Lidoxan menthol

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LIDOKSAN MENTHOL (LIDOKSAN MENTHOL)

Composition:

Active substances: chlorhexidine dihydrochloride, lidocaine hydrochloride;

1 lozenge contains chlorhexidine dihydrochloride 5 mg and lidocaine hydrochloride 1 mg;

Excipients: menthol (levomenthol), anhydrous citric acid, magnesium stearate, sorbitol (E 420).

Pharmaceutical form. Lozenges.

Main physicochemical properties: white or almost white, round tablets with slight speckles, having a minty taste and odor.

Pharmacotherapeutic group. Medicinal products used in throat disorders. Antiseptics. ATC code R02AA05.

Pharmacological Properties.

Pharmacodynamics. Lidocaine hydrochloride is an amide-type local peripheral anesthetic. It produces a surface analgesic effect without delaying nerve impulse conduction at the site of administration.

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 of electrical excitation in peripheral nerves increases, nerve impulse conduction slows down, and action potential recovery weakens, ultimately leading to complete blockade of nerve impulse transmission. 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 important when lidocaine is used as a local anesthetic. The efficacy-toxicity ratio is favorable. Allergic reactions caused by lidocaine are very rare.

Chlorhexidine is a cationic antiseptic that exerts antibacterial effects against both Gram-positive and Gram-negative microorganisms (e.g., Micrococcus sp., Staphylococcus sp., Streptococcus sp., Bacillus sp., Clostridium sp., Corynebacterium sp.). It also has antifungal activity against dermatophytes and fungi. The drug acts as a bacteriostatic agent at low concentrations and exhibits bactericidal activity at high concentrations.

Chlorhexidine carries a strong positive charge; thus, it is adsorbed onto negatively charged sites of the bacterial cell wall and extracellular structures. The adsorption is specific and localized at corresponding sites of the bacterial cell wall containing phosphates.

Chlorhexidine binds to the bacterial cytoplasmic membrane. It is adsorbed onto the negatively charged surface of teeth, dental plaques, or the mucous membrane of the oral cavity. Small amounts of active substances enter the gastrointestinal tract with saliva. Chlorhexidine is not absorbed systemically. Lidocaine may be absorbed through the mucous membranes of the mouth and pharynx. However, most of it is destroyed before reaching systemic circulation.

Pharmacokinetics.

Chlorhexidine

Absorption

After topical or oral administration, chlorhexidine is poorly absorbed. When applied topically to affected skin areas, chlorhexidine is absorbed into the outer layer of the skin, producing a prolonged bactericidal effect on the skin. Pharmacokinetic studies have shown that approximately 30% of chlorhexidine remains in the oral cavity after rinsing and is gradually released into saliva. Patients swallow about 4% of chlorhexidine.

Distribution

After oral administration, plasma protein binding of chlorhexidine is negligible.

Metabolism and Elimination

Chlorhexidine does not accumulate. Only a small fraction is metabolized. 10% of absorbed active substance is excreted in urine, and 90% in feces.

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, although most of it is metabolized before entering systemic circulation. Absorption from mucous membranes after local application depends on perfusion and total dose. Within 30 minutes after administration, less than 17% of the dose may be excreted unchanged from the gastrointestinal tract and less than 1.5% from other tissues.

The anesthetic effect of lidocaine after local application begins within two to five minutes and lasts from 30 to 45 minutes. Anesthesia is superficial and does not extend to submucosal structures.

Distribution

Lidocaine is well distributed in tissues (kidneys, lungs, liver, heart, adipose tissue). Lidocaine crosses the blood-brain barrier and placenta and is excreted in human breast milk.

Metabolism and Elimination

Lidocaine is metabolized during first-pass liver metabolism. It undergoes dealkylation in the liver. The first two metabolites 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 biological half-life of lidocaine is 1.5–2 hours in adult patients and 3 hours in newborns. The biological half-life of lidocaine metabolites ranges from 2 to 10 hours.

The biological half-life is prolonged in congestive heart failure, liver disease, and myocardial infarction.

