Granzen

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

Composition:

Active substance: dequalinium chloride;

1 vaginal tablet contains 10 mg of dequalinium chloride;

Excipients: lactose monohydrate; microcrystalline cellulose; magnesium stearate; purified water.

Pharmaceutical form. Vaginal tablets.

Main physicochemical properties: white or almost white oval tablets with bevelled edges, uncoated, smooth on both sides.

Pharmacotherapeutic group. Antimicrobial and antiseptic agents used in gynecology. ATC code G01AC05.

Pharmacological properties.

Pharmacodynamics.

Grazophen contains dequalinium chloride – a quaternary ammonium compound with a broad antimicrobial spectrum of activity against various Gram-positive and Gram-negative bacteria, fungi, and unicellular protozoa (Trichomonas vaginalis).

Mechanism of action.

Dequalinium chloride is a surface-active substance. The primary mechanism of action of dequalinium chloride involves increasing the permeability of the bacterial cell membrane, leading to subsequent loss of enzyme activity and resulting in cell death.

Dequalinium chloride exhibits rapid bactericidal and fungicidal effects.

When administered as vaginal tablets, dequalinium chloride acts locally within the vagina. A noticeable reduction in discharge and inflammation usually occurs within 24–72 hours.

Pharmacokinetic / pharmacodynamic relationship.

No limiting influence of pharmacokinetics / pharmacodynamics on the efficacy of Grazophen has been established. Since the bactericidal effect of dequalinium chloride occurs within 30–60 minutes, the decisive factor for efficacy is achieving maximum local concentration during the first hour after administration.

Mechanisms of resistance.

No mechanisms leading to primary resistance of pathogenic microorganisms have been identified. There have been no reports of acquired resistance of microorganisms to dequalinium chloride.

Breakpoints for susceptibility.

Breakpoints have not been defined, and no correlation has been established between minimum inhibitory concentrations (MICs) and clinical efficacy.

Therefore, the information on microbial susceptibility provided below is based on concentrations achieved in the vagina (see section "Pharmacokinetics") and corresponding MIC data for pathogenic microorganisms.

The prevalence of acquired resistance may vary geographically and over time for individual species; thus, it is desirable to have local information on resistance patterns, especially when treating severe infections. If necessary, expert consultation should be sought when local resistance prevalence renders the usefulness of the agent at least questionable for certain types of infections.

Antimicrobial spectrum of activity.

Typically susceptible species

Aerobic Gram-positive bacteria

Enterococcus faecalis,

Listeria spp.,

Staphylococcus aureus,

Streptococcus agalactiae (Group B streptococci),

Streptococcus pyogenes (Group A streptococci)

Aerobic Gram-negative bacteria

Enterobacter spp.,

Escherichia coli,

Klebsiella spp.,

Pseudomonas spp.,

Serratia spp.

Anaerobic bacteria

Atopobium vaginae,

Bacteroides spp.,

Fusobacteria,

Gardnerella vaginalis,

Prevotella spp.,

Peptostreptococci,

Porphyromonas spp.

Species for which acquired resistance may be a concern

Unknown.

Organisms with inherent resistance

Gram-negative bacteria

Proteus sp.,

Chlamydia trachomatis

Other microorganisms

Trichomonas vaginalis.

Pharmacokinetics.

After dissolution of 10 mg of dequalinium chloride (in the form of vaginal tablets) in 2.5–5 mL of vaginal fluid, the concentration of dequalinium chloride in vaginal fluid ranges from 2000 to 4000 mg/L, which is higher than the MIC₉₀ of all studied pathogenic microorganisms.

Preclinical study results indicate that only a small amount of dequalinium chloride is absorbed following vaginal administration.

Due to negligible vaginal absorption, there are no available data on the pharmacokinetics of dequalinium chloride in humans.

Clinical characteristics.

Indications.

• Vaginal infections of bacterial and fungal origin.
• Bacterial vaginosis.
• Candidiasis.

Attention should be paid to official recommendations regarding the appropriate use of antibacterial agents.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients.
• Epithelial ulcers of the vagina and vaginal portion of the cervix.
• Not to be used in young girls who have not yet experienced menarche and who have not reached sexual maturity.

Interaction with other medicinal products and other forms of interaction.

Anionic substances such as soap, detergents, and surfactants may reduce the antimicrobial activity of dequalinium chloride. Therefore, during treatment, the intravaginal use of soap, spermicides, and douching is not recommended. Granzophen does not affect the functionality of latex condoms. There are no data on interactions with non-latex condoms and other intravaginal devices such as diaphragms.

