Lidocaine - instructions for use, dose, side effects, contraindications

Active substance: in 2 ml of solution contains 40 mg of lidocaine hydrochloride anhydrous (in the form of lidocaine hydrochloride monohydrate 43 mg),

Excipients: sodium chloride for parenteral forms (12 mg), water for injections up to 2 ml.

Description:A clear, colorless or almost colorless, odorless solution.

Pharmacotherapeutic group:Local anesthetic

ATX: & nbsp

N.01.B.B Amides

N.01.B.B.02 Lidocaine

C.01.B.B.01 Lidocaine

C.01.B.B Antiarrhythmic drugs Ib class

Pharmacodynamics:Lidocaine is a short-acting local anesthetic of the amide type. The basis of its mechanism of action is a decrease in the permeability of the neuron membrane for sodium ions. As a result, the rate of depolarization decreases and the excitation threshold increases, leading to reversible local numbness. Lidocaine are used to achieve conductive anesthesia in various parts of the body and control arrhythmias.It has a rapid onset of action (about one minute after intravenous administration and fifteen minutes after intramuscular injection), rapidly spreading to surrounding tissues. The action lasts 10-20 minutes and about 60-90 minutes after intravenous and intramuscular injection, respectively.

Pharmacokinetics:

Absorption

Lidocaine is rapidly absorbed from the gastrointestinal tract, but due to the effect of the "primary passage" through the liver, only a small amount of it reaches the systemic blood flow. Systemic absorption of lidocaine is determined by the site of administration, the dose and its pharmacological profile. The maximum concentration in the blood is achieved after intercostal blockade, then (in decreasing order of concentration), after insertion into the lumbar epidural space, brachial plexus and subcutaneous tissues. The main factor.

determining the rate of absorption and concentration in the blood, is the total administered dose, regardless of the site of administration. There is a linear relationship between the amount of lidocaine administered and the resulting maximum concentration of anesthetic in the blood.

Distribution

Lidocaine binds to plasma proteins, including α₁acid glycoprotein (ACG) and albumin. The degree of binding is variable, amounting to approximately 66%. Plasma concentration of ACG in newborns is low, so they have a relatively high content of free biologically active fraction of lidocaine.

Lidocaine penetrates through blood-brain and placental barriers, probably,

through passive diffusion.

Metabolism

Lidocaine is metabolized in the liver, about 90% of the administered dose is exposed N- dealkylation to form mono-ethylglycinexylidide (MEGX) and glycinexylidide (GX). both contribute to the therapeutic and toxic effects of lidocaine. Pharmacological and toxic effects MEGX and GX comparable to those of lidocaine, but less pronounced. GX has a longer lidocaine, half-life (about 10 hours) and can be cumulated upon repeated administration.

Metabolites, formed as a result of subsequent metabolism, are excreted in the urine,

the content of unchanged lidocaine in urine does not exceed 10%.

Excretion

The terminal period of lidocaine half-life after intravenous bolus administration to healthy adult volunteers is 1-2 hours. Terminal half-life GX is about 10 hours, MEGX - 2 hours.

Special patient groups

Due to rapid metabolism, the pharmacokinetics of lidocaine may be affected by conditions that interfere with liver function. In patients with impaired liver function, the half-life of lidocaine may increase two or more times.

Impaired renal function does not affect the pharmacokinetics of lidocaine, but can lead to the cumulation of its metabolites.

In newborns there is a low concentration of ACG, so the connection with plasma proteins can be reduced. Due to the potentially high concentration of free fraction, the use of lidocaine in neonates is not recommended.

Indications:Local and regional anesthesia, conductive anesthesia for large and small interventions.

Contraindications:

- Hypersensitivity to any of the components of the drug and to anesthetics of the amide type;

- atriovetricular blockade of the third degree;

- hypovolemia.

