Tarzhifort^® (Suppositories) Instructions for Use

Marketing Authorization Holder

Avexima JSC (Russia)

Manufactured By

Pharmaprim, LLC (Republic of Moldova)

Packaging and Quality Control Release

Avexima Siberia LLC (Russia)

ATC Code

G01BA (Antibacterial agents in combination with corticosteroids)

Dosage Form

Tarzhifort®

Vaginal suppositories: 7 or 10 pcs.

Dosage Form, Packaging, and Composition

Vaginal suppositories from light yellow with a beige or creamy tint to yellow with a beige or creamy tint, cylindrical-conical in shape; the cut may contain an air core or a funnel-shaped depression.

Excipients: semi-synthetic glycerides (Suppocire AM) – 1635 mg.

5 pcs. – contour cell packs (2) – cardboard boxes.
7 pcs. – contour cell packs (1) – cardboard boxes.

Clinical-Pharmacological Group

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

Pharmacotherapeutic Group

Combined antimicrobial agent (glucocorticosteroid+antimicrobial and antiprotozoal agent+antifungal agent+antibiotic)

Pharmacological Action

Combined medicinal product for intravaginal use.

Metronidazole is an antimicrobial and antiprotozoal agent, a 5-nitroimidazole derivative.

The mechanism of action involves the 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 the DNA of the microorganism’s cell, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Active against Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Mobiluncus spp., as well as against obligate anaerobes: Bacteroides spp., Fusobacterium spp.

Chloramphenicol is a broad-spectrum antibiotic. It has a bacteriostatic effect.

The mechanism of action is associated with the suppression of microbial protein synthesis by binding to the 50S ribosomal subunit and stopping the process of peptide chain formation.

Effective against bacterial strains resistant to penicillin, tetracyclines, sulfonamides.

Active against many gram-positive and gram-negative bacteria, pathogens of purulent infections, typhoid fever, dysentery, meningococcal infection.

Natamycin is a polyene antibiotic of the macrolide group, has a broad spectrum of antifungal action. It has a fungicidal effect.

Natamycin binds to sterols of cell membranes, disrupting their integrity and functions, which leads to the death of microorganisms.

Most pathogenic yeasts, especially Candida albicans, are sensitive to natamycin.

Hydrocortisone is a glucocorticosteroid. It has anti-inflammatory, anti-exudative and anti-allergic effects.

Pharmacokinetics

With intravaginal use, Metronidazole is absorbed into the systemic circulation (about 20%).

The C_max of metronidazole in the blood is determined after 6-12 hours and is approximately 50% of the C_max achieved (after 1-3 hours) after a single oral dose of an equivalent dose of metronidazole.

Plasma protein binding is less than 20%.

Metronidazole is metabolized in the liver; hydroxyl metabolites are active.

The activity of the main metabolite (2-hydroxymetronidazole) is 30% of the activity of the parent compound.

Metronidazole and oxidized metabolites are excreted mainly by the kidneys (20% unchanged) and to a lesser extent through the intestines.

Penetrates the blood-brain barrier and placental barrier, excreted in breast milk.

The pharmacokinetics of chloramphenicol with intravaginal use have not been studied.

Natamycin is not absorbed from the mucous membrane when used intravaginally.

Hydrocortisone is practically not absorbed from the vaginal mucosa when used intravaginally; plasma concentration is below the detection level.

Indications

Vulvovaginitis: bacterial, candidal, trichomonal and/or in association with mixed flora sensitive to the components of the combination; nonspecific vaginitis; prevention of urogenital infections before gynecological surgical interventions, diagnostic procedures and installation of an intrauterine contraceptive.

ICD codes

Dosage Regimen

Administer one suppository intravaginally, once daily, preferably at bedtime.

Complete the full 10-day course of treatment, even if symptoms improve earlier.

For preoperative prophylaxis and before diagnostic procedures or IUD insertion, use one suppository the evening before the intervention.

