Lidoxan menthol spray

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LIDOKSAN MENTHOL SPRAY

Composition:

Active substances: chlorhexidine digluconate, lidocaine hydrochloride;

1 ml of the preparation contains 2 mg of chlorhexidine digluconate, 0.5 mg of lidocaine hydrochloride;

Excipients: citric acid monohydrate; glycerol; sodium saccharin; menthol; cineole; ethanol 96%; purified water.

Pharmaceutical form. Oral spray.

Main physicochemical properties: clear, colorless solution with a mint and alcoholic odor and a refreshing menthol taste.

Pharmacotherapeutic group.

Preparations used in throat disorders. ATC code: R02A.

Pharmacological Properties

Pharmacodynamics

Chlorhexidine is a cationic antiseptic of the bis-biguanide class, exhibiting antibacterial activity against both Gram-positive (e.g., Micrococcus sp., Staphylococcus sp., Streptococcus sp., Bacillus sp., Clostridium sp., Corynebacterium sp.) and, to a lesser extent, Gram-negative microorganisms. It primarily affects the vegetative forms (at room temperature, it is inactive against bacterial spores). It also exerts antifungal activity against dermatophytes and fungi. The drug rapidly inactivates certain lipophilic viruses (e.g., influenza virus, herpes virus, HIV).

Chlorhexidine acts as a bacteriostatic agent at low concentrations and as a bactericidal agent at high concentrations. The chlorhexidine molecule carries a strong positive charge and thus is absorbed onto negatively charged sites of the bacterial cell wall. This absorption is specific and localized at phosphate-containing sites of the bacterial cell wall. This disrupts the integrity of the cell membrane and increases permeability.

Chlorhexidine is absorbed onto the surfaces of teeth, dental plaque, and oral mucosa, allowing the drug to remain in the oral cavity for a prolonged period.

The efficacy of antiseptics and disinfectants depends on concentration, temperature, and exposure time.

Lidocaine hydrochloride is a peripheral local anesthetic of the amide type. It produces a surface analgesic effect.

As a local anesthetic, lidocaine has the same mechanism of action as other drugs in this class: it blocks the generation and conduction of nerve impulses in sensory, motor, and autonomic nerve fibers. It acts directly on cell membranes, inhibiting the influx of sodium ions into nerve fibers through membranes. As the anesthetic effect progressively spreads, the threshold for electrical excitation in peripheral nerves increases, nerve impulse conduction slows, and action potential generation is reduced, ultimately leading to complete blockade of the nerve impulse. Generally, local anesthetics block autonomic nerves, small unmyelinated fibers (pain sensation), and small myelinated fibers (pain, temperature sensation) more rapidly than large myelinated fibers (touch, pressure sensation).

At the molecular level, lidocaine specifically blocks sodium ion channels in their inactive state, thereby preventing the generation of action potentials and blocking nerve impulse conduction when lidocaine is applied locally near a nerve.

The effect on peripheral nerves is particularly important when lidocaine is used as a local anesthetic. The ratio of efficacy to toxicity is favorable. Allergic reactions caused by lidocaine are very rare.

In addition to blocking excitation in peripheral nerves, local anesthetics affect all organs where impulse generation occurs. Effects on the central nervous system, autonomic ganglia, neuromuscular junctions, and all types of muscle fibers may be observed. Lidocaine is also classified as a class Ib antiarrhythmic agent.

Pharmacokinetics

Chlorhexidine

Absorption. After topical or oral administration, chlorhexidine is poorly absorbed. Pharmacokinetic studies have shown that approximately 30% of chlorhexidine remains in the oral cavity after rinsing and is gradually released into saliva.

Distribution. Chlorhexidine is extensively bound to proteins in saliva.

Metabolism and elimination. Chlorhexidine does not accumulate in body tissues. Its metabolism is minimal. After an oral dose of 300 mg chlorhexidine gluconate, approximately 90% of the dose is excreted via bile and feces, and less than 10% is excreted in urine.

