Universal reference book for medicines
Product name: MARCAINE (MARCAINE)

Active substance: bupivacaine

Type: Local anesthetic

Manufacturer: ASTRAZENECA UK (Great Britain) produced by RECIPHARM MONTS (France)
Composition, form of production and packaging
Solution for injection
1 ml 1 fl.

bupivacaine hydrochloride 5 mg 100 mg

20 ml - bottles (5) - packs cardboard.

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2010.

PHARMACHOLOGIC EFFECT

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. With a single epidural injection, the duration of the effect when using a concentration of 5 mg / ml is 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

Bupivacaine has a pKa-8.2 index of the separation coefficient of 346 (at 25 ° C in n-octanol / phosphate buffer pH 7.4).

Bupivacaine is completely absorbed into the blood from the epidural space;
absorption is biphasic, the half-life period for the two phases is 7 min and 6 h, respectively. Slow elimination of bupivacaine is determined by the presence of a slow phase of absorption of the epidural space, which explains the longer T 1/2 after epidural administration compared with intravenous administration.
The total plasma clearance of bupivacaine is 0.58 l / min, the volume of distribution in the equilibrium state is 73 l, the final half-life is 2.7 h, the intermediate hepatic extraction is about 0.38 after IV.
Bupivacaine, mainly, is recalled with 1-acidic plasma glycoproteins (binding to plasma proteins - 95%). Bupivacaine clearance is almost entirely due to the metabolism of the drug on the liver and is more dependent on the activity of the liver's enzyme systems than on liver perfusion. Metabolites have less pharmacological activity than bupivacaine.
The plasma concentration of bupivacaine depends on the dosage of the drug, the method of administration of the drug, the vascularization in the area of ​​administration.

In children aged 1 to 7 years, the pharmacokinetics of the drug are similar to those in adults.

Penetrates through the placenta.
The connection with the plasma proteins in the fetus is lower than in the organism of the uterus, the concentration of the unbound fraction in the fetus and mother is the same.
Bupivacaine is metabolized in the liver, mainly by aromatic hydroxylation to 4-hydroxy-bupivacaine and N-dealkylation to RRB.
Both reactions occur with the participation of cytochrome P4503A4 enzymes. About 1% of bupivacaine is excreted in the urine unchanged during the day after administration, and approximately 5% in the form of PPC. The concentration of PPC and 4-hydroxy-bupivacaine in plasma during and after prolonged bupivacaine administration is low relative to the administered dose of the drug.
INDICATIONS

Various types of local anesthesia (anesthesia in trauma, surgical interventions, including cesarean section, analgesia of labor, painful diagnostic procedures, for example, in arthroscopy):

- local infiltration anesthesia;

- conductive anesthesia (including intercostal blockade, blockage of large and small nerves, nerve blockade in the head and neck area);

- caudal or lumbar epidural block;

- retrobulbar (regional) anesthesia.

DOSING MODE

Adults and children over 12 years of age

The following table is a guide for dosing the drug with the most frequently performed procedures.
When calculating the required dose, it is important to base on clinical experience and assess the patient's physical status.
Dosing recommendations

The doses indicated in the table are considered necessary for successful blockade, and should be considered as recommended for the average adult patient.

For caudal blockade, higher doses may be used (see table).

When performing prolonged blockages with the help of prolonged infusion or fractional administration of the drug, one should consider the possibility of increasing its concentration in the blood plasma to toxic or the probability of local injury of nerve fibers.
The experience accumulated to date shows that administering an adult patient within 24 hours 400 mg of the drug is usually well tolerated. "
When using a large volume of a solution containing epinephrine, one should take into account the possibility of developing systemic effects of epinephrine.

Type of blockade Dose Commencement of action, min Duration, hours Indications (comments)

ml mg

Infiltration? 30-151 1-10 3-8 Surgical interventions and postoperative analgesia

Retrobulbarnaya 2-4 10-20 5 4-8 Ophthalmic surgery (see warnings)

Peribulbar 6-10 30-50 10 4-8 Ophthalmic surgery (see warnings)

Intercostal (per nerve) 2-3 10-15 3-5 4-8 Surgical interventions and postoperative analgesia, anesthesia with trauma

Interpleural blockade 20 100 10-20 4-8 Postoperative analgesia

Blockade of the brachial plexus: axillary supraclavicular, intercostal and subclavian perivascular 30-40 20-30 150-200 100-150 15-30 15-30 4-8 4-8

