Lidocaine

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

Composition:

Active substance: lidocaine;

1 ml of solution contains lidocaine hydrochloride monohydrate 20 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.

A derivative of acetanilide. A local anesthetic agent for terminal, infiltration, and conduction anesthesia. The relative toxicity of lidocaine hydrochloride depends on the concentration of the solution. In low concentrations (0.5%), it does not significantly differ in toxicity from novocaine; as the concentration increases (1% and 2%), toxicity rises (by 40–50%).

Pharmacokinetics.

When applied locally to mucous membranes, lidocaine is absorbed unevenly, depending on the dose and site of application (Cmax is reached within 10–20 minutes); absorption is influenced by the rate of perfusion into the mucous membrane. After intramuscular administration, Cmax is achieved within 5–15 minutes. Plasma protein binding is 60–80% (depending on the dose). Easily penetrates histohematic barriers, including the blood-brain barrier. Initially distributes into well-perfused tissues (heart, lungs, brain, liver, spleen), then into fatty and muscular tissues. Crosses the placenta; in the newborn’s organism, 40–55% of the concentration of the drug administered to the mother is detected.

Metabolized by 90% in the liver via oxidative N-dealkylation, forming active metabolites—monethylglycylxylidine and glycylxylidine—with half-lives (T1/2) of 2 hours and 10 hours, respectively. Exhibits a first-pass effect.

In case of impaired liver function, T1/2 may increase by more than 2 times. 5–20% is excreted unchanged in urine.

Clinical characteristics.

Indications.

Local anesthesia (terminal, infiltration, conduction) in surgery, dentistry, ophthalmology, otolaryngology; blockade of peripheral nerves and nerve plexuses in various pain syndromes.

Contraindications.

Increased individual sensitivity to components of the drug, other amide local anesthetics, history of epileptiform seizures to lidocaine, severe bradycardia, severe arterial hypotension, cardiogenic shock, severe forms of chronic heart failure (grade II–III), 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 in patients with glaucoma.

Interaction with other medicinal products and other forms of interaction.

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

Antiarrhythmic agents (including amiodarone, verapamil, quinidine, disopyramide, ajmaline) – enhanced cardiodepressant effect (prolongation of the QT interval occurs, and in isolated cases, development of AV block or ventricular fibrillation is possible); simultaneous use with amiodarone may lead to seizures.

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

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

Ethanol – enhances the respiratory depressant effect of lidocaine.

Vasoconstrictors (epinephrine, methoxamine, phenylephrine) – promote slower 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.

Guanadrel, guanethidine, mecamylamine, trimethaphan – when used concomitantly for spinal and epidural anesthesia, the risk of pronounced arterial hypotension and bradycardia increases.

β-adrenergic blockers – slow down the metabolism of lidocaine in the liver, enhance the effects of lidocaine (including toxic effects), and increase the risk of bradycardia and arterial hypotension. When β-adrenergic blockers and lidocaine are used simultaneously, the dose of lidocaine should be reduced.

Cardiac glycosides – the cardiotonic effect of cardiac glycosides is reduced.

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.

MAO 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 MAO inhibitors.

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

Anesthetic agents – enhanced respiratory center depressant effect of anesthetic agents (hexobarbital, thiopental sodium intravenously).

Polymyxin B – monitoring of respiratory function is required.

Rifampicin – possible reduction in rifampicin blood concentration.

Propafenone – possible increase in duration and severity of CNS-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.

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

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

Midazolam – increased lidocaine plasma concentration.

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

Special precautions for use.

Lidocaine administration should only be performed by healthcare professionals.

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

ECG monitoring is mandatory during lidocaine use. In case of sinus node dysfunction, prolonged PQ interval, widened QRS complex, or development of new arrhythmias, the dose should be reduced or the drug discontinued.

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

Prior to high-dose lidocaine administration, barbiturates are recommended.

When planning elective subarachnoid anesthesia, monoamine oxidase inhibitors (MAOIs) should be discontinued no later than 10 days before anesthesia.

Extreme caution must be exercised to avoid accidental intravascular (especially when performing local anesthesia in highly vascularized areas) or subdural injection. Careful monitoring for systemic toxic effects of the drug on the cardiovascular system and CNS is required (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, or sepsis.

Smaller doses of lidocaine 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 severe adverse effects may occur, including collapse, respiratory depression, seizures, and reversible blindness.

