Lidocaine

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LIDOCAINE (LIDOCAINE)

Composition:

Active substance: lidocaine;

1 ml of solution contains lidocaine hydrochloride monohydrate 10 mg;

Excipients: sodium chloride, sodium hydroxide 1 M solution, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless or slightly colored liquid.

Pharmacotherapeutic group. Local anesthetics. Lidocaine.

ATC code N01B B02.

Pharmacological properties.

Pharmacodynamics.

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

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

Lidocaine inhibits the stimulus-induced transient increase in permeability to sodium ions and, to a lesser extent, reduces the delayed permeability to potassium and sodium ions, thereby stabilizing neuronal membranes. Lidocaine reduces the degree of depolarization occurring in response to a physiological stimulus, as well as the amplitude of the action potential, and suppresses nerve conduction.

Among various sensory modalities, local anesthetics primarily suppress pain sensitivity, followed by suppression of warmth sensation and tactile perception. Lidocaine absorbed after local application may cause excitation or depression of the central nervous system. Its effect 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 drug administration and the presence or absence of a vasoconstrictor.

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

Lidocaine is rapidly metabolized in the liver, primarily via oxidative N-dealkylation. Its metabolites have the same 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.

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

Contraindications.

Increased individual sensitivity to components of the medicinal product, other amide-type local anesthetics; history of epileptiform seizures induced by lidocaine; severe bradycardia; severe arterial hypotension; cardiogenic shock; severe forms of chronic heart failure (II–III degree); sinus node weakness syndrome; Wolff–Parkinson–White syndrome; Adams–Stokes syndrome; second- and third-degree atrioventricular (AV) block; hypovolemia; severe impairment of liver/kidney function; porphyria; myasthenia. 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 types of interactions.

When lidocaine is used concomitantly with such drugs as chlorpromazine, pethidine, bupivacaine, quinidine, disopyramide, amitriptyline, imipramine, nortriptyline, plasma concentration of lidocaine decreases.

Antiarrhythmic agents (including amiodarone, verapamil, disopyramide, ajmaline), particularly class IA antiarrhythmics (e.g., quinidine, procainamide, disopyramide), and certain antipsychotic agents (e.g., olanzapine, quetiapine), H3-antagonists (e.g., tropisetron, dolasetron) – enhanced cardiodepressant effect (prolongation of QT interval occurs; in isolated cases, development of AV block or ventricular fibrillation is possible); concomitant use with amiodarone may lead to seizures.

Procaine, procainamide – 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. Cimetidine also exerts a synergistic effect when interacting with lidocaine.

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

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

Cardiac glycosides – cardiostimulatory effect of cardiac glycosides is reduced.

Hypnotic or sedative medicinal products – 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 (furazolidone, procarbazine, selegiline) – increased risk of arterial hypotension and prolonged local anesthetic effect. Parenteral administration of lidocaine should not be used during treatment with monoamine oxidase inhibitors.

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

Anesthetic agents – enhanced respiratory center depression by anesthetic agents (e.g., hexobarbital, intravenous sodium thiopental).

Polymyxin B – respiratory function monitoring is required.

Rifampicin – possible reduction in its blood concentration.

Propafenone – possible increase in duration and severity of central nervous system-related adverse effects.

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

Anticonvulsants, barbiturates (phenobarbital) – possible acceleration of lidocaine metabolism in the liver, decreased blood concentration, enhanced cardiodepressant effect.

Isadrine (isoprenaline), glucagon – increased lidocaine clearance.

Noradrenaline – exhibits a synergistic effect when interacting with lidocaine.

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

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

Midazolam – increased plasma concentration of lidocaine.

Medicinal products causing blockade of neuromuscular transmission – enhanced effect of these agents, as they reduce nerve impulse conduction.

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

When lidocaine interacts with other antiarrhythmic agents, e.g., calcium antagonists, inhibitory effects on cardiac conduction occur, which may lead to increased myocardial contractility.

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

Concomitant use of 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 (1:50000 — 1:100000; prepare ex tempore, add 1 drop of 0.1% epinephrine solution per 5–10 mL of lidocaine solution), except in cases where systemic effects of epinephrine (adrenaline) are undesirable (increased sensitivity to epinephrine, arterial hypertension, diabetes mellitus, glaucoma), or when short-term anesthetic action is required. Epinephrine promotes delayed absorption of lidocaine and prolongs its action.

Special precautions for use.

Lidocaine should only be administered by healthcare professionals.

The use of disinfectants containing heavy metals at the injection site increases the risk of local reactions such as pain and swelling.

ECG monitoring is mandatory during lidocaine administration. In case of sinus node dysfunction, prolonged P–Q interval, widened QRS complex, or development of new arrhythmias, the dose should be reduced or the drug discontinued. In the event of pronounced bradycardia, 0.5–1 mg of atropine should be administered intravenously. In case of hypotension, sympathomimetics and/or beta-receptor agonists may be administered intravenously as needed.

