Metrodent®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT METERODENT®

Composition:

Active substances: metronidazole benzoate (metronidazole), chlorhexidine gluconate solution (chlorhexidine);

1 g of gel contains 10 mg of metronidazole benzoate calculated as metronidazole and 2.5 mg of chlorhexidine gluconate solution calculated as chlorhexidine gluconate;

Excipients:

Metrodent® Original: carbomer-934 P, menthol, propylene glycol, sodium saccharin, purified water, triethanolamine, butylhydroxyanisole (E 320), butylhydroxytoluene (E 321), polysorbate 60;

Metrodent® with lemon flavor: carbomer-934 P, menthol, propylene glycol, sodium saccharin, purified water, triethanolamine, butylhydroxyanisole (E 320), butylhydroxytoluene (E 321), polysorbate 60, lemon flavoring;

Metrodent® with strawberry flavor: carbomer-934 P, menthol, propylene glycol, sodium saccharin, purified water, triethanolamine, butylhydroxyanisole (E 320), butylhydroxytoluene (E 321), polysorbate 60, strawberry flavoring;

Metrodent® with pineapple flavor: carbomer-934 P, menthol, propylene glycol, sodium saccharin, purified water, triethanolamine, butylhydroxyanisole (E 320), butylhydroxytoluene (E 321), polysorbate 60, pineapple flavoring.

Pharmaceutical form. Dental gel.

Main physicochemical properties: semitransparent, almost white gel with a characteristic odor.

Pharmacotherapeutic group.
Antimicrobial and antiseptic agents for topical use in dentistry. ATC code A01AB.

Pharmacological Properties

Pharmacodynamics

Metrodent®, dental gel, is a combined antimicrobial agent for comprehensive treatment and prevention of infectious and inflammatory diseases of the oral cavity. The efficacy of the product is due to the presence of the following active ingredients: metronidazole and chlorhexidine gluconate.

Metronidazole is a nitroimidazole derivative exhibiting antiprotozoal and antibacterial activity against anaerobes: Porphyr­omonas gingivalis, Prevotella intermedia, P. denticola, Fusobacterium fusiformis, Wolinella recta, Eikenella corrodens, Borrelia vincenti, Bacteroides melaninogenicus, Selenomonas spp.

Chlorhexidine gluconate is a bactericidal antiseptic active against a broad range of vegetative forms of gram-negative and gram-positive microorganisms, as well as yeasts, dermatophytes, and lipophilic viruses.

The mechanism of action of metronidazole involves biochemical reduction of the 5-nitro group of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group of metronidazole interacts with microbial DNA, inhibiting nucleic acid synthesis, which leads to bacterial cell death.

The bactericidal effect of chlorhexidine is due to the binding of cations to negatively charged bacterial cell walls of extracellular complexes. At low concentrations, chlorhexidine disrupts the osmotic balance of bacterial cells, causing leakage of potassium and phosphorus, resulting in a bacteriostatic effect. At high concentrations, chlorhexidine causes precipitation of the bacterial cytoplasmic contents, ultimately leading to bacterial cell death.

Pharmacokinetics

The minimal inhibitory concentration of metronidazole required to inhibit 50% of strains (MIC50) is below 1 µg/mL for anaerobic bacteria. With topical application, the concentration of metronidazole in the gingival area is higher than with oral administration of the drug, thus reducing the dosing frequency of Metrodent® reduces the risk of developing systemic adverse effects. Metronidazole and its metabolites are primarily excreted from the body via the kidneys. Impaired renal function does not alter the pharmacokinetics of a single dose of metronidazole.

In case of accidental swallowing of excess chlorhexidine during its topical application as part of a dental gel, approximately 1% of the dose reaching the stomach is absorbed from the gastrointestinal tract. Chlorhexidine does not accumulate in the body and undergoes minimal metabolism.

Clinical characteristics.

Indications.

The product is indicated only for dental use.

