Dentagel®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DENTAGEL® (DENTAGEL)

Composition:

Active substances: metronidazole benzoate, chlorhexidine digluconate;

1 g of gel contains: metronidazole benzoate equivalent to 10 mg of metronidazole, 20% solution of chlorhexidine digluconate equivalent to 5 mg of chlorhexidine digluconate;

Excipients: carbomer, propylene glycol, sodium saccharin, disodium edetate (Trilon B), triethanolamine, peppermint oil, purified water.

Pharmaceutical form. Gingival gel.

Main physicochemical properties: white or almost white gel with a characteristic odour. The gel should be homogeneous in appearance.

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

ATC code A01AB.

Pharmacological Properties

Pharmacodynamics

An antimicrobial combination 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 mechanism of action involves 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 spectrum 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. exhibit low sensitivity to chlorhexidine, while acid-resistant bacteria and bacterial spores are insensitive to this agent. Chlorhexidine does not impair the functional activity of lactobacilli.

Pharmacokinetics

The minimal inhibitory concentration (MIC50) of metronidazole against anaerobic bacteria is below 1 μg/mL. When the medicinal product is applied topically (applied to the gums), the concentration of metronidazole at the gingival site is significantly higher than with oral administration, while the level of systemic absorption of metronidazole with topical application is considerably lower than with oral administration. The drug is well absorbed from the gastrointestinal tract and can be detected at bacteriostatic levels in blood and saliva within 1 hour after administration. Metronidazole metabolism occurs primarily 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 ingestion 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.

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

Catarrhal and hypertrophic gingivitis, acute and chronic course.

Acute ulcerative-necrotic 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 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 eyes.

Interaction with other medicinal products and other forms of interaction.

No systemic interactions of Dentagel® gel with other medicinal products have been observed when applied locally at recommended doses. However, caution should be exercised when prescribing Dentagel® gel concomitantly with certain medicinal products.

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

Metronidazole inhibits CYP2C9 and CYP3A4, increases sodium warfarin levels in circulating blood, and enhances warfarin-induced hypoprothrombinemia.

Disulfiram. Concomitant use enhances drug toxicity, which may lead to the development of neurological symptoms.

Phenobarbital, phenytoin, hydantoin-based anticonvulsants. When used concomitantly with metronidazole, the antimicrobial activity of the latter is reduced. This is due to accelerated metabolism of metronidazole. Potentiation of phenytoin by metronidazole likely occurs via inhibition of enzymes metabolizing phenytoin.

Cimetidine. Inhibits metronidazole metabolism, potentially leading to increased metronidazole plasma concentrations.

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

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 treatment with 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 cause brown discoloration of teeth and tongue.

Use of Dentagel® gel may cause temporary alterations in taste sensation.

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

Use during pregnancy or breastfeeding.

The 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 vehicles or potentially hazardous machinery.

Method of Administration and Dosage

Topically, for dental use only!

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

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

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

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

For the treatment of post-extraction alveolitis: after tooth extraction, treat the socket with Dentagel® gel. Afterwards, the patient should independently apply the gel 2–3 times daily for 7–10 days.

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

For prevention of exacerbations of chronic gingivitis and periodontitis, in cases of gum bleeding and unpleasant mouth odor, apply Dentagel® gel in the evening after hygienic tooth brushing by rubbing it into the gum area for 2–3 minutes using finger massage or a cotton swab. After application, spit out any excess gel; do not rinse the mouth.

For prevention of exacerbations in patients with catarrhal gingivitis and generalized mild periodontitis, apply Dentagel® gel by finger massage or cotton swab to the gums for 2–3 minutes twice daily (morning and evening) after hygienic tooth brushing. After the procedure, avoid rinsing the mouth and consuming liquids for one hour. Preventive treatment courses lasting 2 weeks should be performed 2–3 times per year.

Use of the medicinal product Dentagel® does not replace hygienic tooth cleaning; therefore, regular tooth brushing should be continued during treatment.

Children

The use of Dentagel® is not recommended for children under 18 years of age.

Overdose

Cases of overdose with Dentagel® gel following topical application are unknown.

Accidental or intentional ingestion of a large amount of the gel may lead to exacerbation of adverse reactions primarily caused by metronidazole (chlorhexidine is practically not absorbed from the gastrointestinal tract). These reactions may include nausea, vomiting, and dizziness. In more severe cases, paresthesia and seizures may occur. High doses and prolonged systemic treatment with metronidazole are associated with the development of 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 requires gastric lavage and, if necessary, symptomatic therapy.