Carefully:

- In patients with coagulation. Therapy with anticoagulants (eg, heparin). NSAIDs or plasma solvents increase the tendency to bleeding. Accidental damage to blood vessels can lead to severe bleeding.If necessary, check bleeding time, activated partial thromboplastin time (APTT) and platelet count:

- Patients with complete and incomplete blockade of intracardiac conduction, as local anesthetics can depress AV-holding;

- it is necessary to carefully monitor patients with convulsive disorders for symptomatology from the central nervous system. Low doses of lidocaine can also increase convulsive readiness. In patients with Melkersson-Rosenthal syndrome, allergic and toxic reactions from the nervous system in response to the introduction of local anesthetics can develop more often;

third trimester of pregnancy.

Pregnancy and lactation:

Fertility

There are no data on the effect of lidocaine on fertility in humans.

Pregnancy

Lidocaine may be used during pregnancy and breastfeeding. It is necessary to adhere strictly to the prescribed dosage regimen. With complications or bleeding in an anamnesis, epidural anesthesia with lidocaine in obstetrics is contraindicated.

Lidocaine was used in a large number of pregnant women and women of childbearing age.Any reproductive disorders are not registered, i.e. an increase in the frequency of malformations was not noted.

Due to the potential achievement of a high concentration of local anesthetics in the fetus after paracervical blockade, it may develop unwanted reactions, such as fetal bradycardias. Concerning lidocaine in a concentration exceeding 1%, in obstetrics do not apply.

In animal studies, no harmful effects on the fetus were detected.

Breastfeeding period:

Lidocaine in a small amount penetrates into breast milk, its oral bioavailability is very low, so the expected amount coming with breast milk is very small, therefore, the potential harm to the baby is very low. The doctor decides whether to use lidocaine during breastfeeding.

Dosing and Administration:

Dosing regimen

The dosage regimen should be selected based on the patient's reaction and place of administration. The drug should be administered at the lowest concentration and at the lowest dose giving the desired effect. The maximum dose for adults should not exceed 300 mg.

The volume of solution to be administered depends on the size of the anesthetized area. If there is a need to introduce a larger volume with a low concentration, the standard solution is diluted with physiological saline (0.9% solution of sodium chloride). Dilution is carried out immediately before administration.

For children, elderly and weakened patients, the drug is administered in smaller doses corresponding to their age and physical condition.

In adults and children aged 12-18 years, a single dose of lidocaine should not exceed 5 mg / kg with a maximum dose of 300 mg.

Doses recommended for adults

	10 mg / ml	20 mg / ml
Infiltration anesthesia:
Small interventions	2-10 ml (20-100 mg)	-
Large interventions	10-20 ml (100-200 m)d)	5-10 ml (100-200 mg)

Conduction Anesthesia:	3-20 ml (30-200 mg)	1.5-10 ml (30-200 mg)
Anesthesia of the fingers / toes	2-4 ml (20-40 mg)	2-4 ml (40-80 mg)


Epidural, lumbar	25-30 ml (250-300 mg)

Caudal, thoracic blockade	20-30 ml (200-300 mg)

Regional anesthesia	not more than 5 ml (50 mg)	not more than 2.5 ml (50 mg)

Children under the age of 12 years

Experience in children younger than 1 year is limited. The maximum dose in children 1-12 years is not more than 5 mg / kg body weight 1% solution.

Side effects:Undesirable reactions are described in accordance with the system-organ classes MedDRA.Like other local anesthetics, unwanted reactions to lidocaine are rare and, as usually due to accidental intravascular injection, excessive dose or rapid absorption from areas with abundant blood supply, or due to hypersensitivity, idiosyncrasy or reduced patient tolerance. Systemic toxicity reactions are mainly manifested by the central nervous system and / or cardio -vascular system (see section "Overdose").

Immune system disorders:

Hypersensitivity reactions (allergic or anaphylactoid reactions, anaphylactic shock) - see also disorders of the skin and subcutaneous tissues. Skin allergic test on lidocaine is considered unreliable.

Disorders from the nervous system and mental disorders

Neurological symptoms of systemic toxicity include: dizziness, nervousness, tremor, paresthesia around the mouth. numbness of the tongue, drowsiness, convulsions, coma. Reactions from the nervous system may be manifested by its excitation or inhibition.Symptoms of CNS stimulation may be short or do not occur at all, so the first manifestations of toxicity can serve as confusion and drowsiness, followed by coma and respiratory insufficiency.