In the complex treatment of infectious-inflammatory diseases of the oral cavity caused by microorganisms sensitive to metronidazole, such as:

• acute or chronic catarrhal gingivitis;
• acute or chronic hypertrophic gingivitis;
• acute ulcerative-necrotic gingivostomatitis (Vincent's disease);
• acute or chronic generalized periodontitis;
• mucosal trauma caused by the use of dental prostheses;
• alveolitis after tooth extraction;

For the prevention of exacerbations of chronic gingivitis and periodontitis.

Contraindications.

Hypersensitivity to metronidazole, nitroimidazole derivatives, chlorhexidine, or to any other components of the product.

Interaction with other medicinal products and other forms of interaction.

With topical application of Metrodent®, interactions with other medicinal products are minimal; however, the possibility of such reactions cannot be completely excluded, so caution should be exercised when prescribing other drugs.

Warfarin and other coumarin anticoagulants. Metronidazole enhances anticoagulant effects, leading to prolonged prothrombin time.

Disulfiram. Concomitant use increases toxicity of the drugs, potentially leading to the development of neurological symptoms.

Phenobarbital, phenytoin. Concurrent use with metronidazole reduces its antimicrobial activity due to accelerated metabolism of metronidazole.

Cimetidine inhibits the metabolism of metronidazole, which may result in increased plasma concentration of metronidazole.

Special precautions.

Alcohol consumption should be avoided during the use of Metrodent® as it may lead to stomach spasms, nausea, vomiting, headache, and flushing. Care should be taken to prevent the gel from entering the eyes.

Use of the product does not replace dental hygiene procedures.

In patients with concomitant gingivitis or periodontitis, the absence or presence of gum inflammation after treatment with Metrodent® should not be used to assess the overall periodontal condition.

Metrodent® dental gel may cause discoloration of tooth surfaces, fillings, and the dorsal surface of the tongue. Discoloration may be more pronounced in patients with significant dental plaque.

Dental deposits that may appear during the use of the product can be removed from most surfaces using professional prophylactic procedures. If the natural color of these surfaces does not return after such prophylactic measures, Metrodent® should be discontinued.

Use during pregnancy or breastfeeding.

The product should not be used during pregnancy.

If treatment is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

Unknown.

Method of Administration and Dosage.

Metrodent® gel is used in dentistry for adults. Apply the gel to the gums twice daily, with at least 3 hours between applications. For 30 minutes after application, do not eat food or rinse the mouth.

The average duration of treatment is 7–10 days.

Children.

The drug is not recommended for patients under 18 years of age.

Overdose.

Cases of overdose with topical application of Metrodent® gel have not been reported. Accidental or intentional ingestion of a large amount of the gel may exacerbate adverse reactions previously caused by metronidazole (chlorhexidine is poorly absorbed from the gastrointestinal tract).

Symptoms: possible intensification of adverse effects, nausea, vomiting, dizziness. In more severe cases, paresthesia and seizures may occur.

Treatment: gastric lavage, symptomatic therapy.

Adverse Reactions

Following local application of Metrodent®, the risk of developing systemic adverse effects is low; however, the following reactions may occur.

Gastrointestinal tract: metallic taste in the mouth; bitter taste in the mouth; nausea; Metrodent® may cause the appearance of coatings on the oral mucosa, tooth surfaces, and tongue.

Nervous system: headache.

Local reactions: irritation, including burning at the site of application.

Immune system: allergic reactions, including skin rash, itching, urticaria, angioedema; one case of eyelid swelling as a manifestation of angioedema has been reported.

Eyes: if the gel comes into contact with areas near the eyes, tearing, dryness of the mucous membrane, and transient redness may occur.

Shelf life: 2 years.

Storage conditions.

Store in the original packaging, in a place inaccessible to children, at a temperature not exceeding 30 °C. Do not freeze.

Packaging.

20 g per aluminum tube; 1 tube per cardboard box.

Availability category: Over-the-counter (without prescription).

Manufacturer.

Encube Ethicals Private Limited, India.

Manufacturer's address and location of business activity.

Plot No. C-1, Madkaim Industrial Estate, Madkaim, Post Mardol, Ponda, Goa – 403 404, India.