is necessary to enter the minimum dose necessary to achieve sufficient anesthesia.

	Concentration, mg / ml	Volume, ml / kg	Dose, mg / kg	Start of action, min	Duration of action, hours
Acute pain
Caudal epidural anesthesia	2,5	0,6-0,8	1,5-2	20-30	2-6
Lumbar epidural anesthesia	2,5	0,6-0.8	1,5-2	20-30	2-6
Thoracic epidural anesthesia^(b)	2,5	0,6-0,8	1,5-2	20-30	2-6
Regional blockade (for example, blockade and infiltration of small nerves	2,5		0,5-2
	5		0,5-2
Blockade peripheral nerves (eg, blockade iliac-inguinal / iliac-hypogastric nerves)	2,5		0,5-2	a)
	5		0,5-2	a)

a) - the beginning and duration of peripheral nerve blockage depends on the nature of the blockade and dose

b) - with thoracic epidural anesthesia, the drug is administered in ever increasing doses until the desired level of anesthesia is reached.

The dose in children is calculated based on 2 mg per kg of body weight.

In order to prevent the drug from entering the vascular bed, the aspiration test should be performed before and during the administration of the main dose. The drug should be administered slowly, dividing the total dose into several injections, especially with lumbar and thoracic epidural anesthesia, continuously observing the indicators of vital organs.

Peritonsillar infiltration anesthesia in children from 2 years of age: in a dose of 7.5 mg and 12.5 mg per tonsil with a concentration of bupivacaine 2.5 mg / ml.

Blockade of ilio-inguinal / ilio-hypogastric nerves in children from 1 year: 0.1-0.5 mg / kg body weight with a bupivacaine concentration of 2.5 mg / ml, equivalent to 0.25-1.25 mg / kg body weight.

For children aged 5 years and older, the drug can be administered in a concentration of bupivacaine 5 mg / ml, equivalent to 1.25-2 mg / kg.

Blockade of the penis: 0.2-0.5 ml / kg with a bupivacaine concentration of 5 mg / ml, equivalent to 1.0-2.5 mg / kg.

Data on epidural anesthesia in children (bolus or continuous administration) are limited.

Cooking method

If a solution with a concentration of 2.5 mg / ml is required, it is possible to dilute the preparation at a concentration of 5 mg / ml only with compatible solvents, such as a 0.9% sodium chloride solution for injection, since the properties of the preparation may change after dilution, which may lead to precipitation. Breeding should be carried out only by qualified personnel with mandatory visual control before use. It is possible to use only clear solutions without visible particles.

The drug solution is intended for single use only.

Side effects:

The frequency of adverse reactions is determined by the following categories: very frequent (≥1 / 10), frequent (≥1 / 100, <1/10), infrequent (≥1 / 1,000, <1/100), rare (≥1 / 10 000, <1/1 000), very rare (<1/10 000).

Undesirable drug-induced drug reactions may be difficult to distinguish from the physiological manifestations of nerve blockade (eg, lowering blood pressure, bradycardia), reactions, directly (eg, nerve damage) or indirectly caused by administration (eg, epidural abscess), leakage reactions cerebrospinal fluid (eg, post-puncture headache).

Neurological disorders are a rare but well-known undesirable drug reaction caused by local anesthesia, especially with epidural and intrathecal administration of the drug.

Symptoms and tactics of management of acute systemic toxicity are described in the section "Overdose".

System of organs	Frequency	Unwanted drug reactions
From the immune system	Rare (≥1/10 000, <1/1 000)	Allergic reactions, anaphylactic shock.
From the nervous system	Frequent (≥1/100, <1/10)	Paresthesia, dizziness.
	Infrequent (≥1/1 000 , <1/100)	Signs of toxicity from the central nervous system: convulsions, paresthesia in the mouth, numbness of the tongue, hyperacia, visual impairment, loss of consciousness, tremor, slight dizziness, tinnitus, dysarthria.
	Rare (≥1/10 000, <1/1 000)	Neuropathy, peripheral nerve damage, arachnoiditis, paresis, paraplegia.
From the side of the organ of vision	Rare (≥1/10 000, <1/1 000)	Diplopia.
From the heart	Frequent (≥1/100, <1/10)	Bradycardia.
From the heart	Rare (≥1/10 000, <1/1 000)	Cardiac arrest, arrhythmia.
From the side of the vessels	Very Frequent (≥1/10)	Reduced blood pressure.
From the side of the vessels	Frequent (≥1/100, <1/10)	Increase in blood pressure.
On the part of the respiratory system, the organs of the thorax and the mediastinum	Rare (≥1/10 000, <1/1 000)	Inhibition of breathing.
From the gastrointestinal tract	Very Frequent (≥1/10)	Nausea.
From the gastrointestinal tract	Frequent (≥1/100, <1/10)	Vomiting.
From the side of the kidneys and urinary tract	Frequent (≥1/100, <1/10)	Retention of urine.
From the side of the organ of vision	Rare (≥1/10 000, <1/1 000)	Diplopia.
From the heart	Frequent (≥1/100, <1/10)	Bradycardia.
From the heart	Rare (≥1/10 000, <1/1 000)	Cardiac arrest, arrhythmia.
From the side of the vessels	Very Frequent (≥1/10)	Reduced blood pressure.
From the side of the vessels	Frequent (≥1/100, <1/10)	Increase in blood pressure.
On the part of the respiratory system, the organs of the thorax and the mediastinum	Rare (≥1/10 000, <1/1 000)	Inhibition of breathing.
From the gastrointestinal tract	Very Frequent (≥1/10)	Nausea.
From the gastrointestinal tract	Frequent (≥1/100, <1/10)	Vomiting.
From the side of the kidneys and urinary tract	Frequent (≥1/100, <1/10)	Retention of urine.

