Lidocaine, 20 mg/ml 2 ml 5 pcs

Pharmacotherapeutic group

Local anesthetic agent

ATCode

N01BB

Pharmacodynamics: Lidocaine is a short-acting local anesthetic of the amide type. Its mechanism of action is based on reduction of permeability of neuronal membrane for sodium ions. As a result, the rate of depolarization decreases and the excitation threshold increases, resulting in reversible local numbness. Lidocaine is used to achieve conductive anesthesia in various parts of the body and to control arrhythmias. It has a rapid onset of action (about one minute after intravenous injection and fifteen minutes after intramuscular injection) and quickly spreads 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 “primary passage” effect through the liver, only small amounts reach the systemic bloodstream. Systemic absorption of lidocaine is determined by the site of administration and its pharmacological profile. The maximum concentration in the blood is reached after intercostal blockade, then (in order of decreasing concentration) after injection in 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 dose administered, regardless of the site of administration. There is a linear relationship between the amount of lidocaine injected and the resulting maximum blood concentration of the anesthetic.

Distribution

Lidocaine binds to plasma proteins including α1-acid glycoprotein (ACG) and albumin. The degree of binding is variable at approximately 66%. Plasma concentrations of AKG in newborns are low, so they have relatively high levels of free bioactive fraction of lidocaine. Lidocaine penetrates through the blood-brain and placental barriers probably by passive diffusion. Metabolism

Lidocaine is metabolized in the liver about 90% of the administered dose undergoes N-dealkylation to form monoethylglycincylidide (MEGX) and glycincylidide (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 are weaker. GX has a longer half-life than lidocaine (about 10 hours) and may cumulate with repeated administration. Metabolites resulting from subsequent metabolism are excreted in the urine. The content of unchanged lidocaine in the urine is less than 10%.

The terminal elimination half-life of lidocaine after intravenous bolus administration in healthy adult volunteers is 1-2 hours. The terminal half-life of GX is approximately 10 hours MEGX is 2 hours.

Particular patient groups

Due to rapid metabolism, the pharmacokinetics of lidocaine may be affected by conditions that impair hepatic function. In patients with hepatic dysfunction the elimination half-life of lidocaine may be 2 or more times longer. Impaired renal function does not affect the pharmacokinetics of lidocaine but may lead to cumulation of its metabolites.

In newborns there are low concentrations of ACG so binding to plasma proteins may be reduced. Because of the potentially high concentration of the free fraction, the use of lidocaine in neonates is not recommended.

Indications

Active ingredient

Composition

How to take, the dosage

The dosing regimen should be selected based on patient response and site of administration. The drug should be administered at the lowest concentration and in the lowest dose to give the desired effect.

The maximum dose for adults should not exceed 300 mg.

The amount of solution to be administered depends on the size of the area to be anesthetized. If there is a need to administer a larger volume at a lower concentration, the standard solution is diluted with saline solution (09% sodium chloride solution). The dilution is carried out immediately prior to administration.

In elderly and frail patients the drug is administered in lower doses appropriate to their age and physical condition.

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

Doses recommended for adults

10 mg/mL

20 mg/mL

Infiltration anesthesia:

Small interventions

2-4 ml (20-40 mg)

2-4 ml (40-80 mg)

Epidural lumbar

25-30 ml (250-300 mg)

Caudal thoracic blockade

Interaction

The toxicity of lidocaine is increased when used concomitantly with cimetidine and propranololol due to the increased concentration of lidocaine, which requires reduction of the lidocaine dose. Both drugs reduce 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 (e.g., amprenavir atazanavir darunavir lopinavir) may also cause increased serum concentrations of lidocaine.

Hypokalemia caused by diuretics may decrease the effect of lidocaine when used concomitantly (see section “Special Precautions”).

Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally similar to amide local anesthetics (e.g., antiarrhythmic agents such as mexiletine tocainide) because the systemic toxic effects are additive. No separate studies of drug interactions between lidocaine and class III antiarrhythmics (e.g. amiodarone) have been performed, but caution is advised. Patients receiving concomitant antipsychotics that prolong or may prolong the QT interval (e.g., pimozide sertindol olanzain quetiapine zotepine) prenylamine epinephrine (if accidentally administered intravenously) or 5-NTZ-serotonin receptor antagonists (e.g., trosetron dolasetron) may be at increased risk for ventricular arrhythmias.

The concomitant use of quinupristine/dalfopristine may increase lidocaine concentrations and thereby increase the risk of ventricular arrhythmias; their concomitant use should be avoided.

In patients receiving concomitant myorelaxants (e.g., suxamethonium), the risk of increased and prolonged neuromuscular blockade may be increased. Cardiovascular failure has been reported in patients receiving verapamil and timolol after the use of bupivacaine; lidocaine is similar in structure to bupivacaine.

Dopamine and 5-hydroxytryptamines lower the seizure threshold for lidocaine. Opioids probably have a proconvulsant effect, which is supported by data that lidocaine lowers the seizure threshold to fentanyl in humans.

