Mepivacaine in dentistry instructions for use. Experience in the clinical use of local anesthetics based on mepivacaine. International non-proprietary name

"Mepivacaine (Mepivacaine)" used in the treatment and / or prevention of the following diseases (nosological classification - ICD-10):

Molecular formula: C15-H22-N2-O

CAS Code: 22801-44-1

Description

Characteristic: Anesthetic amide type.

Mepivacaine hydrochloride is a white, odorless crystalline powder. Soluble in water, resistant to both acid and alkaline hydrolysis.

pharmachologic effect

Pharmacology: Pharmacological action - local anesthetic. Being a weak lipophilic base, it passes through the lipid layer of the nerve cell membrane and, turning into a cationic form, binds to receptors (remnants of S6 transmembrane helical domains) of sodium channels of membranes located at the endings of sensory nerves. It reversibly blocks voltage-dependent sodium channels, prevents the flow of sodium ions through the cell membrane, stabilizes the membrane, increases the threshold for electrical stimulation of the nerve, reduces the rate of occurrence of the action potential and lowers its amplitude, and ultimately blocks the depolarization of the membrane, the occurrence and conduction of an impulse along the nerve fibers.

Causes all types of local anesthesia: terminal, infiltration, conduction. It has a fast and strong effect.

When it enters the systemic circulation (and creates toxic concentrations in the blood), it can have a depressing effect on the central nervous system and myocardium (however, when used in therapeutic doses, changes in conductivity, excitability, automatism, and other functions are minimal).

Dissociation constant (pK_a) - 7.6; medium fat solubility. The degree of systemic absorption and plasma concentration depend on the dose, route of administration, vascularization of the injection site and the presence or absence of epinephrine in the composition of the anesthetic solution. The addition of a dilute solution of epinephrine (1:200,000, or 5 µg/mL) to a solution of mepivacaine usually reduces the absorption of mepivacaine and its plasma concentration. Plasma protein binding is high (about 75%). Penetrates through the placenta. Not affected by plasma esterases. It is rapidly metabolized in the liver, the main metabolic pathways are hydroxylation and N-demethylation. In adults, 3 metabolites have been identified - two phenolic derivatives (excreted as glucuronides) and an N-demethylated metabolite (2",6"-pipecoloxylidide). T_1/2 in adults - 1.9-3.2 hours; in newborns - 8.7-9 hours. More than 50% of the dose in the form of metabolites is excreted in the bile, then reabsorbed in the intestine (a small percentage is found in the feces) and excreted in the urine after 30 hours, incl. unchanged (5-10%). Cumulates in violation of liver function (cirrhosis, hepatitis).

Loss of sensitivity is noted after 3-20 minutes. Anesthesia lasts 45-180 minutes. The time parameters of anesthesia (start time and duration) depend on the type of anesthesia, the technique used for its implementation, the concentration of the solution (dose of the drug) and the individual characteristics of the patient. The addition of vasoconstrictor solutions is accompanied by prolongation of anesthesia.

Studies to evaluate carcinogenicity, mutagenicity, effects on fertility in animals and humans have not been conducted.

Indications for use

Application: Local anesthesia for interventions in the oral cavity (all types), tracheal intubation, broncho- and esophagoscopy, tonsillectomy, etc.

Contraindications

Contraindications: Hypersensitivity, incl. to other amide anesthetics; elderly age, severe myasthenia gravis, severe liver dysfunction (including with cirrhosis of the liver), porphyria.

Restrictions on use: Pregnancy, lactation.

Use during pregnancy and lactation: During pregnancy, it is possible if the expected effect of therapy outweighs the potential risk to the fetus (may cause narrowing uterine artery and fetal hypoxia). With caution during breastfeeding (no data on penetration into breast milk).

Side effects

Side effects: From the side nervous system and sensory organs: agitation and / or depression, headache, ringing in the ears, weakness; violation of speech, swallowing, vision; convulsions, coma.

From the side of cardio-vascular system and blood (hematopoiesis, hemostasis): hypotension (or sometimes hypertension), bradycardia, ventricular arrhythmia, cardiac arrest is possible.

Allergic reactions: sneezing, urticaria, pruritis, erythema, chills, fever, angioedema.

Other: oppression respiratory center, nausea, vomiting.

Interaction: Beta-blockers, calcium channel blockers, antiarrhythmic drugs increase the inhibitory effect on myocardial conduction and contractility.

Overdose: Symptoms: hypotension, arrhythmia, increased muscle tone, loss of consciousness, convulsions, hypoxia, hypercapnia, respiratory and metabolic acidosis, dyspnea, apnea, cardiac arrest.

Treatment: hyperventilation, maintenance of adequate oxygenation, assisted breathing, relief of convulsions and seizures

(appointment of thiopental 50-100 mg IV or diazepam 5-10 mg IV), normalization of blood circulation, correction of acidosis.