Lidocaine

Absorption. The extent of systemic absorption of lidocaine depends on the site and route of administration. It is rapidly absorbed from the gastrointestinal tract, mucous membranes, and through damaged skin.

In healthy adults using a 2% oral rinse solution, lidocaine is not detectable in blood plasma. In children and immunocompromised adults, lidocaine is reabsorbed through the oral mucosa into blood plasma. Plasma lidocaine concentrations are approximately 0.2 µg/mL, whereas the toxic plasma concentration is 5 µg/mL.

The anesthetic effect of lidocaine after local application begins within 2–5 minutes and lasts for 30–45 minutes. The anesthesia is superficial and does not extend to submucosal structures.

Distribution. Lidocaine is extensively distributed throughout all tissues (kidneys, lungs, liver, heart, subcutaneous fat). Lidocaine crosses the blood-brain and placental barriers and is excreted in breast milk.

Metabolism and elimination. Lidocaine undergoes extensive first-pass metabolism in the liver. Its bioavailability after oral administration is approximately 35%. About 90% is dealkylated in the liver. The first two metabolites (monoethylglycinexylidide and glycinexylidide) are pharmacologically active. In some patients, these two metabolites may exert toxic effects on the central nervous system.

Lidocaine is primarily eliminated by the kidneys as metabolites, with 10% excreted unchanged. The biological half-life of lidocaine is 1.5–2 hours in adult patients. The biological half-life of lidocaine metabolites ranges from 2 to 10 hours.

Clinical characteristics.

Indications.

Inflammatory and infectious diseases of the oral cavity and pharynx, such as stomatitis, gingivitis, pharyngitis, accompanied by pain during swallowing and irritation.

Contraindications.

• Hypersensitivity to the active substances (chlorhexidine or lidocaine), or to any of the excipients of the medicinal product, or to local anesthetics of the amide type.
• Children under 6 years of age.
• Alcohol dependence.
• Contraindicated in children with a history of muscle seizures (including febrile seizures), as this medicinal product contains menthol.

Interaction with other medicinal products and other forms of interaction.

Lidocaine is an inhibitor of the CYP1A2 enzyme and to a lesser extent of the 2D6 and 3A4 isoenzymes; however, interactions with substrates of these enzymes when the medicinal product is used at recommended doses are clinically insignificant.

Patients should not take Lidoxan Menthol Spray simultaneously with cholinesterase inhibitors (e.g., neostigmine, distigmine, pyridostigmine) or with other medicinal products used to treat severe myasthenia gravis.

During treatment with chlorhexidine/lidocaine, other local antiseptics should not be used for simultaneous disinfection of the throat. This does not apply to other medicinal products containing chlorhexidine/lidocaine due to the presence of the same active ingredient. When using both the spray and lozenges simultaneously, patients should not exceed the daily dose (see section "Method of administration and dosage").

Children should not use a combination of the spray and lozenges.

Lidoxan Menthol Spray is incompatible with certain substances commonly found in toothpastes. Therefore, the interval between tooth brushing and administration of the medicinal product should be at least 30 minutes.

Special precautions for use.

Bacterial infections accompanied by elevated body temperature should be treated separately.

In such cases, Lidoksan Menthol Spray may be used after consultation with a physician as an additional medicinal product for relief of sore throat pain.

Caution is advised when prescribing the product to patients with heart failure, impaired liver function, and to patients who are concurrently taking lidocaine analogs (class I antiarrhythmic agents), due to the potential for enhanced adverse effects of lidocaine.

Lidoksan Menthol Spray should be used with caution in patients prone to hypersensitivity reactions.

Patients should not use this medicinal product for more than 3–4 days. It is recommended to use it only until relief from pain and irritation of the throat caused by inflammation is achieved. If the patient's condition does not improve within this period, treatment should be discontinued and medical advice sought.

