Metrogyl^® Plus (Gel) Instructions for Use

Marketing Authorization Holder

Unique Pharmaceutical Laboratories (A Division of J. B. Chemicals & Pharmaceuticals Ltd.) (India)

ATC Code

G01AF20 (Imidazole derivative combinations)

Active Substances

Clotrimazole (Rec.INN registered by WHO)

Metronidazole (Rec.INN registered by WHO)

Dosage Form

Metrogyl® Plus

Vaginal gel 20 mg+10 mg/1 g: 30 g or 50 g tubes with applicator

Dosage Form, Packaging, and Composition

Vaginal gel opalescent, homogeneous, white or almost white in color.

Excipients: methyl hydroxybenzoate, propyl hydroxybenzoate, disodium edetate, propylene glycol, carbomer-940, benzyl alcohol, sodium hydroxide, purified water.

20 g – aluminum tubes (1) with applicator – cardboard packs.
20 g – plastic tubes (1) with applicator – cardboard packs.
30 g – aluminum tubes (1) with applicator – cardboard packs.
30 g – plastic tubes (1) with applicator – cardboard packs.

Clinical-Pharmacological Group

A drug with antibacterial, antiprotozoal, and antifungal action for topical use in gynecology

Pharmacotherapeutic Group

Antimicrobial preparations and antiseptics used in gynecology. Antimicrobial preparations and antiseptics, excluding combinations with corticosteroids. Imidazole derivatives

Pharmacological Action

A combined drug for intravaginal use, the effectiveness of which is due to the presence of two components in its composition: metronidazole and clotrimazole.

Metronidazole is active against protozoa: Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, as well as gram-negative anaerobes: Bacteroides fragilis, Fusobacterium spp., Prevotella spp. (Prevotella bivia, Prevotella buccae, Prevotella disiens), Gardnerella vaginalis and some gram-positive microorganisms: Clostridium perfringens, Clostridium difficile, Peptococcus spp., Peptostreptococcus spp. The MIC for these strains is 0.125-6.25 µg/ml.

Clotrimazole has a fungicidal and bactericidal effect. It inhibits the biosynthesis of ergosterol, which regulates the permeability of the microbial cell wall. In low concentrations, it acts fungistatically, and in high concentrations, it acts fungicidally. In fungicidal concentrations, it interacts with peroxidases and mitochondrial enzymes, resulting in an increase in the concentration of hydrogen peroxide to a toxic level, which also leads to the death of fungi. It has high activity against fungi Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, dermatophytes (Trichophyton mentagrophytes, Microsporum canis, Epidermophyton foccosum), Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii; protozoa Trichomonas vaginalis; gram-positive bacteria: Streptococcus spp., Staphylococcus spp., Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis.

Pharmacokinetics

Metronidazole

Absorption

After intravaginal administration, Metronidazole undergoes systemic absorption (about 56%). The relative bioavailability of metronidazole in the form of a vaginal gel is 2 times higher than the bioavailability of metronidazole in the form of vaginal tablets when used once at a dose of 500 mg. After a single intravaginal administration of the gel at a dose of 5 g (50 mg of metronidazole), the average C_max in the serum of healthy women is 237 ng/ml, which is 2% of the average C_max of metronidazole when taken orally at a dose of 500 mg. The time to reach C_max is 6-12 hours.

Distribution

It penetrates into most tissues, passes through the blood-brain barrier and the placental barrier. It is excreted in breast milk. Plasma protein binding is less than 20%.

Metabolism and Excretion

It is metabolized in the liver by hydroxylation, oxidation, and glucuronidation. The activity of the main metabolite (2-hydroxymetronidazole) is 30% of the activity of the parent compound. It is excreted by the kidneys 60-80% (20% unchanged), through the intestines – 6-15%.

Clotrimazole

When clotrimazole is applied intravaginally, no more than 3-10% is absorbed. High concentrations in the vaginal secretion and low concentrations in the blood persist for 48-72 hours. In the liver, Clotrimazole is rapidly metabolized to inactive metabolites.

Indications

• Bacterial vaginosis of various etiologies, confirmed by clinical and microbiological data;
• Candidal vulvitis and vulvovaginitis;
• Urogenital trichomoniasis.

ICD codes

Dosage Regimen

Administer the gel intravaginally using the supplied applicator.

Insert one full applicator (5 g of gel) twice daily, in the morning and evening.

Complete the full course of treatment, which is five days.

If symptoms persist, repeat the course after a two-week interval only on medical advice.

Thoroughly wash hands before and after application.

Refrain from sexual intercourse for the duration of the treatment course.

Continue use during menstruation; use sanitary pads instead of tampons.

Avoid concurrent consumption of alcohol due to risk of disulfiram-like reactions.

Discontinue use and consult a physician if severe local irritation, burning, or any systemic adverse effects occur.

Adverse Reactions

Local reactions burning sensation or frequent urination; in the sexual partner – burning sensation or irritation of the penis.

Systemic reactions dizziness, headache, nausea, and cramping abdominal pain are possible.

Allergic reactions skin rash, urticaria.

The patient should be warned to stop using the drug and consult a doctor if any undesirable side effects occur.

Contraindications

• Leukopenia (including history);
• Organic lesions of the central nervous system (including epilepsy);
• Hepatic insufficiency;
• First trimester of pregnancy;
• Hypersensitivity to the components of the drug.

Use in Pregnancy and Lactation

The drug is contraindicated in the first trimester of pregnancy. The use of the drug in the second and third trimester of pregnancy is possible only for strict medical reasons and under medical supervision (without using the applicator).

If the drug is prescribed during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Contraindicated in hepatic insufficiency.

Special Precautions

When using the drug, alcohol consumption is contraindicated (a disulfiram-like reaction may develop: cramping abdominal pain, nausea, vomiting, headache, sudden flushing of the face).

Metronidazole can immobilize treponemes and lead to a false-positive Nelson test.

The drug is intended for intravaginal use only. Avoid getting the drug into the eyes.

During the course of therapy, it is necessary to refrain from sexual intercourse.

Overdose

No cases of drug overdose when prescribed in recommended doses have been observed.

Drug Interactions

With simultaneous use, the drug enhances the effect of indirect anticoagulants.

Concomitant use with non-depolarizing muscle relaxants (vecuronium) is not recommended.

With simultaneous use with lithium preparations, an increase in the concentration of lithium in the blood plasma is possible.

Phenobarbital accelerates the metabolism of metronidazole due to the induction of liver microsomal enzymes, cimetidine reduces it.

Amphotericin B, nystatin, natamycin reduce the effectiveness of clotrimazole when used simultaneously.

With simultaneous use with ethanol, the drug can cause disulfiram-like reactions.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.