Dosage and method of application

Dosage and administration: The amount of solution and the total dose depend on the type of anesthesia and the nature of the intervention. For injection use a 3% solution of mepivacaine (the maximum dose for adults is 4.4 mg / kg, but not more than 300 mg per visit) or a 2% solution in combination with epinephrine (1:80,000, 1:100,000) or norepinephrine ( 1:200000) (maximum dose - 6.6 mg/kg, but not more than 400 mg of mepivacaine per visit). Maximum dose mepivacaine (in mg) for children is calculated taking into account the body weight of the child.

Precautions: Use with caution in patients with hepatitis, liver cirrhosis, liver failure, severe renal dysfunction, acidosis.

A local anesthetic of medium duration of action of the amide group. Causes a reversible blockade of nerve conduction by reducing the permeability of neuronal membranes for sodium ions. Compared to lidocaine, mepivacaine causes less vasodilation and has a faster onset and longer duration of action.

Systemic absorption of mepivacaine depends on the dose, concentration, route of administration, degree of tissue vascularization, degree of vasodilation. With anesthesia of the teeth of the upper and lower jaws, the effect develops in 0.5-2 and 1-4 minutes, respectively. Anesthesia of the dental pulp lasts for 10-17 minutes, anesthesia of soft tissues in adults lasts 60-100 minutes. With epidural administration, the effect of mepivacaine develops after 7-15 minutes, the duration of action is 115-150 minutes.

Distributed in all tissues, the maximum concentrations are in well-perfused organs, including the liver, lungs, heart and brain. Mepivacaine undergoes rapid hepatic metabolism and inactivation by hydroxylation and N-demethylation. 3 inactive metabolites are known: two phenolic derivatives, which are excreted as glucuronic conjugates, and 2",6"-pipcoloxylide. Approximately 50% of pepivacaine is excreted in the bile as metabolites and undergoes enterohepatic recirculation followed by excretion via the kidneys. Only 5-10% is excreted in the urine unchanged. Some of the drug is metabolized in the lungs. The metabolism of mepivacaine in newborns is limited, the drug is excreted in them unchanged. The half-life is 1.9-3.2 hours in adults and 8.7-9 hours in newborns. Penetrates through the placenta by passive diffusion.

Indications

Infiltration and transtracheal anesthesia, peripheral, sympathetic, regional (Beers method) and epidural nerve block in surgical and dental interventions. Not recommended for subarachnoid administration.

Application

Infiltration anesthesia:

Adults up to 40 ml of 1% solution (400 mg) or 80 ml of 0.5% solution (400 mg) fractionally over 90 minutes.

For blockade of the cervical nerves, brachial plexus, intercostal nerves:

Adults - 5-40 ml of 1% solution (50-400 mg) or 5-20 ml of 2% solution (100-400 mg).

Paracervical block:

Adults up to 10 ml of 1% solution on each side. Enter slowly with an interval of 5 minutes between injections on the other side.

Blockade of peripheral nerves:

Adults 1-5 ml 1-2% solution (10-100 mg) or 1.8 ml 3% solution (54 mg).

Infiltration anesthesia in dentistry: Adults - 1.8 ml of 3% solution (54 mg). Infiltration is performed slowly with frequent aspiration. In adults, 9 ml (270 mg) of 3% solution is usually sufficient to anaesthetize the entire oral cavity. The total dose should not exceed 400 mg.

Children: 1.8 ml of 3% solution (54 mg). Infiltration is performed slowly with frequent aspiration. The maximum dose should not exceed 9 ml (270 mg) of 3% solution.

Epidural or caudal anesthesia:

Adults - 15-30 ml of 1% solution (150-300 mg), 10-25 ml of 1.5% solution (150-375 mg) or 10-20 ml of 2% solution (200-400 mg ).

Maximum doses:

Adults: 400 mg as a single regional dose; maximum daily dose- 1000 mg.

Children: 5–6 mg/kg. For children under the age of 3 years or weighing less than 13.6 kg, mepivacaine solutions are used at concentrations up to 2%.

Contraindications

Hypersensitivity to amide local anesthetics, coagulopathy, simultaneous use of anticoagulants, thrombocytopenia, infections, sepsis, shock. Relative contraindications are AV blockade, an increase in the duration Q-T, severe heart and liver disease, eclampsia, dehydration, arterial hypotension, severe pseudoparalytic myasthenia gravis, pregnancy and lactation.

Side effects

Nausea, vomiting, arterial hypotension, dizziness, headache, agitation, sinus bradycardia, atrial fibrillation, lengthening P–R And Q-T, AV block, cardiac arrest, respiratory depression, uterine depression, fetal acidosis and bradycardia, injection site reactions, anaphylactic reactions, pruritus, rash, urticaria, tremor, seizures, urinary incontinence.

special instructions

It is forbidden to / in, in / a, intrathecal administration of mepivacaine.

Interactions

Local anesthetics(especially when administered in high doses) may have an antagonistic effect on cholinesterase inhibitors on neuromuscular transmission.

