Excipients: Witepsol S55 1436.75 mg.
Vaginal suppositories in the form of a flat body with a rounded end, from white to slightly yellowish.
pharmachologic effect
Neo-Penotran Forte-L suppositories contain miconazole, which has an antifungal effect, metronidazole, which has an antibacterial and antitrichomonal effect, and lidocaine, which gives a local anesthetic effect.Miconazole, which is a synthetic derivative of imidazole, has antifungal activity and has a wide spectrum of action. Particularly effective against pathogenic fungi, including Candida albicans. In addition, miconazole is effective against gram-positive bacteria. The action of miconazole is the synthesis of ergosterol in the cytoplasmic membrane. Miconazole modifies the permeability of Candida species mycotic cells and inhibits glucose uptake in vitro.
Metronidazole, which is a derivative of 5-nitroimidazole, is an antiprotozoal and antibacterial agent effective against several infections caused by anaerobic bacteria and protozoa, such as Trichomonas vaginalis, Gardnerella vaginalis and anaerobic bacteria, incl. anaerobic streptococci.
Miconazole and metronidazole do not have a synergistic or antagonistic effect when taken simultaneously.
Lidocaine stabilizes the neuronal membrane by inhibiting the ion currents necessary for the generation and conduction of impulses, thereby exerting a local anesthetic effect.
Indications for use
- vaginal candidiasis caused by Candida albicans;- bacterial vaginitis caused by anaerobic bacteria and Gardnerella vaginalis, Trichomonas vaginitis caused by Trichomonas vaginalis;
- mixed vaginal infections.
Mode of application
Unless otherwise recommended by the doctor, 1 suppository is injected deep into the vagina at night for 7 days.In case of recurrent disease or vaginitis resistant to other treatment, it is recommended to extend the course of treatment up to 14 days.
Suppositories should be inserted in the supine position deep into the vagina using the supplied disposable fingertips.
Interaction
As a result of the absorption of metronidazole, the following interactions may occur:Alcohol: disulfiram-like reactions.
Oral anticoagulants: increased anticoagulant effect.
Phenytoin: Increased phenytoin levels and decreased blood levels of metronidazole.
Phenobarbital: decrease in the level of metronidazole in the blood.
Disulfiram: changes from the side of the central nervous system are possible (for example, mental reactions).
Cimetidine: it is possible to increase the level of metronidazole in the blood and, therefore, increase the risk of neurological side effects. Lithium: Lithium toxicity may increase.
Astemizole and terfenadine: metronidazole and miconazole inhibit the metabolism of these compounds and increase their plasma concentration.
There is an effect on blood levels of liver enzymes, glucose (when determined by the hexokinase method), theophylline and procainamide.
Side effect
Rarely, hypersensitivity reactions have been observed ( skin rashes) and side effects such as abdominal pain, headache, vaginal itching, burning, and irritation of the vagina.The incidence of systemic side effects is very low, as vaginal application metronidazole contained in Neo-Penotran Forte-L vaginal suppositories, the plasma concentration of metronidazole is very low (2-12% compared with oral administration).
Miconazole nitrate, like all other antifungal agents based on imidazole derivatives that are injected into the vagina, can cause vaginal irritation (burning, itching) (2-6%). Such symptoms can be eliminated by the local anesthetic action of lidocaine. In case of severe irritation, treatment should be discontinued.
For side effects due to systemic application metronidazole, include hypersensitivity reactions (rarely), leukopenia, ataxia, psychoemotional disorders, peripheral neuropathy in overdose and prolonged use, convulsions; diarrhea (rare), constipation, dizziness, headache, loss of appetite, nausea, vomiting, pain or cramps in abdominal cavity, change taste sensations(rarely), dry mouth, metallic or unpleasant taste, increased fatigue. These side effects occur in extremely rare cases, since blood levels of metronidazole with intravaginal use are very low.
Contraindications
- I trimester of pregnancy;- porphyria;
- epilepsy;
- severe liver dysfunction;
- Hypersensitivity to the components of the drug.
Use during pregnancy and lactation
Metronidazole and lidocaine belong to category B, miconazole - to category C. After the first trimester of pregnancy, Neo-Penotran Forte-L can be used under medical supervision in cases where the intended benefit outweighs the potential risk to the fetus.
