Lidocain Velpharm (Solution) Instructions for Use

Marketing Authorization Holder

Velpharm, LLC (Russia)

ATC Code

N01BB02 (Lidocaine)

Active Substance

Lidocaine (Rec.INN registered by WHO)

Dosage Forms

	Lidocaine Velpharm	Solution for injection 10 mg/ml: 5 ml or 10 ml amp. 5 or 10 pcs.
		Solution for injection 20 mg/ml: 2 ml, 5 ml or 10 ml amp. 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for injection colorless or slightly yellowish, transparent.

Excipients : sodium chloride, water for injections.

5 ml – ampoules of neutral glass (5) – contour cell packaging (1) – cardboard packs.
5 ml – ampoules of neutral glass (5) – contour cell packaging (2) – cardboard packs.
10 ml – ampoules of neutral glass (5) – contour cell packaging (1) – cardboard packs.
10 ml – ampoules of neutral glass (5) – contour cell packaging (2) – cardboard packs.

Solution for injection colorless or slightly yellowish, transparent.

Excipients : sodium chloride, water for injections.

2 ml – ampoules of neutral glass (5) – contour cell packaging (1) – cardboard packs.
2 ml – ampoules of neutral glass (5) – contour cell packaging (2) – cardboard packs.
5 ml – ampoules of neutral glass (5) – contour cell packaging (1) – cardboard packs.
5 ml – ampoules of neutral glass (5) – contour cell packaging (2) – cardboard packs.
10 ml – ampoules of neutral glass (5) – contour cell packaging (1) – cardboard packs.
10 ml – ampoules of neutral glass (5) – contour cell packaging (2) – cardboard packs.

Clinical-Pharmacological Group

Local anesthetic

Pharmacotherapeutic Group

Anesthetics; local anesthetics; amides

Pharmacological Action

It is a local anesthetic of the amide type, short-acting. Its mechanism of action is based on decreasing the permeability of the neuron membrane to sodium ions. As a result, the rate of depolarization decreases and the excitation threshold increases, leading to reversible local numbness.

Lidocaine is used to achieve conduction anesthesia in various parts of the body and to control arrhythmia. It has a rapid onset of action (about 1 minute after IV administration and 15 minutes after IM administration) and rapidly spreads into surrounding tissues.

The effect lasts 10-20 minutes after IM administration and about 60-90 minutes after IV administration.

Pharmacokinetics

The systemic absorption of lidocaine is determined by the site of administration, dose, and its pharmacological profile. C_max is achieved after intercostal block, followed (in descending order of concentration) by administration into the lumbar epidural space, brachial plexus, and subcutaneous tissues.

The main factor determining the rate of absorption and blood concentration is the total administered dose, regardless of the site of administration. There is a linear relationship between the amount of lidocaine administered and the resulting C_max in blood plasma.

It is excreted in breast milk (up to 40% of the concentration in maternal plasma). It is metabolized in the liver, with about 90% of the administered dose undergoing N-dealkylation to form monoethylglycinexylidide and glycinexylidide.

Glycinexylidide has a longer T_1/2 than Lidocaine (about 10 hours) and can accumulate with repeated administration. Metabolites formed as a result of subsequent metabolism are excreted in the urine, the content of unchanged lidocaine in urine does not exceed 10%.

T_1/2 during continuous infusion for 24-48 hours is about 3 hours. Acidification of urine promotes increased excretion of lidocaine.

Indications

Local and regional anesthesia, conduction anesthesia for major and minor surgical interventions.

ICD codes

Dosage Regimen

The dosage regimen is set individually, depending on the type of anesthesia and the site of administration, the size of the anesthetized area, and the patient’s age.

The agent should be administered in the lowest concentration and the smallest dose that gives the required effect.

The maximum dose for adults should not exceed 300 mg.

For adults, children and adolescents aged 12-18 years, a single dose of lidocaine (except for spinal anesthesia) should not exceed 4.5 mg/kg, with a maximum of 300 mg.

For children, elderly and debilitated patients, Lidocaine is administered in lower doses corresponding to their age and physical condition.

Adverse Reactions

From the cardiovascular system arterial hypotension, bradycardia, arterial hypertension, depression of myocardial contractility (negative inotropic effect), arrhythmias, cardiac arrest or circulatory failure are possible.

From the nervous system dizziness, paresthesia, convulsions, perioral paresthesia, tongue numbness, hyperacusis, visual impairment, tremor, drowsiness, tinnitus, confusion, dysarthria, neuropathy, peripheral nerve damage, arachnoiditis.

From the digestive system vomiting.

From the immune system hypersensitivity reactions, skin rash, urticaria, angioedema, anaphylactic shock.

From the organ of vision: blurred vision, diplopia.

