Maksikain - instructions for use, doses, side effects, contraindications

auxiliary substances: sodium chloride - 8 mg, 1 M solution of sodium hydroxide or 1 M solution of hydrochloric acid - to a pH of 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:

Bupivacaine is an anesthetic of long-acting, amide type. Reversibly blocks the impulse through the nerve fiber due to the effects on the sodium channels. has an antihypertensive effect, slows down the frequency ofRedundant reductions.

With intrathecal injection, the effect occurs quickly, and its duration varies from medium to long. The duration of the effect depends on the dose.

Maksikain solution isobaric.

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). The pharmacological activity of metabolites is lower than that of bupivacaine.

The slow elimination of bupivacaine is determined by the presence of a slow absorption phase, which explains the longer half-life after subarachnoid administration compared with intravenous administration.

The concentration of bupivacaine in the blood plasma after the intrathecal blockade is lower compared to other types of regional anesthesia, since lower doses are required for intrathecal anesthesia.In general, the increase in the maximum concentration of the drug in the blood plasma is about 0.4 mg / L for every 100 mg of the drug administered. This means that a dose of 20 mg creates a concentration in the blood plasma of approximately 0.1 mg / L.

The total plasma clearance of bupivacaine is 580 ml / min, the volume of distribution is 73 liters, the final half-life (T_1/2) - 2.7 hours. The index of hepatic extraction is about 0.38.

Bupivacaine is mainly associated with α1-acid plasma glycoproteins (binding to plasma proteins of 96%). Bupivacaine clearance is almost entirely due to the metabolism of the drug in the liver and is more dependent on the activity of the liver's enzyme systems than on liver perfusion.

Bupivacaine is metabolized in the liver, mainly by aromatic hydroxylation to 4-hydroxybupivacaine and N-dealkylation to 2,6-pipecyloxylidine (PPX). Both reactions occur with the participation of cytochrome P450 3A4 isoenzymes. About 1% of bupivacaine is excreted urine unchanged during the day after administration, and approximately 5% in the form of PPX. The concentration of PPX and 4-hydroxybupivacaine in plasma during and after prolonged bupivacaine administration is low relative to the administered dose of the drug.

Penetrates through the placental barrier.The connection with the fetal plasma proteins is lower than that of the mother, the concentration of the unbound fraction in the fetus and the mother is the same.

Bupivacaine penetrates into breast milk in quantities that do not pose a risk to the baby.

Indications:

Spinal anesthesia during surgical operations on the lower extremities, including operations on the hip joint, lasting 3-4 hours and not requiring a pronounced motor block (see section "Method of administration and dose").

Contraindications:

- Hypersensitivity to bupivacaine and / or to any of the drug components or other local anesthetics of the amide type.

General contraindications to intrathecal anesthesia should be taken into account:

- aboutacute diseases of the central nervous system (CNS), such as, meningitis, poliomyelitis, intracranial hemorrhage, as well as neoplasms of the central nervous system;

- fromspinal canal and spine disease in the exacerbation phase (spondylitis, swelling) or recent spinal injury;

- fromepticemia;

- megaloblastnaya anemia with subacute combined degeneration of the spinal cord;

- gvaginal skin lesion at the site of the proposed puncture or bordering on the puncture site;

- the patients with severe arterial hypotension, such as cardiogenic or hypovolemic shock;

- coagulation disorder or concomitant anticoagulant therapy.

Carefully:

Weakened elderly patients or patients with severe concomitant diseases, such as atrioventricular blockade of grade II and III, severe renal failure, but regional anesthesia is more preferable for these groups of patients.

Patients taking antiarrhythmic drugs of grade III (for example, amiodarone), need careful monitoring and monitoring of the ECG due to the possibility of developing unwanted effects from the cardiovascular system (see section "Interaction with other drugs").

There is an increased risk of high or complete spinal blockage in elderly patients (over 65 years) and in patients late in pregnancy. Therefore, in such patients it is recommended to use reduced doses of the drug.

Care should be taken when conducting intrathecal anesthesia in patients with neurological diseases such as multiple sclerosis, hemiplegia,paraplegia and neuromuscular disorders, although it has not been proven that intrathecal anesthesia leads to deterioration in these diseases. Before carrying out intrathecal anesthesia in such cases, it is necessary to make sure that the potential benefit to the patient exceeds the possible risk.

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), because of the possibility of developing an additive toxic effect.

Pregnancy and lactation:

The drug during pregnancy should be used only if the expected benefit to the mother exceeds the possible risk to the fetus. Patients on late gestation are recommended to use reduced doses of the drug (see the section "Method of administration and dose")

Lactation

Bupivacaine penetrates into breast milk in quantities that do not pose a risk to the baby.

