Markain Spinale - instructions for use, dose, side effects, contraindications

Composition:Composition per ml of solution:
Active ingredient: bupivacaine hydrochloride monohydrate 5.28 mg corresponding to 5.0 mg bupivacaine hydrochloride.
Excipients: sodium chloride 8.6 mg, sodium hydroxide to adjust the pH to 5.0-6.5, water for injection up to 1 ml.

Description:A clear, colorless solution.

Pharmacotherapeutic group:local anesthetic

ATX: & nbsp

N.01.B.B.01 Bupivacaine

Pharmacodynamics:Bupivacaine - local anesthetic of the amide type. With intrathecal injection, the effect occurs quickly, and its duration varies from medium to long. The duration of the effect depends on the dose.
Bupivacaine reversibly inhibits impulses along the nerve fiber by blocking the passage of sodium ions through the cell membrane.
Markain Spinal is a weak hyperbaric solution (in comparison with cerebrospinal fluid) at a temperature of 20 ° C and has the properties of a weak hypobaric solution at a temperature of 37 ° C. In general, the solution of the drug can be considered as isobaric, since gravity affects its distribution in the subarachnoid space. Compared with the Markane Spinal Heavy drug, which contains dextrose and has the properties of a hyperbaric solution, Markain Spinal has a less predictable level of blockade, but a longer duration of the effect.

Pharmacokinetics:

Bupivacaine has a pKa-8,2 index of separation of 346 (at 25 ° C in a noctanol / phosphate buffer pH 7.4). The pharmacological activity of metabolites is lower than that of bupivacaine.

Bupivacaine is completely absorbed from the subarachnoid space; Absorption is biphasic, the half-life for the two phases is 50 and 408 minutes, respectively. The slow elimination of bupivacaine is determined by the presence of a slow absorption phase, which explains the longer half-life (T1 / 2) after epidural 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.

After 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 hours, the intermediate hepatic extraction is about 0.38 after IV. Bupivacaine, mainly binds to α1-acid plasma glycoproteins (binding to plasma proteins - 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 penetrates the placental barrier with a rapid balance in the unbound fraction. The degree of binding to plasma proteins in the fetal blood flow is lower than that of the mother, which leads to a lower concentration of the drug in fetal plasma compared to the total concentration of the drug in the mother's blood plasma.

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

Bupivacaine is metabolized in the liver, mainly by aromatic hydroxylation to 4-hydroxy-bupivacaine and N-dealkylation to PPX. 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 PPX. The concentration of PPX and 4-hydroxy-bupivacaine in plasma during and after prolonged bupivacaine administration is low relative to the administered dose of the drug.

Indications:Intrathecal anesthesia (subarachnoid, spinal) during surgical interventions.Surgical operations on the lower extremities (including the hip joint) lasting 1.5-4 hours (see section "Method of administration and dose").

Contraindications:Hypersensitivity to any of the components of the drug or to other local anesthetics of the amide type.
General contraindications to intrathecal anesthesia should be taken into account:
- Acute diseases of the central nervous system (CNS), such as meningitis, poliomyelitis, intracranial hemorrhage, as well as neoplasms of the central nervous system.
- the constriction of the spinal canal and spine disease in the phase of exacerbation (spondylitis, swelling) or recent injury (fracture) of the spine
-septicemia.
-pernicious anemia with subacute combined degeneration of the spinal cord.
pustular lesions of the skin at the site of the proposed puncture or bordering on the puncture site;
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 hepatic or renal failure, but regional anesthesia is more preferable for these patient groups. 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 and in patients late in pregnancy. Therefore, in such patients it is recommended to use reduced doses of the drug (see the section "Method of administration and dose").
Caution should be exercised in carrying out 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:Pregnancy
Bupivacaine was used in a large number of pregnant women and women of childbearing age. Effects of the drug on reproductive function or an increase in the frequency of malformations were not noted (see the section "Pharmacokinetics"). It is recommended to use reduced doses of the drug in late pregnancy (see 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:

Intrathecal

Adults

These recommendations are indicative for the average adult.