Undesirable reactions in children are similar to those in adults, however, early signs of local anesthetic toxicity in children are more difficult to recognize if the blockade is performed under sedation or anesthesia.

Overdose:

Acute systemic intoxication

Symptoms

Toxic reactions are manifested mainly from the central nervous and cardiovascular systems. They arise due to the high concentration of local anesthetic in the blood, which can be caused by accidental intravascular injection, overdose or extremely fast absorption from the area of highly vascularized tissues (see section "Special instructions").

Symptoms of CNS damage for all local anesthetics of the amide type are similar, whereas the symptoms of cardiovascular damage differ qualitatively and quantitatively.

Unintentional intravascular injection of a local anesthetic can lead to immediate systemic toxic reactions (within a few seconds-minutes).Signs of systemic toxicity in case of an overdose appear later (15-60 minutes after administration), as the concentration of local anesthetic in the blood plasma increases slowly.

From the central nervous system

Intoxication of the central nervous system manifests itself gradually. The initial signs of intoxication, as a rule, are: dizziness, paresthesia around the mouth, numbness of the tongue, hyperacusis, tinnitus and visual impairment. More serious manifestations are dysarthria and myofasciculation, which may precede the onset of generalized seizures. These phenomena should not be mistaken for a neurotic disorder. Following them, loss of consciousness and the development of a large convulsive fit lasting from a few seconds to several minutes are possible. In connection with increased muscular activity and insufficient ventilation (disruption of the normal breathing process), hypoxia and hypercapnia rapidly build up during seizures. In severe cases, breathing may stop. Concomitant acidosis increases the toxic effect of local anesthetics.

The resolution of symptoms is due to the metabolism of the local anesthetic andits redistribution from the central nervous system. The described phenomena quickly stop, if the overdose was not excessive.

From the side of the cardiovascular system

The defeat of the cardiovascular system, as a rule, indicates more severe intoxication. It is usually preceded by signs of central nervous system damage that can be erased if the patient is in anesthesia or deep sedation caused by drugs such as benzodiazepines or barbiturates. Due to the high concentration of local anesthetics in blood plasma, there may be a drop in blood pressure, bradycardia, arrhythmias and cardiac arrest.

Toxic manifestations of the cardiovascular system are often caused by myocardial depression and myocardial conduction disturbance, which cause a decrease in cardiac output, lowering of arterial pressure, atrioventricular blockade (AV blockade), bradycardia, ventricular arrhythmia, including ventricular tachycardia and ventricular fibrillation, cardiac arrest. These phenomena are often preceded by severe signs of CNS involvement, including convulsions, but in rare cases, cardiac arrest occurs without concomitant signs from the CNS.

After a very rapid intravenous injection, the concentration of bupivacaine in the blood plasma can be quite high. In this case, he quickly reaches the coronary arteries, and the symptoms of circulatory disorders occur earlier than signs of CNS damage. This mechanism causes myocardial depression and may be the first manifestation of intoxication.

When the blockade is performed under general anesthesia in children, the early signs of intoxication are difficult to detect, and careful monitoring is therefore required.

Treatment

If a spinal block arises, adequate ventilation should be provided (ensure airway patency, oxygen supply, if necessary, intubation and artificial ventilation). With a decrease in blood pressure and / or bradycardia, it is necessary to introduce a vasopressor with an inotropic effect.

When symptoms of acute systemic intoxication occur, the administration of the drug should be stopped immediately. It is necessary to ensure proper ventilation, oxygenation and maintain blood circulation.

In all cases, it is necessary to adjust the supply of oxygen,if necessary, intubation and controlled ventilation (in some cases with hyperventilation).

When convulsions are injected diazepam, with bradycardia - atropine. With circulatory failure - dobutamine intravenously, the administration of norepinephrine is allowed (starting from 0.05 μg / kg / min, if necessary, the dose is increased by 0.05 μg / kg / min every 10 minutes), in more severe cases, the dose is titrated according to the results of monitoring hemodynamics. The administration of ephedrine is possible. With severe damage to the cardiovascular system, resuscitation can continue for several hours. Any acidosis is subject to elimination.

When cupping systemic intoxication in children, the dose of the drug should be selected according to their age and body weight.

Interaction:

Caution should be exercised while using bupivacaine with other local anesthetics or antiarrhythmics Ib class, as they can enhance the toxic effects of each other.