Blockade of the sciatic nerve 10-35 50-200 15-30 4-8 Surgical interventions

Blockade of the femoral nerve, obstructive nerve and lateral cutaneous nerve of the femur (3 in 1) 10-35 50-200 15-30 4-8 Surgical operations

Epidural (at the lumbar level) 15-30 75-150 15-30 2-3 Surgical interventions, including cesarean section, analgesia of labor and postoperative analgesia (dose allows for a trial test)

Epidural (at the thoracic level) 5-10 25-50 10-15 2-3 Surgical interventions (dose allows for a trial test)

Caudal anesthesia 20-30 100-150 15-30 2-3 Intraoperative and postoperative analgesia.
Therapy of pain syndromes and anesthesia in diagnostic procedures (the dose takes into account the test test)
The drug should be administered with caution to avoid the development of acute toxic reactions with accidental intravascular administration of the drug.
It is recommended that the aspiration sample be thoroughly performed before and during the administration of the preparation. If a large dose is required, for example, with an epidural block, it is recommended that the test dose be pre-introduced: 3-5 ml of bupivacaine with epinephrine. In the case of accidental intravascular injection of the drug, transient tachycardia, easily detected by a physician, may occur. The main dose is administered slowly at a rate of 25-50 mg / min or fractional bolus, constantly maintaining verbal contact with the patient. When signs of intoxication appear, the drug should be discontinued immediately.
For children under 12 years of age, the dose should be calculated taking into account the body weight (on average, up to 2 mg / kg), for lumbosacral -1.5-2 μ / kg weight, for thoracolumbular -1.5-2.5 mg / kg body weight.
The addition of epinephrine increases the duration of the blockade by 50-100%.
SIDE EFFECT

Adverse reactions to Markain are similar to the side reactions that occur when intrathecal injection of other local long-acting anesthetics.
Adverse reactions caused by the drug itself are difficult to distinguish from the physiological manifestations of nerve blockade (eg, arterial hypotension, bradycardia, temporary urinary retention), reactions caused directly (eg, spinal hematoma) or indirectly (eg, meningitis, epidural abscess) by insertion of a needle, or reactions associated with leakage of the cerebrospinal fluid (eg, post-puncture headache).
Very frequent (> 1/10) From the side of the cardiovascular system: hypotension From the digestive tract: nausea

Frequent (> 1/100, <1/10) From the side of the nervous system: paresthesia, dizziness From the cardiovascular system: bradycardia, increased blood pressure From the digestive tract: vomiting From the genitourinary system: urinary retention, incontinence

Less frequent (> 1/1000, <1/100) From the side of the nervous system: signs and symptoms of toxicity from the central nervous system and cardiovascular system (convulsions, paresthesia, numbness of the tongue, visual disturbances, tremor, chills, loss of consciousness, noise and ringing in the ears, dysarthria, headache)

Rare (<1/1000) From the side of the cardiovascular system: cardiac arrest From the nervous system side: unintended total spinal block, paraplegia, paralysis, neuropathy, arachnoiditis Respiratory system: respiratory depression On the part of the eyes: diplopia General: allergic reactions , in the most severe cases - anaphylactic shock.

CONTRAINDICATIONS

- CNS diseases (as with epidural injection of other local anesthetics);

- arterial hypotension;

- Children's age (up to 2 years);

- hypersensitivity to any of the components of the drug (eg methylparahydroxybenzoate) or to local anesthetics of the amide type.

The drug is not used for intravenous regional anesthesia (Bira blockade) (accidental penetration of bupivacaine into the bloodstream can cause the development of acute systemic toxic reactions);

With caution: cardiovascular insufficiency (possibly progression), heart block, inflammatory diseases or infection of the injection site (with infiltration anesthesia), cholinesterase deficiency, kidney failure, elderly age (over 65), late pregnancy (III trimester), general a severe condition, a decrease in hepatic blood flow (for example, in chronic heart failure, liver diseases), simultaneous administration of antiarrhythmic agents (including beta-blockers), it is necessary
paracervical anesthesia, children's age (up to 12 years);
with epidural appointment (caudal and lumbar anesthesia) - previous neurological diseases, septicemia, difficulty in performing the puncture due to deformity of the spine.

