Lidocaine Velpharm solution for injection 20mg / ml, 2ml No. 10

The dosage regimen should be selected based on the patient's response and the site of administration. The drug should be administered at the lowest concentration and lowest dose that gives the desired effect.

The maximum adult dose should not exceed 300 mg. The volume of solution to be administered depends on the size of the area to be anesthetized. If there is a need for the introduction of a large volume with a low concentration, then the standard solution is diluted with saline (0.9% sodium chloride solution).

Dilution is carried out immediately before administration.

For children, elderly and debilitated patients, the drug is administered in smaller doses appropriate to their age and physical condition. In adults and children 12-18 years old, a single dose of lidocaine (with the exception of spinal anesthesia) should not exceed 5 mg / kg, with a maximum dose of 300 mg.

Children under the age of 1

Experience with children under 1 year of age is limited. The maximum dose in children 1-12 years old is 5 mg / kg of body weight of a 1% solution.

Active ingredient: lidocaine hydrochloride monohydrate (in terms of lidocaine hydrochloride) - 10.0 mg, 20.0 mg.

Excipients: sodium chloride, water for injection.

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

• atrioventricular (AV) block of 3 degrees;

• hypovolemia.

  Carefully

• The introduction of lidocaine should be carried out with caution in patients with myasthenia gravis, epilepsy, chronic heart failure, bradycardia and respiratory depression, coagulopathy, complete or incomplete blockade of intrauterine conduction, convulsive disorders, Melkersson-Rosenthal syndrome, porphyria, and pregnancy as well as in the third trimester

Pharmacodynamics

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 areas of the body and to control arrhythmias. Has a rapid onset of action (about one minute after intravenous administration and fifteen minutes after intramuscular administration), rapidly spreads into the surrounding tissues. The action lasts 10-20 minutes and about 60-90 minutes after intravenous and intramuscular administration, respectively.

Pharmokinetics

Absorption

Lidocaine is rapidly absorbed from the gastrointestinal tract, but due to the effect of 'primary passage' through the liver, only a small amount reaches the systemic circulation. Systemic absorption of lidocaine is determined by the site of administration, dose, and pharmacological profile. The maximum concentration in the blood is reached after intercostal blockade, then (in order of decreasing concentration), after injection into the lumbar epidural space, brachial plexus and subcutaneous tissues. The main factor determining the rate of absorption and blood concentration is the total dose administered, 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 ai-acid glycoprotein (ACG) and albumin. The degree of binding is variable, approximately 66%. 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 blood-brain and placental barriers, probably through passive diffusion. By 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 is longer than lidocaine,half-life (about 10 hours) and can cumulate with 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%.

Withdrawal

The terminal half-life of lidocaine after intravenous bolus administration to healthy adult volunteers is 1Ц2 hours. The terminal half-life of GX is about 10 hours, MEGX is about 2 hours.

Special patient groups

Due to its rapid metabolism, the pharmacokinetics of lidocaine can be influenced by conditions that impair liver function. In patients with hepatic dysfunction, the half-life of lidocaine can be increased by 2 or more times. Impaired renal function does not affect the pharmacokinetics of lidocaine, but can lead to the accumulation of its metabolites. In newborns, a low concentration of LHC is noted, therefore, the connection with plasma proteins may be reduced. Due to the potentially high concentration of the free fraction, the use of lidocaine in neonates is not recommended.

Overdose

Symptoms

Central nervous system toxicity is manifested by symptoms that increase in severity. At first, paresthesia around the mouth, numbness of the tongue, and dizziness may develop. nausea, vomiting, euphoria, hypsracusia, and tinnitus. Visual impairment and muscle tremors or muscle twitching are indicative of more severe toxicity and precede generalized seizures. Loss of consciousness and large seizures may then occur, lasting from a few seconds to several minutes. Convulsions lead to a rapid increase in hypoxia and hypercapnia caused by 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.With a 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 an 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 adequate circulation, and control acidosis (if it develops). In appropriate cases, it is necessary to ensure airway patency and prescribe oxygen, as well as establish an auxiliary ventilation of the lungs (mask or with the help of an Ambu bag). Circulation is maintained 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. Seizure control can be achieved through intravenous diazepam (0.1 mg / kg) or sodium thiopental (1-3 mg / kg), it should be borne in mind that anticonvulsants can also inhibit respiration and blood circulation. Prolonged seizures can impede ventilation and oxygenation of the patient, and early endotracheal intubation should be considered. In case of cardiac arrest, standard cardiopulmonary resuscitation is initiated. The effectiveness of dialysis in the treatment of acute overdose of lidocaine is very low.In case of cardiac arrest, standard cardiopulmonary resuscitation is initiated. The effectiveness of dialysis in the treatment of acute overdose of lidocaine is very low.When cardiac arrest occurs, standard cardiopulmonary resuscitation is initiated. The effectiveness of dialysis in the treatment of acute overdose of lidocaine is very low.

Side effects

Adverse reactions are described according to MedDRA system organ classes. Frequency is defined as follows: Like other local anesthetics, adverse reactions to lidocaine are rare and are usually due to increased plasma concentrations due to inadvertent intravascular administration, overdose, or rapid absorption from areas with an abundant blood supply, or due to hypersensitivity, idiosyncrasy, or decreased patient tolerance. Systemic toxicity reactions are mainly manifested by the central nervous and (or) cardiovascular system (see also the 'Overdose' section),

Immune system disorders

Hypersensitivity reactions (allergic or anaphylactoid reactions, anaphylactic shock) - see also skin and subcutaneous tissue disorders. The lidocaine allergy skin test is considered unreliable.