A separate study of the interaction of local anesthetics and antiarrhythmic drugs of the third class (for example, amiodarone) was not carried out, nevertheless, it is advisable to use caution when using them simultaneously (see section "Special instructions").

The alkalinization can lead to precipitation, since the solubility of bupivacaine at pH> 6.5 decreases.

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

Special instructions:

Regional and local anesthesia should be carried out by experienced specialists in an appropriately equipped room with availability of ready-to-use equipment and preparations necessary for cardiac monitoring and resuscitation.

Personnel performing anesthesia should be qualified and trained in the technique of performing anesthesia, should be familiar with the diagnosis and treatment of systemic toxic reactions, adverse events and reactions, and other complications.

There are reports of cardiac arrest or death while using bupivacaine for epidural anesthesia or peripheral blockade.In some cases, resuscitation has been difficult or impossible, despite adequate treatment.

Blockade of the main peripheral nerves may require the introduction of large amounts of local anesthetics into the well-blood-supplying areas of the body, often near large blood vessels. In such cases, the risk of intravascular bupivacaine or systemic absorption increases, which can lead to a high concentration of local anesthetic in the blood.

Like other local anesthetics, bupivacaine can cause acute toxic reactions from the central nervous and cardiovascular systems, if during the procedure of local anesthesia there is a high concentration in the blood. Most often this is manifested in the case of unintentional intravascular injection or with a good blood supply to the site of administration. Certain types of local anesthesia can lead to the development of serious adverse reactions, for example:

Epidural anesthesia, especially against the background of hypovolemia, can lead to depression of the cardiovascular system. Care should be taken in patients with cardiovascular disease.

With retrobulbar injection, the drug can occasionally enter the cranial subarachnoid space, causing temporary blindness, apnea, convulsions, collapse and other undesirable reactions. The coping of these reactions must be carried out immediately.

With retrobulbar and peribulbar injection of local anesthetics, there is a certain risk of a persistent impairment of the function of the eye muscles. The main causes are trauma and / or local toxic effects on muscles and / or nerves.

If unintentional intravascular injection into the head or neck area, even at low doses, the drug is able to cause cerebral symptoms.

The severity of the undesirable reactions described above depends on the size of the injury, the concentration of the local anesthetic and the duration of its effect on the tissue. Therefore, as with other local anesthetics, it is necessary to administer the lowest effective dose of bupivacaine.

Care should be taken in patients with AV blockade II and III degree, as local anesthetics can disrupt intracardiac patency.

Care should be taken when administering the drug to elderly patients and patients with severe liver disease, severe renal failure, or a general unsatisfactory condition.

It is necessary to carry out careful monitoring and continuous ECG monitoring in patients receiving Class III antiarrhythmic drugs (for example, amiodarone), since the summation of their cardiovascular effects with those of bupivacaine is possible.

When conducting epidural anesthesia, there may be a drop in blood pressure and a bradycardia. Reduce the likelihood of such complications can be through the introduction of crystalloid and colloidal solutions. With a decrease in blood pressure, immediate intravenous sympathomimetics are indicated (eg, 5-10 mg ephedrine); if necessary, repeat the introduction.

According to the post-registration data, in some patients who received long-term local anesthetic injections into the joint cavity after the operation, chondrolisis arose. In most cases, chondrolisis of the shoulder joint. The causal relationship with the administration of bupivacaine has not been conclusively confirmed,Chondrolisis is due to several factors. Contradictory data on the mechanism of the onset of this state are described in the literature. Prolonged intra-articular injection is not an approved indication for the use of the drug.

The solution does not contain preservatives, so it must be injected immediately after opening the ampoule. Remains of the solution are subject to destruction.

The drug contains sodium, so in the case of a salt-free diet with a limited consumption of it, you should take into account the sodium content in the preparation.

Children

The safety and effectiveness of bupivacaine in children under the age of 1 year have not been studied, only limited data are available.

Data on the intra-articular blockade of bupivacaine in children 1-12 years are absent.

Data on the bupivacaine blockade of large nerves in children 1-12 years are absent.

With epidural anesthesia, the drug should be administered slowly, guided by age and body weight, since especially with epidural anesthesia at the breast level severe hypotension and respiratory failure can occur.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Solution for injection, 5 mg / ml.

Packaging:

For 10 ml in an ampoule of colorless glass of hydrolytic class No. 1 with a line or a break point and two marking rings of blue color (for the manufacturer HBM Pharma sr.o.).

5 ampoules per cell pack of PVC film without coating (pallet). One cell pack together with the instruction for use is placed in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006093/10

Date of registration:29.06.2010 / 06.10.2016

Expiration Date:Unlimited

The owner of the registration certificate:GRINDEX, JSC GRINDEX, JSC Latvia

Manufacturer: & nbsp

HBM PHARMA, s.r.o. The Slovak Republic

Santonika, UAB Lithuania

Representation: & nbspGrindeks Rus, Open CompanyGrindeks Rus, Open CompanyRussia

Information update date: & nbsp20.04.2017

Illustrated instructions

Instructions

Bupivacaine Grindeks (Bupivacaine Grindeks)