Lidocaine

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

Composition:

Active substance: lidocaine;

1 ml of solution contains lidocaine hydrochloride (calculated as anhydrous substance) 20 mg;

Excipients: sodium chloride, sodium hydroxide, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless or slightly colored solution, practically free from particles.

Pharmacotherapeutic group.
Local anaesthetics. Lidocaine. ATC code N01B B02.

Pharmacological properties.

Pharmacodynamics.

A derivative of acetanilide. A local anesthetic agent producing terminal, infiltration, and conduction anesthesia. The relative toxicity of lidocaine hydrochloride depends on the concentration of the solution. At low concentrations (0.5%), its toxicity is not significantly different from that of procaine; as the concentration increases (1% and 2%), toxicity rises (by 40–50%).

Pharmacokinetics.

When applied locally to mucous membranes, lidocaine is absorbed to varying degrees, depending on the dose and site of application (maximum concentration (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). It readily crosses histohematologic barriers, including the blood-brain barrier. Initially distributes into tissues with good blood supply (heart, lungs, brain, liver, spleen), then into fatty and muscular tissues. It crosses the placenta; in the newborn, 40–55% of the concentration administered to the mother is detected.

Metabolized by 90% in the liver via oxidative N-dealkylation, forming active metabolites: monoethylglycinexylidide and glycinexylidide, with elimination half-lives (T½) of 2 hours and 10 hours, respectively. Exhibits a "first-pass" effect.

In hepatic impairment, T½ may increase by more than 2 times. 5–20% is excreted unchanged in urine.

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to the components of the medicinal product or to other amide-type local anesthetics; history of epileptiform seizures following lidocaine administration; severe pronounced bradycardia; severe pronounced arterial hypotension; cardiogenic shock; severe forms of chronic heart failure (grades II–III); sinus node dysfunction syndrome; Wolff-Parkinson-White syndrome; Adams-Stokes syndrome; atrioventricular (AV) block of grade II and III; hypovolemia; severe hepatic/renal dysfunction; porphyria; myasthenia; retrobulbar administration in patients with glaucoma.

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 lidocaine concentration increases due to reduced hepatic metabolism.

Antiarhythmics (including amiodarone, verapamil, quinidine, disopyramide, ajmaline) and class IA antiarrhythmics (including quinidine, procainamide, disopyramide) or certain antipsychotic agents (including olanzapine, quetiapine) or 5-HT3 antagonists (including tropisetron, dolasetron) – enhanced cardiodepressive effect (prolongation of QT interval occurs; AV block or ventricular fibrillation may develop in isolated cases); concomitant use with amiodarone may lead to seizures.

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

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

Ethanol enhances lidocaine’s respiratory depressant effect.

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

Cimetidine reduces hepatic clearance of lidocaine (reduced metabolism 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, increased risk of pronounced arterial hypotension and bradycardia.

β-adrenergic blockers slow lidocaine metabolism in the liver, enhance lidocaine 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.

Cardiac glycosides – reduced cardiotonic effect of cardiac glycosides.

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

Sedatives or sedative medicinal products – possible enhancement of CNS depressant effects of sedatives and hypnotics.

Narcotic analgesics (e.g., morphine, etc.) – enhanced analgesic effect of narcotic analgesics and respiratory depression.

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

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

Anesthetic agents – enhanced respiratory center depressant effect of anesthetics (e.g., hexobarbital, sodium thiopental administered 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 cardiodepressive effect.

Isadrine, glucagon – increased lidocaine clearance.

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

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

Midazolam – increased lidocaine concentration in plasma.

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

Special precautions for use.

Lidocaine administration should be performed only by healthcare professionals.

When injection sites are disinfected with solutions containing heavy metals, the risk of local reactions such as pain and swelling increases.

ECG monitoring is mandatory during lidocaine use. In case of sinus node dysfunction, P-Q interval prolongation, QRS widening, or development of new arrhythmia, the dose should be reduced or the drug discontinued. In case of pronounced bradycardia, 0.5–1 mg atropine should be administered intravenously. In case of arterial hypotension, sympathomimetics and/or β-receptor agonists should be administered intravenously if necessary.