The use of local anesthetics with ganglion blockers may increase the risk of arterial hypotension and bradycardia.

Patients taking MAO inhibitors simultaneously with local anesthetics have an increased risk of arterial hypotension.

Local anesthetics may have an additive hypotensive effect in patients taking antihypertensive drugs and organic nitrates.

Catad_pgroup Local anesthetics

Mepivacaine-Binergia - instructions for use

Registration number:

Trade name:

Mepivacaine-Bynergia

International non-proprietary name:

mepivacaine

Dosage form:

injection

Composition

1 ml of the drug contains:
active substance: mepivacaine hydrochloride - 30 mg;
Excipients: sodium chloride, water for injection.

Description

Clear colorless solution

Pharmacotherapeutic group

Local anesthetic

ATC code:

Pharmacological properties

Pharmacodynamics
Mepivacaine is an amide-type local anesthetic. Injected next to sensitive nerve endings or nerve fibers, mepivacaine reversibly blocks voltage-dependent sodium channels, prevents the generation of impulses at the endings of sensory nerves and the conduction of pain impulses in the nervous system. Mepivacaine is lipophilic with a pKa value of 7.6. Mepivacaine penetrates the nerve membrane in its basic form, then, after reprotonation, it has pharmachologic effect in ionized form. The ratio of these forms of mepivacaine is determined by the pH value of the tissues in the anesthetized area. At low tissue pH values, such as in inflamed tissues, the main form of mepivacaine is present in small amounts, and therefore anesthesia may be insufficient.
Unlike most local anesthetics with vasodilating properties, mepivacaine does not have a pronounced effect on blood vessels and can be used in dentistry without a vasoconstrictor.
The time parameters of anesthesia (start time and duration) depend on the type of anesthesia, the technique used for its implementation, the concentration of the solution (dose of the drug) and the individual characteristics of the patient.
With peripheral nerve blockade, the effect of the drug occurs after 2-3 minutes.
Average duration action during pulp anesthesia is 20-40 minutes, and during soft tissue anesthesia - 2-3 hours.
The duration of motor blockade does not exceed the duration of anesthesia.

Pharmacokinetics
suction, distribution
When injected into the tissues of the maxillofacial region by conduction or infiltration anesthesia, the maximum concentration of mepivacaine in the blood plasma is reached approximately 30-60 minutes after the injection. The duration of action is determined by the rate of diffusion from the tissues into the bloodstream. The distribution coefficient is 0.8. Plasma protein binding is 69-78% (mainly with alpha-1-acid glycoprotein).
The degree of bioavailability reaches 100% in the field of action.
Metabolism
Mepivacaine is rapidly metabolized in the liver (subject to hydrolysis by microsomal enzymes) by hydroxylation and dealkylation to m-hydroxymepivacaine, p-hydroxymepivacaine, pipecolylxylidine, and only 5-10% is excreted unchanged by the kidneys.
It undergoes hepato-intestinal recirculation.
breeding
Excreted by the kidneys, mainly in the form of metabolites. Metabolites are mainly excreted from the body with bile. The half-life (T 1/2) is long and ranges from 2 to 3 hours. The plasma half-life of mepivacaine is increased in patients with impaired hepatic function and/or in the presence of uremia. In liver pathology (cirrhosis, hepatitis), mepivacaine may accumulate.

Indications for use

Infiltration, conduction, intraligamentary, intraosseous and intrapulpal anesthesia in surgical and other painful dental interventions.
The drug does not contain a vasoconstrictor component, which allows it to be used in patients with diseases of the cardiovascular system, diabetes mellitus, angle-closure glaucoma.

Contraindications

• hypersensitivity to mepivacaine (including other local anesthetic drugs of the amide group) or other excipients, which is part of the drug;
• severe liver disease: cirrhosis, hereditary or acquired porphyria;
• myasthenia gravis;
• childhood up to 4 years (body weight less than 20 kg);
• heart rhythm and conduction disturbances;
• acute decompensated heart failure;
• arterial hypotension;
• intravascular administration (before the administration of the drug, it is necessary to conduct an aspiration test, see the section "Special Instructions").

Carefully

• conditions accompanied by a decrease in hepatic blood flow (for example, chronic heart failure, diabetes, liver disease);
• progression of cardiovascular insufficiency;
• inflammatory diseases or infection at the injection site;
• pseudocholinesterase deficiency;
• kidney failure;
• hyperkalemia;
• acidosis;
• old age (over 65 years);
• atherosclerosis;
• vascular embolism;
• diabetic polyneuropathy.

Use during pregnancy and during breastfeeding

Pregnancy
During pregnancy, local anesthesia is considered the safest method for relieving pain during dental procedures. The drug does not affect the course of pregnancy, however, due to the fact that mepivacaine can cross the placenta, it is necessary to evaluate the benefit to the mother and the risk to the fetus, especially in the first trimester of pregnancy.
breastfeeding period
Local anesthetics, including mepivacaine, are excreted to a small extent into breast milk. With a single use of the drug, a negative effect on the child is unlikely. It is not recommended to carry out breast-feeding within 10 hours after application of the drug.