Neurological complications of spinal anesthesia include transient neurologic symptoms, such as lower back pain, buttocks and legs. These symptoms develop, usually within 24 hours after anesthesia and are resolved within a few days. Following spinal anesthesia, lidocaine and similar agents describe individual cases of arachnoiditis and horse tail syndrome with persistent paresthesia, bowel and urinary tract dysfunction, or paralysis of the lower extremities. Most cases are due to the hyperbaric concentration of lidocaine or prolonged spinal infection.

Disturbances on the part of the organ of sight

Signs of toxicity of lidocaine can be blurred vision, diplopia and transient amaurosis. Bilateral amaurosis can also be a consequence of the accidental introduction of lidocaine into the optic nerve bed during ophthalmic procedures.After retro or peribulbar anesthesia, inflammation of the eye and diplopia have been reported (see section "special instructions").

Violations from the organ of hearing and labyrinth

Ringing in the ears, giuracusia

Disorders from the cardiovascular system

Cardiovascular reactions are manifested by arterial hypotension, bradycardia, myocardial depression (negative inotropic effect), arrhythmias, possible, cardiac arrest or circulatory insufficiency

Disturbances from the respiratory system, chest and mediastinal organs Shortness of breath, asthma, respiratory depression, respiratory arrest

Disorders from the gastrointestinal tract

Nausea, vomiting

Disturbances from the skin and subcutaneous tissues

Rash, hives, angioedema, edema of the face

Report on adverse reactions suspected of treatment

The report of the suspects in connection with the treatment of unwanted reactions that occurred after the registration of the drug is very important. These measures allow monitoring of the ratio of the benefits and risks of the drug. Medical workers should report all suspects for treatment of adverse reactions through pharmacovigilance systems.

Overdose:

Symptoms:

Toxicity from the central nervous system is manifested by symptoms, increasing in severity. First, paresthesia around the mouth, numbness of the tongue, dizziness, hyperacusis and tinnitus can develop. Visual impairment and muscle tremor or muscle twitching indicate more serious toxicity and precedes generalized seizures. These signs should not be confused with neurotic behavior. Then, loss of consciousness and large seizures can occur from a few seconds to several minutes. Seizures lead to a rapid increase in hypoxia and hypercapnia due to increased muscle activity and respiratory failure. In severe cases, apnea may develop. Acidosis increases the toxic effects of local anesthetics. In severe cases, there are violations of the cardiovascular system. At a high systemic concentration, hypotension, bradycardia, arrhythmia and cardiac arrest may develop, which can be fatal.

The resolution of an overdose is due to the redistribution of the local anesthetic from the central nervous system and its metabolism,it can proceed quickly enough (unless a very large dose of the drug has been administered).

Treatment:

If there are signs of an overdose, the injection of the anesthetic should be stopped immediately.

Convulsions, oppression of C11C and cardiogoxicity require medical intervention. The main goals of therapy are to maintain oxygenation, stopping seizures, maintaining blood circulation and stopping acidosis (if it develops). Where appropriate, it is necessary to ensure airway patency and designate oxygen, and also to establish auxiliary ventilation of the lungs (masochnuyu or using an Ambu bag). Maintenance of blood circulation is carried out by infusion of plasma or infusion solutions. If long-term maintenance of blood circulation is necessary, the possibility of introducing vasopressors should be considered, but they increase the risk of CNS excitation. Control of seizures can be achieved by intravenous diazepam (0.1 mg / kg) or thiopental sodium (1-3 mg / kg), while it should be borne in mind that anticonvulsants can also inhibit respiration and circulation.Prolonged convulsions can interfere with lung ventilation and oxygenation of the patient, in connection with which. should consider the possibility of early endotracheal intubation. When the heart is stopped, they start a standard cardiopulmonary resuscitation.

The effectiveness of dialysis in the treatment of acute overdose with lidocaine is very low.