Therefore, during treatment and for at least 12 hours after treatment, the use of non-latex condoms and other intravaginal devices is not recommended.

Special precautions for use.

To minimize the risk of exposure of the newborn to dequalinium chloride, vaginal tablets should not be used within 12 hours before delivery.

There are no data on the efficacy and safety of retreatment in patients who did not respond or who experienced a recurrence of the disease immediately after primary treatment with the drug. Patients should be advised to consult their physician if symptoms persist at the end of treatment or if there is a recurrence of the disease.

Exceeding the recommended daily dose or duration of treatment increases the risk of vaginal epithelial ulceration.

There are no data on the efficacy and safety of treatment of bacterial vaginosis in women under 18 years of age or over 55 years of age.

Use during pregnancy or breastfeeding.

Pregnancy.

Limited data from four clinical studies involving 181 pregnant women treated with dequalinium chloride indicate no adverse effects of dequalinium chloride on pregnancy or on the health of the fetus/newborn.

Reproductive toxicity studies in animals have not been conducted due to the expected low degree of absorption of dequalinium chloride following vaginal administration.

Granofen should be used during pregnancy only if clearly needed.

Breastfeeding period.

Since absorption of Granofen is negligible, harmful effects on the newborn/infant are unlikely.

Granofen may be used during lactation if there is a clinical need.

Fertility.

Studies on the effects on fertility in animals have not been conducted.

Ability to affect reaction rate when driving or operating machinery.

Studies on the ability to affect reaction speed when driving vehicles or operating machinery have not been conducted.

Method of Administration and Dosage

It is recommended to use 1 vaginal tablet daily for 6 days.

Vaginal tablets should be inserted deeply into the vagina in the evening before going to bed. It is best to do this while lying on your back, with knees slightly bent.

During menstruation, treatment should be discontinued and resumed after menstruation ends.

Although reduction of discharge and inflammation usually occurs within 24–72 hours, treatment must be continued even if discomfort symptoms (such as itching, discharge, odor) have already subsided.

Treatment lasting less than 6 days may lead to recurrence.

Grenzophen contains excipients that are not completely soluble. Residues of the tablet may sometimes be found on underwear. This does not affect the efficacy of Grenzophen.

In some cases, when vaginal dryness is present, the vaginal tablet may not dissolve and may be expelled from the vagina intact. As a result, such treatment may not be effective. To prevent this, the tablet can be moistened with a small amount of water before insertion into a dry vagina.

Patients should use sanitary or daily pads. The medicinal product does not change the color of underwear.

Women aged 55 years and older

There are no data on the efficacy and safety of using dequalinium chloride in women aged 55 years and older.

Children

There are no data on the efficacy and safety of using dequalinium chloride in children under 18 years of age.

Overdose

Cases of overdose have not been reported. However, exceeding the daily dose may lead to the formation of vaginal epithelial ulcers. In case of overdose with dequalinium chloride and associated adverse effects, vaginal irrigation should be performed.

Adverse Reactions

The adverse reactions are listed below by system organ classes according to MedDRA. Frequency of occurrence: 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); or not known (cannot be estimated from available data).

Reproductive system and breast disorders.

Common: vaginal discharge, vulvovaginal pruritus, burning sensation in the vulvovaginal area.

Uncommon: vaginal bleeding, vaginal pain.

Not known: ulceration and maceration of vaginal epithelium, uterine bleeding, erythema, vaginal dryness.

Infections and infestations.

Common: vaginal candidiasis.

Uncommon: bacterial vaginosis, fungal skin infection, vulvitis, vulvovaginitis.

Not known: cystitis.

Nervous system disorders.

Uncommon: headache.

Gastrointestinal disorders.

Uncommon: nausea.

General disorders and administration site conditions.

Not known: allergic reactions with symptoms such as urticaria, erythema, exanthema, edema, rash, or pruritus, fever.

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report any suspected adverse reactions and lack of efficacy through the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach and sight of children.

Packaging.

6 tablets in a blister, 1 blister per cardboard pack.

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

Kusum Healthcare Pvt Ltd.

Manufacturer's address and place of business.

Plot No. M-3, Indore Special Economic Zone, Phase-II, Pithampur, Distt. Dhar, Madhya Pradesh, Pin 454774, India.