The combination of opioids and antiemetics sometimes used for sedation in children may lower the seizure threshold to lidocaine and increase its CNS depressant effects.

The use of epinephrine with lidocaine may reduce systemic absorption but if accidentally administered intravenously, the risk of ventricular tachycardia and ventricular fibrillation increases dramatically.

The concomitant use of other antiarrhythmic β-adrenoblockers and slow calcium channel blockers may further decrease AV conduction through the ventricles and contractility.

The concomitant use of vasoconstrictors increases the duration of action of lidocaine.

The concomitant use of lidocaine and ergot alkaloids (e.g., ergotamine) may cause severe arterial hypotension.

Perhaps caution should be exercised when using sedatives as they may interfere with the CNS effects of the local anesthetic.

Periodic use of antiepileptics (phenytoin) barbiturates and other microsomal liver enzyme inhibitors must be used with caution as this may decrease efficacy and result in increased need for lidocaine.

On the other hand, intravenous phenytoin may increase the cardiac depressant effect of lidocaine.

The analgesic effect of local anesthetics may be enhanced by opioids and clonidip.

Ethyl alcohol, especially with prolonged abuse, may reduce the effects of local anesthetics.

Lidocaine is incompatible with amphotericin B methohexitone and nitroglycerin. Mixing lidocaine with other drugs is not recommended.

Special Instructions

Regional and local anesthesia must be administered by experienced personnel in an appropriately equipped room with equipment and medications readily available for immediate use for cardiac monitoring and resuscitation. The staff performing anesthesia must be qualified and trained in anesthesia techniques and must be familiar with the diagnosis and management of systemic toxic reactions, adverse events and reactions and other complications.

. It should be used with caution in patients with myasthenia gravis epilepsy chronic heart failure bradycardia and respiratory depression and in combination with drugs interacting with lidocaine and leading to increase its bioavailability potentiation of effects (eg phenytoin) or prolongation of excretion (eg in hepatic or terminal renal failure in which lidocaine metabolites may cumulate). Patients receiving class III antiarrhythmic drugs (e.g., amiodarone) should be monitored closely and ECG monitoring should be established as the effects on the heart may be potentiated.

There have been post-registration reports of chondrolysis in patients undergoing prolonged intra-articular infusion of local anesthetics after surgery. In most cases chondrolysis was noted in the shoulder joint. Due to multiple contributing factors and inconsistencies in the scientific literature regarding the mechanism of effect realization, a cause-effect relationship has not been identified. Prolonged intra-articular infusion is not an approved indication for lidocaine. Intramuscular administration of lidocaine may increase creatine phosphokinase activity, which may complicate the diagnosis of acute myocardial infarction.

It has been shown that lidocaine can cause porphyria in animals its use in persons with porphyria should be avoided.

The effect of lidocaine may be reduced when injected into inflamed or infected tissue.

Hypokalemia, hypoxia and acid-base imbalance should be corrected before starting intravenous lidocaine administration.

Some local anesthetic procedures may produce serious adverse reactions regardless of the local anesthetic used.

Conductive anesthesia of the spinal nerves may result in cardiovascular depression, particularly with hypovolemia, and therefore caution should be exercised when performing eidural anesthesia in patients with cardiovascular disorders.

Epidural anesthesia may result in arterial hypotension and bradycardia. The risk can be reduced by prior administration of crystalloid or colloidal solutions. Arterial hypotension should be managed immediately. In some cases, paracervical block in pregnancy may lead to fetal bradycardia or tachycardia; therefore, careful monitoring of fetal heart rate is required (see section “Administration during pregnancy and breastfeeding”).

Injection into the head and neck region may lead to unintentional arterial injection with the development of cerebral symptoms, even at low doses. Retrobulbar injection can rarely lead to entry into the subarachnoid space of the skull leading to serious/severe reactions including cardiovascular failure apnea seizures and temporary blindness. Retro- and peribulbar injection of local anesthetics carries a low risk of persistent oculomotor dysfunction. The main causes include trauma and/or local toxic effects on muscles and/or nerves.

The severity of such reactions depends on the degree of trauma, the concentration of the local anesthetic, and the duration of its exposure to the tissue. Therefore, any local anesthetic should be used at the lowest effective concentration and dose. Lidocaine injection solution is not recommended for use in infants. The optimal serum concentration of lidocaine to avoid toxicity such as seizures and arrhythmias in neonates has not been established. Intravascular administration should be avoided unless directly indicated.

Precautionary use:

– In patients with coagulopathy. Therapy with anticoagulants (e.g., heparin) NSAIDs or plasma substitutes increases the tendency to bleeding. Accidental vascular injury can lead to severe bleeding. If necessary, the activated partial thromboplastin time (APT) and platelet count should be checked;

Patients with complete or incomplete intracardiac conduction block because local anesthetics may inhibit AV conduction;

Patients with seizure disorders should be closely monitored for CNS symptoms. Low doses of lidocaine may also increase seizure readiness. Allergic and toxic nervous system reactions in response to local anesthetics may be more frequent in patients with Melkersson-Rosenthal syndrome;

The third trimester of pregnancy.

