Metrogyl denta®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT METROGYL DENTA® (metrogyl denta®)

Composition:

Active substances: metronidazole benzoate, chlorhexidine gluconate;

1 gram of gel contains: metronidazole benzoate 16 mg, equivalent to 10 mg of metronidazole; solution of chlorhexidine gluconate (20%) 2.5 mg, equivalent to 0.5 mg of chlorhexidine gluconate;

Excipients: saccharin, sodium hydroxide, disodium edetate, levomenthol, propylene glycol, carbomer homopolymer (type C), purified water.

Pharmaceutical form. Dental gel.

Main physicochemical characteristics: opalescent soft gel, white or almost white in color.

Pharmacotherapeutic group. Agents for use in dentistry. Antimicrobial and antiseptic agents for local application in dentistry.

ATC code A01AB.

Pharmacological properties.

Pharmacodynamics.

An antimicrobial combined medicinal product intended for comprehensive treatment and prevention of certain infectious-inflammatory diseases of the oral cavity.

The efficacy of the medicinal product is due to the presence of two antibacterial components – metronidazole and chlorhexidine.

Metronidazole is a nitroimidazole derivative with antiprotozoal and antibacterial activity. It is active against anaerobic bacteria causing periodontal diseases: Porphyromonas gingivalis, Prevotella intermedia, Prevotella denticola, Fusobacterium fusiformis, Wolinella recta, Eikenella corrodens, Borrelia vincenti, Bacteroides melaninogenicus, Selenomonas spp.

Chlorhexidine is a bactericidal antiseptic. Its action consists in increasing the permeability of bacterial cell walls, allowing chlorhexidine to penetrate into the bacterial cytoplasm, resulting in cell death. It is active against a broad range of vegetative forms of gram-negative (Treponema spp., Neisseria gonorrhoeae, Trichomonas spp., Chlamydia spp., Ureaplasma spp., Bacteroides fragilis) and gram-positive microorganisms, as well as yeasts, dermatophytes, and lipophilic viruses.

Some strains of Pseudomonas spp. and Proteus spp. have low sensitivity to chlorhexidine, while acid-resistant bacteria and bacterial spores are insensitive to this substance. Chlorhexidine does not impair the functional activity of lactobacilli.

Pharmacokinetics.

The minimal inhibitory concentration (MIC50) of metronidazole against anaerobic bacteria is below 1 mcg/mL. When the medicinal product is applied locally (application to the gums), the concentration of metronidazole at the gingival site is significantly higher than with oral administration of the drug, while the level of systemic absorption of metronidazole with local application is considerably lower than with oral administration. The drug is well absorbed from the gastrointestinal tract and can be detected at bacterially inhibitory levels in blood and saliva within 1 hour after administration. Metronidazole is predominantly metabolized in the liver. The main route of elimination of metronidazole and its metabolites is 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 local 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.

For the treatment of inflammatory and infectious diseases of the periodontium and oral mucosa.

Catarrhal and hypertrophic gingivitis, acute and chronic course.

Acute necrotizing ulcerative gingivitis (Vincent's gingivitis).

Generalized periodontitis, chronic and acute exacerbation.

Trauma of the oral mucosa caused by dental prostheses.

Alveolitis (inflammation of the tooth socket after tooth extraction).

For the prevention of exacerbations of chronic gingivitis and periodontitis.

Contraindications.

Hypersensitivity to metronidazole, chlorhexidine, nitroimidazole derivatives, or to any component of the medicinal product (see section "Composition").

Contraindicated in patients with confirmed blood dyscrasias or history of blood dyscrasias.

Contraindicated in patients with diseases of the peripheral and central nervous system.

Children under 18 years of age.

Special precautions.

Avoid contact of the gel with the eyes.

Interaction with other medicinal products and other forms of interaction.

No systemic interactions of Metrogyl Denta® gel with other medicinal products have been observed when used topically at recommended doses. However, caution should be exercised when prescribing Metrogyl Denta® gel concomitantly with certain medicinal products.

Warfarin and other coumarin anticoagulants. Metronidazole potentiates the anticoagulant effect, leading to prolonged prothrombin time.

Metronidazole inhibits CYP2C9 and CYP3A4, increases the level of sodium warfarin in the systemic circulation, and enhances warfarin-induced hypoprothrombinemia.

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

Phenobarbital, phenytoin, and hydantoin-based anticonvulsants. Concurrent use with metronidazole reduces the latter's antimicrobial activity due to accelerated metabolism of metronidazole.

Phenytoin potentiation by metronidazole likely occurs via inhibition of enzymes responsible for phenytoin metabolism.

Cimetidine. Inhibits the metabolism of metronidazole, potentially leading to increased metronidazole concentration in blood serum.

Alcohol. Metronidazole causes alcohol intolerance. Concurrent intake of alcohol and metronidazole may result in symptoms of toxic psychosis, nausea, arterial hypotension, tachycardia, diaphoresis, or dyspnea; in some cases, severe arterial hypotension and shock may occur. These reactions typically occur within 24 hours but may appear within a period up to 2 weeks after alcohol consumption.

Special precautions for use.

The use of the medicinal product may cause allergic reactions (skin rash, itching, urticaria, angioedema, and anaphylaxis, including shock).

Alcohol consumption must be avoided during use of this medicinal product, as it may lead to gastric spasms, nausea, vomiting, headache, and facial flushing.

Metronidazole should not be used concomitantly with disulfiram, as it may cause psychotic reactions and confusion.

Prolonged use may result in brown discoloration of teeth and tongue.

Use of Metrogyl Denta® gel may cause temporary disturbances in taste sensation.