Thoroughly wash hands before and after handling the suppository.

Remove the suppository from its foil packaging immediately prior to administration.

Assume a supine position with knees bent for insertion; gently insert the suppository deep into the vagina.

Discontinue use and consult a physician immediately if severe local irritation, burning, or signs of a hypersensitivity reaction occur.

Refrain from sexual intercourse during the entire treatment period.

Ensure simultaneous treatment of the sexual partner to prevent reinfection in cases of trichomoniasis.

Avoid consuming alcoholic beverages during and for at least 48 hours after completion of therapy due to risk of disulfiram-like reactions.

Adverse Reactions

Local reactions: burning sensation, pain, irritation and swelling at the application site, erythema, vaginal dryness, especially at the beginning of treatment, which do not require discontinuation of treatment and are determined by the effect of this agent on the irritated vaginal mucosa.

From the hematopoietic and lymphatic system: decrease in the number of blood leukocytes (leukopenia).

From the immune system: rash, skin itching, urticaria, anaphylactic reactions.

From the mental status: anxiety, mood lability.

From the nervous system: headache, with prolonged use of the drug – peripheral neuropathy (sensation of numbness and tingling (paresthesia), convulsions, tremor.

From the vestibular apparatus: motor disturbances (ataxia), dizziness.

From the digestive system: abdominal pain or cramps, “metallic” taste in the mouth, taste change, dry mouth, constipation, diarrhea, loss of appetite, nausea, vomiting.

Contraindications

Hypersensitivity to the components of the combination; severe impairment of liver and kidney function; pregnancy, breastfeeding period; children and adolescents under 18 years of age.

With caution

Severe acute or chronic diseases of the central and peripheral nervous system (including with permanent or progressive neuropathies); hematopoiesis disorders (history of leukopenia).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindicated for use in severe liver dysfunction.

Use in Renal Impairment

Contraindicated for use in severe renal dysfunction.

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

During treatment, it is recommended to refrain from sexual intercourse.

In case of infection of the sexual partner and to exclude the possibility of reinfection, simultaneous treatment of both partners is mandatory.

In case of using this combination together with oral metronidazole, especially during a repeated course, monitoring of the peripheral blood picture is necessary (risk of leukopenia). If a decrease in the number of leukocytes is detected, treatment should be discontinued.

If motor disturbances, dizziness, confusion, paresthesia, or convulsions appear during treatment, treatment should be discontinued.

Metronidazole, which is part of the drug, is able to immobilize treponemes, which leads to a false-positive Nelson test.

Effect on ability to drive vehicles and mechanisms

A possible negative impact on the ability to drive vehicles and potentially dangerous mechanisms cannot be ruled out, so caution should be exercised during treatment. If side effects from the central nervous system occur, the patient should refrain from driving vehicles.

Drug Interactions

With simultaneous use with oral anticoagulants (e.g., warfarin), an increase in the concentration of anticoagulants in plasma, enhancement of the effect and, consequently, the risk of bleeding is possible; it is necessary to control the prothrombin level and monitor prothrombin time; it is necessary to adjust the dose of oral anticoagulants during treatment and for one week after the end of treatment.

With simultaneous use with lithium preparations, an increase in the toxicity of the latter is possible.

With simultaneous use with cyclosporine, an increase in the concentration of cyclosporine in plasma is possible.

With simultaneous use with disulfiram, psychotic reactions (delirium attacks, confusion) are possible; should not be prescribed to patients who have taken disulfiram within the last 2 weeks.

With simultaneous use with medicines containing ethanol, or when consuming ethanol, the development of disulfiram-like reactions (feeling of heat, facial skin redness, vomiting, tachycardia) is possible.

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

With simultaneous use with phenobarbital, the concentration of metronidazole in the blood decreases.

With simultaneous use with cimetidine, an increase in the concentration of metronidazole in the blood is possible.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.