From the respiratory system dyspnea, bronchospasm, respiratory depression, respiratory arrest.

Contraindications

Hypersensitivity to lidocaine and other amide-type anesthetics; severe sinoatrial block, sick sinus syndrome, third-degree AV block, severe intraventricular conduction disorders, Wolff-Parkinson-White syndrome; cardiogenic or hypovolemic shock, acute decompensation of heart failure; children under 1 year of age (for 10 mg/ml solution), children under 18 years of age (for 20 mg/ml solution).

For subarachnoid anesthesia (additionally) – complete heart block, bleeding, arterial hypotension, shock, infection at the lumbar puncture site, septicemia.

With caution

Myasthenia gravis; epilepsy, complete or incomplete intracardiac conduction block, chronic heart failure, bradycardia, respiratory depression, coagulopathy, Melkersson-Rosenthal syndrome; use in combination with drugs that interact with lidocaine and lead to an increase in its bioavailability, potentiation of effects (for example, phenytoin) or slowing of excretion (for example, in hepatic or end-stage renal failure, in which lidocaine metabolites can accumulate); elderly patients (over 65 years of age); third trimester of pregnancy.

Subarachnoid anesthesia should be performed with caution in back pain, brain infection, benign and malignant brain tumors, migraine, subarachnoid hemorrhage, arterial hypertension, arterial hypotension, psychosis, hysteria.

Use in Pregnancy and Lactation

Lidocaine is allowed for use during pregnancy and breastfeeding.

It is necessary to strictly adhere to the prescribed dosage regimen. It should be used with caution in the third trimester of pregnancy.

In some cases, paracervical block during pregnancy can lead to bradycardia or tachycardia in the fetus, therefore careful monitoring of the fetal heart rate is required.

In case of complications or a history of bleeding, epidural anesthesia with lidocaine in obstetrics is contraindicated.

Animal studies have not revealed harmful effects on the fetus.

Lidocaine is excreted in small amounts in breast milk. However, its oral bioavailability is very low, so the amount of lidocaine that can be ingested with breast milk is insignificant; the potential risk to the child is considered small. The decision on the possibility of using lidocaine during breastfeeding is made by the doctor.

Use in Hepatic Impairment

It should be used with caution in hepatic insufficiency.

Use in Renal Impairment

It should be used with caution in renal insufficiency.

Pediatric Use

Contraindications: children under 1 year of age (for 10 mg/ml solution), children under 18 years of age (for 20 mg/ml solution).

Lidocaine is administered to children in lower doses corresponding to their age and physical condition.

Geriatric Use

It should be used with caution in elderly patients (over 65 years of age).

Special Precautions

Before injection into tissues with abundant blood supply, an aspiration test is recommended.

Before starting IV administration of lidocaine, it is necessary to correct hypokalemia, hypoxia and acid-base imbalance.

Regional and local anesthesia should be performed by experienced specialists in an appropriately equipped room, with readily available equipment and drugs necessary for cardiac monitoring and resuscitation. The personnel performing anesthesia must be qualified and trained in anesthesia techniques, and must be familiar with the diagnosis and treatment of systemic toxic reactions and complications.

Lidocaine should be used with caution in combination with drugs that interact with lidocaine and lead to an increase in its bioavailability, potentiation of effects (for example, phenytoin) or prolongation of excretion (for example, in hepatic or end-stage renal failure, in which lidocaine metabolites can accumulate).

When using the agent in patients receiving class III antiarrhythmic drugs (for example, amiodarone), careful observation and ECG monitoring should be established, since the effect on the heart may be potentiated.

IM administration of lidocaine may increase CPK activity, which may complicate the diagnosis of acute myocardial infarction.

When administered into inflamed or infected tissues, the effect of lidocaine may be reduced.

Conduction anesthesia of the spinal nerves can lead to depression of the cardiovascular system, especially against the background of hypovolemia, therefore, when performing epidural anesthesia in patients with impaired cardiovascular function, caution should be exercised.

Epidural anesthesia can lead to arterial hypotension and bradycardia. The risk can be reduced by preliminary administration of crystalloid or colloid solutions. Arterial hypotension must be immediately relieved.

Injection into the head and neck area may lead to unintentional entry into an artery with the development of cerebral symptoms even at low doses.

Retrobulbar injection in rare cases may lead to entry into the cranial subarachnoid space, leading to serious/severe reactions, including cardiovascular failure, apnea, convulsions and temporary blindness.

Retro- and peribulbar administration of local anesthetics carries a low risk of persistent oculomotor dysfunction. The main causes include trauma and/or local toxic effects on muscles and/or nerves.

The severity of such reactions depends on the degree of injury, the concentration of the local anesthetic and the duration of its exposure in the tissues. In this regard, any local anesthetic should be used in the lowest effective concentration and dose.

