Lidocaine

INSTRUCTIONS for medical use of the medicinal product LIDOCAINE (LIDOCAIN)

Composition:

Active substance: lidocaine;

1 ampoule (2 ml) of solution contains lidocaine hydrochloride anhydrous (in the form of lidocaine hydrochloride monohydrate) 40 mg;

Excipients: sodium chloride, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless or almost colorless odorless aqueous solution.

Pharmacotherapeutic group. Local anesthetics. ATC code N01B B02.

Pharmacological properties.

Pharmacodynamics.

Lidocaine is an amide-type membrane-stabilizing agent for local anesthesia. It inhibits sensitive nerve endings of the skin and mucous membranes, thereby causing reversible suppression of conduction in neural tissue elements (neuron, axon, synapses).

The mechanism of action of local anesthetics involves inhibition of ionic fluxes essential for the generation of an impulse across neuronal membranes.

Lidocaine suppresses the transient increase in sodium ion permeability induced by stimulation and, to a lesser extent, reduces the delayed permeability for potassium and sodium ions, thus stabilizing neuronal membranes. Lidocaine decreases the degree of depolarization occurring in response to a physiological stimulus, reduces the amplitude of the action potential, and inhibits nerve conduction.

Among various sensory modalities, local anesthetics primarily suppress pain sensation, followed by suppression of warmth perception and tactile sensation. Lidocaine absorbed after local application may cause excitation or depression of the central nervous system. Its effects on the cardiovascular system may manifest as conduction disturbances and peripheral vasodilation.

Pharmacokinetics.

After parenteral administration, lidocaine is completely absorbed. The extent of absorption depends on the site of administration and the presence or absence of a vasoconstrictor.

Except for intravascular injection, the highest plasma lidocaine levels are observed during intercostal nerve block, and the lowest after subcutaneous administration. Plasma protein binding ranges from 60% to 80%. Lidocaine crosses the placental and blood-brain barriers.

Lidocaine is rapidly metabolized in the liver, primarily via oxidative N-dealkylation. Its metabolites have similar pharmacological and toxicological effects as the parent compound but are less potent. Almost 90% of the administered lidocaine dose is excreted as metabolites. Approximately 10% of the administered dose is excreted unchanged by the kidneys. The elimination half-life is 1.5–2 hours. In patients with hepatic disease, the elimination half-life is prolonged.

Clinical characteristics.

Indications.

For local anesthesia (terminal, infiltration, conduction) in surgery, ophthalmology, dentistry, otolaryngology; as a solvent for antibacterial agents of the cephalosporin group.

Contraindications.

Hypersensitivity to the components of the drug, other amide-type local anesthetics; history of epileptiform seizures after lidocaine administration; severe bradycardia, severe arterial hypotension, cardiogenic shock, severe forms of chronic heart failure (grade II–III), sick sinus syndrome, Wolff–Parkinson–White syndrome, Adams–Stokes syndrome, second- and third-degree atrioventricular (AV) block, hypovolemia, severe hepatic/renal dysfunction, porphyria, myasthenia gravis; retrobulbar administration is contraindicated in patients with glaucoma; contraindicated in patients during the first three months after myocardial infarction with reduced left ventricular ejection fraction (less than 35% of normal); coagulation disorders, anticoagulant therapy; infections at the injection site; contraindicated in non-cooperative patients; significant impairment of left ventricular function.

Interaction with other medicinal products and other forms of interaction.

When lidocaine is used concomitantly with drugs such as chlorpromazine, pethidine, bupivacaine, quinidine, disopyramide, amitriptyline, imipramine, nortriptyline, plasma concentration of lidocaine increases due to reduced hepatic metabolism.

Antiarrhythmic agents (including amiodarone, verapamil, disopyramide, ajmaline) and class IA antiarrhythmics (including quinidine, procainamide, disopyramide) or certain antipsychotics (including olanzapine, quetiapine) or 5-HT3 antagonists (including tropisetron, dolasetron) – enhanced cardiodepressive effects (prolongation of the QT interval may occur, and in isolated cases, development of AV block or ventricular fibrillation); concurrent use with amiodarone may lead to seizures.

Procaine, procainamide, quinidine – possible central nervous system (CNS) excitation, delirium, hallucinations.

Curare-like agents – enhanced muscle relaxation (respiratory muscle paralysis possible).

Ethanol enhances the respiratory depressant effect of lidocaine.

Vasoconstrictors (epinephrine, methoxamine, phenylephrine) promote delayed absorption of lidocaine and prolong its action.

