LIDOCAINE-DARNITSA

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

Composition:

Active substance: lidocaine;

1 ml of solution contains lidocaine hydrochloride 20 mg;

Excipients: sodium chloride, sodium hydroxide, 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 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 does not significantly differ from that of procaine; as the concentration increases (1% and 2%), toxicity increases.

Pharmacokinetics.

When applied locally to mucous membranes, lidocaine is absorbed to varying degrees depending on the dose and site of application (maximum concentration is reached within 10–20 minutes); absorption is influenced by the rate of perfusion through the mucous membrane. After intramuscular administration, maximum concentration is achieved within 5–15 minutes. Plasma protein binding is 60–80% (depending on the dose).

Lidocaine readily crosses histohematic barriers, including the blood-brain barrier. Initially, it distributes into well-perfused tissues (heart, lungs, brain, liver, spleen), followed by distribution into fat and muscle tissues. It crosses the placenta; in the newborn organism, 40–55% of the concentration administered to the mother is detected.

Approximately 90% is metabolized in the liver via oxidative N-dealkylation, forming active metabolites: monoethylglycinexylidide and glycinexylidide, with elimination half-lives of 2 and 10 hours, respectively. It exhibits the "first-pass" effect.

In case of impaired liver function, the elimination half-life may increase by more than two-fold. 5–20% is excreted unchanged in urine.

Clinical characteristics.

Indications.

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

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; AV block of II and III degree; complete heart block; sinoatrial node weakness syndrome; Wolff-Parkinson-White syndrome, Adams-Stokes syndrome; severe forms of heart failure (grades II–III); pronounced arterial hypotension; severe bradycardia; cardiogenic shock; myasthenia; hypovolemia; porphyria; severe renal and/or hepatic insufficiency; retrobulbar administration 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.

Chlorpromazine, pethidine, bupivacaine, quinidine, disopyramide, amitriptyline, imipramine, nortriptyline – when used concomitantly with lidocaine, the plasma concentration of the latter is reduced.

Antiarrhythmic agents (including amiodarone, verapamil, quinidine, disopyramide, ajmaline) – when used concomitantly with lidocaine, cardiodepressive effects are enhanced, including QT interval prolongation, and in isolated cases, development of AV block or ventricular fibrillation is possible. Concurrent use with amiodarone may lead to seizures.

Procainamide – when used concomitantly with lidocaine, delirium and hallucinations are possible.

Novocaine, novocainamide – when used concomitantly with lidocaine, central nervous system excitation and hallucinations are possible.

Curare-like agents – when used concomitantly with lidocaine, myorelaxation is enhanced (paralysis of respiratory muscles is possible).

Ethanol – when used concomitantly with lidocaine, the respiratory depressant effect of lidocaine is enhanced.

Vasoconstrictors (epinephrine, methoxamine, phenylephrine) – when used concomitantly with lidocaine, they slow down lidocaine absorption and prolong its action.

Cimetidine – when used concomitantly, it reduces hepatic clearance of lidocaine (due to inhibition of microsomal oxidation), increases its concentration, and increases the risk of toxic effects.

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

β-adrenergic blockers – when used concomitantly, they slow down lidocaine metabolism in the liver, enhance lidocaine effects (including toxic ones), 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 – when used concomitantly with lidocaine, the cardiotonic effect of cardiac glycosides is reduced.

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

Sedatives or hypnotics – when used concomitantly with lidocaine, the CNS depressant effects of sedatives and hypnotics may be enhanced.

Narcotic analgesics (morphine) – when used concomitantly with lidocaine, the analgesic effect of narcotic analgesics is enhanced, but respiratory depression is also intensified.

Monoamine oxidase inhibitors (furozolidone, procarbazine, selegiline) – when used concomitantly with lidocaine, the risk of arterial hypotension increases and the local anesthetic effect of lidocaine is prolonged. Parenteral administration of lidocaine should be avoided during treatment with monoamine oxidase inhibitors.

Anticoagulants (including ardeparin, dalteparin, danaparoid, enoxaparin, heparin, warfarin) – when used concomitantly with lidocaine, the risk of bleeding increases.

Anesthetic agents – when used concomitantly with lidocaine, the latter enhances the respiratory center depressant effect of anesthetics (hexobarbital, thiopental sodium intravenously).

Polymyxin B – when used concomitantly with lidocaine, monitoring of respiratory function is required.