Nervous System Disorders and Mental Disorders

Neurological signs of systemic toxicity include dizziness, headache, nervousness, tremors, paresthesia around the mouth, tongue numbness, drowsiness, seizures, weakness, restlessness, nystagmus, loss of consciousness, coma. Reactions from the nervous system can be manifested by its excitement or depression. Signs of CNS stimulation may be short-lived or not occur at all, as a result of which the first manifestations of toxicity may be signs of CNS depression - confusion and drowsiness, followed by coma and respiratory failure. Neurological complications of spinal anesthesia include transient neurological symptoms such as pain in the lower back, buttocks, and legs. These symptoms usually develop within 24 hours after anesthesia and resolve within a few days.After spinal anesthesia with lidocaine and similar agents, isolated cases of arachnoiditis and cauda equina syndrome with persistent paresthesia, bowel and urinary tract dysfunction, or paralysis of the lower extremities have been described. Most cases are due to hyperbaric lidocaine concentration or prolonged spinal infusion.

Violations of the organ of vision

Blurred vision, diplopia, and transient amaurosis can be signs of lidocaine toxicity. Bilateral amaurosis can also result from accidental insertion into the optic nerve bed during ophthalmic procedures. After retro- and peribulbar anesthesia, ocular inflammation and diplopia have been reported (see section 'Special instructions'). Hearing and labyrinth disorders Tinnitus, hypsrakusia.

Disorders of the cardiovascular system

Cardiovascular reactions are manifested by arterial hypotension, bradycardia, suppression of myocardial contractile function (negative inotropic effect), arrhythmias, possible cardiac arrest or circulatory failure, peripheral vasodilation, collapse.

Respiratory, Chest and Mediastinal Disorders

Shortness of breath, bronchospasm, respiratory depression, respiratory muscle paralysis, respiratory arrest, paralysis of the respiratory center.

Gastrointestinal disorders

Nausea, vomiting, involuntary defecation.

From the urinary system

Involuntary urination

Skin and subcutaneous tissue disorders

Rash, urticaria, itching of the skin, angioedema, facial edema.

Local reactions With spinal anesthesia - back pain, with epidural anesthesia - accidental entry into the subarachnoid space.

Other

Persistent anesthesia, hypothermia.

Drug interactions

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. Antiviral agents (eg, amprenavir, atazanavir, darunavir, lopinavir) can also cause an increase in serum lidocaine concentration. Hypokalemia caused by diuretics can reduce the effect of lidocaine when they are used simultaneously (see section 'Special instructions').such as mexiletine, tocainide), since the 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 advised. In patients concurrently receiving antipsychotics that prolong or can prolong the QT interval (eg, pimozide, sertindole, olanzapine, quetiapine, zotepin), prenylamine, epinephrine (if inadvertently administered intravenously), or 5-PTZ serotonin receptor antagonists (eg tropisetron, dolasetron), the risk of ventricular arrhythmias may increase. The simultaneous use of quinupristine / dalfopristin may increase the concentration of lidocaine and, thus, increase the risk of ventricular arrhythmias; their simultaneous use should be avoided. In patientssimultaneously receiving muscle relaxants (for example, suxamethonium), the risk of increased and prolonged neuromuscular blockade may increase. After using bupivacaine in patients receiving verapamil and timolol. reported the development of cardiovascular failure; lidocaine is similar in structure to bupivacan. Dopamine and 5-hydroxytryptamine lower the seizure threshold for lidocaine. Opioids are likely to have a pro-convulsive effect, as evidenced by the evidence that lidocaine lowers the seizure threshold to fentanyl in humans. A combination of opioids and antiemetics, sometimes used for sedation in children, can lower the seizure threshold for lidocaine and increase its depressant effect on the central nervous system. The use of epinephrine with lidocaine can reduce systemic absorption,but with accidental intravenous administration, the risk of ventricular tachycardia and ventricular fibrillation increases dramatically. The simultaneous use of other antiarrhythmics, ?-blockers and blockers of 'slow' calcium channels can further reduce AV conduction, ventricular conduction and contractility. The simultaneous use of vasoconstrictors increases the duration of the 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 as they can interfere with the effect of local anesthetics on the central nervous system. Caution should be exercised with long-term 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 may increase the inhibitory effect of lidocaine on the heart. The analgesic effect of local anesthetics may be enhanced by opioids and clonidine. Ethyl alcohol, especially with prolonged abuse, can reduce the effect of local anesthetics. Lidocaine is not compatible with amphotericin B. methohexitone and nitroglycerin. With the simultaneous use of lidocaine with narcotic analgesics, an additive effect develops, which is used when conducting epidural anesthesia, but increases the depression of the central nervous system and respiration. Vasoconstrictors (epinephrine, methoxamine,phenylephrine) prolong the local anesthetic effect of lidocaine and can cause an increase in blood pressure and tachycardia. The use with monoamine oxidase inhibitors (furazolidone, procarbazine, seleginine) probably enhances the local anesthetic effect of lidocaine and increases the risk of lowering blood pressure. G'uanadrel, guanethidine, mecamylamine, grimstafan camsylate increase the risk of a pronounced decrease in blood pressure and bradycardia. Anticoagulants (including ardeparin sodium, dalteparin sodium, danaparoid sodium, enoxalarin sodium, heparin, warfarin, etc.) increase the risk of bleeding. Lidocaine reduces the cardiotonic effect of digitoxin. Lidocaine reduces the effect of anti-myasthenic drugs, enhances and lengthens the effect of muscle relaxant drugs.When treating the injection site with disinfectant solutions containing heavy metals, the risk of developing a local reaction in the form of pain and swelling increases. It is not recommended to mix lidocaine with other drugs.