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

PREGNANCY AND LACTATION

With caution: in the third trimester of pregnancy.

Use the drug only if the expected benefit for the mother exceeds the possible risk to the fetus.

Bupivacaine was used in a large number of pregnant women and women of childbearing age, however, until now no specific changes in the reproductive function, for example, increased the frequency of developmental defects.

The addition of epinephrine to bipuvacaine may reduce blood flow in the uterus and its contractility, especially when the anesthetic solution is accidentally injected into the mother's vessels.
Side effects caused by the action of local anesthetic in the fetus, such as bradycardia, are most often detected with paracervical blockade (the anesthetic at the same time reaches the fetus in high concentrations).
As with other local anesthetics, bupivacaine can penetrate into breast milk in small amounts that do not pose a risk to the newborn.

APPLICATION FOR FUNCTIONS OF THE LIVER

With caution: kidney failure.

APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

With caution: decreased hepatic blood flow (eg, in chronic heart failure, liver disease).

APPLICATION FOR CHILDREN

Contraindicated in children under 2 years.

With caution: 2 to 12 years.

APPLICATION IN ELDERLY PATIENTS

With caution: the elderly (over 65 years).

SPECIAL INSTRUCTIONS

There are reports of cardiac arrest or death while using bupivacaine for epidural anesthesia or peripheral blockade.
In some cases, resuscitation was difficult or impossible, despite the undoubtedly good preparation and anesthesia.
Like other local anesthetics, bupivacaine can cause acute toxic reactions from the central nervous and cardiovascular systems if its use for local anesthesia leads to a high concentration of the drug in the blood.
Most often this is manifested in the case of unintentional intravascular injection or with high vascularization of the site of administration. Against the background of a high concentration of bupivacaine in the plasma, cases of ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death were documented.
Regional and local anesthesia, with the exception of small procedures, 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.
When performing large blockades before the introduction of a local anesthetic, it is recommended to install an intravenous catheter. Staff should undergo appropriate training in the technique of anesthesia and should be familiar with the diagnosis and treatment of the side effects of the drug, systemic toxic reactions and other complications (see "Overdose").
The periphyric nerve blockade is associated with the introduction of a larger volume of local anesthetic into the region of high vascularization, often close in large vessels, where the risk of unintentional intravascular injection of local anesthetic or systemic absorption of a large dose of the drug increases, which in turn can lead to an increase in plasma concentration.

When conducting regional anesthesia, you should be especially attentive to the following groups of patients:

- Patients receiving class III antiarrhythmic drugs (eg, amiodarone) should be closely monitored, because of the possible risk of complications from the cardiovascular system

- Older patients and weakened patients

- Patients with partial or complete cardiac blockade, since local anesthetics can impair myocardial conductivity.

- Patients with progressive liver disease or with severe renal dysfunction.

Certain types of blockades, regardless of the local anesthetic used, can be associated with serious adverse reactions, for example:

- Central blockades, especially against the background of hypovolemia, can lead to inhibition of the cardiovascular system.

- Large peripheral blockages may require the use of a large amount of local anesthetic in areas of high vascularization, often near large vessels, where the risk of intravascular injection and / or systemic absorption increases, which can lead to a high concentration of the drug in the plasma.

- With retrobulbar injection, the drug can accidentally enter the cranial subarachnoid space, causing temporary blindness, apnea, convulsions, collapse and other side effects.
Developed complications should be timely diagnosed and stopped.
- With retrobulbar and peribulbar injection of local anesthetics, there is a small risk of permanent damage to the function of the eye muscles.
The main causes are trauma and / or local toxic effects on muscles and / or seals. The severity of these tissue reactions depends on the degree of injury, the concentration of the local anesthetic and the duration of exposure of the tissue with a local anesthetic. Therefore, as with other local anesthetics, the lowest effective concentration and dose of the drug should be used. Vasoconstrictors and other additives can enhance tissue reactions and should only be used according to indications.
- When injected into the neck or head, the drug may accidentally enter the artery, and in these cases, even with low doses, serious adverse reactions may develop.

- Paracervical blockade sometimes leads to bradycardia / tachycardia in the fetus, so careful monitoring of the heart rhythm in the fetus is mandatory.