Rifampicin – when used concomitantly with lidocaine, a decrease in lidocaine blood concentration is possible.

Propafenone – when used concomitantly with lidocaine, an increase in duration and severity of adverse effects on the central nervous system is possible.

Prenylamine – when used concomitantly with lidocaine, the risk of developing ventricular arrhythmia of the "torsades de pointes" type increases.

Anticonvulsants, barbiturates (phenytoin) – when used concomitantly with lidocaine, accelerated hepatic metabolism of lidocaine, decreased blood concentration, and enhanced cardiodepressive effect are possible.

Isadrine, glucagon – when used concomitantly with lidocaine, lidocaine clearance increases.

Norepinephrine, mexiletine – when used concomitantly with lidocaine, clearance of the latter decreases (toxicity is enhanced); hepatic blood flow is reduced.

Acetazolamide, thiazide and loop diuretics – when used concomitantly with lidocaine, due to development of hypokalemia, the effect of lidocaine is reduced.

Midazolam – when used concomitantly with lidocaine, the plasma concentration of the latter increases.

Agents causing neuromuscular blockade – when used concomitantly with lidocaine, the action of agents causing neuromuscular blockade is enhanced, as they reduce nerve impulse conduction.

Special precautions.

Lidocaine administration must be performed only by healthcare professionals.

When disinfecting the injection site with antiseptic 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, prolonged P-Q interval, widened QRS complex, or development of new arrhythmias, the dose should be reduced or the drug discontinued.

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

When performing planned subarachnoid anesthesia, monoamine oxidase inhibitors should be discontinued at least 10 days prior to anesthesia.

Particular caution should be exercised when administering the drug in areas rich in blood vessels during local anesthesia. Injection should avoid intravascular placement.

Aspiration test is recommended before injecting into vascularized tissues.

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

Care should be taken to avoid accidental subdural or intravascular injection. Close monitoring for systemic toxic effects on the cardiovascular and central nervous systems is required (since doses used for epidural anesthesia are always higher than those for subdural administration).

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

Smaller doses should be used when injecting in the head and neck area, including retrobulbar and dental injections, as well as for stellate ganglion block, due to the risk of systemic toxic effects entering cerebral circulation via retrograde blood flow.

Extreme caution is required with retrobulbar injection, as serious adverse effects may occur, including collapse, respiratory depression, seizures, and reversible blindness.

It should be remembered that lidocaine exerts a pronounced antiarrhythmic effect and may itself act as an arrhythmogenic factor. Therefore, prior to administration, a thorough history regarding arrhythmia symptoms should be obtained, 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 atrioventricular block, intraventricular conduction disturbances, moderate liver or kidney dysfunction (creatinine clearance not less than 10 ml/min), respiratory impairment, 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.

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, or hepatic and renal insufficiency.

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

Use during pregnancy or breastfeeding.

The use of the drug during pregnancy is contraindicated.

If drug use is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

After drug administration, activities requiring rapid psychomotor reactions should be avoided.

Method of Administration and Dosage

Prior to the use of lidocaine hydrochloride, a skin test for hypersensitivity to the drug must be performed; signs include swelling and redness at the injection site.

For local anesthesia, administer by injection (subcutaneously, intramuscularly) or locally onto mucous membranes. Intravascular administration must be avoided.

For conduction anesthesia (including anesthesia of the brachial and sacral plexus), inject 5–10 mL of solution (100–200 mg of the drug).

For anesthesia of fingers, toes, nose, and ears, inject 2–3 mL of solution (40–60 mg of the drug). The maximum dose of the drug for adults when used for conduction anesthesia is 10 mL (200 mg of lidocaine hydrochloride).

For all types of injectable anesthesia, lidocaine may be combined with epinephrine (1:50000–1:100000; prepare 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-duration anesthetic effect is required. Epinephrine slows the absorption of lidocaine and prolongs its action.

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

For topical anesthesia on mucous membranes, apply lidocaine solution in a volume not exceeding 20 mL for adults at a dose of up to 2 mg/kg body weight; duration of anesthesia is 15–30 minutes. The maximum dose of solution for adults is 20 mL.

In children, for all types of peripheral anesthesia, the total dose of lidocaine hydrochloride must not exceed 3 mg/kg body weight.

Children.

The drug is not administered to children under 12 years of age.

