Klion-D vaginal tablets, No. 10

• local treatment of vaginitis of mixed etiology, simultaneously caused by Trichomonas spp. and Candida spp.

Intravaginally.

1 vaginal tablet (pre-moistened with water) is injected deep into the vagina in the evening before going to bed for 10 days in combination with taking metronidazole inside.

Active substance:

metronidazole - 100 mg

miconazole nitrate - 100 mg

Excipients: sodium lauryl sulfate, colloidal silicon dioxide, magnesium stearate, povidone K30, sodium bicarbonate, tartaric acid, sodium carboxymethyl starch (type A), crospovidone, hypromellose, lactose monohydrate.

• hypersensitivity to metronidazole, to other nitromidazole derivatives, to miconazole, to imidazoles and to other components of the drug;

• leukopenia (including history);

• organic lesions of the central nervous system (including epilepsy);

• hepatic impairment (in the case of large doses);

• I trimester of pregnancy;

• lactation period (breastfeeding);

• children under 12 years of age.

With care: diabetes mellitus, microcirculation disorders.

Clinical and pharmacological group: Drug with antibacterial, antiprotozoal and antifungal action for local use in gynecology

Pharmaco-therapeutic group: Antimicrobial combined agent (antimicrobial and antiprotozoal agent + antifungal agent)

pharmachologic effect

Combined preparation for intravaginal use containing metronidazole and miconazole.

Metronidazole is an antiprotozoal and antimicrobial drug derived from nitro-5-imidazole. The mechanism of action consists in the biochemical reduction of the 5-nitro group of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group of metronidazole interacts with the DNA of the cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria and protozoa.

Active against Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia lamblia, as well as obligate anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides ovatus, Bacteroides distasonis, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella spp. (Prevotella bivia, Prevotella buccae, Prevotella disiens) and some gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.). The MIC for these strains is 0.125-6.25 ?g / ml.

Aerobic microorganisms and facultative anaerobes are resistant to metronidazole , but in the presence of mixed flora (aerobes and anaerobes), metronidazole acts synergistically with antibiotics effective against aerobes.

Miconazole has antifungal effect against dermatophytes and yeasts. With intravaginal use, it is active mainly against Candida albicans. Miconazole inhibits the biosynthesis of ergosterol in fungi and changes the composition of other lipid components in the membrane, which leads to the death of fungal cells. Miconazole does not alter the composition of normal microflora and vaginal pH.

Pharmacokinetics

Absorption and distribution

With intravaginal administration, metronidazole is absorbed into the systemic circulation. Cmax of metronidazole in the blood is determined after 6-12 hours and is approximately 50% of the Cmax that is reached (after 1-3 hours) after a single dose of an equivalent dose of metronidazole inside.

Metronidazole passes into breast milk and most tissues, crosses the BBB and the placental barrier.
Plasma protein binding is less than 20%.

Metabolism and excretion

It is metabolized in the liver by hydroxylation, oxidation and glucuronidation. The activity of the main metabolite (2-oxymetronidazole) is 30% of the activity of the parent compound.

It is excreted by the kidneys - 60-80% of the dose of the drug of systemic action (20% of this amount unchanged).

The metabolite of metronidazole, 2-oxymetronidazole, stains urine red-brown, due to the presence of a water-soluble pigment formed as a result of the metabolism of metronidazole. The intestines are excreted - 6-15% of the dose of the drug of systemic action.

Systemic absorption of miconazole after intravaginal administration is low. It is rapidly destroyed in the liver.

Poorly overcomes histohematogenous barriers. 8 hours after application of the drug, 90% of miconazole is still present in the vagina. Unchanged miconazole is not found in either plasma or urine.

Indications

• local treatment of vaginitis of mixed etiology, simultaneously caused by Trichomonas spp. and Candida spp.

Dosage regimen

Intravaginally. 1 vaginal tablet (pre-moistened with water) is injected deep into the vagina in the evening before going to bed for 10 days in combination with taking the drug metronidazole inside.

Side effect

From the digestive system: epigastric pain, nausea, vomiting, diarrhea; inflammation of the oral mucosa (glossitis, stomatitis), taste disturbances ('metallic' taste in the mouth), loss of appetite, anorexia, dryness of the oral mucosa, constipation; pancreatitis (reversible cases); discoloration of the tongue / 'coated tongue' (due to excessive growth of fungal microflora).

