Instructions for Klion-d 100 vaginal tablets No. 10
Composition
active ingredients: metronidazole, miconazole nitrate;
1 tablet contains metronidazole 100 mg and miconazole nitrate 100 mg;
Excipients: sodium lauryl sulfate, colloidal anhydrous silica, magnesium stearate, povidone, sodium bicarbonate, tartaric acid, sodium starch glycolate (type A), crospovidone, hypromellose, lactose monohydrate.
Dosage form
Vaginal tablets.
Main physicochemical properties: biconvex vaginal tablets of oval shape with a pointed end, almost white in color, approximately 24 mm × 14 mm in size, engraved with “100” on one side.
Pharmacotherapeutic group
Gynecological antimicrobials and antiseptics. Imidazole derivatives. ATX code G01A F20.
Pharmacological properties
Pharmacodynamics
Clinical efficacy and safety. Metronidazole is an anti-trichomonas agent for topical and oral use. Miconazole nitrate is an effective antifungal agent that acts on dermatophytes and fungi of the genus Candida, in addition, it has a pronounced bacteriostatic effect against certain gram-positive bacteria in topical therapy.
The purpose of topical application of this combination drug is the local treatment of trichomoniasis and the prevention of vaginal mycoses, which often develop after the use of metronidazole.
The drug can be used for primary vaginal mycoses.
Pharmacokinetics
Absorption: When applied topically, metronidazole and miconazole nitrate are absorbed through the mucous membrane in insignificant amounts. According to studies, metronidazole and miconazole nitrate are absorbed in quantities that are difficult to determine, values are 0.2 μg/ml and 0.3 μg/ml, respectively.
Metronidazole is usually well absorbed after oral administration, reaching peak serum concentrations within 1–3 hours. A single oral dose of 250 mg results in peak plasma concentrations of 5 μg/mL as determined by gas chromatography. Oral bioavailability is nearly 100%.
Distribution: Studies in patients and healthy volunteers have shown that metronidazole rapidly penetrates the cerebrospinal fluid and reaches therapeutic concentrations in brain abscess and lung abscess. It has a large volume of distribution, and less than 20% of the circulating metronidazole is bound to plasma proteins. It penetrates the bile and reaches concentrations similar to those in plasma.
Elimination: The elimination half-life of metronidazole from the body of healthy volunteers averages 8 hours. Metronidazole and its metabolites are mainly (60-80% of the dose) excreted by the kidneys, with 6% to 15% of the administered dose excreted through the intestines.
Indication
Topical treatment of urogenital trichomoniasis and/or fungal infections in women.
Contraindication
Hypersensitivity to the active substances or to any excipients of the medicinal product.
First trimester of pregnancy.
Interaction with other medicinal products and other types of interactions
There are no data on the interaction of vaginal use of metronidazole and miconazole nitrate with other drugs.
When using the Klion-D 100 vaginal tablet simultaneously with oral metronidazole, the following types of drug interactions may occur:
increased effect of oral anticoagulants, resulting in prolonged prothrombin time, which requires a review of the anticoagulant dose; enzyme inducers (e.g. phenytoin, phenobarbital) may accelerate the elimination of metronidazole, which will lead to a decrease in its level in the blood plasma with a simultaneous increase in phenytoin clearance; enzyme inhibitors (e.g. cimetidine) may increase the half-life, reduce the plasma clearance of metronidazole; drinking alcoholic beverages during metronidazole therapy may cause adverse reactions similar to disulfiram (spasmodic abdominal pain, nausea, vomiting, headache and skin flushing); simultaneous use of metronidazole with disulfiram is not recommended (may cause an additive effect, psychotic states, confusion); Metronidazole may increase the level of lithium in the blood plasma, therefore, it is necessary to reduce the dose of lithium or stop taking the lithium drug before starting metronidazole therapy; simultaneous administration of cyclosporine with metronidazole may lead to an increase in the level of cyclosporine in the blood plasma; if combination therapy is necessary, it is recommended to monitor the level of cyclosporine in the blood plasma; metronidazole reduces the clearance of 5-fluorouracil and increases its toxicity; metronidazole may affect the results of studies of serum biochemical parameters, such as aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glucose-hexokinase and triglyceride levels.
Application features
During treatment with Klion-D 100 vaginal tablets and for at least 1 day after the end of treatment, it is forbidden to drink alcoholic beverages.
If treatment is ineffective, it is recommended to conduct another systemic anti-trichomoniasis or antifungal therapy.
In case of sensitivity or irritation of the vaginal mucosa, treatment should be discontinued.
Cases of severe hepatotoxicity/acute hepatic failure, including fatal cases occurring very rapidly after the start of treatment, have been reported in patients with Cockayne syndrome during treatment with metronidazole-containing products. Therefore, metronidazole should be used in such patients only after careful benefit/risk assessment and only if no alternative treatment is available. Liver function tests should be monitored before, during and after treatment until they return to normal or to baseline. If significantly elevated liver function tests occur during treatment, treatment should be discontinued. Patients with Cockayne syndrome should be advised to immediately report any symptoms of possible liver damage to their doctor and to discontinue metronidazole.
Excipients
This medicine contains sodium lauryl sulphate, which may cause local skin reactions (such as a tingling or burning sensation) or increase skin reactions caused by other products when applied to the same area.