If symptoms do not improve or worsen, or if new symptoms occur, use of this medicinal product should be discontinued and medical advice should be sought.

Use during pregnancy or breastfeeding.

This medicinal product should not be used during pregnancy.

Breastfeeding should be discontinued for the duration of treatment with this medicinal product.

Ability to affect reaction speed when driving or operating machinery.

It is unknown whether the use of the combination of chlorhexidine and metronidazole affects the ability to drive or operate potentially hazardous machinery.

Method of Administration and Dosage

Topical use only for dental purposes!

The medicinal product should be used after consultation with a dentist.

For adults with gingivitis: Apply Metrogyl Denta® gel to the gums using finger massage or a cotton swab twice daily. Do not rinse the mouth, drink, or eat for 30 minutes after application. The average duration of treatment is 7–10 days.

For periodontitis: After removal of dental deposits, periodontal pockets should be treated with Metrogyl Denta® gel, and the gel should also be applied to the gums. Application time is 30 minutes. The number of procedures depends on the severity of the disease. Subsequently, the patient performs gel applications independently. Apply Metrogyl Denta® to the affected gum areas twice daily for 7–10 days.

For prevention of exacerbations of chronic gingivitis and periodontitis: Apply Metrogyl Denta® gel to the gums twice daily for 7–10 days. Preventive treatment courses should be carried out 2–3 times per year.

For the treatment of post-extraction alveolitis: After tooth extraction, treat the socket with Metrogyl Denta® gel. Afterwards, the patient should self-administer the gel 2–3 times daily for 7–10 days.

For the prevention of exacerbations of chronic gingivitis and periodontitis, apply Metrogyl Denta® gel twice daily to affected areas for 7–10 days. Preventive courses should be conducted 2–3 times per year.

For the prevention of exacerbations of chronic gingivitis and periodontitis, in cases of gum bleeding and unpleasant breath odor, apply Metrogyl Denta® gel to the gum area using finger massage or a cotton swab after evening oral hygiene procedures. Massage gently for 2–3 minutes, then spit out the gel without rinsing the mouth.

For prevention of exacerbations in patients with catarrhal gingivitis and generalized mild periodontitis, apply Metrogyl Denta® gel using finger massage or a cotton swab for 2–3 minutes after morning and evening oral hygiene. After the procedure, avoid rinsing the mouth and refrain from drinking liquids for one hour. Preventive treatment courses lasting 2 weeks should be conducted 2–3 times per year.

The use of Metrogyl Denta® does not replace routine dental hygiene; therefore, tooth brushing should be continued during treatment with this medicinal product.

Children

The use of this medicinal product is not recommended for children under 18 years of age.

Overdose

Cases of overdose with Metrogyl Denta® gel during topical application are unknown.

Accidental or intentional ingestion of a large amount of the gel may exacerbate adverse reactions primarily associated with metronidazole (chlorhexidine is poorly absorbed from the gastrointestinal tract). These reactions include nausea, vomiting, and dizziness. In more severe cases, paresthesia and seizures may occur. High doses and prolonged systemic metronidazole therapy have been associated with leukopenia, neutropenia, increased risk of peripheral neuropathy, and central nervous system toxicity. Keep out of reach of children. In case of ingestion, seek immediate medical attention. Treatment of overdose may include gastric lavage and, if necessary, symptomatic therapy.

Adverse reactions.

When Metrogyl Denta® gel is used locally, the risk of systemic adverse effects is negligible; however, the following reactions may occasionally occur.

Immune system disorders: allergic reactions, including skin rash, pruritus, urticaria, angioneurotic edema, anaphylaxis, including anaphylactic shock. One case of eyelid swelling as a manifestation of angioneurotic reaction has been reported.

Nervous system disorders: headache.

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

Gastrointestinal disorders: metallic taste in the mouth, bitter taste in the mouth, nausea, possible appearance of coating in the oral cavity, on the tooth surfaces and on the tongue.

Application site reactions: burning sensation at the application site, irritation at the application site.

Clinical trial data

Placebo-controlled studies with sufficient data on adverse effects associated with the use of the combination of chlorhexidine and metronidazole were not available.

Post-marketing surveillance data.

Immune system side effects: very rare – hypersensitivity reactions.

Skin and subcutaneous tissue side effects: very rare – angioneurotic edema.

With oral use of chlorhexidine, possible side effects include hypersensitivity, including anaphylactic symptoms, mouth irritation, discoloration of teeth and tongue, increased tartar formation, altered taste sensation, bitter taste in the mouth, as well as burning, numbness, dryness, and pain in the oral mucosa.

Post-marketing use has reported urticaria with facial, lip, oral, or throat swelling, sensation of itching, difficulty breathing, hoarseness, fainting, and allergic reactions (anaphylaxis) in the oral cavity on open wounds.

If any of these or other adverse effects occur, discontinue treatment and consult a physician.

Reporting of adverse reactions

Reporting adverse reactions following drug registration is essential for ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: 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.

20 g in aluminum or laminated plastic tubes. 1 tube per cardboard box.

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

Manufacturer.

"Unique Pharmaceutical Laboratories" (a division of J. B. Chemicals & Pharmaceuticals Ltd.).

Manufacturer's address and place of business.

Plot No. 304-308, G.I.D.C. Industrial Area, City: Panoli - 394 116, Dist: Bharuch, India.

Marketing Authorization Holder.

Johnson & Johnson Ukraine LLC.

Address of the Marketing Authorization Holder.

32/2 Ostrivskykh Knyaziv St., Kyiv, 01010, Ukraine.

+38 (044) 498 0888

+38 (044) 498 7392