Lidocaine hydrochloride

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

Composition:

Active substance: lidocaine hydrochloride;

1 ml of solution contains 20 mg of lidocaine hydrochloride, calculated as the anhydrous substance;
Excipients: sodium chloride, water for injections.

Pharmaceutical form. Injection solution.

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

Pharmacotherapeutic group. Local anesthetics. Amides. Lidocaine.

ATC code N01B B02.

Pharmacological Properties

Pharmacodynamics.

Lidocaine is a local anesthetic agent. Its local anesthetic effect is due to stabilization of the neuronal membrane by decreasing its permeability to sodium ions, thereby preventing the generation of action potentials and conduction of nerve impulses. Antagonism with calcium ions is possible. It is effective for all types of local anesthesia. Lidocaine suppresses conduction not only of pain impulses but also of impulses of other modalities. It is rapidly hydrolyzed in the slightly alkaline tissue environment and, after a short latent period, acts for 1–1.5 hours. The anesthetic effect of lidocaine is 2–6 times stronger than that of procaine. Anesthetic activity decreases in inflamed tissues. When applied locally, it dilates blood vessels and does not produce local irritant effects.

Pharmacokinetics.

After intramuscular administration, maximum blood concentration is reached within 5–15 minutes. In plasma, it binds to blood proteins by 33–80%. The extent of binding largely depends on the drug concentration and the level of alpha-1-acid glycoprotein in blood plasma. Binding to plasma proteins increases in patients with uremia and in kidney transplant recipients, and is enhanced after acute myocardial infarction, which is characterized by increased levels of alpha-1-acid glycoprotein. High protein binding may reduce the effect of free lidocaine or lead to a general increase in drug concentrations in plasma. The therapeutic effect develops at concentrations of 1.5–5 mcg/mL. It rapidly distributes into tissues, with a volume of distribution of 1 L/kg. Initially, it accumulates in tissues with high blood flow: heart, brain, kidneys, lungs, liver, spleen, followed by adipose and muscle tissues. It readily penetrates histohematic barriers, including the blood-brain and placental barriers. In newborns, 40–55% of the maternal drug concentration is detected. It is metabolized in the liver by microsomal enzymes, forming metabolites: monoethylglycinexylidide and glycinexylidide. The rate of metabolism is determined by hepatic blood flow and, consequently, may be impaired in patients after myocardial infarction and/or in patients with congestive heart failure. It is excreted by the kidneys, mainly as metabolites (approximately 90%) and in unchanged form (10%). Renal excretion of unchanged drug partially depends on urine pH. Acidic urine leads to increased excretion of the unchanged drug in urine. The elimination half-life after intravenous bolus administration is 1.5–2 hours. The half-lives of metabolites are 2 and 10 hours, respectively. In hepatic impairment, the elimination half-life may increase.

Clinical characteristics.

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

Contraindications.

Individual hypersensitivity to the components of the drug, as well as to other amide-type local anesthetics; history of epileptiform seizures associated with administration of lidocaine hydrochloride; second- and third-degree AV block, sick sinus syndrome, Wolff-Parkinson-White syndrome, Adams-Stokes syndrome, severe forms of heart failure (II–III degree), marked arterial hypotension, bradycardia, cardiogenic shock; myasthenia; hypovolemia; porphyria; severe renal and/or hepatic insufficiency; retrobulbar injection in patients with glaucoma, coagulation disorders, anticoagulant therapy; infections at the injection site; uncooperative patients.

Interaction with other medicinal products and other types of interactions.

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

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

Procaine, procainamide – possible excitation of the central nervous system, delirium, hallucinations.

Curare-like agents – enhanced myorelaxation (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 reduced metabolism caused by inhibition of microsomal oxidation), increases its concentration and risk of toxic effects.

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

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

Cardiac glycosides – reduced cardiotonic effect of cardiac glycosides.

Digitalis glycosides – in the context of lidocaine intoxication, severity of AV block may be enhanced.

Hypnotics or sedatives – possible enhancement of CNS depressant effects of hypnotic and sedative drugs.

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 anesthetics (hexobarbital, thiopental sodium intravenously).

Polymyxin B – respiratory function monitoring is required.

Rifampicin – possible reduction in its blood concentration.

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

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

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

Isadrine (isoprenaline), glucagon – increased lidocaine clearance.

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

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

Midazolam – increased lidocaine concentration in plasma.

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

Norepinephrine – synergistic effect when interacting with lidocaine.

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

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

Concomitant use of myorelaxants (e.g., succinylcholine) may result in a synergistic effect.

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 slower absorption of lidocaine and prolongs its action.

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 local reactions such as pain and swelling increases.

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

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

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

Extreme caution is required 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 should be used when administering lidocaine in the head and neck area, including retrobulbar and dental injections, as well as for stellate ganglion blockade, because systemic toxic effects may reach cerebral circulation via retrograde flow.