Breastfeeding should be stopped, because. metronidazole passes into breast milk. Feeding can be resumed 24-48 hours after the end of treatment. It is not known whether lidocaine passes into breast milk. A lactating woman should take lidocaine with caution.
Overdose
Symptoms: nausea, vomiting, abdominal pain, diarrhea, itching, metallic taste in the mouth, ataxia, paresthesia, convulsions, leukopenia, dark urine. Symptoms of an overdose of miconazole nitrate are nausea, vomiting, dryness in the larynx and mouth, anorexia, headache, diarrhea.Treatment:
- in case of accidental ingestion of a large dose of the drug, if necessary, gastric lavage can be done. There is no specific antidote;
- symptomatic treatment is applied. Treatment should be administered to persons who have taken a dose of 12 g of metronidazole.
special instructions
Not recommended for use in children and virgins.It is necessary to avoid alcohol during treatment and at least for 24-48 hours after the end of the course due to possible disulfiram-like reactions. Large doses and prolonged systematic use of the drug can cause peripheral neuropathy and convulsions. Caution should be exercised when using suppositories simultaneously with contraceptive diaphragms and condoms due to the possible interaction of rubber with the suppository base.
In patients diagnosed with trichomonas vaginitis, simultaneous treatment of the sexual partner is necessary.
At kidney failure the dose of metronidazole should be reduced.
In severe hepatic impairment, the clearance of metronidazole may be impaired.
Metronidazole may cause symptoms of encephalopathy due to elevated plasma levels and should therefore be used with caution in patients with hepatic encephalopathy.
In patients suffering from hepatic encephalopathy, the daily dose of metronidazole should be reduced to 1/3.
In patients with reduced liver function, the half-life of lidocaine may increase two or more times.
Decreased renal function does not affect the pharmacokinetics of lidocaine, but may cause accumulation of metabolites.
Influence on the ability to drive vehicles and control mechanisms
Suppositories Neo-Penotran Forte-L do not affect the ability to drive a car and work with mechanisms.
Preclinical safety data
Preclinical studies of safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity have not identified a potential risk to humans.
Instructions for use
Active ingredients
Release form
suppositories
Compound
In 1 suppository: Metronidazole (metronidazole) 750 mg; miconazole (miconazole) 200 mg; lidocaine (lidocaine) 100 mg. Excipients: Witepsol S55 1436.75 mg.
Pharmacological effect
Neo-Penotran Forte-L suppositories contain miconazole, which has an antifungal effect, metronidazole, which has an antibacterial and antitrichomonas effect, and lidocaine, which gives a local anesthetic effect. Miconazole, which is a synthetic derivative of imidazole, has antifungal activity and has a wide spectrum of action. Particularly effective against pathogenic fungi, including Candida albicans. In addition, miconazole is effective against gram-positive bacteria. The action of miconazole is the synthesis of ergosterol in the cytoplasmic membrane. Miconazole modifies the permeability of the mycotic cell of Candida species and inhibits glucose uptake in vitro. Metronidazole, which is a 5-nitroimidazole derivative, is an antiprotozoal and antibacterial agent effective against several infections caused by anaerobic bacteria and protozoa such as Trichomonas vaginalis, Gardnerella vaginalis and anaerobic bacteria, incl. h. anaerobic streptococci. Miconazole and metronidazole do not have a synergistic or antagonistic effect when taken simultaneously. Lidocaine stabilizes the neuronal membrane by inhibiting the ion fluxes necessary for the occurrence and conduction of impulses, thereby providing a local anesthetic effect.
Pharmacokinetics
Miconazole nitrate: The absorption of miconazole nitrate when administered intravaginally is very small (approximately 1.4% of the dose). Miconazole nitrate can be determined in plasma within three days after intravaginal administration of Neo-Penotran Forte-L suppositories. Metronidazole: the bioavailability of metronidazole with intravaginal administration is 20% compared with oral administration. The equilibrium concentration of metronidazole in plasma is 1.1-5.0 μg / ml after daily intravaginal administration of Neo-Penotran Forte-L suppositories for 3 days. Metronidazole is metabolized in the liver by oxidation. The main metabolites of metronidazole are hydroxy derivatives and acetic acid compounds, which are excreted by the kidneys. The biological activity of hydroxy metabolites is 30% of the biological activity of metronidazole. T1 / 2 of metronidazole is 6-11 hours. After oral or intravenous administration of metronidazole, 60-80% of the dose is excreted by the kidneys (about 20% - unchanged, and in the form of metabolites). Lidocaine: the action begins after 3-5 minutes. Lidocaine is absorbed when applied superficially to damaged skin and mucous membranes and is rapidly metabolized in the liver. Metabolites and medicinal product unchanged (10% of the administered dose) is excreted through the kidneys. After daily intravaginal administration of Neo-Penotran Forte-L suppositories for 3 days, lidocaine is absorbed in a minimal amount, and its plasma levels are 0.04-1 μg / ml.