Since lidocaine exerts a pronounced antiarrhythmic effect but may also act as an arrhythmogenic agent and potentially trigger arrhythmias, a thorough history regarding previous episodes of arrhythmia should be obtained before administration, and the drug should be used cautiously in patients with a history of arrhythmias.

The drug should be used cautiously 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 ≥10 mL/min), respiratory dysfunction, epilepsy, following cardiac surgery, in patients with genetic predisposition to malignant hyperthermia, debilitated patients, and elderly patients.

Intramuscular administration of lidocaine may increase serum creatinine concentration, potentially leading to diagnostic errors in cases of suspected acute myocardial infarction.

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

Use during pregnancy or breastfeeding.

Lidocaine is contraindicated during pregnancy. If use of the drug is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

After administration of the drug, activities requiring fast psychomotor reactions (e.g., driving vehicles or operating machinery) are not recommended.

Method of Administration and Dosage.

The drug is administered by injection (subcutaneously, intramuscularly) and locally to mucous membranes. Intravascular administration of the drug must be avoided. Prior to administration, a skin sensitivity test for lidocaine must be performed; signs of hypersensitivity include swelling and redness at the injection site.

For terminal anesthesia: mucous membranes in adults are coated with the drug at a dose of up to 2 mg/kg of lidocaine. The duration of anesthesia is 15–30 minutes. The maximum dose of the drug for adults is 20 ml.

For conduction anesthesia (including anesthesia of the brachial and sacral plexuses), 5–10 ml (100–200 mg of lidocaine) of the drug is administered; for anesthesia of fingers, toes, nose, and ears – 2–3 ml (40–60 mg) of the drug. The maximum dose of the drug for adults is 10 ml (200 mg).

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

In children aged 12 years and older for all types of peripheral analgesia, the total dose of lidocaine should not exceed 3 mg/kg body weight.

For all types of injectable analgesia, lidocaine may be combined with epinephrine (1:50,000, 1:100,000; prepared ex tempore by adding 1 drop of 0.1% epinephrine solution to 5–10 ml of 2% lidocaine solution), except when systemic effects of epinephrine (adrenaline) are undesirable (hypersensitivity to epinephrine, arterial hypertension, diabetes mellitus, glaucoma), or when a short-term anesthetic effect is required. Epinephrine slows the absorption of lidocaine and thereby prolongs its action.

Children. The drug is administered to children aged 12 years and older.

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. Initial 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 respiration must be ensured. Central nervous system (CNS) 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) is used; for arterial hypotension – sympathomimetics in combination with β-adrenoceptor agonists. In case of cardiac arrest, immediate resuscitation measures are indicated. Endotracheal intubation and artificial ventilation of the lungs may be performed. Dialysis is ineffective during the acute phase of overdose. There is no specific antidote.

Adverse Reactions.

Central nervous system: CNS stimulation (when used in high doses), anxiety, headache, dizziness, sleep disturbances, confusion, drowsiness, loss of consciousness, coma, sensory disturbances, numbness of the tongue and lips (with dental use), motor block; in patients with increased sensitivity – euphoria, tremor, trismus, motor restlessness, paresthesia, seizures.

Eye disorders: nystagmus, reversible blindness, diplopia, flickering "floaters" before the eyes, photophobia, conjunctivitis.

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

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

Gastrointestinal disorders: nausea, vomiting.

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

Allergic reactions: very rarely – skin rashes, urticaria, pruritus, generalized exfoliative dermatitis, angioneurotic edema, anaphylactic reactions (including anaphylactic shock).

Other: sensation of heat, cold or numbness in extremities, edema, weakness, malignant hyperthermia.

Local reactions: mild burning sensation, which disappears as the anesthetic effect increases (within 1 minute), hyperemia. With spinal or epidural anesthesia, back pain, leg pain, partial or complete spinal block may occur, accompanied by decreased arterial pressure, defecation disorders, involuntary urination, impotence, loss of sensation in the perineal area (the likelihood of these effects increases when higher doses are used or in case of accidental intrathecal administration of lidocaine intended for epidural space, if the dose meant for epidural administration enters the intrathecal space); in individual cases, recovery of motor, sensory, and/or autonomic function after such intervention may be slow (over several months) or incomplete.

Incompatibility.

The preparation 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.

Shelf life. 2 years.

Storage conditions. Store in original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 2 ml in a vial; 10 vials in a cardboard box with partitions, or 5 vials in a single blister; 2 blisters per box.

Prescription status. Prescription only.

Manufacturer. Private Joint-Stock Company "Lekhym-Kharkiv".

Manufacturer's address and location of business activity.

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