Dosing and Administration:

The route of administration is intrathecal.

Spinal administration of the drug is carried out only after a clear definition of the subarachnoid space with lumbar puncture.Do not administer the drug until a clear cerebrospinal fluid (CSF) is obtained. It is necessary to use the smallest dose required for adequate anesthesia. The duration of anesthesia depends on the dose, while the distribution of the drug across segments is difficult to predict, especially when using an isobaric (simple) solution.

Recommended doses for Maxicaquin:

Suggested recommendations are for an average adult patient.

There are large individual differences in the nature of the distribution, the beginning and duration of the drug, so the recommended dosages given in the table should be considered as indicative.

Level of anesthesia

Concentration mg / ml

Dose

The beginning of the action,

mines

Duration

actions,

clock

Indications: operations on the lower limbs, including the hip joint

5,0

2-4

10-20

5-8

1,5-4

The recommended area of administration is below L3.

In elderly patients and Patients in late pregnancy it is recommended to use a reduced dose of the drug.

Children (up to 40 kg)

Maksikain can be used in children.In newborns and infants, the volume of cerebrospinal fluid is relatively large, so they need a higher dose per kilogram of body weight than for adults, to reach the same level as adults. Regional anesthesia should be performed by a doctor who has experience working with children and who has the appropriate technique of administration.

Weight, kg)	Dose (mg/tod)
<5	0.4-0.5 mg/kg
5-15	0.3-0.4 mg/kg
15-40	0,25-0,3 mg / kg

Doses in children, given in the table, are indicative. Variability is possible. 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.

Side effects:

Adverse reactions to Maksikain are similar to adverse reactions that occur when intrathecal administration 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 the injection of a needle, or reactions associated with leakage of cerebrospinal fluid (eg, post-puncture headache).

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

Very Frequent

(>1/10)

From the side of the cardiovascular system: arterial hypotension, bradycardia

From the digestive tract: nausea

Frequent

(>1/100, <1/10)

From the nervous system: post-puncture headache

From the digestive tract: vomiting

From the genitourinary system: urinary retention, incontinence

Less frequent

(<1/1000, > 1/100)

From the nervous system: paresthesia, paresis, dysesthesia

From the side of the musculoskeletal system: muscle weakness, pain in the lumbar region

Rare

(<1/1000)

From the cardiovascular system: heart failure

From the nervous system: total spinal block, paraplegia, paralysis, neuropathy, arachnoiditis

From the respiratory system: respiratory depression

Are common: allergic reactions, in the most severe cases - anaphylactic shock.

Overdose:

Acute Systemic Toxicity

The use of the drug in accordance with the recommendations does not lead to a concentration of the drug in the plasma, at which systemic toxic manifestations may occur. However, when the drug is used in combination with other local anesthetics, acute systemic toxicity can develop through the addition of toxic effects.

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. Especially it can be manifested in the case of an unintended intravascular 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. However, the doses normally used for intrathecal anesthesia do not result in a high systemic concentration of the drug.

From the central and peripheral nervous system

With the use of bupivacaine, intoxication manifests itself gradually as signs and symptoms of impaired central nervous system function 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. Impaired vision and tremor are more serious signs and precede the development of generalized seizures. These phenomena should not be mistakenly regarded as neurotic behavior. Following them, loss of consciousness and the development of large convulsive seizures, which can last from a few seconds to a few minutes. After the onset of seizures as a result of increased muscular activity and disruption of the normal breathing process, hypoxia and hypercapnia. In severe cases, it can developsleep apnea. Acidosis infromoozetoxic effect of local anesthetics. These phenomena are due to the redistribution of local anesthetic from the central nervous system and the metabolism of the drug. Coping toxic effects can occur quickly, unless anesthetic has been introduced in a very large amount.

Acute Systemic Toxicity Treatment

When the first signs of acute systemic toxicity or the total spinal block appear, discontinue the drug immediately and conduct symptomatic therapy of cardiovascular and neurological (seizures, CNS depression) disorders.

In the event of cardiac arrest, cardiopulmonary resuscitation should immediately be used.

It is vital to maintain lung ventilation, blood circulation and adequate oxygenation, and also to correct acidosis.

When oppressing the activity of the cardiovascular system (arterial hypotension, bradycardia), intravenous injection of 5-10 mg of ephedrine is necessary, which, if necessary, can be repeated after 2-3 minutes.

Children It is necessary to enter a dose of ephedrine in accordance with their age and weight.

