Gynomax^® (Suppositories) Instructions for Use

ATC Code

G01AF20 (Imidazole derivative combinations)

Active Substances

Tinidazole (Rec.INN WHO registered)

Tioconazole (Rec.INN WHO registered)

Clinical-Pharmacological Group

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

Pharmacotherapeutic Group

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

Pharmacological Action

The drug Gynomax^® is a combination of tioconazole and tinidazole. Tioconazole is a synthetic antifungal agent with high activity against yeast-like and other fungi (dermatophytes). It is also effective against bacterial pathogens: Gardnerella vaginalis, Bacteroides spp., and some Gram-positive bacteria (including Staphylococcus and Streptococcus spp.).

The mechanism of action of tioconazole involves increasing the permeability of the fungal cell membrane by inhibiting the synthesis of ergosterol, its main component. The increased permeability of the cell membrane disrupts the intracellular ionic balance, leading to cell death. Clinical studies have shown that Tioconazole is more effective than miconazole both in clinical terms (98% and 78%, respectively) and microbiologically (eradication of the pathogen in 76% and 67% of cases, respectively). Furthermore, the use of tioconazole was subjectively twice as comfortable for patients compared to miconazole.

Tinidazole is effective against both protozoan pathogens ( Trichomonas vaginalis, Entamoeba histolytica, and Giardia lamblia) and most anaerobic bacteria ( Gardnerella vaginalis, Bacteroides fragilis, Bacteroides melaninogenicus, Bacteroides spp., Clostridium spp., Eubacterium spp., Peptostreptococcus spp., and Veillonella spp.).

The mechanism of action of tinidazole is not fully understood. The reduction of the nitro group is mediated by the ferredoxin system and a low redox potential generated only by anaerobic bacteria. This fact may explain why tinidazole uptake is more active in anaerobes than in aerobes, although Tinidazole penetrates the cell membranes of both. The reductive reaction produces active intermediates and increases the diffusion gradient, which enhances the uptake of tinidazole.

Although cross-resistance is generally characteristic of the 5-nitroimidazole group, 65-70% of Trichomonas vaginalis strains highly resistant to metronidazole exhibit increased sensitivity to tinidazole.

According to clinical studies, the efficacy of the combination of tioconazole with tinidazole for intravaginal administration is 90-100%, with a microbiological cure rate of 85%.

Pharmacokinetics

With intravaginal application, both Tioconazole and Tinidazole are minimally absorbed. Therefore, the absorption of the two drugs in combination is expected to be low.

Indications

• Treatment of vaginitis caused by pathogens of the genera Candida, Trichomonas, and Gardnerella (vaginal candidiasis, trichomonal vulvovaginitis, gardnerella vaginitis, nonspecific vaginitis), as well as mixed infections.

ICD codes

Dosage Regimen

Suppositories

Intravaginally.

The drug is prescribed as 1 vaginal suppository at night for 7 days. An alternative regimen: 1 vaginal suppository 2 times a day (in the morning and at night) for 3 days.

Vaginal suppositories should be inserted deep into the vagina using the disposable finger cots contained in the package.

Elderly patients

No dosage adjustment is required when prescribing the drug to elderly patients (over 65 years of age).

Adverse Reactions

Adverse effects according to clinical study results. In clinical studies of the combination of tinidazole 150 mg with tioconazole 100 mg in the form of a cream or vaginal tablets, clinical and microbiological outcomes were evaluated in a total of 348 patients, with both regimens (3 or 7 days) assessed.

Based on the study results, the safety of this combination was rated as high. The following adverse effects were observed: allergic reactions (in 3.3-4.5% of cases), local itching (1.9%), and burning sensation (1.7%). In most cases, the adverse effects were of moderate severity, with only 0.75% of patients discontinuing treatment due to allergic reactions.

Post-marketing experience.

In post-marketing practice of the drug’s use, the following adverse events have been additionally reported:

Local reactions rarely – swelling, irritation of the vaginal mucosa.

Central and peripheral nervous system rarely – headache, fatigue.

Urinary system rarely – darkening of urine.

Allergic reactions rarely – skin rash, urticaria, in isolated cases – angioedema.

Although no cases of transient leukopenia were noted with the intravaginal use of the tioconazole and tinidazole combination, cases of this symptom, associated with neurological or gastrointestinal symptoms, have been described in connection with the systemic use of tinidazole.

Contraindications

• Current or history of organic diseases of the nervous system;
• Leukemia, hematopoietic disorders;
• First trimester of pregnancy, lactation period;
• Virginity, age under 18 years;
• Hypersensitivity to the active components or their derivatives, other components of the drug.

Use in Pregnancy and Lactation

Tinidazole crosses the fetoplacental barrier and passes into breast milk. The effects of the components of this drug on fetal and newborn development are unknown.

The use of the drug Gynomax^® is contraindicated in the first trimester of pregnancy. Breastfeeding should be discontinued during treatment with Gynomax^®. The use of Gynomax^® in the third trimester of pregnancy should be assessed by the attending physician from the standpoint of the potential benefit to the mother versus possible risks to the fetus.

Pediatric Use

Contraindicated in children under 18 years of age, virgins.

Geriatric Use

No dosage adjustment is required when prescribing the drug to elderly patients (over 65 years of age).

Special Precautions

Although clinical studies have not revealed persistent hematological disorders associated with the drug’s use, Tinidazole should not be taken by patients with current or history of diseases of the hematopoietic system (leukemia, hematopoietic disorders).

The drug Gynomax^® should not be used simultaneously with mechanical contraceptive devices (condoms, contraceptive caps, or diaphragms), as the suppository base may react with the latex base of these devices.

Alcohol consumption should be avoided during the drug intake and for 2 days after the last dose. The drug should not be stored in the refrigerator.

Effect on ability to drive vehicles and operate machinery

The use of the drug Gynomax^® does not affect the ability to drive vehicles and operate machinery.

Overdose

In case of accidental ingestion of a large amount of the drug, gastric lavage is performed. There is no specific antidote; symptomatic therapy is carried out.

Drug Interactions

Concomitant use of alcohol and tinidazole in a systemic dosage form may cause intestinal colic, nausea and vomiting, and skin flushing.

Although the use of tinidazole in vaginal suppositories minimizes the drug’s entry into the systemic circulation, the interaction with alcohol must be considered when prescribing the drug.

Storage Conditions

Store at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

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.