Lidoxane® strawberry

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LIDOKSAN® STRAWBERRY (LIDOKSAN® STRAWBERRY)

Composition:

Active substances: chlorhexidine dihydrochloride, lidocaine hydrochloride;

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

Excipients: menthol, anhydrous citric acid, strawberry flavor 502301 TP 0551, sucralose, magnesium stearate, sorbitol (E 420).

Pharmaceutical form. Lozenges.

Main physicochemical properties: white or whitish, slightly mottled, round lozenges with strawberry flavor and odor.

Pharmacotherapeutic group. Preparations used in throat disorders. ATC code: R02A A05.

Pharmacological properties.

Pharmacodynamics.

Lidocaine hydrochloride is an amide-type peripheral local anaesthetic. It exerts a surface analgesic effect without delaying the conduction of nerve impulses at the site of administration.

As a local anaesthetic, 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 fibres. Lidocaine directly affects cell membranes, inhibiting the influx of sodium ions into nerve fibres through membranes. As the anaesthetic effect progressively spreads, the threshold for electrical excitation in peripheral nerves increases, nerve impulse conduction slows down, and the restoration of the action potential is weakened, ultimately leading to complete blockade of the nerve impulse. Overall, local anaesthetics block autonomic nerves, small unmyelinated fibres (pain sensation), and small myelinated fibres (pain, temperature sensation) more rapidly than large myelinated fibres (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 anaesthetic. The ratio between efficacy and toxicity is favorable. Allergic reactions caused by lidocaine are very rare.

Chlorhexidine is a cationic antiseptic agent active against Gram-positive bacteria (e.g., Micrococcus sp., Staphylococcus sp., Streptococcus sp., Bacillus sp., Clostridium sp., Corynebacterium sp.) and, to a lesser extent, against Gram-negative bacteria, primarily in their vegetative forms (at room temperature, it is ineffective against bacterial spores). It also exerts antifungal activity against dermatophytes and fungi. Chlorhexidine rapidly inactivates certain lipophilic viruses (e.g., influenza virus, herpes virus, HIV). The agent acts as a bacteriostatic 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. This adsorption is specific and localized to phosphate-containing regions of the bacterial cell wall. This disrupts the integrity of the cell membrane and increases its permeability.

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, resulting in 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.

Chlorhexidine is adsorbed onto negatively charged surfaces of teeth, dental plaque, or oral mucosa, thereby remaining in the oral cavity for a prolonged period.

Distribution

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

Metabolism and elimination

Chlorhexidine does not accumulate. Only a small fraction is metabolized. 10% of the absorbed active substance is excreted in urine, and 90% is excreted 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 a large portion 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 anaesthetic effect of lidocaine after local application begins within 2–5 minutes and lasts from 30 to 45 minutes. Anaesthesia is superficial and does not extend to submucosal structures.

The bioavailability of lidocaine after oral administration is 35%.

Distribution

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

Metabolism and elimination

Lidocaine undergoes first-pass metabolism in the liver. It 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. Both metabolites can be hydrolyzed to xylidine, which is then oxidized to 4-hydroxyxylidine—the main metabolite found in urine. In humans with normal liver function, lidocaine is primarily metabolized by the CYP1A2 enzyme. It is mainly 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 accompanied by pain on swallowing and irritation.

Contraindications.

• Hypersensitivity to the active substances (chlorhexidine or lidocaine), to any of the excipients of the medicinal product, 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 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 product is used at recommended doses are clinically insignificant.

Patients should not take this medicinal product concomitantly with cholinesterase inhibitors (e.g., neostigmine, distigmine, pyridostigmine) or with other medicinal products used to treat severe myasthenia gravis.

During treatment with this product, 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. When using the spray and lozenges concomitantly, 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 the lozenges should be at least 30 minutes.

Special precautions for use.

In bacterial infections accompanied by elevated body temperature, chlorhexidine/lidocaine should be used as an additional medicinal product after consultation with a physician.

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

The medicinal product should be used with caution in patients prone to hypersensitivity reactions.

This medicinal product should not be used for more than 3–4 days. It is recommended for use only to relieve 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.

Food and drink should not be consumed, and teeth should not be brushed, for at least 1 hour after taking the product.

The lozenges contain 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.

Use of the medicinal product during pregnancy and lactation is not recommended, except when the expected benefit outweighs the potential risk.

Pregnancy

Chlorhexidine

There are currently no adequate controlled studies on the effects of chlorhexidine during pregnancy.

Lidocaine

Pharmacokinetic and pharmacodynamic changes of lidocaine during pregnancy may lead to symptoms of toxicity.