Cimetidine reduces hepatic clearance of lidocaine (due to inhibition of microsomal oxidation), increases its concentration and risk of toxic effects. It also has a synergistic effect when combined with lidocaine.

Guanadrel, guanethidine, mica-milamine, trimethaphan – when used in combination for spinal and epidural anesthesia, increased risk of pronounced arterial hypotension and bradycardia.

β-Adrenergic blockers (e.g., propranolol, metoprolol) slow down hepatic metabolism of lidocaine, enhance lidocaine effects (including toxic effects), and increase the risk of bradycardia and arterial hypotension. When β-blockers and lidocaine are used concurrently, the dose of lidocaine should be reduced. β-Blockers also have a synergistic effect with lidocaine; inhibitory effects on cardiac conduction may occur, potentially leading to increased myocardial contractility.

Cardiac glycosides – reduced cardiotonic effect of cardiac glycosides.

Hypnotics or sedatives – possible enhancement of CNS depressant effects of hypnotics and sedatives.

Narcotic analgesics (morphine) – enhanced analgesic effect of narcotic analgesics and respiratory depression.

Monoamine oxidase inhibitors (MAOIs) (furazolidone, procarbazine, selegiline) – increased risk of arterial hypotension and prolonged local anesthetic effect. Parenteral lidocaine should not be used during treatment with MAOIs.

Anticoagulants (including ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin) increase the risk of bleeding.

Anesthetic agents – enhanced respiratory depressant effect of anesthetics (e.g., hexobarbital, thiopental sodium intravenously).

Polymyxin B – requires monitoring of respiratory function.

Rifampicin – possible reduction in plasma concentration of lidocaine.

Propafenone – possible increase in duration and severity of adverse effects on the central nervous system.

Prenylamine – increased risk of ventricular arrhythmia of the "torsades de pointes" type.

Anticonvulsants, barbiturates (phenobarbital) – possible acceleration of lidocaine metabolism in the liver, reduced plasma concentration, enhanced cardiodepressive effect.

Isadrine (isoprenaline), glucagon – increased lidocaine clearance.

Norepinephrine, mexiletine – reduced lidocaine clearance (increased toxicity); decreased hepatic blood flow.

Acetazolamide, thiazide and loop diuretics reduce lidocaine effect due to hypokalemia.

Midazolam – increased plasma concentration of lidocaine.

Drugs causing neuromuscular blockade – enhanced effect of these drugs, as they reduce nerve impulse conduction.

Norepinephrine – has a synergistic effect when combined with lidocaine.

In acidosis, free lidocaine concentration in plasma increases, increasing the risk of toxic effects.

Interaction of lidocaine with other antiarrhythmic agents, e.g., calcium channel blockers, results in inhibitory effects on cardiac conduction, potentially leading to increased myocardial contractility.

Medicinal products affecting hepatic metabolism and microsomal enzyme induction (e.g., phenytoin) may reduce lidocaine efficacy.

Concomitant use with muscle relaxants (e.g., succinylcholine) may result in a synergistic effect.

Use with caution when combined with diazepam.

For all types of injection anesthesia, lidocaine may be combined with epinephrine (1:50,000–1:100,000; prepare extempore, add 1 drop of 0.1% epinephrine solution per 5–10 mL of lidocaine solution), except when systemic effects of epinephrine (adrenaline) are undesirable – hypersensitivity to epinephrine, arterial hypertension, diabetes mellitus, glaucoma, or when short-term anesthetic action is required. Epinephrine promotes delayed absorption of lidocaine and prolongs its effect.

Special precautions.

Lidocaine administration must be performed only by healthcare professionals.

When disinfectants containing heavy metals are used to prepare the injection site, the risk of local reactions such as pain and swelling increases.

Continuous cardiac monitoring with ECG is mandatory during lidocaine use. If sinus node dysfunction occurs, prolongation of the P–Q interval, QRS complex widening, or development of new arrhythmias are observed, the dose should be reduced or the drug discontinued. In cases of marked bradycardia, 0.5–1 mg of atropine should be administered intravenously. In cases of hypotension, intravenous sympathomimetics and/or beta-receptor agonists may be required.

Before administering lidocaine in patients with cardiac disorders (hypokalemia reduces lidocaine efficacy), serum potassium levels must be normalized.

Prior to high-dose lidocaine administration, barbiturates are recommended. When planning subarachnoid anesthesia, MAO inhibitors should be discontinued at least 10 days before anesthesia.