Patients should avoid contact of the product with eyes. In case of accidental eye contact, rinse thoroughly with clean water or eye irrigation solution for at least 15 minutes, keeping the eyelids open.

Do not eat or drink, or brush teeth within 1 hour after application.

This medicinal product contains 41.6% v/v ethanol (alcohol). The maximum single dose for adults and children aged 12 years and older contains up to 144.84 mg of ethanol (equivalent to 3.67 ml of beer or 1.53 ml of wine). The maximum single dose for children aged 6 to 12 years contains 86.90 mg of ethanol (equivalent to 2.20 ml of beer or 0.92 ml of wine per dose). After first opening, the product should be used within 3 months, but not beyond the expiry date indicated on the packaging.

Lidoksan Menthol Spray is harmful for individuals with alcoholism.

The ethanol content should be taken into account when prescribing the product to pregnant women, breastfeeding women, children, and individuals in high-risk groups, such as patients with liver disease or epilepsy.

Patients with diabetes mellitus. Lidoksan Menthol Spray does not contain sucrose and therefore can be used by patients with diabetes mellitus.

Use during pregnancy or breastfeeding.

Lidocaine. Altered pharmacokinetics and/or pharmacodynamics of lidocaine during pregnancy may lead to toxic effects. Lidocaine is excreted in breast milk.

Chlorhexidine. There are insufficient published data from controlled studies on the use of chlorhexidine during pregnancy. There are no data on the excretion of chlorhexidine into breast milk.

Lidoksan Menthol Spray is not recommended during pregnancy and breastfeeding because the product contains ethanol as an excipient.

Effect on ability to drive and use machines.

No studies on the effect of the product on the ability to drive or operate machinery have been conducted.

Method of Administration and Dosage.

Dosage.

Adults and children aged 12 years and older: 3–5 consecutive presses on the spray nozzle; repeat the procedure 6 to 10 times daily.

Children aged 6 to 12 years: 2–3 consecutive presses on the spray nozzle; repeat the procedure 3 to 5 times daily.

The maximum single dose for adults is 0.85 mg of chlorhexidine digluconate and 0.21 mg of lidocaine hydrochloride.

The maximum daily dose for adults is 8.5 mg of chlorhexidine digluconate and 2.1 mg of lidocaine hydrochloride.

Method of Administration.

The medicinal product is intended for use in the throat area.

Lidoxan Menthol Spray is intended for individual use.

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After each use, the tube should be turned downwards again to prevent the spray from dispersing through the nozzle.

If Lidoksan Menthol Spray is not to be used for a period of time, it is recommended to clean the nozzle by performing the following steps:

1. Turn the bottle upside down with the cap facing downwards and press the spray nozzle until the tube is completely emptied (the solution no longer sprays).
2. Remove the tube from the bottle and place it in a container with warm water for several minutes.
3. Remove the tube from the water and allow it to dry.
4. To lock the nozzle, reattach the tube to the bottle with the tube facing downwards.

Duration of treatment.

Lidoksan Menthol Spray should not be used for more than 3–4 consecutive days or too frequently. If the patient's condition does not improve during this period or if the patient develops a bacterial infection accompanied by fever, medical advice must be sought.

Children. Not recommended for children under 6 years of age.

Overdose.

There is a risk of overdose if the product is accidentally ingested, especially in children.

Chlorhexidine is absorbed from the gastrointestinal tract in negligible amounts. Lidocaine is absorbed more rapidly, but its bioavailability after oral administration is only 35%. Toxic effects of lidocaine occur at plasma concentrations exceeding 6 mg/L. After administration of excessive doses (more than the content of one bottle), swallowing difficulties may occur (reduced control over the swallowing reflex). Systemic intoxication results from effects on the central nervous and cardiovascular systems. The initial signs of overdose are manifestations of central nervous system involvement.