From the immune system: angioedema, anaphylactic shock.

From the side of the central nervous system: peripheral sensory neuropathy; headache, convulsions, dizziness; the development of encephalopathy (for example, confusion) and subacute cerebellar syndrome (impaired coordination and synergism of movements, ataxia, dysarthria, gait disturbances, nystagmus and tremor) have been reported, which undergo a regression after discontinuation of metronidazole; aseptic meningitis.

Mental disorders : mental disorders, including confusion, hallucinations; depression, insomnia, irritability, hyperexcitability.

From the side of the organ of vision: transient visual impairments such as diplopia, myopia, blurred vision, decreased visual acuity, impaired color perception; neuropathy / optic neuritis.

From the side of the organ of hearing and labyrinth disorders: hearing impairment / hearing loss (including sensorineural deafness); noise in ears.

On the part of the blood and lymphatic system: agranulocytosis, leukopenia, neutropenia and thrombocytopenia.

From the liver and biliary tract: increased activity of hepatic enzymes (AST, ALT and ALP), the development of cholestatic or mixed hepatitis and hepatocellular liver damage, sometimes accompanied by jaundice. In patients who received treatment with metronidazole in combination with other antibiotics, there were cases of liver failure, which required liver transplantation.

On the part of the skin and subcutaneous tissues: rash, pruritus, flushing of the skin, flushing of the skin, urticaria; pustular skin rash; acute generalized exanthematous pustulosis; fixed drug rash; Stevens-Johnson syndrome, toxic epidermal necrolysis.

On the part of the kidneys and urinary tract: it is possible to stain urine in a brown-reddish color, due to the presence of metronidazole metabolite in the urine; dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

General disorders and disorders at the injection site: fever, nasal congestion, arthralgia, weakness; a burning sensation or irritation of the penis in a sexual partner, a burning sensation or increased urination, vulvavaginitis (itching, burning pain or hyperemia of the mucous membrane in the external genital area).

Infectious and parasitic diseases: after discontinuation of the drug, vaginal candidiasis may develop.

Laboratory and instrumental data: flattening of the T wave on the ECG.

Contraindications for use

• hypersensitivity to metronidazole, to other nitromidazole derivatives, to miconazole, to imidazoles and to other components of the drug;

• leukopenia (including history);

• organic lesions of the central nervous system (including epilepsy);

• hepatic impairment (in the case of large doses);

• I trimester of pregnancy;

• lactation period (breastfeeding);

• children under 12 years of age.

With care: diabetes mellitus, microcirculation disorders.

Application during pregnancy and lactation

Klion-D 100 is contraindicated for use in the first trimester of pregnancy. The use of the drug in the II and III trimesters is possible only in cases where the potential benefit to the mother outweighs the risk to the fetus.

Metronidazole is excreted in breast milk. If necessary, the use of the drug during lactation should stop breastfeeding.

Application for violations of liver function

Contraindicated in liver failure.

Application in children

It is contraindicated for use in children under 12 years of age.

special instructions

Since the simultaneous administration of metronidazole with alcohol (ethanol) can have an effect similar to the effect of disulfiram (flushing of the skin, flushing of the skin, vomiting, tachycardia), the patient should be warned that during treatment and for at least one day after after the end of the use of the drug, you should not consume alcoholic beverages or drugs containing ethanol.

The indications for long-term use of the drug (more than 10 days) should be carefully weighed and, in the absence of strict indications, its prolonged use should be avoided. If, in the presence of strict indications (carefully weighing the ratio between the expected effect and the potential risk of complications), the drug is used for a longer time than is usually recommended, then the treatment should be carried out under the control of hematological parameters (especially leukocytes) and adverse reactions, such as peripheral or central neuropathy, manifested by paresthesias, ataxia, dizziness, convulsions, upon the appearance of which treatment should be discontinued.

When treating Trichomonas vaginitis in women and Trichomonas urethritis in men, it is necessary to refrain from sexual intercourse. Simultaneous treatment of sexual partners is mandatory. Treatment does not stop during menstruation. After trichomoniasis therapy, control tests should be carried out for 3 successive cycles before and after menstruation.