Breastfeeding

Chlorhexidine

It is unknown whether chlorhexidine passes into breast milk. A risk to newborns/infants cannot be excluded.

Lidocaine

Metabolites of lidocaine pass into breast milk. However, there have been no reports of adverse effects in newborns/infants to date.

Reproductive function

There are no data available on the effects of chlorhexidine or lidocaine on human reproductive function.

Ability to influence reaction rate while driving or operating machinery.

No studies have been conducted on the effects of the medicinal product on the ability to drive or 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.

For adults and children aged 12 years and older, the maximum daily dose of chlorhexidine is 50 mg, and the maximum daily dose of lidocaine is 10 mg, corresponding to 10 lozenges.

Children aged 6 to 12 years

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

For children aged 6 to 12 years, the maximum daily dose of chlorhexidine is 25 mg, and the maximum daily dose of lidocaine is 5 mg, corresponding to 5 lozenges.

The maximum single dose for adults and children aged 6 years and older is 5 mg of chlorhexidine (0.08 mg/kg body weight) and 1 mg of lidocaine (0.02 mg/kg body weight), equivalent to 1 lozenge.

Method of administration

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

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

After using the medicinal product, it is recommended not to eat or drink for at least one hour.

To achieve optimal effect, it is recommended not to use the product immediately before or after tooth brushing. A waiting period of at least 30 minutes between using the product and tooth brushing is advised.

Duration of treatment

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

Children. The product is not indicated for children under 6 years of age.

Overdose

Although the medicinal product contains only a small fraction of a toxic dose and is applied locally, the possibility of accidental overdose, especially during treatment of children, should be considered.

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 20 lozenges per day), swallowing difficulties (reduced control of the swallowing reflex) may occur; in such cases, immediate medical attention is required. Systemic intoxication results from effects on the central nervous system and cardiovascular system. The first signs of overdose are related to central nervous system toxicity.

Symptoms that may occur in systemic intoxication:

• Central nervous system:

headache, hallucinations, vertigo, lethargy, 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:

cardiovascular insufficiency, 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: throat swelling, necrotic lesions of the esophagus, increased serum aminotransferase activity (more than 30 times above normal), vomiting, erosions of the stomach and duodenum 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, for example: alkylbenzene sulfonate, alkyl sulfonate, or sodium alkyl sulfate. In more severe cases, the patient should be hospitalized for respiratory and circulatory support and to prevent dehydration. Diazepam is used to treat seizures.

Side effects

Adverse reactions are listed by organ systems 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);
Frequency not known (cannot be estimated from available data).

Blood and lymphatic system disorders

Frequency not known: Methemoglobinemia.

Immune system disorders

Common: Hypersensitivity skin reactions.
Rare: Severe hypersensitivity reactions, including anaphylactic shock.
Very rare: Urticaria.
Frequency not known: Delayed-type hypersensitivity reactions (contact allergy, photosensitivity), or other skin or dental reactions.

Psychiatric disorders

Frequency not known: Restlessness, excitement, euphoria.

Nervous system disorders

Frequency not known: Drowsiness, dizziness, disorientation, confusion (including speech confusion), vertigo, tremor, psychosis, nervousness, paresthesia, numbness, seizures, loss of consciousness, coma.

Eye disorders

Frequency not known: Visual disturbances, including blurred vision and diplopia.

Ear and labyrinth disorders

Frequency not known: Tinnitus (ringing in the ears).

Respiratory, thoracic and mediastinal disorders

Frequency not known: Dyspnea, respiratory distress syndrome, respiratory depression, respiratory arrest, asthma.

Gastrointestinal disorders

Common: Nausea, vomiting, abdominal pain.
Frequency not known: Difficulty swallowing, oral ulcers.

Skin and subcutaneous tissue disorders

Rare: Contact dermatitis.
Frequency not known: Lichenoid reactions, skin peeling, parotid gland swelling.

Musculoskeletal and connective tissue disorders

Frequency not known: Muscle twitching or tremor.

General disorders

Frequency not known: Asthenia, transient taste disturbances or burning sensation of the tongue, sensation of heat or cold.

Prolonged and continuous use of chlorhexidine may cause temporary brown discoloration of teeth. However, this discoloration can be removed.

Shelf life. 2 years.

Storage conditions. Store at a temperature not exceeding 25 °C. Keep out of reach of children.

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

Supply category. Over-the-counter.

Manufacturer.

(Batch release)

Lek Pharmaceuticals d.d.

Manufacturer's location and address of place of business.

Verovškova 57, Ljubljana 1526, Slovenia