Interaction:

The toxicity of lidocaine increases with its simultaneous use with cimetidine and ipropranolol due to increased concentrations of lidocaine, this requires a reduction in the dose of lidocaine. Both drugs reduce hepatic blood flow. Besides, cimetidine and inhibits microsomal activity. Ranitidine slightly reduces the clearance of lidocaine, which leads to an increase in its concentration. Elevated serum concentrations of lidocaine may also be caused by antiretroviral agents (eg, amprenavir, atazanavir, darunavir, lopinavir).

Hypokalemia caused by diuretics can reduce the effect of lidocaine when they are used simultaneously (see section "Special instructions").

Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally similar to local anesthetics of the amide type (eg, antiarrhythmics, such as mexiletine. gokainid), since systemic toxic effects are additive.

Separate studies of drug interactions between lidocaine and class III antiarrhythmics (eg, amiodarone) have not been conducted, but caution is advisable.

In patients who are simultaneously receiving antipsychotic drugs, prolonging or being able to extend the QT interval (eg, pimozide. sertindole, olanzapine, quetiapine. zotepin). prenylamine, epinephrine (for occasional intravenous administration) or antagonists of 5-HT3-serotonium receptors (for example, tropospheric, dolasstron), the risk of ventricular arrhythmias may increase.

The simultaneous use of hyuuprustia / dalfopristin can increase the concentration of lidocaine and thus increase the risk of ventricular arrhythmias; their simultaneous use should be avoided.

In patients simultaneously receiving muscle relaxants (eg, suxamethonium), the risk of an intensified and prolonged neuromuscular blockade may increase. After using bupivacaine in patients who received verapamil and timolol, reported on the development of cardiovascular failure; lidocaine is close in structure to bupivacaine. Dopamine and 5-hydroxytryptamine lower the threshold of convulsive readiness for lidocaine. Opioids probably have a seizure effect, which is confirmed by the data that lidocaine reduces the convulsive threshold to fenganil in humans.

The combination of onoids and antiemetics, sometimes used for sedation in children, can reduce the convulsive threshold to lidocaine and increase its inhibitory effect on the central nervous system. The use of epinephrine along with lidocaine can reduce systemic absorption, but with occasional intravenous administration, the risk of ventricular tachycardia and ventricular fibrillation increases dramatically.

Simultaneous use of other antiarrhythmics, β-blockers and blockers of "slow" calcium channels can further reduce AV-hold-up. holding by the ventricles and contractility.

Simultaneous use of vasoconstrictor increases the duration of action of lidocaine.

Simultaneous use of lidocaine and ergot alkaloids (eg, ergotamine) can cause severe arterial hypotension.

Caution should be exercised when using sedatives, as they may affect the action of local anesthetics on the CNS.

Caution should be exercised with prolonged use of antiepileptic drugs (phenytopine). barbiturates and other inhibitors of microsomal liver enzymes, as this can lead to a decrease in efficacy and, as a consequence, increased demand for lidocaine.

On the other hand, intravenous administration of phenytoin can increase the inhibitory effect of lidocaine on the heart.

The analgesic effect of local anesthetics can be exacerbated by opioids and clonidine. Ethyl alcohol, especially with prolonged abuse, can reduce the effect of local anesthetics.

Lidocaine is not compatible with amphotericin B, methohexiton and nitroglycerin. To mix lidocaine with other medicinal products is not recommended.

Special instructions:

The introduction of lidocaine should be carried out by specialists with experience in carrying out and equipment for resuscitation. When introducing local anesthetics, it is necessary to have equipment for resuscitation.

It should be used with caution in patients with myasthenia gravis, epilepsy, chronic heart failure, bradycardia and respiratory depression, as well as in combination with drugs,interacting with lidocaine and leading to an increase in its bioavailability, potentiation of effects (eg, phenytoin), or lengthening of excretion (eg, in hepatic or terminal renal failure, in which metabolites of lidocaine can be cumulated).

Patients receiving class III antiarrhythmic drugs (for example, amiodarone) it is necessary to establish close monitoring and ECG monitoring, since the influence on the heart can be potentiated.