Side effects

With local application of Dentagel® gel, the risk of developing systemic adverse effects is negligible; however, reactions described below may occasionally occur.

Immune system disorders: Allergic reactions, including skin rash, pruritus, urticaria, angioedema, anaphylaxis, including anaphylactic shock. One case of eyelid swelling as a manifestation of angioedema 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 surface of teeth and 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 chlorhexidine and metronidazole combination were not available.

Post-marketing surveillance data

Adverse reactions identified during post-marketing experience with the chlorhexidine and metronidazole combination are listed below. The frequency of adverse reactions is categorized as follows: 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), and not known (cannot be estimated from available data).

Immune system disorders: Very rare – hypersensitivity reactions.

Skin and subcutaneous tissue disorders: Very rare – angioedema.

Oral use of chlorhexidine may lead to hypersensitivity, including symptoms of anaphylaxis, oral irritation, discoloration of teeth and tongue, increased formation of dental calculus, altered taste sensation, bitter taste in the mouth, as well as burning, numbness, dryness, and pain of the oral mucosa.

Post-marketing reports include cases of urticaria with facial, lip, mouth, or throat swelling, itching sensation, dyspnea, hoarseness, syncope, and allergic reactions (anaphylaxis) in the oral cavity affecting open wounds.

If any of these or other undesirable effects occur, treatment should be discontinued and medical advice should be sought.

Reporting of adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals, patients, or their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua .

Shelf life

2 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25°C. Keep out of reach of children.

Packaging

20 g in tubes; 1 tube per carton.

Prescription status

Over-the-counter (without prescription).

Manufacturer: JSC "FITOPHARM"

Manufacturer's address and location of operations

2 Sybirtseva Street, Bakhmut, Donetsk region, 84500, Ukraine.

Marketing authorization holder: JSC "FITOPHARM"

Address of the marketing authorization holder

7, Verkhovnoyi Rady Boulevard, Kyiv, 02100, Ukraine, floor 3, room 18.

INSTRUCTION

for medical use of the medicinal product

DENTAGEL®

(DENTAGEL)

Composition:

Active substances: metronidazole benzoate, chlorhexidine digluconate;

1 g of gel contains: metronidazole benzoate equivalent to 10 mg of metronidazole, 20% solution of chlorhexidine digluconate equivalent to 0.5 mg of chlorhexidine digluconate;

Excipients: carbomer, propylene glycol, sodium saccharin, disodium edetate (EDTA), triethanolamine, peppermint oil, purified water.

Pharmaceutical form. Dental gel.

Main physicochemical properties: white or almost white gel with a characteristic odor. It should be homogeneous in appearance.

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

ATC code A01AB.

Pharmacological properties.

Pharmacodynamics.

An antimicrobial combination medicinal product for comprehensive treatment and prevention of certain infectious and 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 vincentii, 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, whereas acid-resistant bacteria and bacterial spores are not susceptible to this agent. Chlorhexidine does not impair the functional activity of lactobacilli.

Pharmacokinetics.

The minimal inhibitory concentration (MIC50) of metronidazole against anaerobic bacteria is below 1 μg/mL. When the medicinal product is applied topically (applied to the gums), the concentration of metronidazole at the gingival site is significantly higher than with oral administration, while the level of systemic absorption of metronidazole with topical application is considerably lower than with oral administration. The medicinal product is well absorbed from the gastrointestinal tract and can be detected at bacteriostatic levels in blood and saliva within 1 hour after administration. Metronidazole metabolism occurs predominantly 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 ingestion 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.

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

Catarrhal, hypertrophic gingivitis, acute and chronic course.

Acute ulcerative-necrotizing gingivitis (Vincent's gingivitis).

Generalized periodontitis, chronic and exacerbated course.

Trauma of the oral mucosa caused by dental prostheses.

Alveolitis (inflammation of the socket after tooth extraction).

For the prevention of exacerbations of chronic gingivitis and periodontitis.

Contraindications.

Hypersensitivity to metronidazole, chlorhexidine, as well as nitroimidazole derivatives or any components 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 eyes.

Interaction with other medicinal products and other types of interactions.

With topical application at recommended doses, no systemic interactions of Dentagel® gel with other medicinal products have been reported. However, caution should be exercised when prescribing Dentagel® gel concomitantly with certain medicinal products.

