Lidocaine

Package leaflet (information for patients)

Tradename
Lidocaine

Dosage form
Solution for injection 20 mg / ml.

Description
Transparent liquid of light yellow color with a weak odor.

Structure
1 ml of solution contains:
Active ingredients: Lidocaine 20mg.
Auxiliary components: sodium chloride for parenteral forms - 12 mg, water d / i - up to 2 ml.

Pharmacotherapeutic group
Antiarrhythmic agent

Pharmacological properties
Lidocaine is a short-acting local anesthetic of the amide type. Its mechanism of action is based on 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 is used to achieve local anesthesia in various parts of the body and to control arrhythmias. It has a quick onset of action (about one minute after intravenous administration and 15 minutes after intramuscular injection), rapidly spreads into the surrounding tissues. The action lasts 10-20 minutes and about 60-90 minutes after i / v and i / m administration, respectively.
Pharmacokinetics
Suction
Lidocaine is rapidly absorbed from the gastrointestinal tract, but due to the "first pass" effect through the liver, only a small amount reaches the systemic circulation. Systemic absorption of lidocaine is determined by the site of administration, dose, and its pharmacological profile. Cmax in the blood is achieved after intercostal blockade, then (in order of decreasing concentration), after injection into the lumbar epidural space, brachial plexus and subcutaneous tissues. The main factor that determines the rate of absorption and concentration in the blood is the total dose administered, regardless of the site of administration. There is a linear relationship between the amount of injected lids and the Cmax of the anesthetic in the blood.
Distribution
Lidocaine binds to plasma proteins, including α1-acid glycoprotein (ACG) and albumin. The degree of binding is variable, approximately 66%. The plasma concentration of ACG in newborns is low; therefore, they have a relatively high content of the free biologically active fraction of lidocaine.
Lidocaine crosses the BBB and the placental barrier, probably through passive diffusion.
Metabolism
Lidocaine is metabolized in the liver, about 90% of the administered dose undergoes N-dealkylation to form monoethylglycinexylidide (MEGX) and glycinexylidide (GX), both contributing to the therapeutic and toxic effects of lidocaine. The pharmacological and toxic effects of MEGX and GX are comparable to those of lidocaine, but less pronounced. GX has a longer T1 / 2 than lidocaine (about 10 hours) and can accumulate with repeated administration.
Metabolites resulting from subsequent metabolism are excreted in the urine.
Withdrawal
Terminal T1 / 2 of lidocaine after intravenous bolus administration to healthy adult volunteers is 1-2 hours. Terminal T1 / 2 GX is about 10 hours, MEGX - 2 hours. The content of unchanged lidocaine in urine does not exceed 10%
Pharmacoki netics in special patient groups
Due to its rapid metabolism, the pharmacokinetics of lidocaine can be influenced by conditions that impair liver function. In patients with impaired liver function, T1 / 2 of lidocaine may increase by a factor of 2 or more.
Renal impairment does not affect the pharmacokinetics of lidocaine, but can lead to the accumulation of its metabolites.
In newborns, a low concentration of AKG is noted, therefore, binding to plasma proteins may be reduced. Due to the potentially high concentration of the free fraction, the use of lidocaine in newborns is not recommended.

Indications for use
In cardiology practice: treatment and prevention of ventricular arrhythmias (extrasystole, tachycardia, flutter, fibrillation), incl. in the acute period of myocardial infarction, with implantation of an artificial pacemaker, with glycosidic intoxication, anesthesia.
For anesthesia: terminal, infiltration, conduction, spinal (epidural) anesthesia in surgery, obstetrics and gynecology, urology, ophthalmology, dentistry, otorhinolaryngology; blockade of peripheral nerves and nerve nodes.

Method of administration and dosage
As an antiarrhythmic agent for adults with the introduction of a loading dose in / in - 1-2 mg / kg for 3-4 minutes; the average single dose is 80 mg. Then they immediately switch to drip infusion at a rate of 20-55 μg / kg / min. The drip infusion can be carried out within 24-36 hours. If necessary, against the background of the drip infusion, the intravenous jet administration of lidocaine at a dose of 40 mg can be repeated 10 minutes after the first loading dose.
IM is administered at 2-4 mg / kg, if necessary, repeated administration is possible after 60-90 minutes.
Children with intravenous administration of a loading dose - 1 mg / kg, if necessary, re-introduction is possible after 5 minutes. For continuous intravenous infusion (usually after administration of a loading dose) - 20-30 mcg / kg / min
For use in surgical and obstetric practice, dentistry, ENT practice, the dosage regimen is set individually, depending on the indications, the clinical situation and the dosage form used.
Maximum doses: for adults, with intravenous administration, a loading dose is 100 mg, with subsequent drip infusion - 2 mg / min; with i / m administration - 300 mg (about 4.5 mg / kg) for 1 hour.
For children, in the case of repeated administration of a loading dose with an interval of 5 minutes, the total dose is 3 mg / kg; with continuous intravenous infusion (usually after administration of a loading dose) - 50 μg / kg / min.