Ability to influence reaction speed when driving vehicles or other mechanisms
Klion-D 100 vaginal tablets do not affect the ability to drive or operate other mechanisms.
Use during pregnancy or breastfeeding
Pregnancy. In the first trimester of pregnancy, the use of Klion-D 100 vaginal tablets is contraindicated.
Metronidazole, taken orally, penetrates the placental barrier and quickly enters the fetal bloodstream.
Reproductive toxicity studies in rats have used doses five times higher than those used in humans. These studies have not revealed any evidence of impaired fertility or adverse effects on the fetus due to metronidazole. When administered intraperitoneally to pregnant mice, metronidazole was fetotoxic at doses approximately equivalent to those used in humans. However, no fetotoxic effects were observed when administered orally to pregnant mice. However, there are currently no adequate and well-controlled studies in pregnant women.
Based on a meta-analysis of studies conducted in the first trimester of pregnancy, it was concluded that no increase in fetotoxicity was observed. During the second and third trimesters of pregnancy, Klion-D 100 vaginal tablets can be prescribed only after a careful assessment of the expected benefits and negative consequences of using the drug.
Breastfeeding. Orally administered metronidazole is excreted in breast milk in concentrations equal to those in plasma. It may impart a bitter taste to breast milk. To avoid any adverse effects on the infant, metronidazole should be discontinued or breastfeeding should be discontinued during treatment with metronidazole and for 12 to 24 hours after discontinuation, taking into account the importance of the therapy for the mother.
Method of administration and doses
The drug should be used intravaginally only. It is recommended to slightly moisten the vaginal tablet and insert it deep into the vagina.
Trichomoniasis. Simultaneously with oral metronidazole, 1 vaginal tablet of Klion-D 100 should be used once a day (in the evening before going to bed) for 10 days. During these 10 days, take 1 metronidazole tablet orally 2 times a day (2 × 250 mg) daily (one in the morning and one in the evening) during or immediately after meals, without chewing.
To ensure long-term recovery, it is advisable to simultaneously treat the sexual partner with oral metronidazole tablets.
If the treatment is ineffective, the 10-day course of treatment can be repeated.
Fungal infection. Apply 1 vaginal tablet of Klion-D 100 once a day (in the evening before bedtime) for 10 days.
Children
Safety and efficacy in children and adolescents have not been established. No data available.
Overdose
The drug is intended exclusively for intravaginal use. In case of accidental ingestion of a large dose, gastric lavage can be performed.
If symptoms of intoxication appear in case of overdose (nausea, vomiting, ataxia), symptomatic therapy should be carried out (gastric lavage, use of activated charcoal and hemodialysis), since there is no specific antidote. Metronidazole and its metabolites are well eliminated by hemodialysis.
Adverse reactions
Cases of irritation at the site of application have been reported during therapy with Klion-D 100 vaginal tablets. Local hypersensitivity reactions may rarely occur.
Adverse reactions are listed by system organ class and frequency: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); rare (< 1/10,000).
The following adverse reactions may occur when used concomitantly with oral metronidazole.
Infections and infestations
Blood and lymphatic system disorders
Rare: neutropenia (leukopenia), thrombocytopenia.
On the part of the immune system
Rare: anaphylactic reactions.
Nutritional and metabolic
Uncommon: decreased appetite.
Mental disorders
Isolated: confusion.
Central nervous system
Very common: headache.
Uncommon: peripheral neuropathy (hypoesthesia), convulsions, drowsiness, dizziness, impaired coordination, taste disturbances (metallic taste in the mouth).
Gastrointestinal tract
Very common: nausea.
Common: lower abdominal pain, lower abdominal cramps, diarrhea.
Rare: vomiting, coated tongue.
Hepatobiliary system
Rare: cholestasis, jaundice.
Skin and subcutaneous tissue disorders
Uncommon: angioedema, pruritus, rash, urticaria.
Rare: erythema multiforme.
Systemic and injection site disorders
Uncommon: injection site irritation, pyrexia.
Laboratory indicators
Uncommon: change in urine colour (darkening of urine is caused by a metabolite of metronidazole, this is of no clinical significance).
Rare: increased liver enzymes.
Peripheral neuropathy (numbness of the extremities), headache, convulsions, drowsiness, dizziness, impaired coordination and confusion have been observed in isolated cases with prolonged use and treatment with high doses of the drug. After reducing the dose or stopping therapy, all of the above symptoms resolved without treatment.
Adverse reactions associated with miconazole nitrate
In most cases, adverse reactions are rare and mild. Irritation and burning have been reported with topical application.
Reporting of suspected adverse reactions
It is important to receive reports of suspected adverse reactions after the registration of a medicinal product. This allows monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions.
Expiration date
5 years.
Storage conditions
Store at a temperature not exceeding 30 °C in the original packaging to protect from light and moisture.
Keep the drug out of the reach of children!
Packaging
10 vaginal tablets in a strip. 1 strip in a cardboard box.
Vacation category
According to the recipe.
Producer
Gedeon Richter OJSC, Hungary.
Location of the manufacturer and its business address
H-1103, Budapest, Demrei Street 19-21, Hungary.