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

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

Extreme caution should be exercised to avoid accidental intravascular (especially when performing local anesthesia in areas rich in blood vessels) 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 before injection into vascularized tissues.

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

Smaller doses of the drug should be used for administration in 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 flow.

Extreme caution is required during retrobulbar injection, as adverse effects such as collapse, respiratory distress, seizures, and reversible blindness may occur.

Since lidocaine has a pronounced antiarrhythmic effect and may itself act as an arrhythmogenic factor, 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 AВ-blockade, intraventricular conduction disturbances, moderate hepatic or renal impairment (creatinine clearance not less than 10 mL/min), respiratory dysfunction, epilepsy, after cardiac surgery, in patients with genetic predisposition to malignant hyperthermia, debilitated patients, and elderly patients.

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

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

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

Use with caution in patients with central nervous system disorders who are using narcotics, as sudden cardiovascular adverse effects may occur. During prolonged use, serum electrolyte levels should be monitored. Use cautiously in patients with seizure predisposition, in shock, or with hypoxia.

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

The efficacy of local anesthetics is reduced when injection is administered into inflamed or infected tissue.

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

This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is nearly sodium-free.

Use during pregnancy or breastfeeding.

The drug crosses the placental barrier and may cause fetal bradycardia; therefore, its use during pregnancy is not recommended. If use during lactation is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

Lidocaine affects central nervous system function; therefore, driving or operating machinery after its administration is not recommended.

Method of Administration and Dosage

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

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

Maximum dose: no more than 300 mg and no more than 4.5 mg/kg body weight.

For conduction anesthesia (including anesthesia of brachial and sacral plexuses): administer 10–20 mL of the drug (100–200 mg lidocaine); for finger, toe, nose, and ear anesthesia: 4–6 mL (40–60 mg) of the drug. Maximum dose: no more than 300 mg and no more than 4.5 mg/kg body weight.

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

Children.

Doses for children should be reduced according to age, body weight, and physical condition.

It is difficult to recommend a maximum dose of the drug for children, as it varies depending on age and weight. For children aged 3 years and older with body weight within the normal range, the maximum dose is determined based on the child's weight. For example, in a 5-year-old child weighing approximately 23 kg, the dose of lidocaine hydrochloride should not exceed 75–100 mg (3.2–4.3 mg/kg). The use of more diluted solutions (i.e., 0.25–0.5%) and a total dose not exceeding 3 mg/kg is recommended for intravenous administration for local anesthesia in children.

To prevent systemic toxicity, the smallest effective dose should be administered. In some cases, available concentrations should be diluted with 0.9% sterile sodium chloride solution to achieve the required concentration.

Overdose.

May result in an 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, oxygen supply, and/or artificial ventilation should be ensured. Central nervous system symptoms are managed with short-acting benzodiazepines/barbiturates. If overdose occurs during anesthesia, a short-acting non-depolarizing 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. Dialysis is ineffective during the acute phase of lidocaine overdose. There is no specific antidote.

Adverse Reactions.

Nervous system side effects: anxiety, drowsiness, dizziness, headache, sleep disturbances, confusion, loss of consciousness up to coma, sensory disturbances, muscle twitching, convulsions, 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 system side effects: methemoglobinemia.

Dental use: numbness of the 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, flashing spots before the eyes, photophobia, conjunctivitis.

Ear and labyrinth disorders: vertigo, hearing disturbances, tinnitus, hyperacusis.

Cardiovascular system side effects: when used in high doses – arrhythmia, bradycardia, slowed cardiac conduction, heart block, cardiac arrest, peripheral vasodilation, collapse; tachycardia, increased/decreased arterial pressure, chest pain, flushing.

Gastrointestinal side effects: nausea, vomiting.

Respiratory system side effects: dyspnea, rhinitis, respiratory depression or respiratory arrest.

Immune system side effects: 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 side effects: sensation of heat, cold or numbness in extremities, malignant hyperthermia, edema, weakness.

Local reactions: reactions at the injection site, mild burning sensation which disappears as anesthetic effect increases within 1 minute, thrombophlebitis, hyperemia.

After spinal or epidural anesthesia, back pain, leg pain, partial/complete spinal block may occur, accompanied by arterial hypotension, defecation disorders, involuntary urination, impotence, and loss of sensation in the perineal area (the likelihood of these effects increases when higher doses are used or if lidocaine is accidentally administered into the intrathecal space instead of the epidural space). In individual cases, recovery of motor, sensory and/or autonomic function after such procedures may be slow (over several months) or incomplete.

Shelf life.

3 years.

Storage conditions.

Store in original packaging at a temperature not exceeding 25 °C. Keep out of reach of 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. 3.5 ml or 5 ml in ampoules; 10 or 100 ampoules per carton, or 5 ampoules in a blister, 2 blisters per carton.

Prescription status.

By prescription only.

Manufacturer.

Private joint-stock company "Lekhym-Kharkiv".

Manufacturer's address and location of manufacturing activities.

36 Severina Pototskogo Street, Kharkiv, Kharkiv Oblast, 61115, Ukraine.