Side effects
From the nervous system: dizziness, headache, weakness, restlessness, nystagmus, loss of consciousness, drowsiness, visual and auditory disturbances, tremor, trismus, convulsions (the risk of their development increases against the background of hypercapnia and acidosis), cauda equina syndrome (paralysis of the legs, paresthesia), paralysis of the respiratory muscles, respiratory arrest, motor and sensory block, respiratory paralysis (often develops with subarachnoid anesthesia), numbness of the tongue (when used in dentistry).
From the side of the cardiovascular system: increase or decrease in blood pressure, tachycardia - when administered with a vasoconstrictor, peripheral vasodilation, collapse, chest pain.
From the digestive system: nausea, vomiting, involuntary defecation.
Allergic reactions: skin rash, urticaria (on the skin and mucous membranes), itching of the skin, angioedema, anaphylactic shock.
Local reactions: with spinal anesthesia - back pain, with epidural anesthesia - accidental entry into the subarachnoid space; with local application in urology - urethritis.
Others: involuntary urination, methemoglobinemia, persistent anesthesia, decreased libido and / or potency, respiratory depression, up to a stop, hypothermia; with anesthesia in dentistry: loss of sensitivity and paresthesia of the lips and tongue, lengthening of anesthesia.

Contraindication
Severe bleeding, shock, arterial hypotension, infection of the intended injection site, severe bradycardia, cardiogenic shock, severe forms of chronic heart failure, SSS in elderly patients, AV block II and III degree (except when a probe is inserted to stimulate the ventricles), severe liver dysfunction.
For subarachnoid anesthesia - complete heart block, bleeding, arterial hypotension, shock, infection of the lumbar puncture site, septicemia.
Hypersensitivity to lidocaine and other local anesthetics of the amide type.
It should be used with caution in conditions accompanied by a decrease in hepatic blood flow (including chronic heart failure, liver diseases), progressive cardiovascular failure (usually due to the development of heart block and shock), in severe and debilitated patients, in elderly patients age (over 65); for epidural anesthesia - for neurological diseases, septicemia, impossibility of puncture due to spinal deformity; for subarachnoid anesthesia - with back pain, brain infections, benign and malignant brain tumors, with coagulopathies various origins, migraine, subarachnoid hemorrhage, hypertension, hypotension, paresthesia, psychosis, hysteria, in uncooperative patients, the impossibility of puncture and due to spinal deformity.

Overdose
Symptoms
CNS toxicity is manifested by symptoms that increase in severity. At first, paresthesia around the mouth, numbness of the tongue, dizziness, hyperacusis and tinnitus may develop. Visual impairment and muscle tremors or muscle twitching indicate more severe toxicity and precede generalized seizures. These signs should not be confused with neurotic behavior. Loss of consciousness and large seizures can then occur, lasting from a few seconds to several minutes. Convulsions lead to a rapid increase in hypoxia and hypercapnia, due to increased muscle activity and respiratory failure. In severe cases, apnea can develop. Acidosis enhances the toxic effects of local anesthetics. In severe cases, violations of the cardiovascular system occur. At high systemic concentration, arterial hypotension, bradycardia, arrhythmia and cardiac arrest can develop, which can be fatal.
Overdose resolution occurs due to the redistribution of the local anesthetic from the central nervous system and its metabolism; it can proceed quite quickly (if a very large dose of the drug has not been administered).
Treatment
If there are signs of overdose, the administration of the anesthetic should be stopped immediately.
Seizures, CNS depression, and cardiotoxicity require medical attention. The main goals of therapy are to maintain oxygenation, stop seizures, maintain circulation, and stop acidosis (if it develops). In appropriate cases, it is necessary to ensure airway patency and prescribe oxygen, as well as establish auxiliary ventilation (mask or with the help of an Ambu bag). Circulation is maintained by plasma infusion 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. Seizure control can be achieved by intravenous administration of diazepam (0.1 mg / kg) or sodium thiopental (1-3 mg / kg), while it should be borne in mind that anticonvulsants can also inhibit breathing and blood circulation. Prolonged convulsions can interfere with ventilation and oxygenation of the patient, and therefore, early endotracheal intubation should be considered. When cardiac arrest occurs, standard cardiopulmonary resuscitation is initiated. The effectiveness of dialysis in the treatment of acute overdose of lidocaine is very low.

Precautions
Caution should be exercised in cases of liver and kidney disease, hypovolemia, severe heart failure with impaired contractility, genetic predisposition to malignant hyperthermia. In children, debilitated patients, elderly patients, dose adjustment is necessary in accordance with age and physical status. When injected into vascularized tissues, it is recommended to perform an aspiration test.
When applied topically, use with caution in case of infection or injury at the site of application.
If during the period of application of the plate there is a burning sensation or redness of the skin, it must be removed and not applied until the redness disappears. Used plates must not be accessible to children or pets. Dispose of the plate immediately after use.