During epidural anesthesia hypotension and bradycardia may occur.
The probability of these complications can be reduced by the preliminary administration of crystalloid and colloidal solutions. With the development of hypotension, immediately introduce sympathomimetics intravenously; If necessary, their introduction should be repeated. In children, the doses used should be appropriate for age and weight.
The solution contains no preservatives and should be used immediately after opening the vial.
Remains of solution should be discarded.
OVERDOSE

Acute systemic intoxication

In case of accidental intravascular injection, a toxic reaction occurs within 1-3 minutes, while in case of an overdose, the maximum plasma concentrations of the drug can be reached within 20-30 minutes depending on the injection site, and the signs of intoxication appear slowly.
Toxic reactions are manifested mainly from the central nervous and cardiovascular system.
Against the background of a high concentration of bupivacaine in the plasma, cases of ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death were documented.

From the central nervous system

Intoxication manifests itself gradually in the form of signs and symptoms of impaired function of the central nervous system with an increasing degree of severity.Initial manifestations of intoxication are: paresthesia around the mouth, dizziness, numbness of the tongue, pathologically increased perception of ordinary sounds and tinnitus.
Violation of the functions of the debate and the tremors are more serious symptoms and precede the onset of generalized convulsions. These events should not be mistakenly viewed as neurotic behavior. Following them, possible loss of consciousness and the development of large seizures that can last from several seconds to several minutes. Due to increased muscle activity and disruption of the normal respiratory process after onset seizures appear quickly hypoxia and hypercapnia. In severe cases apnea may occur. Acidosis increases the toxic effects of local anesthetics.
These phenomena are due to redistribution of the local anesthetic agent from the central nervous system and metabolism of the drug. Relief of toxic effects can occur quickly if the anesthetic was not introduced in a very large number.
Treatment of acute toxicity
If signs of intoxication should immediately discontinue administration of the drug. Therapy should be aimed at maintaining ventilation, treatment of seizures and maintain circulation. Use oxygen and establish artificial ventilation when required (using the mask and bag). If convulsions do not stop spontaneously within 15-20 seconds, enter anticonvulsant drugs intravenously. Intravenous administration of 100-150 mg of thiopental rapidly relieves cramps, instead you can enter 5-10 mg diazepam intravenously, although it acts more slowly. Suxamethonium quickly relieves muscle cramps, however, at its use is required intubation and mechanical ventilation, so the drug should be used only for those who own methods of data.
By explicitly inhibition function of the cardiovascular system (reduced blood pressure and bradycardia) intravenously 5-10 mg ephedrine, if necessary after 2-3 minutes is repeated administration. During cardiac arrest, immediately start to cardiopulmonary resuscitation is vital to optimize oxygenation and ventilation and circulation support, together with the correction of acidosis, since hypoxia and acidosis will enhance systemic toxic effects of local anesthetic. As quickly as possible enter epinephrine (0.1-0.2 mg intravenously or intracardiac) administration should be repeated if necessary.
In cardiac arrest may require prolonged resuscitation.
DRUG INTERACTION

Bupivacaine should be used with caution in patients receiving other medications or local anesthetics which are similar in structure to local anesthetics of amide type, such as antiarrhythmic drugs (e.g., lidocaine, mexiletine), because of the potential toxic effect of the additive. The combined use of bupivacaine with antiarrhythmic drugs of class III (e.g., amiodarone) alone has not been studied, but caution is recommended with concomitant administration of these drugs (see. "Special instructions" section).
Monoamine oxidase inhibitors or tricyclic antidepressants increase the risk of pronounced increase in blood pressure.
Preparations containing oxytocin or ergotamine, promote the development of a sustainable increase in blood pressure with possible complications of the cardiovascular and cerebrovascular system.
The combination of a general inhalation anesthesia with halothane increases the risk of arrhythmia.
When applied to the site of injection of local anesthetic disinfectant solutions containing heavy metals, increases the risk of local reaction as pain and swelling.
Drugs structurally similar to local anesthetics, such as tocainide, increase the risk of additive toxic effects.
In a joint application with drugs depressing the central nervous system, local anesthetics increase CNS depression.
Bupivacaine reduced solubility at pH> 6.5, it should be taken into account when added to alkaline solutions, as can form a precipitate.
TERMS OF RELEASE FROM PHARMACY

On prescription.

TERMS AND CONDITIONS OF STORAGE

List B. The temperature is not above 25 ° C, the reach of children, do not freeze.
Shelf life - 3 years.
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