Dosage and administration

The amount of solution and the total dose depend on the type of anesthesia and the nature of the surgical intervention or manipulation.
The rate of administration should not exceed 1 ml of the drug in 1 minute.
To avoid intravenous administration aspiration control should always be carried out.
Use the smallest dose of the drug that provides sufficient anesthesia.
The average single dose is 1.8 ml (1 cartridge).
Do not use already opened cartridges to treat other patients. Cartridges with unused residue of the drug must be disposed of.
adults
The recommended maximum single dose of mepivacaine hydrochloride is 300 mg (4.4 mg/kg body weight), which corresponds to 10 ml of the drug (about 5.5 cartridges).
Children over 4 years of age (weighing over 20 kg)
The amount of the drug depends on age, body weight and the nature of the surgical intervention. The average dose is 0.75 mg / kg of body weight (0.025 ml of the drug / kg of body weight).
The maximum dose of mepivacaine is 3 mg/kg of body weight, which corresponds to 0.1 ml of the drug/kg of body weight.

Special patient groups
In the elderly, an increase in the concentration of the drug in the blood plasma is possible due to a slowdown in metabolism. In this group of patients, it is necessary to use the minimum dose that provides sufficient anesthesia.
In patients with renal or hepatic insufficiency, as well as in patients with hypoxia, hyperkalemia or metabolic acidosis it is also necessary to use the minimum dose that provides sufficient anesthesia.
In patients with diseases such as vascular embolism, atherosclerosis or diabetic polyneuropathy, it is necessary to reduce the dose of the drug by a third.

Side effect

Possible side effects when using the drug Mepivacaine-Binergia are similar to the side effects that occur when taking local anesthetics of the amide type. The most common disorders are those of the nervous system and the cardiovascular system. Serious side effects are systemic.
Side effects grouped by systems and organs in accordance with the MedDRA dictionary and the WHO classification of the incidence of adverse reactions: very often (≥1/10), often (≥1/100 to<1/10), нечасто (≥1/1000 до <1/100), редко (≥1/10000 до <1/1000), очень редко (<1 /10000), частота неизвестна (частота не может быть определена на основе имеющихся данных).

Overdose

Overdose is possible with unintentional intravascular administration of the drug or as a result of exceptionally rapid absorption of the drug. The critical threshold dose is a concentration of 5-6 micrograms of mepivacaine hydrochloride per 1 ml of blood plasma.
Symptoms
From the side of the central nervous system
Mild intoxication - paresthesia and numbness of the oral cavity, tinnitus, "metallic" taste in the mouth, fear, anxiety, tremor, muscle twitching, vomiting, disorientation.
Moderate intoxication - dizziness, nausea, vomiting, speech disorder, numbness, drowsiness, confusion, tremor, choreiform movements, tonic-clonic convulsions, dilated pupils, rapid breathing.
Severe intoxication - vomiting (risk of suffocation), sphincter paralysis, loss of muscle tone, lack of reaction and akinesia (stupor), irregular breathing, respiratory arrest, coma, death.
From the side of the heart and blood vessels
Mild intoxication - increased blood pressure, rapid heartbeat, rapid breathing.
Moderate intoxication - palpitations, arrhythmia, hypoxia, pallor. Severe intoxication - severe hypoxia, cardiac arrhythmia (bradycardia, lowering blood pressure, primary heart failure, ventricular fibrillation, asystole).
Treatment
When the first signs of an overdose appear, it is necessary to immediately stop the administration of the drug, as well as provide support for respiratory function, if possible with the use of oxygen, monitor pulse and blood pressure.
In case of respiratory failure - oxygen, endotracheal intubation, artificial ventilation of the lungs (central analeptics are contraindicated).
In case of hypertension, it is necessary to raise the upper part of the patient's torso, if necessary - nifedipine sublingually.
In case of hypotension, it is necessary to bring the position of the patient's body to a horizontal position, if necessary, intravascular administration of an electrolyte solution, vasoconstrictor drugs. If necessary, the volume of circulating blood is compensated (for example, with crystalloid solutions).
With bradycardia, atropine (0.5 to 1 mg) is administered intravenously.
With convulsions, it is necessary to protect the patient from concomitant injuries, if necessary, intravenous diazepam (5 to 10 mg) is administered. With prolonged convulsions, sodium thiopental (250 mg) and a short-acting muscle relaxant are administered, after intubation, artificial ventilation of the lungs with oxygen is performed.
In severe circulatory disorders and shock - intravenous infusion of electrolyte solutions and plasma substitutes, glucocorticosteroids, albumin.
With severe tachycardia and tachyarrhythmia - intravenous beta-blockers (selective).
In cardiac arrest, cardiopulmonary resuscitation should be performed immediately.
When using local anesthetics, it is necessary to provide access to a ventilator, drugs that increase blood pressure, atropine, anticonvulsants.