Indications
Vaginal candidiasis caused by Candida albicans; bacterial vaginitis caused by anaerobic bacteria and Gardnerella vaginalis, Trichomonas vaginitis caused by Trichomonas vaginalis; mixed vaginal infections.
Contraindications
I trimester of pregnancy; porphyria; epilepsy; severe liver dysfunction; hypersensitivity to the components of the drug.
Precautionary measures
Use during pregnancy and lactation
Metronidazole and lidocaine belong to category B, miconazole - to category C. After the first trimester of pregnancy, Neo-Penotran Forte-L can be used under medical supervision in cases where the intended benefit outweighs the potential risk to the fetus. Breastfeeding should be stopped, because . metronidazole passes into breast milk. Feeding can be resumed 24-48 hours after the end of treatment. It is not known whether lidocaine passes into breast milk. A lactating woman should take lidocaine with caution.
Dosage and administration
Unless otherwise recommended by the doctor, 1 suppository is injected deep into the vagina at night for 7 days. In case of recurrent disease or vaginitis resistant to other treatment, it is recommended to extend the course of treatment up to 14 days. disposable fingertips.
Side effects
In rare cases, hypersensitivity reactions (skin rashes) and side effects such as abdominal pain, headache, vaginal itching, burning and irritation of the vagina are observed. The incidence of systemic side effects is very low, because with vaginal use of metronidazole contained in vaginal suppositories Neo-Penotran Forte-L, the plasma concentration of metronidazole is very low (2-12% compared with oral administration). Miconazole nitrate, like all other antifungal agents based on imidazole derivatives that are injected into the vagina, can cause irritation of the vagina (burning , itching) (2-6%). Such symptoms can be eliminated by the local anesthetic action of lidocaine. In case of severe irritation, treatment should be discontinued. Side effects associated with the systemic use of metronidazole include hypersensitivity reactions (rarely), leukopenia, ataxia, psychoemotional disorders, peripheral neuropathy with overdose and prolonged use, convulsions; diarrhea (rare), constipation, dizziness, headache, loss of appetite, nausea, vomiting, abdominal pain or cramps, change in taste (rare), dry mouth, metallic or unpleasant taste, increased fatigue. These side effects occur in extremely rare cases, since blood levels of metronidazole with intravaginal use are very low.
Overdose
Symptoms: nausea, vomiting, abdominal pain, diarrhea, itching, metallic taste in the mouth, ataxia, paresthesia, convulsions, leukopenia, dark urine. Symptoms of an overdose of miconazole nitrate are nausea, vomiting, dryness in the larynx and mouth, anorexia, headache, diarrhea. Treatment: in case of accidental ingestion of a large dose of the drug, gastric lavage can be done if necessary. There is no specific antidote; symptomatic treatment is applied. Treatment should be administered to persons who have taken a dose of 12 g of metronidazole.
Interaction with other drugs
As a result of the absorption of metronidazole, the following interactions may occur: Alcohol: disulfiram-like reactions. Oral anticoagulants: increased anticoagulant effect. Phenytoin: increased phenytoin levels and decreased blood levels of metronidazole. (for example, mental reactions). Cimetidine: it is possible to increase the level of metronidazole in the blood and, therefore, increase the risk of neurological side effects. Lithium: lithium toxicity may increase. Astemizol and terfenadine: metronidazole and miconazole inhibit the metabolism of these compounds and increase their plasma concentration. There is an effect on blood levels of liver enzymes, glucose (when determined by the hexokinase method), theophylline and procainamide.