Particular caution is required during retrobulbar injection, as adverse effects such as collapse, dyspnea, seizures, and reversible blindness may occur.

Since lidocaine exerts a pronounced antiarrhythmic effect and may itself act as an arrhythmogenic factor potentially causing arrhythmias, a thorough medical history should 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 liver or kidney dysfunction (creatinine clearance not less than 10 mL/min), respiratory impairment, epilepsy, after 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.

Particular caution is required during local anesthesia of highly vascularized tissues (e.g., neck during thyroid surgery) to avoid 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 using lidocaine in patients with circulatory insufficiency, hypovolemia, arterial hypotension, and hepatic or renal impairment.

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

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, its use during pregnancy is not recommended. If use of the drug is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery

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

Method of Administration and Dosage

The drug should be administered by injection (subcutaneously, intramuscularly) and locally on mucous membranes.

Intravascular administration of the drug should be avoided.

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

Maximum dose of the drug for adults: 20 ml.

For conduction anesthesia (including anesthesia of brachial and sacral plexuses), inject 5–10 ml (100–200 mg of lidocaine) of the drug; for finger, nose, or ear anesthesia: 2–3 ml (40–60 mg of the drug). Maximum dose of the drug for adults: 10 ml (200 mg).

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 and adolescents.

Children should be prescribed the lowest possible total dose according to body weight and in greater dilution (0.5%; 0.1%). The maximum single dose of lidocaine is 3 mg/kg body weight.

The maximum single dose must not be administered repeatedly within 24 hours.

For children under 3 years of age, the maximum dose is 1.25 mL, including in children with impaired renal function. Within 24 hours, the total dose should not exceed 4 doses.

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 body weight.

Maximum dosing for children under 3 years of age: no more than 1.25 mL applied locally on a swab every 3 hours or 10 mL within 24 hours. For children aged 3 years and older, the dose is 5 mL. For children under 12 years of age with pharyngeal or oral cavity inflammation, the child's age, weight, and method of drug administration (body surface area when applying soft dosage forms) must be taken into account. The drug should be administered to children only after obtaining parental consent.

The drug must not be re-applied topically within 2 hours after previous administration.

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

Overdose.

Exacerbation of adverse reactions is possible.

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. With significant overdose, impaired consciousness, respiratory depression, shock, and myocardial infarction may occur. Initial symptoms of overdose appear at blood lidocaine concentrations exceeding 0.006 mg/kg; seizures occur at 0.01 mg/kg.

Treatment: discontinue drug administration, oxygen therapy, vasopressors (norepinephrine, mesaton), anticonvulsants, anticholinergics. The patient should remain in a horizontal position; fresh air, oxygen supply, and/or artificial ventilation must be ensured. Central nervous system symptoms are managed with benzodiazepines or 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. Endotracheal intubation and artificial ventilation of the lungs may be performed. Hemodialysis is ineffective during the acute phase of lidocaine overdose. There is no specific antidote.

Adverse reactions.

Central nervous system: central nervous system excitation (when used in high doses), anxiety, headache, dizziness, sleep disturbances, confusion, drowsiness, loss of consciousness, coma, sensory disturbances, muscle twitching, numbness of tongue and lips (when used in dentistry), motor block, dysarthria, dysphagia; persistent anesthesia, paresis or paralysis of lower limbs and loss of sphincter control (e.g., cauda equina syndrome), skin tingling in patients with hypersensitivity – euphoria, tremor, trismus, motor restlessness, paresthesia, seizures.

Psychiatric disorders: anorexia, irritability, restlessness, hallucinations, depression; after administration of high doses – agitation, euphoria.

Eye disorders: visual disturbances, nystagmus, reversible blindness, diplopia, photopsia (flashing "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, tachycardia, increased/decreased arterial pressure, chest pain.

Gastrointestinal disorders: nausea, vomiting.

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

Immune system disorders: allergic reactions, including edema, skin reactions, urticaria, pruritus, angioneurotic edema, hypersensitivity reactions including anaphylactoid reactions (e.g., anaphylactic shock), generalized exfoliative dermatitis; immune system suppression.

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

Local reactions: reactions at the injection site, mild burning sensation which disappears as anesthetic effect increases (within 1 minute), hyperemia. With spinal or epidural anesthesia, back pain, leg pain, partial/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 with higher doses or accidental intrathecal administration of lidocaine intended for epidural space, when the dose designated for epidural administration inadvertently 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.

Shelf life. 3 years.

Storage conditions.

Store in original packaging at 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, methohexital or sulfadiazine. Depending on the pH of the solution, lidocaine may be incompatible with ampicillin.

Packaging. 2 ml in an ampoule, 10 ampoules in a blister pack, 1 blister pack in a carton; 2 ml in an ampoule, 10 ampoules in a box.

Prescription status. Prescription only.

Manufacturer: JSC "Halychpharm".

Manufacturer's location and address of business activity.

6/8 Opryshkivska St., Lviv, 79024, Ukraine.