Interaction with other drugs

Appointment while taking monoamine oxidase (MAO) inhibitors (furazolidone, procarbazine, selegiline) increases the risk of lowering blood pressure.
Vasoconstrictors (epinephrine, methoxamine, phenylephrine) prolong the local anesthetic effect of mepivacaine.
Mepivacaine enhances the inhibitory effect on the central nervous system caused by other drugs. With simultaneous use with sedatives, a dose reduction of mepivacaine is required.
Anticoagulants (sodium ardeparin, dalteparin, enoxaparin, warfarin) and low molecular weight heparin preparations increase the risk of bleeding.
When treating the injection site of mepivacaine with disinfectant solutions containing heavy metals, the risk of developing a local reaction in the form of pain and swelling increases.
Enhances and prolongs the action of muscle relaxant drugs.
When administered with narcotic analgesics, an additive inhibitory effect on the central nervous system develops.
There is antagonism with antimyasthenic drugs in terms of action on skeletal muscles, especially when used in high doses, which requires additional correction in the treatment of myasthenia gravis.
Cholinesterase inhibitors (antimyasthenic drugs, cyclophosphamide, thiotepa) reduce the metabolism of mepivacaine.
With simultaneous use with blockers of H 2 -histamine receptors (cimetidine), an increase in the level of mepivacaine in the blood serum is possible.
With simultaneous use with antiarrhythmic drugs (tocainide, sympatholytics, digitalis preparations), side effects may increase.

special instructions

It is necessary to cancel MAO inhibitors 10 days before the planned introduction of a local anesthetic.
Use only in a medical institution.
After opening the ampoule, immediate use of the contents is recommended.
The drug must be administered slowly and continuously. When using the drug, it is necessary to control the patient's blood pressure, pulse and diameter of the pupils.
Before using the drug, it is necessary to provide access to resuscitation equipment.
Patients treated with anticoagulants have an increased risk of bleeding and bleeding.
The anesthetic effect of the drug may be reduced when injected into an inflamed or infected area.
When using the drug, unintentional injury to the lips, cheeks, mucous membrane and tongue is possible, especially in children, due to a decrease in sensitivity.
The patient should be warned that eating is possible only after the restoration of sensitivity.
Before the introduction of the drug, it is always necessary to carry out aspiration control to avoid intravascular injection.
Regional and local anesthesia should be performed by experienced professionals in an appropriately equipped room with the availability of ready-to-use equipment and drugs necessary for cardiac monitoring and resuscitation. Anesthesia personnel should be qualified and trained in anesthesia technique and should be familiar with the diagnosis and treatment of systemic toxic reactions, adverse events and reactions, and other complications.
1 ml of the drug contains 0.05 mmol (1.18 mg) of sodium.

Influence on the ability to drive vehicles, mechanisms

The drug has a slight effect on the ability to drive vehicles and mechanisms. During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and psychomotor speed.

Release form

Solution for injections 30 mg/ml.
1.7 ml, 1.8 ml of the drug in transparent colorless glass cartridges of the 1st hydrolytic class, sealed on one side with plungers made of elastomeric material, and on the other hand with combined caps for dental cartridges for local anesthesia, consisting of a disk of elastomeric material and anodized aluminum cap.
10 cartridges in a contour plastic package (pallet) or in a contour cell package; or in an insert for fixing the cartridges.
1.5, 10 blister packs (pallets) or blister packs or inserts with cartridges along with instructions for use in a cardboard pack.
Two protective labels with the company logo are glued onto the pack with cartridges (first opening control).
2 ml of the drug in ampoules of transparent colorless glass of the 1st hydrolytic class or neutral glass of the HC-3 brand.
5 ampoules in a contour plastic package (pallet).
1, 2 contour plastic packages (pallets) with ampoules along with instructions for use and an ampoule knife or an ampoule scarifier in a cardboard pack.
When using ampoules with a colored break point and a notch or a colored break ring, the ampoule knife or ampoule scarifier is not inserted.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C. Do not freeze.
Keep out of the reach of children.

Best before date

5 years
Do not use after the expiry date stated on the packaging.

Holiday conditions

Released by prescription.

Legal entity in whose name the registration certificate is issued / Organization accepting claims:

CJSC "Binergia", Russia, 143910, Moscow region, Balashikha, st. Krupeshina, d. 1.

Manufacturer and place of production:

FKP "Armavir biofactory", Russia, 352212, Krasnodar Territory, Novokubansky district, Progress settlement, st. Mechnikova, 11.

Gross formula

Pharmacological group of the substance Mepivacaine

Nosological classification (ICD-10)

CAS code

Characteristics of the substance Mepivacaine

Anesthetic amide type.

Mepivacaine hydrochloride is a white, odorless crystalline powder. Soluble in water, resistant to both acid and alkaline hydrolysis.