When seizures occur, therapy should be provided to maintain the cardiovascular system, provide adequate oxygenation and arrest seizures. If necessary, provide oxygen supply and artificial ventilation of the lungs (using an Ambu bag or intubation of the trachea). If the convulsions do not stop for 15-20 seconds,should use anticonvulsants: thiopental sodium 1-3 mg / kg IV provides rapid arrest of seizures; you can use 0.1 mg / kg diazepam IV (the effect develops more slowly compared with the action of thiopental). Prolonged convulsions can interfere with ventilation and oxygenation. In such cases, for rapid arrest of seizures, intubation of the trachea and administration of a muscle relaxant (eg, succinylcholine 1 mg / kg) can be used.

Interaction:

Bupivacaine should be used with caution in patients receiving other local anesthetics or drugs that are similar in structure to local anesthetics of the amide type, such as antiarrhythmics (eg, lidocaine, mexiletine), because of the possibility of developing an additive toxic effect.

Joint use of bupivacaine with antiarrhythmic etcepeaRatami tolassa III (eg, amiodarone) has not been studied separately, but caution should be exercised while prescribing these drugs simultaneously (see also "Special instructions").

When treating the site of injection of a local anesthetic with disinfectant solutions containing heavy metals, the risk of developing a local reaction like soreness and edema increases.

When combined with drugs that depress the central nervous system, local anesthetics increase CNS depression.

Monoamine oxidase inhibitors or tricyclic antidepressants together with bupivacaine increase the risk of a marked increase in blood pressure.

The combination of bupivacin with a common inhalation anesthesia halothane increases the risk of arrhythmia.

Incompatibility

It is not recommended to mix solutions for intrathecal anesthesia with other drugs.

Special instructions:

Intrathecal anesthesia should be performed only under the supervision of an experienced specialist in an appropriately equipped operating room. Drugs and medical equipment for resuscitation should be prepared for use.

Prior to the initiation of intrathecal anesthesia, venous access should be provided, for example, as an intravenous catheter.

Personnel conducting anesthesia should be appropriately trained and trained in the diagnosis and treatment of possible side effects, systemic toxic reactions or other possible complications (see "Overdose").

Especially it can be manifested in the case of unintentional intravascular diseasea great introduction. On the background high concentrations of bupivacaine in plasma, there were recorded cases of ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death. However, the doses normally used for intrathecal anesthesia do not result in a high systemic concentration of the drug.

A rare, but at the same time, serious side reaction that can develop with spinal anesthesia is a high or complete spinal block, leading to inhibition of cardiovascular and respiratory systems.

Disorders from the cardiovascular system are caused by extensive sympathetic blockade, which can lead to hypotension, bradycardia and even cardiac arrest.

The blockade of the innervation of the respiratory muscles, including the diaphragm, causes respiratory failure.

In patients with hypovolemia during intrathecal anesthesia, severe arterial hypotension may develop, regardless of the local anesthetic used.

Damage to nerve endings is a rare complication of intrathecal anesthesia and can lead to paresthesia, anesthesia, muscle weakness and paraplegia. Occasionally these violations are permanent.

The drug Maksikain contains no preservatives, the ampoule is intended for single use. Remains of solution should be discarded. Do not re-sterilize the drug.

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 other complications.

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

In addition to direct anesthetic action, local anesthetics can have a depressing effect on cognitive functions, coordination of movements and cause temporary impairment of motor function. During the period of drug use, one should refrain from driving and other potentially dangerous activities that require an increased concentration of collection and speed of psychomotor reactions.

Form release / dosage:

Solution for injection, 5 mg / ml.

Packaging:

4 or 10 ml into neutral glass ampoules.

For 10 ampoules with instructions for use and a vial for opening ampoules or a scarifier ampoule is placed in a box of cardboard for consumer packaging.

5 or 10 ampoules are placed in a contoured cell pack of a polyvinylchloride film or polyethylene terephthalate tape and aluminum foil or paper with a polyethylene coating or without a foil, or without paper.

For 1 or 2 contour packs with instructions for use and a knife for opening ampoules or a scarifier ampullum is placed in a pack of cardboard.

When you pack the ampoules with a break ring or break point, the ampoule opener or ampoule scapper is not put in.

Storage conditions:

At a temperature of 2 to 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003624

Date of registration:13.05.2016 / 25.12.2017

Expiration Date:13.05.2021

The owner of the registration certificate:NOVOSIBHIMFARM, OJSC NOVOSIBHIMFARM, OJSC Russia

Manufacturer: & nbsp

NOVOSIBHIMFARM, OJSC Russia

Representation: & nbspNOVOSIBHIMFARM, OJSCNOVOSIBHIMFARM, OJSC

Information update date: & nbsp30.03.2018

Illustrated instructions

Instructions

Maksikain® (Moxicaine)