Lidocaine solution for injection 20 mg/ml is not approved for intrathecal administration (subarachnoid anesthesia).

Contraindications

– Hypersensitivity to the components of the drug and to amide type anesthetics;

– 3rd degree atrioventricular (AV) block;

– hypovolemia.

Side effects

Unwanted reactions are described according to MedDRA system-organ classes. The 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 accidental intravascular overdose administration or rapid absorption from sites with 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 section “Overdose”).

Immune system disorders

Hypersensitivity reactions (allergic or anaphylactoid reactions anaphylactic shock) – see also skin and subcutaneous tissue disorders. Skin allergy test for lidocaine is considered unreliable.

Nervous system disorders and psychiatric disorders

Neurological signs of systemic toxicity include dizziness nervousness tremors paresthesias around the mouth tongue numbness sleepiness seizures coma. Nervous system reactions may manifest as se agitation or oppression. Signs of CNS stimulation may be short-lived or not occur at all, whereby confusion and somnolence followed by coma and respiratory failure may be the first manifestations of toxicity. Neurological complications of spinal anesthesia include transient neurological symptoms such as low back pain in the 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 concentration of lidocaine or prolonged spinal infusion.

Visual disturbances

The signs of lidocaine toxicity may include blurred vision diplopia and transient amaurosis.

Bilateral amaurosis can also result from accidental injection into the optic nerve bed during ophthalmic procedures. Ocular inflammation and diplopia have been reported after retro- and peribulbar anesthesia (see “Special Precautions”).

Hearing and labyrinth disorders

Tinnitus hyperacusis.

Cardiovascular disorders

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

Respiratory system disorders of the chest and mediastinum organs Dyspnea bronchospasm suppression of breathing respiratory arrest.

Gastrointestinal disorders

Nausea vomiting.

Skin and subcutaneous tissue disorders

Rash urticaria angioedema facial edema.

Overdose

Symptoms

The central nervous system toxicity is manifested by symptoms of increasing severity. Paresthesias around the mouth, numbness of the tongue, dizziness, hyperacusis and tinnitus may first develop. Visual disturbance and muscle tremor or muscle twitching are indicative of more severe toxicity and precede generalized seizures. These signs should not be confused with neurotic behavior. Loss of consciousness and grand mal seizures lasting from a few seconds to several minutes may then occur. Seizures lead to a rapid increase in hypoxia and hypercapnia due to increased muscle activity and respiratory disturbances. Apnea may develop in severe cases. Acidosis increases the toxic effects of local anesthetics.

In severe cases, cardiovascular disorders occur. At high systemic concentrations, arterial hypotension, bradycardia, arrhythmia and cardiac arrest may develop and can be fatal.

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

Treatment

If signs of an overdose occur, the anesthetic administration should be stopped immediately.

Convulsive CNS depression and cardiotoxicity require medical intervention. The primary goals of therapy are to maintain oxygenation to stop convulsions

Maintain blood circulation and control acidosis (if it develops). When appropriate, it is necessary to ensure airway patency and administer oxygen and assisted lung ventilation (mask or Ambu bag). Circulation is maintained by infusion of plasma or infusion solutions. If prolonged circulatory support is necessary, vasopressors should be considered; however, they increase the risk of CNS agitation. Seizure control can be achieved with intravenous diazepam (01 mg/kg) or sodium thiopentane (1-3 mg/kg), but note that anticonvulsants may also depress respiration and circulation. Prolonged seizures may interfere with the ventilation and oxygenation of the patient and early endotracheal intubation should be considered. If cardiac arrest occurs, standard cardiopulmonary resuscitation is initiated.

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

Pregnancy use

Fertility

There are no data on the effect of lidocaine on human fertility.

Pregnancy

Lidocaine may be used during pregnancy and breastfeeding. The prescribed dosing regimen must be strictly adhered to. If there is a history of complications or bleeding, epidural anesthesia with lidocaine is contraindicated in obstetrics.

Lidocaine has been used in a large number of pregnant women and women of childbearing age. No reproductive abnormalities have been reported, i.e., no increase in the incidence of malformations has been noted.

With the potential for the fetus to achieve high concentrations of local anesthetics after paracervical blockade, the fetus may develop adverse reactions such as fetal bradycardia. Therefore, lidocaine in concentrations exceeding 1% is not used in obstetrics. No adverse effects on the fetus have been found in animal studies.

Breastfeeding

Lidocaine in small amounts penetrates into the breast milk its oral bioavailability is very low. Thus the expected amount taken in breast milk is very small hence the potential harm to the baby is very low. The decision to use lidocaine while breastfeeding is up to the physician.

Similarities