Gyneclin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GINEKLIN

Composition:

Active substances: 1 vaginal capsule contains clindamycin phosphate equivalent to clindamycin 100 mg, clotrimazole 00 mg;

Excipients: polyethylene glycol 4000, polyethylene glycol 400, propylene glycol, gelatin, glycerin, Ponceau 4R (E 124), titanium dioxide (E 171), purified water.

Pharmaceutical form. Soft vaginal capsules.

Main physicochemical characteristics: soft gelatin vaginal capsules of oval shape, pink in color.

Pharmacotherapeutic group.

Antibacterial and antiseptic agents used in gynecology. ATC code G01A.

Pharmacological properties.

Pharmacodynamics.

Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis by acting on bacterial ribosomes. The antibiotic binds primarily to the 50S ribosomal subunit and interferes with the initiation of the protein chain. Although clindamycin phosphate is inactive in vitro, it is rapidly hydrolyzed in vivo to form clindamycin, which exhibits antibacterial activity.

Clindamycin is active in vitro against microorganisms causing bacterial vaginosis, including Gardnerella vaginalis, Mobiluncus mulieris, Mobiluncus curtisii, Mycoplasma hominis, and anaerobes (species of Peptostreptococcus and Bacteroides). All these microorganisms are sensitive to clindamycin, as evidenced by their MIC₉₀ values (minimum inhibitory concentration that inhibits 90% of strains). No geographical or temporal variations have been observed.

Susceptibility of vaginal bacteria associated with bacterial vaginosis to clindamycin

Clotrimazole is an imidazole derivative with a broad spectrum of local antifungal activity against most pathogenic fungi. The mechanism of action of clotrimazole involves inhibition of nucleic acid and protein synthesis, as well as inhibition of ergosterol synthesis in fungal cells, resulting in damage to their cell membrane and cell death. Clotrimazole is primarily active against dermatophytes (Epidermophyton floccosum, Microsporum canis, Trichophyton mentagrophytes, Trichophyton rubrum), yeast-like and mold fungi (Candida sp., Cryptococcus neoformans), dimorphic fungi (Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis), Nocardia species, and Trichomonas vaginalis.

Pharmacokinetics.

Clindamycin phosphate is rapidly hydrolyzed in the body to form clindamycin, which exhibits antibacterial activity. After intravaginal administration, approximately 30% (6.5–70%) of clindamycin enters the systemic circulation; however, no systemic accumulation occurs with prolonged use. The systemic elimination half-life following vaginal administration ranges from 1.5 to 2.6 hours.

Following vaginal administration, only a minimal amount of clotrimazole is absorbed (3–10% of the dose). The plasma concentration of unchanged active substance after administration of the drug is below the limit of detection—10 ng/mL—and does not result in systemic effects or adverse reactions. Clotrimazole is metabolized in the liver to inactive hydroxylated derivatives through oxidation and degradation of the imidazole ring (deamination, O-dealkylation) and is predominantly excreted via bile into the feces.

Clinical characteristics.

Indications.

The drug is indicated for local treatment of bacterial vaginosis, prevention and treatment of gynecological infections and superinfections caused by microorganisms sensitive to clindamycin and/or clotrimazole, including fungi (usually of the genus Candida). For sanitation of the mucous membranes of female genital organs.

Contraindications.

Hypersensitivity to lincomycin or to any of the excipients of the drug.

Contraindicated in patients with regional enteritis, ulcerative colitis, or antibiotic-associated colitis in medical history.

Special precautions.

Avoid contact with eyes. Do not swallow.

Consult a physician before use in the following cases:

• Recurrent vaginal candidiasis occurring more than twice within the last 6 months;
• History of sexually transmitted infections or presence of a sexual partner with active sexually transmitted infections;
• Pregnancy or suspected pregnancy.

Consult a physician during treatment in the following cases:

• If symptoms persist for longer than 7 days;
• If symptoms recur within the last 2 months;
• If the patient develops elevated body temperature (38 °C or higher), lower abdominal pain, back pain, purulent vaginal discharge with unpleasant odor, nausea, vaginal bleeding accompanied by back pain.

Interaction with other medicinal products and other forms of interaction.

Information on concomitant use with other intravaginal medicinal products is not available.

When clotrimazole is used concomitantly with nystatin, the activity of clotrimazole may be reduced.

Dexamethasone, when administered in high doses, reduces the antifungal activity of clotrimazole.

The antimicrobial action of clotrimazole is enhanced by high local concentrations of propyl ester of p-hydroxybenzoic acid.

When used concomitantly, clotrimazole reduces the activity of amphotericin B and other polyene antibiotics.

Concomitant treatment with vaginal clotrimazole and oral tacrolimus (FK-506; immunosuppressant) may lead to increased plasma levels of tacrolimus. Therefore, patients should be carefully monitored for symptoms of tacrolimus overdose, and, if necessary, plasma levels of tacrolimus should be checked.

Clindamycin phosphate exhibits neuromuscular blocking properties and may enhance and prolong the effect of other neuromuscular blocking agents.

Special precautions for use

Since both the vagina and the external genitalia are usually affected, combined treatment of both areas is recommended. If the external genitalia and adjacent areas are infected, topical treatment with a topical cream should also be applied.