special instructions
It is necessary to avoid alcohol during treatment and at least for 24-48 hours after the end of the course due to possible disulfiram-like reactions. Large doses and prolonged systematic use of the drug can cause peripheral neuropathy and convulsions. Caution should be exercised when using suppositories simultaneously with contraceptive diaphragms and condoms due to the possible interaction of rubber with the suppository base. In patients diagnosed with trichomonas vaginitis, simultaneous treatment of the sexual partner is necessary. In renal failure, the dose of metronidazole should be reduced. metronidazole. Metronidazole can cause symptoms of encephalopathy due to elevated plasma levels and therefore should be used with caution in patients with hepatic encephalopathy. In patients suffering from hepatic encephalopathy, the daily dose of metronidazole should be reduced to 1/3. In patients with reduced liver function the half-life of lidocaine may increase two or more times. A decrease in kidney function does not affect the pharmacokinetics of lidocaine, but may cause the accumulation of metabolites. mechanisms. Preclinical safety data Nonclinical studies of safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity have not identified a potential risk to humans.
Neo-Penotran Forte L is a three-component drug in the form of vaginal suppositories used in gynecological practice. Therapeutic action The drug is made up of pharmacological effects each of its components. Miconazole is produced synthetically from imidazole. The substance has antimycotic activity and a wide therapeutic range. Fungi of the genus Candida are especially sensitive to it. The drug is also effective in infections caused by gram-positive bacteria. Metronidazole inhibits the growth and development of protozoa (Trichomonas, gardnerella) and anaerobic microorganisms, including streptococci. Both of the above substances do not potentiate, but do not weaken the effect of each other when used together. Lidocaine brings neuronal membranes to a stable state, suppressing the transmembrane current of ions necessary for the generation and conduction of nerve impulses. The result is a local anesthetic effect. According to general recommendations, the drug is used 1 time per day for a week. Single dose - 1 vaginal suppository. In case of recurrence of the disease or vaginal infections caused by microorganisms resistant to other treatment, the drug course can be extended up to two weeks. When introducing suppositories, the body should be in horizontal position. The drug has a favorable safety profile and is generally well tolerated. In rare cases, allergic reactions of a dermatological nature, headaches and epigastric pains, local itching and burning, irritation of the skin and mucous membranes at the injection site are possible. The low risk of unwanted adverse reactions is extremely low, tk. with local administration of metronidazole, only a very small part of the administered substance enters the systemic circulation in comparison with the oral form.
Possible itching and burning in the vagina is due to the presence of miconazole in the preparation. With use, this effect is leveled. local anesthetic lidocaine. Neo-Penotran Forte L is not used in the initial trimester of pregnancy (from the 1st to the 12th - 13th obstetric weeks), with porphyrin disease, epilepsy, liver diseases in advanced stages, individual intolerance to the components. IN pediatric practice, as well as in women with preserved hymen is not used. Reception of Neo-Penotran Forte L is not compatible with the consumption of ethanol, because. possible disulfiram-like reactions due to systemic absorption of metronidazole. When a woman is diagnosed with trichomonas colpitis, treatment is also indicated for her sexual partner. Dose adjustments may be required in severe renal impairment. The drug is of particular value in cases where the cause of inflammation of the vulvar and vaginal mucosa is not established or the infection is provoked by several microorganisms. Qualitative and quantitative composition active ingredients in the drug Neo-Penotran Forte L allow you to start pharmacotherapy even before the results are obtained laboratory research. The presence of disposable silicone fingertips for insertion included in the package ensures ease of use, and a special technology for the production of suppositories prevents their contents from leaking out of the vagina. The frequency of use of the drug (1 time per day) ensures high compliance (adherence to treatment).
Pharmacology
Neo-Penotran Forte-L suppositories contain miconazole, which has an antifungal effect, metronidazole, which has an antibacterial and antitrichomonal effect, and lidocaine, which gives a local anesthetic effect.
Miconazole, which is a synthetic derivative of imidazole, has antifungal activity and has a wide spectrum of action. Particularly effective against pathogenic fungi, including Candida albicans. In addition, miconazole is effective against gram-positive bacteria. The action of miconazole is the synthesis of ergosterol in the cytoplasmic membrane. Miconazole modifies the permeability of Candida species mycotic cells and inhibits glucose uptake in vitro.
