Lidoxan lemon spray

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LIDOKSAN LEMON SPRAY (LIDOKSAN LEMON 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; sucralose; lemon flavor; propylene glycol; glycerin; ethanol 96%; purified water.

Pharmaceutical form. Oral spray.

Main physicochemical properties: clear, colorless solution with a lemon and alcohol odor and lemon taste.

Pharmacotherapeutic group.
Preparations used in throat diseases. ATC code: R02A.

Pharmacological Properties

Pharmacodynamics

Chlorhexidine is a cationic antiseptic of the biguanide class that exerts 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 exhibits 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 adsorbed onto negatively charged sites of the bacterial cell wall. This adsorption is specific and localized at phosphate-containing sites of the bacterial cell wall. This disrupts the integrity of the cell membrane and leads to increased permeability.

Chlorhexidine is adsorbed 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 directly affects 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 recovery is weakened, 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 essential when lidocaine is used as a local anesthetic. The benefit-risk ratio is favorable. Allergic reactions to lidocaine are very rare.

In addition to blocking excitation in peripheral nerves, local anesthetics affect all organs where impulse excitation 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 subsequently gradually released into saliva.

Distribution. Chlorhexidine binds extensively to proteins in saliva.

Metabolism and elimination. Chlorhexidine does not accumulate in body tissues. Its metabolism is minimal. After oral administration of 300 mg of 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 was not detected in plasma. In children and immunocompromised adults, lidocaine is reabsorbed through the oral mucosa into plasma. Plasma lidocaine concentrations reach approximately 0.2 µg/mL, whereas 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 about 35%. Approximately 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 excreted by the kidneys as metabolites, with 10% excreted unchanged. The elimination half-life of lidocaine is 1.5–2 hours in adult patients. The elimination 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, and pharyngitis, accompanied by pain on 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.

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. Lidocaine should not be used concomitantly with disinfectant solutions containing heavy metals. Iontophoresis of vasoactive substances may significantly affect transdermal delivery of lidocaine.

Clinically insignificant interactions of lidocaine with the following medicinal products have been described: neuromuscular blocking agents, other antiarrhythmics, hydantoins (antiepileptic agents), adrenaline, opioids, beta-blockers, cimetidine, and the antiarrhythmic mexiletine. Insignificant interactions have also been observed in patients with cocaine-induced myocardial infarction.

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

The combination of spray and lozenges should not be used in children.

Chlorhexidine is incompatible with anionic surfactants (e.g., sodium lauryl sulfate) and certain other substances (e.g., alginates, tragacanth, insoluble powders such as kaolin, and insoluble calcium, magnesium, or zinc compounds), which are often present 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 Lemon Spray should be used as an additional medicinal product for relief of throat pain after consultation with a physician.

Extreme caution should be exercised when prescribing the drug to patients with heart failure, impaired liver function, and to patients who are concurrently taking lidocaine analogs (class I antiarrhythmics), due to the potential for enhanced adverse effects of lidocaine.

Lidoksan Lemon 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. If the patient's condition does not improve within this time, treatment should be discontinued and medical advice should be 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 eyelids open.

Do not eat, drink, or brush teeth immediately after application.

This medicinal product contains 29.7% v/v ethanol. One dose (one spray press – 0.085 mL) contains 0.02 g of ethanol and 0.017 g of propylene glycol. The maximum single dose for adults and children aged 12 years and older (5 sprays) contains up to 104.46 mg of ethanol (equivalent to 2.64 mL of beer or 1.10 mL of wine). The maximum single dose for children aged 6 to 12 years (3 sprays) contains 62.68 mg of ethanol (equivalent to 1.58 mL of beer or 0.66 mL of wine per dose). After first opening, the product should be used within 6 months, but not beyond the expiry date indicated on the packaging.

Lidoksan Lemon 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 high-risk groups, such as patients with liver disease or epilepsy.

Propylene glycol may cause symptoms similar to those associated with alcohol abuse.

Patients with diabetes mellitus. Lidoksan Lemon 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 is 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 Lemon Spray is not recommended during pregnancy and breastfeeding because this product contains ethanol as an excipient.

Fertility

There are no data on the effects of lidocaine and chlorhexidine on human fertility.

Ability to affect reaction speed when driving or operating machinery

No studies have been conducted on the effect of the medicinal product on reaction speed when driving or operating machinery.

Method of Administration and Dosage.

Dosage.

Adults and children aged 12 years and older: 3–5 consecutive actuations of the spray nozzle; repeat the procedure 6 to 10 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.

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

One actuation of the spray nozzle (85 mg, equivalent to 0.085 mL) releases 0.17 mg of chlorhexidine digluconate and 0.04 mg of lidocaine hydrochloride.

Method of Administration.

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

Lidoksan Lemon Spray is intended for individual use.

After each use, the tube should be turned downwards again to prevent the medication from spraying out of the nozzle.

If Lidoksan Lemon Spray is not to be used for some 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 thoroughly.
4. To lock the nozzle, reattach the tube to the bottle with it facing downwards.

Duration of treatment.

Lidoksan Lemon Spray must not be used for more than 3–4 consecutive days. If the patient's condition does not improve during this period, or if a bacterial infection develops accompanied by an increase in body temperature, medical advice must be sought.

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

Overdose.

Overdose is possible in case of accidental ingestion, 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 first 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 the following symptoms: throat swelling, necrotic lesions of the esophagus, 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 medication must be stopped immediately. Induce vomiting and perform gastric lavage. Administer anion-binding agents such as alkylbenzene sulfonate, alkyl sulfonate, or sodium alkyl sulfate. In more severe cases, the patient should be hospitalized to support cardiovascular and respiratory function and to prevent dehydration. Diazepam is used to treat seizures.

Adverse reactions.

Adverse events 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, teeth, or simultaneous occurrence 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 (ringing in the ears).

Respiratory, thoracic and mediastinal disorders

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

Gastrointestinal disorders

Common: nausea, vomiting, abdominal pain.

Unknown: difficulty swallowing, oral ulcers.

Skin and subcutaneous tissue disorders

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 disturbances or burning sensation of the tongue, sensation of heat or cold.

With prolonged and continuous use of chlorhexidine, temporary brown staining of teeth may occur. However, this discoloration can be removed. There have been no reports of tooth discoloration during use of the medicinal product for treatment of throat disorders.

Reporting of suspected adverse reactions after authorization of the medicinal product is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare 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: https://aisf.dec.gov.ua.

Shelf life: 36 months.

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.

Prescription status. 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.