Before lidocaine administration in patients with heart disease (hypokalemia reduces lidocaine efficacy), potassium levels in blood should be normalized.

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

Before planned subarachnoid anesthesia, MAO inhibitors should be discontinued at least 10 days prior to anesthesia.

Extreme caution should be exercised to avoid accidental intravascular (especially during 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 required (since doses for epidural anesthesia are always higher than for subdural). Aspiration test is recommended when injecting into vascularized tissues.

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

Smaller doses of the drug should be used 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.

Extreme caution is required during retrobulbar injection, as severe adverse effects may occur: collapse, dyspnea, seizures, reversible blindness.

Since lidocaine exerts a pronounced antiarrhythmic effect and may itself act as an arrhythmogenic factor, potentially causing arrhythmia, a history of arrhythmia symptoms should be obtained before administration, and the drug should be used cautiously in individuals 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 and renal dysfunction (creatinine clearance not less than 10 mL/min), respiratory function impairment, epilepsy, after cardiac surgery, in patients with genetic predisposition to malignant hyperthermia, debilitated patients, and elderly patients.

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

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

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

Use during pregnancy or breastfeeding.

The drug 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 use of the drug, activities requiring rapid psychomotor reactions are not recommended.

Administration and dosage.

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

For topical anesthesia, mucous membranes in adults are lubricated with the drug at a dose of up to 2 mg/kg lidocaine; anesthesia duration – 15–30 minutes. Maximum dose/volume of the drug for adults – 4.5 mg/kg body weight; maximum total dose is 300 mg.

For conduction anesthesia (including anesthesia of brachial and sacral plexuses), 5–10 mL (100–200 mg lidocaine) of the drug is administered; for anesthesia of fingers, nose, ears – 2–3 mL (40–60 mg) of 2% lidocaine injection solution. Maximum dose of the drug for adults – 10 mL (200 mg).

For ophthalmologic anesthesia, 2 drops of the drug are instilled into the conjunctival sac 2–3 times with 30–60 second intervals immediately before examination or surgery.

Children aged 12 years and older for all types of peripheral analgesia: total lidocaine dose 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 per 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 short-term anesthetic action is required. Epinephrine promotes delayed absorption of lidocaine and prolongs its action.

Children.

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

Overdose.

Possible intensification of adverse reactions.

Symptoms: psychomotor agitation, dizziness, general weakness, reduced arterial pressure, tremor, visual disturbances, tonic-clonic seizures, coma, collapse, AV block, asphyxia, apnea. Initial symptoms of overdose occur at blood lidocaine concentration above 0.006 mg/kg; seizures occur at 0.01 mg/kg.

Treatment: discontinue drug administration, oxygen therapy, anticonvulsants, vasoconstrictors (norepinephrine, mesaton), cholinolytics. The patient should be kept in a horizontal position; fresh air access, oxygen supply, and/or artificial respiration should be ensured. 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-adrenergic receptor agonists are used. In case of cardiac arrest, immediate resuscitation is indicated. Intubation and artificial ventilation of the lungs may be performed. Dialysis is ineffective in the acute phase of overdose. No specific antidote is available.

Adverse Reactions.

Central nervous system: central nervous system 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 (when used in dentistry), motor block, disorientation; in patients with increased sensitivity – euphoria, tremor, trismus, motor restlessness, paresthesia, seizures.

Blood system: methemoglobinemia.

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

Ear 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 system: nausea, vomiting.

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

Allergic reactions: skin rash, urticaria, pruritus, generalized exfoliative dermatitis, angioneurotic edema, anaphylactic reactions (including anaphylactic shock), edema.

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

Local reactions: mild burning sensation, which disappears as the anesthetic effect increases (within 1 minute), hyperemia. During 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); 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 product should not be mixed with other medicinal products in the same syringe. Lidocaine precipitates when mixed with amphotericin, methohexitone, 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 pack made of film, 1 or 2 blisters in a carton.

2 ml in an ampoule; 10 ampoules in a cardboard package with cardboard partitions.

Prescription status. Prescription only.

Manufacturer.

JSC "Lubnipharm".

Manufacturer's address and location of business activity.

16 Barvinкова Street, Lubny, Poltava Region, 37500, Ukraine.