Metronidazole, which is a derivative of 5-nitroimidazole, is an antiprotozoal and antibacterial agent effective against several infections caused by anaerobic bacteria and protozoa, such as Trichomonas vaginalis, Gardnerella vaginalis and anaerobic bacteria, incl. anaerobic streptococci.
Miconazole and metronidazole do not have a synergistic or antagonistic effect when taken simultaneously.
Lidocaine stabilizes the neuronal membrane by inhibiting the ion currents necessary for the generation and conduction of impulses, thereby exerting a local anesthetic effect.
Pharmacokinetics
Miconazole nitrate: The absorption of miconazole nitrate when administered intravaginally is very small (approximately 1.4% of the dose). Miconazole nitrate can be determined in plasma within three days after intravaginal administration of Neo-Penotran Forte-L suppositories.
Metronidazole: The bioavailability of metronidazole when administered intravaginally is 20% compared with oral administration. The equilibrium concentration of metronidazole in plasma is 1.1-5.0 μg / ml after daily intravaginal administration of Neo-Penotran Forte-L suppositories for 3 days. Metronidazole is metabolized in the liver by oxidation. The main metabolites of metronidazole are hydroxy derivatives and acetic acid compounds, which are excreted by the kidneys. The biological activity of hydroxy metabolites is 30% of the biological activity of metronidazole. T 1/2 of metronidazole is 6-11 hours. After oral or intravenous administration of metronidazole, 60-80% of the dose is excreted by the kidneys (about 20% - unchanged, and in the form of metabolites).
Lidocaine: the action begins in 3-5 minutes. Lidocaine is absorbed when applied superficially to damaged skin and mucous membranes and is rapidly metabolized in the liver. Metabolites and the drug unchanged (10% of the administered dose) are excreted through the kidneys. After daily intravaginal administration of Neo-Penotran Forte-L suppositories for 3 days, lidocaine is absorbed in a minimal amount, and its plasma levels are 0.04-1 μg / ml.
Release form
Vaginal suppositories in the form of a flat body with a rounded end, from white to slightly yellowish.
Excipients: Witepsol S55 1436.75 mg.
7 pcs. - plastic blisters (1) complete with fingertips - packs of cardboard.
Dosage
In case of recurrent disease or vaginitis resistant to other treatment, it is recommended to extend the course of treatment up to 14 days.
Suppositories should be inserted in the supine position deep into the vagina using the supplied disposable fingertips.
Overdose
Symptoms: nausea, vomiting, abdominal pain, diarrhea, itching, metallic taste in the mouth, ataxia, paresthesia, convulsions, leukopenia, dark urine. Symptoms of an overdose of miconazole nitrate are nausea, vomiting, dryness in the larynx and mouth, anorexia, headache, diarrhea.
Treatment: in case of accidental ingestion of a large dose of the drug, if necessary, gastric lavage can be done. There is no specific antidote; symptomatic treatment is applied. Treatment should be administered to persons who have taken a dose of 12 g of metronidazole.
Interaction
As a result of the absorption of metronidazole, the following interactions may occur:
Alcohol: disulfiram-like reactions.
Oral anticoagulants: increased anticoagulant effect.
Phenytoin: Increased phenytoin levels and decreased blood levels of metronidazole.
Phenobarbital: decrease in the level of metronidazole in the blood.
Disulfiram: changes from the side of the central nervous system are possible (for example, mental reactions).
Cimetidine: it is possible to increase the level of metronidazole in the blood and, therefore, increase the risk of neurological side effects. Lithium: Lithium toxicity may increase.
Astemizole and terfenadine: metronidazole and miconazole inhibit the metabolism of these compounds and increase their plasma concentration.
There is an effect on blood levels of liver enzymes, glucose (when determined by the hexokinase method), theophylline and procainamide.
Side effects
In rare cases, hypersensitivity reactions (skin rashes) and side effects such as abdominal pain, headache, vaginal itching, burning and irritation of the vagina are observed.
The incidence of systemic side effects is very low, since with vaginal use of metronidazole contained in Neo-Penotran Forte-L vaginal suppositories, the plasma concentration of metronidazole is very low (2-12% compared with oral administration).
Miconazole nitrate, like all other antifungal agents based on imidazole derivatives that are injected into the vagina, can cause vaginal irritation (burning, itching) (2-6%). Such symptoms can be eliminated by the local anesthetic action of lidocaine. In case of severe irritation, treatment should be discontinued.