Pharmacology

Being a weak lipophilic base, it passes through the lipid layer of the nerve cell membrane and, turning into a cationic form, binds to receptors (remnants of S6 transmembrane helical domains) of sodium channels of membranes located at the endings of sensory nerves. It reversibly blocks voltage-dependent sodium channels, prevents the flow of sodium ions through the cell membrane, stabilizes the membrane, increases the threshold for electrical stimulation of the nerve, reduces the rate of occurrence of the action potential and lowers its amplitude, and ultimately blocks the depolarization of the membrane, the occurrence and conduction of an impulse along the nerve fibers.

Causes all types of local anesthesia: terminal, infiltration, conduction. It has a fast and strong effect.

When it enters the systemic circulation (and creates toxic concentrations in the blood), it can have a depressing effect on the central nervous system and myocardium (however, when used in therapeutic doses, changes in conductivity, excitability, automatism, and other functions are minimal).

Dissociation constant (pK a) - 7.6; medium fat solubility. The degree of systemic absorption and plasma concentration depend on the dose, route of administration, vascularization of the injection site and the presence or absence of epinephrine in the composition of the anesthetic solution. The addition of a dilute solution of epinephrine (1:200,000, or 5 µg/mL) to a solution of mepivacaine usually reduces the absorption of mepivacaine and its plasma concentration. Plasma protein binding is high (about 75%). Penetrates through the placenta. Not affected by plasma esterases. It is rapidly metabolized in the liver, the main metabolic pathways are hydroxylation and N-demethylation. In adults, 3 metabolites have been identified - two phenolic derivatives (excreted as glucuronides) and an N-demethylated metabolite (2",6"-pipecoloxylidide). T 1/2 in adults - 1.9-3.2 hours; in newborns - 8.7-9 hours. More than 50% of the dose in the form of metabolites is excreted in the bile, then reabsorbed in the intestine (a small percentage is found in the feces) and excreted in the urine after 30 hours, incl. unchanged (5-10%). Cumulates in violation of liver function (cirrhosis, hepatitis).

Loss of sensitivity is noted after 3-20 minutes. Anesthesia lasts 45-180 minutes. The time parameters of anesthesia (start time and duration) depend on the type of anesthesia, the technique used for its implementation, the concentration of the solution (dose of the drug) and the individual characteristics of the patient. The addition of vasoconstrictor solutions is accompanied by prolongation of anesthesia.

Studies to evaluate carcinogenicity, mutagenicity, effects on fertility in animals and humans have not been conducted.

The use of the substance Mepivacaine

Local anesthesia for interventions in the oral cavity (all types), tracheal intubation, broncho- and esophagoscopy, tonsillectomy, etc.

Contraindications

Hypersensitivity, incl. to other amide anesthetics; old age, severe myasthenia gravis, severe liver dysfunction (including liver cirrhosis), porphyria.

Application restrictions

Pregnancy, breastfeeding.

Use during pregnancy and lactation

During pregnancy, it is possible if the expected effect of therapy outweighs the potential risk to the fetus (may cause narrowing of the uterine artery and fetal hypoxia). With caution during breastfeeding (no data on penetration into breast milk).

side effects of mepivacaine

From the nervous system and sensory organs: agitation and/or depression, headache, tinnitus, weakness; violation of speech, swallowing, vision; convulsions, coma.

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): hypotension (or sometimes hypertension), bradycardia, ventricular arrhythmia, possible cardiac arrest.

Allergic reactions: sneezing, urticaria, pruritis, erythema, chills, fever, angioedema.

Others: depression of the respiratory center, nausea, vomiting.

Interaction

Beta-blockers, calcium channel blockers, antiarrhythmic drugs increase the inhibitory effect on myocardial conduction and contractility.

Overdose

Symptoms: hypotension, arrhythmia, increased muscle tone, loss of consciousness, convulsions, hypoxia, hypercapnia, respiratory and metabolic acidosis, dyspnea, apnea, cardiac arrest.

Treatment: hyperventilation, maintenance of adequate oxygenation, assisted breathing, relief of convulsions and seizures

(appointment of thiopental 50-100 mg IV or diazepam 5-10 mg IV), normalization of blood circulation, correction of acidosis.

Tradename

Mepivastezin

International non-proprietary name

mepivacaine

Dosage form

Solution for submucosal injections in dentistry 3% 1.7 ml

Composition

1 ml of solution contains

active substance- mepivacaine hydrochloride 30 mg,

Excipients: sodium hydroxide solution 9.0%, sodium chloride, water for injection.

Description

Colorless, transparent, non-opalescent solution.

Pharmacotherapeutic group

Anesthetics. Local anesthetics. Amides. mepivacaine.

ATX code N01BB03

Pharmacological properties

Pharmacokinetics

Mepivacaine hydrochloride is rapidly and largely absorbed. Plasma protein binding is 60-78% and the elimination half-life is about 2 hours.

The volume of distribution is 84 liters. Clearance - 0.78 l / min.

It is mainly decomposed in the liver, metabolic products are excreted through the kidneys.