Clinical characteristics.

Indications.

Inflammatory and infectious diseases of the oral cavity and pharynx — such as stomatitis, gingivitis, 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 medicine, or to local anesthetics of the amide type.
• Children under 6 years of age;
• Contraindicated in children with a history of muscle seizures (including febrile seizures), as this medicinal product contains levomenthol.

Interaction with other medicinal products and other forms of interaction.

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

Lidocaine should not be used in combination 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 reported: neuromuscular blockers, 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 Menthol lozenges concurrently with cholinesterase inhibitors (e.g., neostigmine, distigmine, pyridostigmine) or with other medicinal products used to treat severe myasthenia gravis.

During treatment with Lidoksan Menthol lozenges, patients should not use other local antiseptics 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. A single dose of lozenges should replace a single dose of the spray. When using both the spray and lozenges simultaneously, patients should not exceed the daily dose. Also, the spray and lozenges should not be used simultaneously in children.

Chlorhexidine is incompatible with anionic surfactants (e.g., sodium lauryl sulfate) and certain other substances (e.g., alginates, tragacanth) commonly found in toothpastes. Therefore, the interval between tooth brushing and taking Lidoksan Menthol lozenges should be at least 30 minutes.

Special precautions for use.

Bacterial infections accompanied by elevated body temperature should be treated separately. In such cases, after consultation with a physician, Lidoxan Lemon may be used as an additional medicinal product for relief of throat pain.

Caution should be exercised when prescribing the drug to patients with heart failure, impaired liver function, and also to patients who are concurrently taking lidocaine analogs (class I antiarrhythmic agents), due to an increased risk of enhanced adverse effects of lidocaine.

Lidoxan Menthol 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 sought.

After application, patients should refrain from eating or drinking and from tooth brushing.

This medicinal product contains sorbitol (E 420). If you have been diagnosed with intolerance to certain sugars, consult your doctor before taking this medicinal product.

Use during pregnancy or breastfeeding.

Changes in the pharmacokinetics and/or pharmacodynamics of lidocaine during pregnancy may lead to toxic effects. There are no adequate and well-controlled studies on the use of chlorhexidine in pregnant women.

Metabolites of lidocaine are excreted in breast milk; however, no adverse effects have been observed in breastfed infants. It is unknown whether chlorhexidine passes into breast milk. Nevertheless, the use of this medicinal product in pregnant women and breastfeeding mothers is not recommended unless the potential risk is outweighed by the expected benefit of treatment.

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

Effect on the ability to drive vehicles or operate machinery.

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

The medicinal product has no effect or has a negligible effect on the ability to drive vehicles and operate machinery.

Method of Administration and Dosage

Adults and children aged 12 years and older

The recommended dose is 6 to 10 lozenges per day, depending on the severity of symptoms. Each lozenge should be slowly dissolved in the mouth every 2.5–4 hours.

Children aged 6 to 12 years

The recommended dose for children aged 6 years and older is half the adult dose, i.e. 3 to 5 lozenges per day, depending on the severity of symptoms. Lidoksan Menthol lozenges should be slowly dissolved in the mouth every 5–8 hours.

The maximum single dose for adults is 5 mg of chlorhexidine (0.08 mg/kg body weight) and 1 mg of lidocaine (0.02 mg/kg body weight), corresponding to 1 lozenge.

The maximum daily dose of chlorhexidine is 50 mg, and the maximum daily dose of lidocaine is 10 mg, corresponding to 10 lozenges.

Method of administration

Lidoksan Menthol lozenges must be sucked until completely dissolved. The product is intended for local application in the oral cavity and throat.

It is not advisable to use the product during or immediately after eating.

Treatment duration

Lidoksan Menthol should not be used for longer than 3–4 days. If the patient's condition does not improve during this period, or if a bacterial infection develops accompanied by fever, treatment should be discontinued and medical advice should be sought.

Patients with diabetes mellitus

Lidoksan Menthol does not contain sugar (sucrose) — it can be used by patients with diabetes mellitus.