Extreme caution must be exercised to avoid accidental intravascular (especially during local anesthesia in highly vascularized areas) or subdural injection. Careful monitoring for systemic toxic effects on the cardiovascular and central nervous systems is essential (since doses used for epidural anesthesia are always higher than those for subdural administration); aspiration test is recommended when injecting into vascularized tissues.

Extreme caution is required when performing spinal anesthesia in patients with neurological disorders, spinal deformities, sepsis, or severe arterial hypertension.

Lower doses of the drug should be used for procedures involving the head and neck area, including retrobulbar and dental injections, as well as for stellate ganglion block, because systemic toxic effects may reach cerebral circulation via retrograde blood flow.

Extreme caution is required during retrobulbar injection due to possible adverse effects such as collapse, respiratory depression, seizures, and reversible blindness.

Since lidocaine exerts a pronounced antiarrhythmic effect and may itself act as an arrhythmogenic factor potentially triggering arrhythmias, a thorough medical history must be obtained before administration, and the drug should be used cautiously in patients with a history of arrhythmias.

Use with caution and in reduced doses in patients with moderate heart failure, moderate arterial hypotension, incomplete AV block, intraventricular conduction disturbances, moderate hepatic or renal impairment (creatinine clearance not less than 10 mL/min), respiratory dysfunction, epilepsy, post-cardiac surgery, genetic predisposition to malignant hyperthermia, debilitated patients, and elderly patients.

Intramuscular administration of lidocaine may increase creatinine concentration, potentially leading to misdiagnosis of acute myocardial infarction.

During local anesthesia of highly vascularized tissues (e.g., neck during thyroid surgery), particular caution is required to prevent intravascular injection.

The safety of amide-type anesthetics in patients predisposed to malignant hyperthermia is questionable; therefore, their use should be avoided in such cases.

Particular caution is required when administering lidocaine to patients with circulatory insufficiency, hypovolemia, arterial hypotension, or hepatic and renal impairment.

Use with caution in patients with central nervous system disorders who are taking narcotics, as sudden cardiovascular adverse effects may occur. Electrolyte levels in blood should be monitored during prolonged use. Use with caution in patients predisposed to seizures, in shock, or with hypoxia.

Paracervical block may cause fetal bradycardia/tachycardia; therefore, careful monitoring of fetal heart rate is required.

The effect of local anesthetics is reduced if injection is performed into inflamed or infected tissue.

Lidocaine, solution for injection, may have a porphyrogenic effect; therefore, it should be prescribed only for life-threatening indications.

This medicinal product contains 6 mg/mL of sodium chloride, i.e., it is practically sodium-free.

Use during pregnancy or breastfeeding.

The drug crosses the placental barrier and may cause fetal bradycardia; therefore, it should not be administered during pregnancy.

If use of the drug is necessary during lactation, breastfeeding should be discontinued.

Ability to affect reaction speed when driving vehicles or operating machinery.

The drug affects central nervous system function; therefore, driving vehicles or operating machinery is not recommended after lidocaine administration.

Administration and Dosage

The drug should be administered by injection (subcutaneously, intramuscularly) and locally on mucous membranes. Intravascular administration of the drug must be avoided.

For terminal anesthesia: apply the drug onto mucous membranes in adults at a dose of up to 2 mg/kg of lidocaine; duration of anesthesia is 15–30 minutes.

Maximum dose of the drug for adults is 4.5 mg/kg body weight; maximum total dose is 300 mg.

For conduction anesthesia (including anesthesia of brachial and sacral plexuses), administer 5–10 mL (100–200 mg of lidocaine) of the drug. For anesthesia of fingers, toes, nose, ears, inject 2–3 mL (40–60 mg) of a 2% lidocaine solution for injection.

For ophthalmic anesthesia: instill 2 drops of the drug into the conjunctival sac 2–3 times at intervals of 30–60 seconds immediately before examination or surgical intervention.

Children.

Administer to children the lowest total dose according to body weight and in greater dilution (0.5%; 1%). The maximum single dose of lidocaine is 3 mg/kg body weight.

The maximum single dose must not be used when administering repeatedly within 24 hours.

The maximum dose for children under 3 years of age is 1.25 ml, including for children with impaired renal function. No more than 4 doses should be administered within 24 hours. There is insufficient data on prolonged topical use of 2% lidocaine in children under 3 years of age; the drug should be used with extreme caution depending on the child's weight.

The maximum dose for children under 3 years of age is 1.25 ml applied topically on a swab every 3 hours, or 10 ml within 24 hours. The dose for children aged 3 years and older is 5 ml. When prescribing doses for children under 12 years of age with pharyngeal and oral cavity inflammation, the child's age, weight, and method of administration (body surface area—when applying the drug in soft dosage forms) must be taken into account. Administration must be performed after obtaining parental consent.