As with any vaginal infections, sexual intercourse during treatment with this medicinal product is not recommended. The base of vaginal capsules may weaken the strength of latex condoms and diaphragms used for contraception. It is not recommended to use such contraceptive methods within 72 hours after treatment, as their contraceptive effectiveness and protection against sexually transmitted infections may be reduced.

The medicinal product must not be used during menstruation. Treatment should be completed before the onset of menstruation.

The safety and efficacy of the medicinal product have not been studied in patients with hepatic impairment, immunodeficiency, or colitis.

Before or immediately after starting treatment, laboratory testing for other infectious agents may be necessary, including Trichomonas vaginalis, Candida albicans, Chlamydia trachomatis, and gonococci.

Use of clindamycin may lead to overgrowth of microorganisms not susceptible to the drug, particularly yeasts.

Symptoms indicating pseudomembranous colitis may occur during or after administration of antimicrobial agents. Cases of pseudomembranous colitis have been reported with nearly all antibacterial agents, including clindamycin; the severity of colitis may range from mild to life-threatening. Therefore, this possibility should be considered in patients who develop diarrhea following antibacterial therapy. If pseudomembranous colitis occurs, clindamycin should be discontinued. Appropriate antibacterial therapy should be initiated. Antiperistaltic agents are contraindicated in this case.

Maculopapular rashes and urticaria have been observed during treatment. Among all adverse reactions, generalized skin rashes of mild to moderate severity have been most frequently reported. Cases of acute generalized exanthematous pustulosis and erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin use. Several cases of anaphylactoid reactions have been reported. If hypersensitivity reactions occur, the drug should be discontinued.

Use during pregnancy or breastfeeding

The safety and efficacy of the medicinal product in pregnant or breastfeeding women have not been established. During the second and third trimesters of pregnancy and during breastfeeding, the medicinal product should be used only if the expected benefit to the woman outweighs the potential risk to the fetus or infant. During pregnancy, the medicinal product should be used only under medical supervision. Use of the medicinal product during the first trimester of pregnancy is not recommended.

It is unknown whether clindamycin and clotrimazole penetrate into breast milk following intravaginal administration. Breastfeeding should be discontinued during treatment with this medicinal product.

Effect on ability to drive and use machines

No effect.

Method of Administration and Dosage.

Vaginally. The capsule should be inserted deeply into the vagina.

Administer 1 capsule once daily, preferably before bedtime. The duration of treatment is determined by the physician. A repeated course of treatment should be conducted only after consultation with a physician.

Treatment should not be carried out during menstruation; therefore, it should be completed before the onset of menstruation. For sanitation of the mucous membranes of female genital organs, the drug should be used once or twice.

Children.

Safety and efficacy of the drug in children have not been studied. Do not use.

Overdose.

Cases of overdose are unknown when following the recommended administration guidelines. In case of accidental oral ingestion, effects related to therapeutic blood concentrations of the active substances may occur. Symptomatic treatment is recommended.

Adverse reactions

Adverse reactions are defined by frequency as uncommon (≥1/1000 to <1/100) and very rare (<1/10,000).

Infections and infestations: Clostridioides difficile–induced colitis.

General disorders and administration site conditions: Uncommon – discomfort, irritation, pruritus, erythema, swelling, burning sensation, and pain at the injection site, fever, generalized pain, pain in the side and back, pelvic pain, abdominal pain.

Central nervous system disorders: Dizziness, headache, arterial hypotension, dyspnea, vertigo.

Respiratory system disorders: Upper respiratory tract infections.

Gastrointestinal disorders: Unpleasant breath odor, altered taste sensation, dyspepsia, heartburn, nausea, vomiting, diarrhea, constipation, flatulence.

Urinary and reproductive system disorders: Skin desquamation in the genital area, vulvovaginal disorders and irritation, menstrual cycle disturbances, vaginal bleeding, vaginal discharge, vaginal pain, cervicitis, endometriosis, pathological labor, urinary tract infections, dysuria, pyelonephritis, proteinuria, abnormalities in microbiological tests.

Skin and subcutaneous tissue disorders: Uncommon – pruritus, rash; very rare – erythema multiforme resembling Stevens–Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, maculopapular rash.

Blood and lymphatic system disorders: Very rare – transient neutropenia (leukopenia), agranulocytosis, thrombocytopenia.

Immune system disorders: Very rare – allergic reactions, syncope, anaphylactoid reaction, urticaria; cases of drug-induced eosinophilia with systemic symptoms (DRESS syndrome) have been reported.

Hepatobiliary disorders: Very rare – jaundice.

Metabolic and nutritional disorders: Hyperthyroidism, glucosuria.

Musculoskeletal and connective tissue disorders: Cases of polyarthritis have been reported.

Renal and urinary disorders: Acute kidney injury.

Other complications: Epistaxis.

Shelf life: 2 years.

Storage conditions:

Store at a temperature not exceeding 25°C.

Keep out of reach and sight of children.

Packaging:

7 capsules in a blister; 1 blister per cardboard box.

Prescription status: Prescription only.

Manufacturer:

Marcan's Pharma Ltd.

Manufacturer’s address and site of operations:

Plot No. L-82, L-83, Verna Industrial Estate, Verna Goa, IN-403 722, India.