The development of severe hepatotoxicity / acute liver failure (including fatal cases) has been reported in patients with Cockayne's syndrome. It should be used with caution and only in the absence of alternative treatment to use metronidazole in this category of patients.

Liver function tests should be performed at the beginning of treatment, during treatment, and within 2 weeks after the end of treatment.

Patients with Cockayne syndrome should be advised to immediately inform their doctor about the development of any symptoms of potential liver damage (such as newly diagnosed persistent abdominal pain, anorexia, nausea, vomiting, fever, malaise, jaundice, dark urine, or itching).

It must be taken into account that metronidazole can immobilize treponemas, which leads to a false positive Nelson's test.

This medicine contains sodium lauryl sulfate, which can cause local skin lesions (such as a tingling sensation or burning sensation) or intensify skin reactions caused by other drugs when applied to the same area.

Influence on the ability to drive vehicles and mechanisms

When using the drug Klion-D 100 intravaginally, there was no negative effect on the ability to drive vehicles, however, given the risk of developing such adverse reactions as confusion, dizziness, hallucinations, visual impairment, it is recommended to refrain from driving or exercising during treatment. other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Overdose

When using the drug in accordance with the instructions for use, an overdose is unlikely. Overdose has been reported with the ingestion of high doses of metronidazole and accidental overdoses.

Symptoms: vomiting, ataxia, slight disorientation.

Treatment: there is no specific antidote for metranidazole overdose. In case of suspicion of a significant excess of the dose, symptomatic and supportive therapy should be carried out.

Drug interactions

There is no data on the interaction of metronidazole and miconazole with intravaginal administration. If Klion-D 100 vaginal tablets are used with oral metronidazole tablets, the following interactions associated with metronidazole should be considered.

With disulfiram: it was reported about the development of psychotic reactions in patients who received simultaneously metronidazole and disulfiram (the interval between the use of these drugs should be at least 2 weeks).

With ethanol: disulfiram-like reactions may occur (flushing of the skin, flushing of the skin, vomiting, tachycardia).

With indirect anticoagulants (warfarin): an increase in the anticoagulant effect and an increased risk of bleeding associated with a decrease in hepatic metabolism of indirect anticoagulants, which can lead to an increase in prothrombin time. In the case of the simultaneous use of metronidazole and indirect anticoagulants, more frequent monitoring of prothrombin time is required and, if necessary, correction of anticoagulant doses.

With lithium preparations: with the simultaneous use of metronidazole with lithium preparations, the concentration of the latter in the blood plasma may increase. With simultaneous use, the concentration of lithium, creatinine and electrolytes in the blood plasma should be monitored.

With cyclosporine: with the simultaneous use of metronidazole with cyclosporine, the concentration of cyclosporine in the blood plasma may increase. If necessary, the simultaneous use of metronidazole and cyclosporine should monitor the concentration of cyclosporine and creatinine in the blood plasma.

With cimetidine: cimetidine inhibits the metabolism of metronidazole, which can lead to an increase in its concentration in blood plasma and an increased risk of side effects.

With drugs that induce microsomal oxidation isoenzymes in the liver (phenobarbital, phenytoin): the simultaneous use of metronidazole with drugs that induce microsomal oxidation isoenzymes in the liver (phenobarbital, phenytoin) can accelerate the excretion of metronidazole, resulting in a decrease in its concentration in the blood.

With fluorouracil: metronidazole reduces the clearance of fluorouracil, leading to an increase in its toxicity.

With busulfan : metronidazole increases the concentration of busulfan in the blood plasma, which can lead to the development of a severe toxic effect of busulfan.

With non-depolarizing muscle relaxants (vecuronium bromide): not recommended for use with non-depolarizing muscle relaxants (vecuronium bromide).

With sulfonamides : sulfonamides enhance the antimicrobial effect of metronidazole.

Storage conditions

The drug should be stored out of the reach of children, in its original packaging, at a temperature not exceeding 30 ? C.

Shelf life

The shelf life is 5 years. Do not use after the expiration date.

Terms of sale

The drug is available with a prescription.

Contacts for inquiries

GEDEON RICHTER JSC (Hungary)