The drug should not be repeatedly applied topically within the first 2 hours after initial application.

Children. Use in children—see section "Administration and dosage".

Overdose.

May result in intensification of adverse reactions.

Symptoms: psychomotor agitation, dizziness, general weakness, decreased arterial pressure, tremor, visual disturbances, tonic-clonic seizures, coma, collapse, AV block, asphyxia, apnea, depression, drowsiness, anxiety, tinnitus. In cases of significant overdose, impaired consciousness, respiratory depression, shock, and myocardial infarction may occur. The first symptoms of overdose in healthy volunteers occur at a blood lidocaine concentration exceeding 0.006 mg/kg; seizures occur at 0.01 mg/kg.

Treatment: discontinue administration of the drug, oxygen therapy, anticonvulsants, vasoconstrictors (norepinephrine, mesaton), anticholinergics. The patient should be placed in a horizontal position; fresh air access, oxygen supply, and/or artificial ventilation must be ensured. Central nervous system symptoms are managed with benzodiazepines/short-acting barbiturates. If overdose occurs during anesthesia, a short-acting muscle relaxant should be administered. For correction of bradycardia and conduction disturbances, atropine (0.5–1 mg intravenously) should be used; for arterial hypotension—sympathomimetics in combination with β-adrenergic agonists.

In case of cardiac arrest, immediate resuscitation measures are indicated. During the acute phase of lidocaine overdose, dialysis is ineffective. There is no specific antidote.

Adverse Reactions.

• Nervous system disorders: anxiety, drowsiness, dizziness, headache, sleep disturbances, confusion, loss of consciousness up to coma, sensory disturbances, muscle twitching, seizures, motor block, dysarthria, dysphagia; persistent anesthesia, paresis or paralysis of lower limbs and loss of sphincter control (e.g., cauda equina syndrome), skin tingling.
• Blood and lymphatic system disorders: methemoglobinemia.
• Application in dentistry: numbness of tongue and lips.
• Psychiatric disorders: anorexia, irritability, restlessness, hallucinations, depression; after administration of high doses – excited state, euphoria, disorientation.
• Eye disorders: visual disturbances, nystagmus, reversible blindness, diplopia, flickering "floaters" before the eyes, photophobia, conjunctivitis.
• Ear and labyrinth disorders: vertigo, hearing disturbances, tinnitus, hyperacusis.
• Cardiac and vascular disorders: when used in high doses – arrhythmia, bradycardia, slowed cardiac conduction, heart block, cardiac arrest, peripheral vasodilation, collapse; tachycardia, increased/decreased blood pressure, chest pain, hot flushes.
• Gastrointestinal disorders: nausea, vomiting.
• Respiratory system disorders: dyspnea, rhinitis, respiratory depression or respiratory arrest.
• Immune system disorders: allergic reactions, including edema, skin reactions, urticaria, pruritus, angioedema, hypersensitivity reactions including anaphylactoid reactions (e.g. anaphylactic shock), generalized exfoliative dermatitis; immune system suppression, edema.
• Other: sensations of heat, cold or numbness in extremities, malignant hyperthermia, edema, weakness.
• Local reactions: reactions at the injection site, mild burning sensation which disappears as the anesthetic effect increases within 1 minute, thrombophlebitis, hyperemia.
• During spinal or epidural anesthesia, back pain, leg pain, partial/complete spinal block accompanied by arterial hypotension, defecation disorders, involuntary urination, impotence and loss of sensation in the perineal area may occur (the likelihood of these effects increases with higher doses or in case of accidental intrathecal administration of lidocaine when the dose intended for epidural space enters the subarachnoid space). In individual cases, recovery of motor, sensory and/or autonomic function after such intervention may be slow (over several months) or incomplete.

Shelf life. 3 years.

Storage conditions.

Store at a temperature not exceeding 25 °C, in a place inaccessible to children.

Incompatibility.

The drug should not be mixed with other medicinal products in the same syringe. Lidocaine precipitates when mixed with amphotericin, metoclopramide or sulfadiazine. Depending on the pH of the solution, lidocaine may be incompatible with ampicillin.

Packaging.

2 ml in an ampoule, 5 ampoules in a blister; 2 blisters or 20 blisters in a cardboard pack.

Prescription category. Prescription only.

Manufacturer.

EGIS Pharmaceuticals PLC.

Manufacturer's address and location of business operations.

1165 Budapest, Bekényföldi Street 118–120, Hungary.