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

Overdose

Although the medicinal product contains only a small fraction of the toxic doses of both active substances and is used locally in the oral cavity, it may be accidentally or carelessly swallowed, particularly by children.

Chlorhexidine is absorbed from the gastrointestinal tract only to a negligible extent. 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 20 lozenges per day), difficulty in swallowing (reduced control over the swallowing reflex) may occur — in such a case, immediate medical attention is required. Systemic intoxication results from effects on the central nervous system and cardiovascular system. The initial manifestations of overdose are related to central nervous system toxicity.

Symptoms that may occur in systemic intoxication:

• Central nervous system:

headache, hallucinations, dizziness, weakness, drowsiness, restlessness, tinnitus, paresthesia, speech and hearing disturbances, perioral numbness, metabolic acidosis, nystagmus, muscle tremor, psychosis, seizures, respiratory arrest, coma, epileptic seizure, altered level of consciousness;

• Cardiovascular system:

circulatory collapse, severe bradycardia, cardiac arrhythmia (sinus node arrest, tachyarrhythmia), cardiac arrest.

In addition, isolated cases of chlorhexidine overdose have been reported with the following symptoms: pharyngeal 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, therapy should be discontinued immediately. Induce vomiting and perform gastric lavage. Administer anion-binding agents such as alkylbenzene sulfonate, alkyl sulfonate, or alkyl sulfate sodium. In more severe cases, hospitalize the patient for respiratory and circulatory support and to prevent dehydration. Diazepam is used to treat seizures.

Adverse Reactions

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

Very common (≥ 1/10);
Common (≥ 1/100 to < 1/10);
Uncommon (≥ 1/1,000 to < 1/100);
Rare (≥ 1/10,000 to < 1/1,000);
Very rare (< 1/10,000);
Not known (cannot be estimated from available data).

Blood and lymphatic system disorders

Not known: Methaemoglobinaemia.

Immune system disorders

Common: Skin hypersensitivity reactions.
Rare: Severe hypersensitivity reactions, including anaphylactic shock.
Very rare: Urticaria.
Not known: Delayed-type hypersensitivity reactions (contact allergy, photosensitivity), or other skin- or tooth-related reactions, or simultaneous development of such reactions.

Psychiatric disorders

Not known: Restlessness, excitement, euphoria.

Nervous system disorders

Not known: Drowsiness, dizziness, disorientation, confusion (including slurred speech), vertigo, tremor, psychosis, nervousness, paraesthesia, numbness, convulsions, loss of consciousness, coma.

Eye disorders

Not known: Visual disturbances, including blurred vision or diplopia.

Ear and labyrinth disorders

Not known: Tinnitus.

Respiratory, thoracic and mediastinal disorders

Not known: Dyspnoea, respiratory distress syndrome, respiratory depression, respiratory arrest, asthma.

Gastrointestinal disorders

Common: Nausea, vomiting, abdominal pain.
Not known: Difficulty in swallowing, oral ulcers.

Skin and subcutaneous tissue disorders

Rare: Contact dermatitis.
Not known: Lichenoid reactions, peeling of the skin, swelling of the parotid gland.

Musculoskeletal and connective tissue disorders

Not known: Muscle twitching or tremor.

General disorders and administration site conditions

Not known: 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 oral cavity surface, temporary brownish discoloration of teeth may occur. However, this discoloration can be removed. 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 registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance System at the following link: https://aisf.dec.gov.ua/.

Shelf life: 3 years.

Storage conditions: Store at temperatures not exceeding 25 °C. Keep out of reach of children.

Packaging: Blister pack containing 12 lozenges; 2 blisters per cardboard box.

Category of supply: Over-the-counter (without prescription).

Manufacturer

(Batch release)

Lek Pharmaceutical Company d.d. / 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.

Manufacturer

(Full-cycle manufacturing)

Laboratoria Qualiphar NV (Qualiphar NV) / Laboratoria Qualiphar NV (Qualiphar NV).

Manufacturer's location and address of place of business:

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