The table is an indicative guide to the dosing of the drug for the most commonly used blockades.When choosing a dose of the drug should be based on clinical experience, taking into account the physical condition of the patient. 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 Marcain Spinal

Level of anesthesia

Concentration,

mg / ml

Dose

ml mg

Start

actions,

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

Recommended area of administration is lower L3.

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

Children (up to 40 kg)

Markain Spinal can be used in children. The difference between children and adults is that in newborns and infants the volume of cerebrospinal fluid is relatively large, so they need a higher dose per kg of body weight than adults to achieve the same level of blockade as adults.

Recommended doses for children

Weight, kg)	Dose (mg / kg)
<5	0,4-0,5 mg / kg
5-15	0,3-0,4 mg / kg
15-40	0,25-0,3 mg / kg

Side effects:

Adverse reactions to Marcain Spinal are analogous to adverse reactions that occur with the 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 insertion of a needle or reactions associated with leakage of cerebrospinal fluid (eg, post-puncture headache).

Very frequent (> 1/10)

From the cardiovascular system: arterial hypotension, bradycardia

From the gastrointestinal tract (GIT): nausea

Frequent (> 1/100, <1/10)

From the nervous system: post-puncture headache From the gastrointestinal tract: vomiting

On the part of the genitourinary system: urinary retention, incontinence

Less frequent (<1/1000,> 1/100)

From the side of the nervous system: paresthesia, paresis, disintegration

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

Rare (<1/1000)

From the cardiovascular system: cardiac arrest

From the side of the nervous system: total spinal block, paraplegia, paralysis, neuropathy, arachnoiditis From the respiratory system: respiratory depression

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

Overdose:

Acute Systemic Toxicity

The use of Markain Spinal in accordance with the recommendations does not lead to such 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 unintentional intravascular injection. 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 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 seizures can occur, which can last from a few seconds to several minutes. Due to increased muscular activity, disruption of the normal breathing process after the onset of seizures, hypoxia and hypercapnia quickly appear. In severe cases, apnea may develop. Acidosis increases the toxic 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 should be given 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 convulsions do not stop on their own within 15-20 seconds, anticonvulsants should be used: 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 anesthetic agents 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 drugs of class III (eg, amiodarone) has not been studied separately, but caution should be exercised while prescribing these drugs (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 prepared and trained in the diagnosis and treatment of possible side effects, systemic toxic reactions or other possible complications (see section "Overdose").
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 unintentional intravascular injection. 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.
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. Arterial hypotension, which usually occurs in adults after an intrathecal blockade, is rarely seen in children under the age of 8 years.
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 preparation Markain Spinal contains no preservatives, the ampoule is intended for single use. Remains of solution should be discarded. Do not re-sterilize the drug.

Effect on the ability to drive transp. cf. and fur:In addition to direct anesthetic action, local anesthetics can have a slight depressant effect on cognitive function and coordination and cause temporary impairment of motor function even in the absence of systemic toxicity.

Form release / dosage:Solution for injection 5 mg / ml.

Packaging:For 4 ml of the drug in ampoules of clear, colorless glass. 5 ampoules placed in a contour mesh PVC / paper package, in a cardboard box with instructions for use.
On an ampoule above a notch (a place of a break) the color point put by a paint is put; above the dot are two colored rings.

Storage conditions:Store at 2-25 ° C. Do not freeze. 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:П N014031 / 01

Date of registration:05.12.2007

The owner of the registration certificate:AstraZeneca ABAstraZeneca AB Sweden

Manufacturer: & nbsp

ASTRAZENECA, AB Sweden

CENEXI France

Information update date: & nbsp2015-12-02

Illustrated instructions

Instructions

Marcain Spinal (Marcaine® Spinal)