Pharmacodynamics

Mepivastezin is used as a local anesthetic in dentistry. Characterized by a rapid onset of action of anesthesia (1-3 minutes after injection), a pronounced analgesic effect and good local tolerance. The duration of action for pulp anesthesia is 20-40 minutes, and for soft tissue anesthesia - from 45 to 90 minutes. Mepivastezin is an amide-type local anesthetic with a rapid onset of anesthesia, which leads to a reversible inhibition of the sensitivity of the autonomic, sensory and motor nerve fibers. The mechanism of action is to block voltage-gated sodium channels on the nerve fiber membrane.

The drug easily diffuses through the nerve fiber membrane into the axoplasm as a base. Inside the axon, it turns into an ionized cationic form (proton) and causes a block of sodium channels. At low pH values, for example, under conditions of inflammation, the effect of the drug is reduced, since the formation of an anesthetic base is difficult.

Indications for use

Infiltration and conduction anesthesia in dentistry:

Uncomplicated tooth extraction

When preparing carious cavities and teeth for a crown

Dosage and administration

As far as possible, the smallest volume of solution that promotes effective anesthesia should be prescribed.

In adults, as a rule, a dose of 1-4 ml is sufficient.

For children aged 4 years and over with a body weight of 20-30 kg, a dose of 0.25-1 ml is sufficient; for children weighing 30 - 45 kg - 0.5-2 ml. The amount of the administered drug should be determined depending on the age and body weight of the child and the duration of the operation. The average dose is 0.75 mg mepivacaine/kg body weight (0.025 ml mepivastezin/kg body weight).

Plasma levels of mepivacaine may be increased in elderly patients due to reduced metabolic processes and a lower volume of distribution of the drug.

The risk of accumulation of mepivacaine increases with repeated applications. A similar effect can be observed with a decrease in the general condition of the patient, as well as with severe violations of the liver and kidneys. Thus, in all such cases, a lower dose of the drug (the minimum amount for sufficient anesthesia) is recommended.

The dose of mepivastezin should be reduced in patients suffering from angina pectoris, atherosclerosis.

Adults:

For adults, the maximum dose is 4 mg mepivacaine per kg of body weight and is equivalent to 0.133 ml of mepivastezin per kg of body weight. This means that 300 mg of mepivacaine or 10 ml of mepivastezin is sufficient for patients weighing 70 kg.

Children aged 4 years and older:

The amount of the administered drug should be determined by the age and body weight of the child and the duration of the operation; do not exceed a value equivalent to 3 mg of mepivacaine per kg of body weight (0.1 ml of mepivastezin per kg of body weight).

The drug is intended for injection as a local anesthetic for dental purposes.

In order to exclude the possibility of intravascular injection, it is always necessary to apply aspiration control in two projections (with a rotation of the needle by 180 °), although its negative result does not always rule out unintentional or unnoticed intravascular injection.

The injection rate should not exceed 0.5 ml in 15 seconds, i.e. 1 cartridge per minute.

Major systemic reactions resulting from accidental intravascular injection can in most cases be avoided by using the following injection technique - after the injection, slowly inject 0.1-0.2 ml and slowly inject the rest of the solution after 20-30 seconds.

Opened cartridges should not be used in other patients.

The rest must be liquidated.

Side effects

Rare (> 0.01%)

metallic taste in the mouth

nausea, vomiting

noise in ears

dizziness

headache

nervousness, anxiety

agitation, anxiety

• blurred vision

  diplopia

  feeling hot, cold, or numb

  increase in respiratory rate

  drowsiness, confusion, tremor, muscle twitching, tonic-clonic convulsions, loss of consciousness, coma and respiratory paralysis, respiratory arrest

  tachypnea

  bradypnea

• cardiovascular failure

Severe cardiovascular attacks are manifested in the form of:

falling blood pressure

conduction disorders

tachycardia

bradycardia

hypotension

• cardiac arrest

Very rarely (<0,01 %)

allergic reactions, including skin rashes, urticaria, anaphylactoid reactions, anaphylactic shock, angioedema, fever.

Contraindications

Hypersensitivity to amide-type local anesthetics or allergy to amide-type local anesthetics

Malignant hyperthermia

Severe disorders of the transmission of nerve impulses and conduction of the heart (for example: AV block II and III degree, severe bradycardia), AV conduction disorders that are not supported by a pacemaker

Decompensated heart failure

severe hypotension

Medically uncontrolled epilepsy

porfiria

Injections into the inflamed area

Children's age up to 4 years.

Drug Interactions

β-blockers, calcium channel blockers increase the inhibition of conduction and myocardial contractility. If sedatives are used to reduce the patient's fear, the dose of anesthetic should be reduced, since the latter, like sedatives, depresses the central nervous system.

During treatment with anticoagulants, the risk of bleeding increases (see section "Special Instructions").

In patients receiving antiarrhythmic drugs, there may be a summation of side effects after the use of MEPIVASTESIN.