Symptoms that may occur in systemic intoxication:

• Central nervous system effects: headache, hallucinations, dizziness, drowsiness, restlessness, tinnitus, paresthesia, speech and hearing disturbances, perioral numbness, metabolic acidosis, nystagmus, muscle tremors, psychosis, seizures, respiratory arrest, coma, epileptic seizure, altered level of consciousness;
• Cardiovascular effects: circulatory collapse, severe bradycardia, cardiac arrhythmia (sinus node arrest, tachyarrhythmia), cardiac arrest.

In addition, cases of chlorhexidine overdose have been reported with symptoms such as pharyngeal swelling, necrotic esophageal lesions, elevated serum aminotransferase levels (more than 30 times above normal), vomiting, gastric and duodenal erosions with active atrophic gastritis, euphoria, visual disturbances, and complete loss of taste (lasting up to 8 hours).

Treatment in case of systemic intoxication

If symptoms of systemic intoxication occur, the use of the product must be immediately discontinued. Induce vomiting and perform gastric lavage. Administer anion-active substances such as alkylbenzene sulfonate, alkyl sulfonate, or sodium alkyl sulfate. In more severe cases, the patient should be hospitalized to support cardiovascular and respiratory functions and to prevent dehydration. Diazepam is used to treat seizures.

Adverse reactions.

Undesirable effects are listed by organ system classes and frequency of occurrence:

very common (≥1/10);

common (≥1/100 to <1/10);

uncommon (≥1/1000 to <1/100);

rare (≥1/10,000 to <1/1000);

very rare (<1/10,000);

unknown (cannot be estimated from available data)

Blood and lymphatic system disorders

Unknown: methemoglobinemia.

Immune system disorders

Common: skin hypersensitivity reactions.

Rare: severe hypersensitivity reactions, including anaphylactic shock.

Very rare: urticaria.

Unknown: delayed-type hypersensitivity reactions (contact allergy, photosensitivity) or other skin or dental reactions, or concurrent development of these reactions.

Psychiatric disorders

Unknown: restlessness, excitement, euphoria.

Nervous system disorders

Unknown: drowsiness, dizziness, disorientation, confusion (including speech confusion), vertigo, tremor, psychosis, nervousness, paresthesia, numbness, seizures, loss of consciousness, coma.

Eye disorders

Unknown: visual disturbances, including blurred vision or diplopia.

Ear and labyrinth disorders

Unknown: tinnitus.

Respiratory, thoracic and mediastinal disorders

Unknown: dyspnea, respiratory distress syndrome, respiratory depression, respiratory arrest, asthma.

Gastrointestinal disorders

Common: nausea, vomiting, abdominal pain.

Unknown: difficulty in swallowing, oral mucosal ulcers.

Skin and subcutaneous tissue disorders

Very rare: contact dermatitis.

Unknown: lichenoid reactions, skin desquamation, parotid gland swelling.

Musculoskeletal and connective tissue disorders

Unknown: muscle twitching or tremor.

General disorders and administration site conditions

Unknown: asthenia, transient taste disturbance or burning sensation of the tongue, sensation of heat or cold.

With prolonged and continuous use of chlorhexidine over the entire surface of the oral cavity, temporary brown discoloration of teeth may occur. However, this discoloration is reversible. There have been no reports of tooth discoloration when the medicinal product is used only in the pharyngeal area.

Reporting of adverse reactions after medicinal product authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua».

Shelf life. 2 years.

Storage conditions. Store at temperatures not exceeding 25 °C in a place inaccessible to children.

Packaging. 30 ml in a bottle, 1 bottle per carton.

Supply category. Over-the-counter.

Manufacturer.

(batch release)

Lek Pharmaceuticals d.d.

Manufacturer's location and address of place of business.

Verovskova ulica 57, Ljubljana 1526, Slovenia / Verovskova ulica 57, Ljubljana 1526, Slovenia.

(full-cycle manufacturing)

Laboratoria Qualiphar NV (Qualiphar NV).

Manufacturer's location and address of place of business.

Rijksweg 9, Bornem, 2880, Belgium / Rijksweg 9, Bornem, 2880, Belgium.