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

Metronidazole inhibits CYP2C9 and CYP3A4, increases sodium warfarin levels in circulating blood, and enhances warfarin-induced hypoprothrombinemia.

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

Phenobarbital, phenytoin, hydantoin-based anticonvulsants. Concurrent use with metronidazole reduces the latter's antimicrobial activity. The reason is accelerated metabolism of metronidazole. Potentiation of phenytoin by metronidazole likely occurs via inhibition of enzymes metabolizing phenytoin.

Cimetidine. Inhibits metronidazole metabolism, potentially causing increased metronidazole concentration in blood serum.

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

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 treatment with 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 Dentagel® gel may cause temporary alterations in taste sensation.

If symptoms persist or worsen, or if new symptoms develop, the 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!

Apply the medicinal product after consultation with a dentist.

Adults:

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

For periodontitis: After removal of dental deposits, treat periodontal pockets with Dentagel® gel and also apply the gel to the gums. Leave the gel in place for 30 minutes. The number of procedures depends on the severity of the disease. Afterwards, the patient should continue self-application of the gel. Apply Dentagel® to the affected gum areas twice daily for 7–10 days.

For prevention of exacerbations of chronic gingivitis and periodontitis: Apply Dentagel® gel to the gums twice daily for 7–10 days. Conduct preventive treatment courses 2–3 times per year.

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

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

For prevention of exacerbations of chronic gingivitis and periodontitis, in cases of gum bleeding and unpleasant breath, apply Dentagel® gel to the gums using finger massage or a cotton swab for 2–3 minutes after evening oral hygiene. After application, spit out the excess gel and do not rinse the mouth.

For prevention of exacerbations in patients with catarrhal gingivitis and mild generalized periodontitis, apply Dentagel® gel using finger massage or a cotton swab for 2–3 minutes twice daily (morning and evening) after oral hygiene. After the procedure, avoid rinsing the mouth and consuming liquids for one hour. Conduct preventive treatment courses lasting 2 weeks, 2–3 times per year.

Use of Dentagel® does not replace regular oral hygiene. Therefore, continue tooth brushing during treatment with this medicinal product.

Children.

The use of Dentagel® is not recommended in children under 18 years of age.

Overdose.

Cases of overdose with Dentagel® gel following topical application are unknown.

Accidental or intentional ingestion of a large amount of the gel may lead to worsening of adverse reactions primarily caused by metronidazole (chlorhexidine is practically not 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. In the event of overdose, gastric lavage should be performed and symptomatic therapy administered as needed.

Adverse reactions.

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

Immune system disorders: Allergic reactions, including skin rash, pruritus, urticaria, angioedema, 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 coatings in the oral cavity, on the surface of teeth and 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 data

Adverse reactions identified during post-marketing experience with the combination of chlorhexidine and metronidazole are listed below. The frequency of adverse reactions is categorized as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), and not known (cannot be estimated from the available data).

Immune system disorders: Very rare – hypersensitivity reactions.

Skin and subcutaneous tissue disorders: Very rare – angioedema.

Oral use of chlorhexidine may lead to hypersensitivity, including symptoms of anaphylaxis, irritation of the mouth, discoloration of teeth and tongue, increased formation of dental calculus, altered taste sensation, bitter taste in the mouth, as well as burning, numbness, dryness, and pain in the oral mucosa.

Post-marketing reports have included urticaria with facial, lip, oral, and throat swelling, sensation of itching, dyspnea, hoarseness, syncope, and allergic reactions (anaphylaxis) in the oral cavity affecting open wounds.

If any of these or other undesirable effects occur, treatment should be discontinued and medical advice should be sought.

Reporting of adverse reactions

Reporting suspected adverse reactions after medicine authorization is of significant importance. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals, patients, and their legal representatives are encouraged to report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua .

Shelf life.

2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C. Keep out of reach of children.

Packaging.

20 g in tubes; 1 tube per carton.

Prescription status.

Over-the-counter.

Manufacturer: JSC "FITOPHARM" (responsible for batch release, excluding batch control/testing).

Manufacturer's address and location of operations.

17 Chumatska Street, Boryspil, Kyiv Oblast, 08303, Ukraine.

Marketing Authorization Holder: JSC "FITOPHARM".

Address of the Marketing Authorization Holder:

7, Verkhovnoyi Rady Avenue, 3rd floor, room 18, Kyiv, 02100, Ukraine.