Warimazol Vag 200 mg 3 vaginal tablets

Pack

3

1. Product Name WARIMAZOL VAG 200mg /VARIMAZOL VAG 200 mg Vaginal Tablets 2. Qualitative and Quantitative Composition 1 vaginal tablet contains 200 mg clotrimazole. For a full list of excipients, see section 6.1. 3. Pharmaceutical Form Vaginal Tablets 4 Clinical Particulars 4.1 Therapeutic Indications Inflammation and discharge of the vagina caused by fungi - usually Candida, as well as superinfection caused by clotrimazole-sensitive bacteria. 4.2 Posology and Method of Administration Dosage Unless otherwise prescribed, one vaginal tablet is inserted as deeply as possible into the vagina in the evening for 3 consecutive days. As a rule, a three-day therapy with WARIMAZOL VAG 200 mg is sufficient for the treatment of vaginal fungal infections. If necessary, a second course of treatment can be carried out for a further 3 days. Method of Administration It is not recommended to carry out treatment during menstruation, and treatment should be completed before its onset. Sexual intercourse should only take place using a condom during treatment and for two days after its completion. The enclosed applicator is intended for multiple use. Patients should be instructed on how to clean it. If a vaginal fungal infection is diagnosed, particular caution is required in the last 4-6 weeks of pregnancy to ensure non-pathogenic conditions in the birth canal. This should be managed under medical supervision. If other types of treatment are not possible during pregnancy, treatment should be carried out using vaginal tablets only - without the applicator. In cases of problematic patients, treatment should be carried out by a doctor. During pregnancy, the use of the applicator may damage the amniotic sac and consequently harm the fetus. If the labia and surrounding areas, as well as the glans and foreskin of the partner's penis, are also infected with a fungal infection, both should be treated with topical antimycotics. To avoid possible re-infection, the partner should also undergo medical examination. Note: The patient should be informed about the correct use of applicators. 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 4.4 Special Warnings and Precautions for Use In the first trimester of pregnancy, vaginal tablets should be used only with extreme caution and after consideration of possible alternative therapeutic agents (see also section 4.2). During pregnancy, the use of the applicator may damage the amniotic sac and the fetus. 4.5 Interactions with Other Medicinal Products and Other Forms of Interaction Clotrimazole reduces the effectiveness of amphotericin and other polyene antibiotics (nystatin, natamycin). High doses of dexamethasone may reduce the effectiveness of clotrimazole. 4.6 Pregnancy and Lactation In the first trimester of pregnancy, vaginal tablets should be used only with extreme caution and after consideration of possible alternative therapeutic agents (see also sections 4.2, 4.4). 4.7 Effects on Ability to Drive and Use Machines No information is available on the effects on the ability to drive and use machines. 4.8 Undesirable Effects The evaluation of undesirable effects is based on the following definitions: very common (≥ 1/10) common (≥ 1/100 - < 1/10) uncommon (≥ 1/1000 to < 1/100) rare (≥ 1/10000 to < 1/1000) very rare (< 1/10000) unknown (frequency cannot be estimated from available data) Skin Disorders Skin reactions (e.g., burning, stinging) may occur uncommonly. Erythema, skin rash, blisters, peeling, pruritus, urticaria, and swelling may rarely develop. Immune System Disorders Contact allergy has been reported very rarely. Allergic skin reactions may occur in case of hypersensitivity to clotrimazole or other excipients. Disorders of the Genital Organs Mild burning sensation in the vagina may occur uncommonly. Mild skin irritation on the labia may occur sometimes uncommonly. If the sexual partner is also being treated, they may experience irritation on the penis and inside the urethra. Other Undesirable Effects Women have very rarely reported abdominal stinging and increased frequency of urination. 4.9 Overdose Unknown. 5. Pharmacological Properties 5.1 Pharmacodynamic Properties Pharmacotherapeutic group: Imidazole derivative; broad-spectrum antimycotic for topical use ATC code: G01AF02 Clotrimazole is a chlorine-substituted triphenylmethyl-imidazole belonging to the class of "imidazole antimycotics" and is primarily fungistatic, but also fungicidal at higher concentrations. Clotrimazole acts only on fungal reproduction. In addition to its antimycotic effect, clotrimazole has in vitro antibacterial effect (e.g., against Gram-positive staphylococci and streptococci), as well as trichomonacidal (Trichomonas vaginalis) and amoebacidal (against Naegleria fowleri) effect. Clotrimazole is a broad-spectrum antimycotic that acts on the vast majority of human pathogenic fungi. Its efficacy is high, and resistance to clotrimazole has only been observed under special experimental conditions. There is no cross-resistance with amphotericin, flucytosine, griseofulvin, and nystatin. The antimycotic effect of clotrimazole, based on current knowledge, may be due to inhibition of ergosterol biosynthesis from lanosterol. Enzymes involved in the conversion of 