Interaction with other medicinal products
The toxicity of lidocaine increases with its simultaneous use with cimetidine and propranolol due to an increase in the concentration of lidocaine, this requires a decrease in the dose of lidocaine. Both drugs decrease hepatic blood flow. In addition, cimetidine inhibits microsomal activity. Ranitidine slightly reduces the clearance of lidocaine, which leads to an increase in its concentration.
Antiretroviral drugs (eg, amprenavir, ata zanavir, darunavir, lopinavir) can also cause elevated serum lidocaine concentrations.
Hypokalemia caused by diuretics can reduce the effect of lidocaine when used simultaneously.
Lidocaine should be used with caution in patients receiving other local anesthetics or agents that are structurally similar to local anesthetics of the amide type (for example, antiarrhythmic agents such as mexiletine, tocainide), since systemic toxic effects are additive in nature.
There have not been separate studies of drug interactions between lidocaine and class III antiarrhythmics (eg, amiodarone), but caution is advised.
In patients who are concurrently receiving antipsychotics that prolong or can prolong the QT interval (eg, pimozide, sertindole, olanzapine, quetiapine, zotepine), prenylamine, epinephrine (if inadvertently administered intravenously), or serotonin 5HT3 receptor antagonists (eg, tropisetron dolasetron), the risk of ventricular arrhythmias may be increased.
Concomitant use of quinupristine / dalfopristin may increase the concentration of lidocaine and, thus, increase the risk of ventricular arrhythmias; simultaneous use should be avoided.
Patients concurrently receiving muscle relaxants (eg, suxamethonium) may have an increased risk of increased and prolonged neuromuscular blockade.
After the use of bupivacaine in patients receiving verapamil and timolol, the development of cardiovascular failure was reported; lidocaine is structurally similar to bupivacaine.
Dopamine and 5-hydroxytryptamine reduce the seizure threshold for lidocaine.
Opioids are likely to have a pro-convulsive effect, which is supported by evidence that lidocaine reduces the seizure threshold for fentanyl in humans.
A combination of opioids and antiemetics, sometimes used to induce sedation in children, can lower the seizure threshold and increase the CNS depressant effect of lidocaine.
The use of epinephrine together with lidocaine can reduce systemic absorption, but with accidental intravenous administration, the risk of ventricular tachycardia and ventricular fibrillation increases sharply.
The simultaneous use of other antiarrhythmic drugs, beta-blockers and slow calcium channel blockers can further reduce AV conduction, intraventricular conduction and contractility.
The simultaneous use of vasoconstrictor agents increases the duration of action of lidocaine.
The simultaneous use of lidocaine and ergot alkaloids (for example, ergotamine) can cause severe arterial hypotension.
Care must be taken when using sedatives because they can interfere with the effect of local anesthetics on the central nervous system.
Caution should be exercised with prolonged use of antiepileptic drugs (phenytoin), barbiturates and other inhibitors of liver microsomal enzymes, as this can lead to a decrease in effectiveness and, as a result, an increased need for lidocaine. On the other hand, intravenous administration of phenytoin can enhance the depressant effect of lidocaine on the heart.
The analgesic effect of local anesthetics can be enhanced by opioids and clonidine.
Ethanol, especially with prolonged abuse, can reduce the effect of local anesthetics.
Lidocaine is incompatible with amphotericin B, metohexitone and nitroglycerin.
It is not recommended to mix lidocaine with other drugs.

Special instructions
Care should be taken to inject lidocaine solutions into tissues with abundant vascularization (for example, in the neck during operations on the thyroid gland); in such cases, lidocaine is used in smaller doses.
With simultaneous use with beta-blockers, with cimetidine, a decrease in the dose of lidocaine is required; with polymyxin B - the respiratory function should be monitored.
During treatment with MAO inhibitors, parenteral lidocaine should not be administered.
Injection solutions containing epinephrine and norepinephrine are not intended for IV administration.
Lidocaine should not be added to transfused blood.
Influence on the ability to drive vehicles and mechanisms
After using lidocaine, it is not recommended to engage in activities that require a high concentration of attention and fast psychomotor reactions.

Pregnancy and elbowing
During pregnancy and lactation, use only for health reasons. Lidocaine is excreted in breast milk.
In obstetric practice, it should be used with caution paracervically for violations of intrauterine fetal development, placental insufficiency, prematurity, postmaturity, gestosis.

Influence on the ability to drive vehicles and work with mechanisms
Does not affect.

Storage conditions
Store in a dry, dark place at a temperature not exceeding 25 ° C, out of the reach of children.

Shelf life
3 years. Do not use after the expiration date printed on the package.

Vacation conditions
On prescription.

Packaging
The solution is in 2 ml glass ampoules. Each ampoule is fixed in a plastic clip for 5 ampoules. 5 ampoules are packed in a cardboard box in a fixer together with an enclosed leaflet.