Toxic synergism is observed when combined with central analgesics, sedatives, chloroform, ether and sodium thiopental.

special instructions

FOR PROFESSIONAL USE ONLY In dental practice.

Before the injection, it is necessary to conduct a skin test for hypersensitivity to the drug. An anamnesis should be collected regarding the simultaneous use of other drugs. Use benzodiazepines for premedication if necessary. The drug should be administered slowly. The introduction of low doses can cause insufficient anesthesia and lead to an increase in the level of the drug in the blood as a result of the accumulation of the drug or its metabolites.

Athletes should be warned that this preparation contains an active ingredient that may give a positive result in doping controls. Since local anesthetics of the amide type are metabolized mainly in the liver and excreted by the kidneys, the drug should be used with caution in patients with liver and kidney disease. In hepatic insufficiency, it is necessary to reduce the dose of mepivacaine. The dose should also be reduced in cases of hypoxia, hyperkalemia or metabolic acidosis. Increased attention should be paid to patients taking anticoagulants (INR monitoring).

There is a risk of unintentional injury to the mucous membrane due to biting of the lip, cheek, tongue. The patient should be warned not to chew during the anesthesia. Erroneous injections and injections into infected or inflamed tissues should be avoided (the effectiveness of local anesthesia decreases).

It is necessary to avoid accidental intravascular injection (see section "Method of administration and doses".

The drug should be used with caution in patients with a history of epilepsy, diabetes mellitus, with cardiovascular diseases, since they have less ability to compensate for the functional changes associated with the prolongation of arteriovenous conduction that drugs cause.

Precautionary measures

Each time a local anesthetic is used, the following drugs/treatments should be available:

Anticonvulsants (seizure medications such as benzodiazepines or barbiturates), muscle relaxants, atropine, vasoconstrictors, adrenaline for acute allergic or anaphylactic reactions;

Resuscitation equipment (especially oxygen sources) for artificial respiration if necessary;

Careful and continuous monitoring of the cardiovascular and respiratory (breathing adequacy) indicators of the state of the body and the state of consciousness of the patient after each injection of local anesthetic. Restlessness, anxiety, tinnitus, dizziness, blurred vision, trembling, depression or drowsiness are the first signs of CNS toxicity (see section "Overdose").

Mepivastezin should be used with extreme caution in cases of:

Severe renal dysfunction

Severe liver disease

angina pectoris

atherosclerosis

Marked decrease in blood clotting

In patients taking anticoagulants (eg, heparin) or acetylsalicylic acid, accidental intravascular injection during injection may increase the likelihood of serious bleeding and hemorrhage (see section "Drug Interactions").

Dosage and administration

Pregnancy and lactation

Pregnancy

There are no sufficient clinical studies regarding the use of Mepivastezin during pregnancy. Animal studies have not provided an adequate understanding of the effects of use during pregnancy, fetal development, childbirth and postpartum development.

Mepivastezin crosses the placental barrier and reaches the fetus in the womb.

When using mepivastezin in the first trimester of pregnancy, the possibility of a risk of malformations cannot be excluded; in early pregnancy, mepivastezin should be used only if other local anesthetics cannot be used.

lactation period

There are no sufficient data at what doses Mepivastezin passes into breast milk. If its use is necessary during lactation, breastfeeding should be stopped and it can be resumed after 24 hours.

Features of the influence of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

In sensitive patients, after an injection of mepivastezin, a temporary worsening of the reaction may occur, for example, during traffic. The issue of allowing a patient to drive a vehicle or work with potentially dangerous mechanisms is decided by the doctor individually in each specific case.

Overdose

Symptoms: may occur immediately, with accidental intravascular injection, or under conditions of abnormal absorption (eg, inflamed or vascularized tissue) and later, and manifest as symptoms of central nervous system dysfunction (metallic taste in the mouth, nausea, vomiting, tinnitus, dizziness, agitation, restlessness, increased respiratory rate, drowsiness, confusion, tremors, muscle twitches, tonic-clonic convulsions, coma and respiratory paralysis) and / or vascular symptoms (drop in blood pressure, conduction disturbances, bradycardia, cardiac arrest).

Treatment: in case of side effects, immediately stop the introduction of local anesthetic.

Basic general measures

Diagnostics (breathing, blood circulation, consciousness), maintenance/restoration of vital functions of respiration and blood circulation, administration of oxygen, intravenous access.

Special Measures

Hypertension: Elevate patient's upper body, give sublingual nifedipine if necessary.

Convulsions: Protect the patient from concomitant bruising, injury, if necessary, diazepam IV.

Hypotension: The horizontal position of the patient's body, if necessary, intravascular infusion of electrolyte solutions, vasopressors (eg, epinephrine IV).

Bradycardia: Atropine IV.

Anaphylactic shock: Contact an emergency physician. In the meantime, put the patient in a horizontal position, raise the lower part of the body. Intensive infusion of electrolyte solutions, if necessary, i.v. epinephrine, i.v. glucocorticoid.