Long-term intra-articular infusion is not an approved indication for the use of lidocaine.

Lidocaine solution for injection 10 mg/ml is not approved for intrathecal administration (subarachnoid anesthesia).

Effect on ability to drive vehicles and mechanisms

During treatment, patients should avoid driving vehicles and engaging in other activities that require high concentration and speed of psychomotor reactions.

Drug Interactions

The toxicity of lidocaine increases when it is used simultaneously with cimetidine due to an increase in lidocaine concentration. Both drugs reduce hepatic blood flow. In addition, cimetidine inhibits microsomal activity. Ranitidine slightly reduces the clearance of lidocaine, leading to an increase in its concentration. Antiviral agents (for example, amprenavir, atazanavir, darunavir, lopinavir) can also cause an increase in serum lidocaine concentration.

Hypokalemia caused by diuretics may reduce the effect of lidocaine when used simultaneously.

Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally similar to amide-type local anesthetics (for example, antiarrhythmic agents such as mexiletine, tocainide), since systemic toxic effects are additive.

Individual studies of drug interaction between lidocaine and class III antiarrhythmic agents (for example, amiodarone) have not been conducted, however, caution is recommended.

In patients simultaneously receiving antipsychotic agents that prolong or may prolong the QT interval (for example, pimozide, sertindole, olanzapine, quetiapine, zotepine), prenylamine, epinephrine (in case of accidental IV administration) or 5-HT₃-serotonin receptor antagonists (for example, tropisetron, dolasetron), the risk of ventricular arrhythmias may increase.

Concomitant use of quinupristin/dalfopristin may increase the concentration of lidocaine and thus increase the risk of ventricular arrhythmias.

In patients simultaneously receiving muscle relaxants (for example, suxamethonium), the risk of enhanced and prolonged neuromuscular blockade may increase.

Cardiovascular failure has been reported after the use of bupivacaine in patients receiving verapamil and timolol; Lidocaine is structurally close to bupivacaine.

Dopamine and 5-hydroxytryptamine lower the convulsive threshold to lidocaine. Opioids probably have an anticonvulsant effect, which is supported by data that Lidocaine lowers the convulsive threshold to fentanyl in humans. The combination of opioids and antiemetics, sometimes used for sedation in children, may lower the convulsive threshold to lidocaine and increase its depressant effect on the CNS.

The use of epinephrine together with lidocaine may reduce systemic absorption, but in case of accidental IV administration, the risk of ventricular tachycardia and ventricular fibrillation increases sharply.

Concomitant use of other antiarrhythmics, beta-blockers and slow calcium channel blockers may further reduce AV conduction, ventricular conduction and contractility.

Concomitant use of vasoconstrictors increases the duration of action of lidocaine.

Concomitant use of lidocaine and ergot alkaloids (for example, ergotamine) may cause severe arterial hypotension.

Caution should be exercised when using sedatives, as they may affect the effect of local anesthetics on the CNS.

Caution should be exercised with long-term use of antiepileptic agents (phenytoin), barbiturates and other inhibitors of liver microsomal enzymes, as this may lead to reduced effectiveness and, as a result, an increased need for lidocaine. On the other hand, intravenous administration of phenytoin may enhance the depressant effect of lidocaine on the heart.

The analgesic effect of local anesthetics may be enhanced by opioids and clonidine.

Ethyl alcohol, especially with long-term abuse, may reduce the effect of local anesthetics.

Lidocaine is incompatible with amphotericin B, methohexitone and nitroglycerin.

When lidocaine is used simultaneously with narcotic analgesics, an additive effect develops, which is used during epidural anesthesia, but it enhances depression of the CNS and respiration. Vasoconstrictors (epinephrine, methoxamine, phenylephrine) prolong the local anesthetic action of lidocaine and may cause increased blood pressure and tachycardia.

Concomitant use with MAO inhibitors (furazolidone, procarbazine, selegiline) probably enhances the local anesthetic action of lidocaine and increases the risk of decreased blood pressure.

Guanadrel, guanethidine, mecamylamine, trimethaphan camsylate increase the risk of pronounced decrease in blood pressure and bradycardia.

Anticoagulants (including ardeparin sodium, dalteparin sodium, danaparoid sodium, enoxaparin sodium, heparin, warfarin) increase the risk of bleeding. Lidocaine reduces the cardiotonic effect of digitoxin.

Lidocaine reduces the effect of antimyasthenic drugs, enhances and prolongs the action of muscle relaxants.

When treating the injection site with disinfectant solutions containing heavy metals, the risk of a local reaction in the form of painful edema increases.

It is not recommended to mix Lidocaine with other drugs.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.