Overdose.

Main symptoms are related to depression of the central nervous and cardiovascular systems: general weakness, drowsiness, depression, dizziness, disorientation, tonic-clonic seizures, coma, tremor, visual disturbances, tinnitus, atrioventricular block, asphyxia, nausea, vomiting, euphoria, psychomotor agitation, asthenia, apnea, bradycardia, decreased arterial pressure, collapse. Initial symptoms of overdose in healthy individuals occur at blood concentrations of lidocaine hydrochloride exceeding 0.006 mg/kg; seizures occur at 0.01 mg/kg.

Treatment: Discontinue administration of the drug, administer oxygen therapy, vasopressors (noradrenaline, mesaton), anticonvulsants, and anticholinergics. The patient should be placed in a horizontal position; ensure access to fresh air, oxygen supply, and/or artificial ventilation if needed. Central nervous system symptoms should be 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, use atropine (0.5–1 mg intravenously); for arterial hypotension, use 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. Dialysis is ineffective during the acute phase of lidocaine overdose. There is no specific antidote.

Adverse reactions.

The following adverse reactions may occur during the use of the drug:

Cardiovascular system: hypotension, tachycardia – when administered with vasopressors; bradycardia, peripheral vasodilation, collapse, tachycardia, palpitations, chest pain, cardiac pain, arrhythmia, slowed cardiac conduction, atrioventricular block, ventricular fibrillation, cardiac arrest; very rarely – arterial hypertension;

Nervous system (central and peripheral): central nervous system excitation (when used in high doses), anxiety, dizziness, confusion, somnolence, sleep disturbances, headache, weakness, motor restlessness, euphoria, nystagmus, loss of consciousness, sensory disturbances, paresthesia, numbness of the tongue and lips (when used in dentistry); in patients with increased sensitivity – euphoria, tremor, trismus, muscle twitching, motor restlessness, seizures (the risk of their development increases in the setting of hypercapnia and acidosis); prolonged anesthesia, paralysis or paresis of lower limbs and loss of sphincter control (e.g., cauda equina syndrome) – occurs more frequently than with other local anesthetics, motor and sensory block, dysarthria, dysphagia, coma;

Eye disorders: visual disturbances, blurred vision, diplopia, nystagmus, flickering "floaters" before the eyes, pupillary dilation, photophobia, reversible blindness, conjunctivitis;

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

Psychiatric disorders: anorexia, irritability, restlessness, hallucinations, depression, anxiety, sleep disturbances, excited state;

Respiratory, thoracic and mediastinal disorders: rhinitis, dyspnea, labored breathing, suffocation sensation, respiratory depression, bronchospasm, paralysis of respiratory muscles, respiratory paralysis (more commonly develops during subarachnoid anesthesia), respiratory arrest;

Gastrointestinal disorders: nausea, vomiting, involuntary defecation, abdominal pain;

Renal and urinary disorders: involuntary urination;

Skin and subcutaneous tissue disorders: hyperemia, pruritus, rash, urticaria;

Reproductive system disorders: decreased libido and/or potency;

Immune system disorders: hypersensitivity reactions, including angioneurotic edema, generalized exfoliative dermatitis, anaphylactic shock, anaphylactic reaction; immune system suppression;

Injection site reactions: mild burning sensation, which disappears as the anesthetic effect develops (within 1 minute), swelling, hyperemia, pruritus, rash, thrombophlebitis, localized nerve injury at the injection site; 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 when higher doses are used or if lidocaine is accidentally administered intrathecally instead of epidurally, when the dose intended for epidural space is injected into the intrathecal space); in individual cases, recovery of motor, sensory and/or autonomic function after such procedures may be slow (over several months) or incomplete;

General disorders: prolonged anesthesia, hypothermia, sensation of heat, cold or numbness of limbs, malignant hyperthermia, increased sweating, pallor, edema syndrome, weakness.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. Do not freeze.

Keep out of reach of children.

Incompatibility.

The drug should not be mixed with other medicinal products in the same container, except for solvents specified in the section "Administration and dosage".

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; 5 ampoules in a blister pack; 2 blister packs in a carton.

Prescription status. Prescription only.

Manufacturer. JSC "Pharmaceutical Company "Darnytsia".

Manufacturer's address and place of business.

13, Boryspylska Street, Kyiv, 02093, Ukraine.