There were post-registration reports on chondrolisis in patients who had a long intra-articular infusion of local anesthetics after the operation. In most cases, chondrolisis was noted in the shoulder joint. Due to the many contributing factors and the inconsistency of the scientific literature on the mechanism for effecting the effect, a cause-and-effect relationship has not been identified. Prolonged intra-articular infusion is not an approved indication for the use of lidocaine.

Intramuscular injection of lidocaine may increase the activity of creatine phosphokinase, which may make it difficult to diagnose acute myocardial infarction.

Shown, that lidocaine can cause porphyria in animals, its use in persons with porphyria should be avoided.

When administered to inflamed or infected tissues, the effect of lidocaine may be reduced. Before the initiation of intravenous lidocaine, hypokalemia, hypoxia and acid-base disruption must be eliminated.

Some local anesthetic procedures can lead to serious adverse reactions, regardless of the local anesthetic used.

Conduction anesthesia of the spinal nerves can lead to depression of the cardiovascular system, especially against the background of hypovolemia, therefore caution should be taken when conducting epidural anesthesia in patients with cardiovascular disorders.

Epidural anesthesia can lead to arterial hypotension and bradycardia. The risk can be reduced by the preliminary administration of crystalloid or colloidal solutions. It is necessary to immediately stop arterial hypotension.

In some cases, paranervical blockade in pregnancy can lead to bradycardia or tachycardia in the fetus, in connection with which. A careful monitoring of the fetal heart rate is required (see Fig.section "Application during pregnancy and during breast-feeding").

Introduction to the head and neck can lead to unintentional entry into the artery with the development of cerebral symptoms even in low doses.

Retrobulbar administration in rare cases can lead to entry into the subarachnoid space of the skull, leading to severe / severe reactions, including cardiovascular failure, apnea, convulsions and temporary blindness.

Retro- and peribulbar injection of local anesthetics carries a low risk of persistent oculomotor dysfunction. The main reasons include trauma and (or) local toxic effect on muscles and (or) nerves.

The severity of such reactions depends on the degree of injury, the concentration of the local anesthetic and the duration of its exposure in tissues. In this regard, any local anesthetic should be used in the lowest effective concentration and dose.

Solution for injection of lidocaine is not recommended for use in newborns. The optimal serum concentration of lidocaine, which avoids such toxicity as convulsions and arrhythmias, is not established in newborns.

Avoid intravascular injection, if not directly indicated.

Use with caution:

- in patients with coagulomy. Therapy with anticoagulants (eg, heparin). NSAIDs or plasma solvents increase the tendency to bleeding. Accidental damage to blood vessels can lead to severe bleeding. If necessary, check bleeding time, activated partial thromboplastin time (APTT) and platelet count:

- Patients with complete and incomplete blockade of intracardiac conduction, as local anesthetics can depress AV-holding;

third trimester of pregnancy.

Lidocaine, injection 10. 20 mg / ml is not allowed for intrathecal administration (subarachnoidal anesthesia).

Effect on the ability to drive transp. cf. and fur:After the introduction of local anesthetics, a temporary sensory and / or motor blockade may develop. Until the disappearance of these effects, patients should not drive vehicles and work with mechanisms.

Form release / dosage:Solution for injection 20 mg / ml.

Packaging:2 ml per ampoule with a break point and a green code ring. 5 ampoules in a contoured cell pack sealed with a transparent film of PVC // PET / PE. 20 contour mesh packages in a cardboard box, sealed with a label, together with instructions for use.

Storage conditions:At a temperature of 15 to 25 ° C. in a place inaccessible to children.

Shelf life:5 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014235 / 01

Date of registration:12.05.2008 / 20.10.2014

Expiration Date:Unlimited

Date of cancellation:2018-04-09

The owner of the registration certificate:EGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Manufacturer: & nbsp

EGIS Pharmaceutical Plant, ZAO Hungary

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp09.04.2018

Illustrated instructions

Instructions

Lidocaine (Lidocaine)