24-methylenedihydrolanosterol to 14-desmethylsterol (both are intermediates between lanosterol and ergosterol) are blocked. Since ergosterol is an essential component of the fungal cell membrane, clotrimazole strongly affects the composition and characteristics of the membrane. However, this process is not instantaneous but delayed, as cytoplasmic ergosterol is used first. The normal permeability and structure of the membrane are disrupted, ultimately leading to cell lysis. In addition, clotrimazole interferes with mitochondrial and peroxisomal enzymes at fungistatic concentrations. As a result, toxic concentrations of hydrogen peroxide increase, which likely contributes to cell necrosis (autodegradation by hydrogen peroxide). In vitro studies have shown that clotrimazole can inhibit cholesterol synthesis at very high doses. The clinical significance of these experimental findings has not been established. 5.2 Pharmacokinetic Properties When used topically, systemic bioavailability can be ruled out even under unfavorable conditions (skin lesions, occlusive dressing). The concentration of clotrimazole when applied to the skin (with a special ointment base mixture) decreases sharply as it passes through the different layers of the skin from the epidermis (especially the stratum corneum, tissue concentration measured at approx. 1 mg/mL) to the corium (dermis, tissue concentration from 2 to 30 mg/mL) and subcutaneous tissue (tissue concentration less than 0.1 mg/mL). Nevertheless, a sufficiently microbiologically effective concentration is achieved or exceeded 6 hours after application of this special mixed preparation. After vaginal use, the systemic bioavailability of clotrimazole is approximately 3-10%. The fungicidal concentration can be maintained for more than 3 days after application. The plasma protein binding of the small amount absorbed is approximately 98%. This means that the substance is almost completely metabolized and excreted via the kidneys and feces in a microbiologically inactive form. 5.3 Preclinical Safety Data a) Data on the local tolerance of intravaginal dosage forms: Clotrimazole tolerance tests were performed using vaginal tablets (100 mg clotrimazole). Tests were conducted on dogs and monkeys using vaginal tablets (100 mg clotrimazole). No local intolerance was observed on the vaginal mucosa 1, 4, and 24 hours after tablet application. Application was repeated in dogs and monkeys: the vaginal mucosa was observed during the application period and after the 14th day of treatment. Serum analysis was performed concurrently. Local tolerance was good. Histological examinations revealed no pathological findings. No significant concentrations were detected in the serum. b) Data on systemic tolerance Acute toxicity The acute toxicity, denoted as LD50, is 700 to 900 mg/kg body weight (oral) for mice and rats, 1000 to 2000 mg/kg body weight (oral) for rabbits, 1000 and 2000 mg/kg body weight (oral) for cats and dogs respectively; in these cases, LD50 could only be roughly determined due to severe vomiting. Chronic toxicity Prolonged oral treatment with high doses in rats, dogs, and monkeys caused changes in the liver and adrenal glands. Dose-dependent liver hypertrophy occurred (cellular hypertrophy and increased total weight) due to induction of microsomal enzymes in hepatocytes (no signs of intrahepatic cholestasis or pathological changes were observed in dogs or monkeys; only in rats were degenerative changes in hepatocytes observed when they were given less than 200 mg/kg body weight of clotrimazole due to high sensitivity). This functional hypertrophy is rapidly reversible after completion of therapy. Thickening of the adrenal cortex occurred due to increased fat accumulation in the reticular and fascicular zones; no damage to the parenchymal tissue was observed. These changes are also reversible after discontinuation of therapy, but persist longer than liver changes. Carcinogenic and mutagenic potential Carcinogenicity was not observed during chronic toxicity testing. The existing mutagenicity test is negative, but insufficient for a definitive assessment. Reproductive toxicology Teratogenicity studies were conducted using mice, rats, and rabbits; all were given up to 200 mg of clotrimazole per kg of body weight orally, and rats were also given 100 mg of clotrimazole per kg of body weight intravaginally. In these studies, clotrimazole had no effect on fertility; the substance is neither embryotoxic nor teratogenic. Existing experience with topical use of clotrimazole in pregnant women does not confirm embryotoxic and fetotoxic effects, accordingly. 6. Pharmaceutical Particulars 6.1 List of Excipients Lactose monohydrate, corn starch, polysorbate 80, magnesium stearate, sodium hydrogen carbonate, adipic acid, stearic acid, colloidal anhydrous silica 6.2 Incompatibilities Unknown. 6.3 Shelf Life 3 years 6.4 Special Precautions for Storage Do not store above 30°C 6.5 Type and Contents of Container Blister foil made of aluminum polyethylene. The packaging contains 3 vaginal tablets; each tablet contains 200 mg clotrimazole; applicator for multiple use 6.6 Special Precautions for Disposal and Other Handling There are no special precautions for disposal and other handling. See also: Clotri-Denk 100mg 6 vaginal tablets