Side effects caused by the systemic use of metronidazole include hypersensitivity reactions (rarely), leukopenia, ataxia, psycho-emotional disorders, peripheral neuropathy with overdose and prolonged use, convulsions; diarrhea (rare), constipation, dizziness, headache, loss of appetite, nausea, vomiting, abdominal pain or cramps, change in taste (rare), dry mouth, metallic or unpleasant taste, increased fatigue. These side effects occur in extremely rare cases, since blood levels of metronidazole with intravaginal use are very low.
Indications
- vaginal candidiasis caused by Candida albicans;
- bacterial vaginitis caused by anaerobic bacteria and Gardnerella vaginalis, Trichomonas vaginitis caused by Trichomonas vaginalis;
- mixed vaginal infections.
Contraindications
- I trimester of pregnancy;
- porphyria;
- epilepsy;
- severe liver dysfunction;
- hypersensitivity to the components of the drug.
Application features
Use during pregnancy and lactation
Metronidazole and lidocaine belong to category B, miconazole - to category C. After the first trimester of pregnancy, Neo-Penotran Forte-L can be used under medical supervision in cases where the intended benefit outweighs the potential risk to the fetus.
Breastfeeding should be stopped, because. metronidazole passes into breast milk. Feeding can be resumed 24-48 hours after the end of treatment. It is not known whether lidocaine passes into breast milk. A lactating woman should take lidocaine with caution.
Application for violations of liver function
Contraindicated in severe liver failure.
In patients with reduced liver function, the half-life of lidocaine may increase by a factor of two or more.
Application for violations of kidney function
It is necessary to avoid alcohol during treatment and at least for 24-48 hours after the end of the course due to possible disulfiram-like reactions. Large doses and prolonged systematic use of the drug can cause peripheral neuropathy and convulsions. Caution should be exercised when using suppositories simultaneously with contraceptive diaphragms and condoms due to the possible interaction of rubber with the suppository base.
In patients diagnosed with trichomonas vaginitis, simultaneous treatment of the sexual partner is necessary.
In renal insufficiency, the dose of metronidazole should be reduced.
In severe hepatic impairment, the clearance of metronidazole may be impaired.
Metronidazole may cause symptoms of encephalopathy due to elevated plasma levels and should therefore be used with caution in patients with hepatic encephalopathy.
In patients suffering from hepatic encephalopathy, the daily dose of metronidazole should be reduced to 1/3.
In patients with reduced liver function, the half-life of lidocaine may increase two or more times.
Decreased renal function does not affect the pharmacokinetics of lidocaine, but may cause accumulation of metabolites.
Influence on the ability to drive vehicles and control mechanisms
Suppositories Neo-Penotran Forte-L do not affect the ability to drive a car and work with mechanisms.
Preclinical safety data
Preclinical studies of safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity have not identified a potential risk to humans.
Compound
Active ingredients: metronidazole and miconazole nitrate;
1 suppository contains 750 mg of metronidazole and 200 mg of miconazole nitrate
Excipients: witepsol.
Dosage form"type="checkbox">
Dosage form
Suppositories are vaginal.
Basic physical and chemical properties: suppositories from white to yellowish color.
Pharmacological group"type="checkbox">
Pharmacological group
Antimicrobial, antiprotozoal, antifungal agents.
ATX code G01A F20.
Pharmacological properties"type="checkbox">
Pharmacological properties
Pharmacological.
Neo-Penotran® Forte contains miconazole nitrate with antifungal activity and metronidazole with antibacterial and antitrichomonal activity. Miconazole nitrate, is an antifungal agent, a synthetic derivative of imidazole, has a wide range activity and is particularly effective against pathogenic fungi, including Candida albicans. In addition, miconazole nitrate is effective against gram-positive bacteria. Miconazole exerts its action through the synthesis of ergosterol in the cytoplasmic membrane. Miconazole nitrate alters the permeability of Candida species and inhibits glucose utilization in vitro.
Metronidazole, a 5-nitroimidazole derivative, is an antiprotozoal and antibacterial agent; it is effective against several infections caused by anaerobic bacteria and protozoa such as Trichomonas vaginalis, Gardnerella vaginalis, and anaerobic bacteria including anaerobic streptococci.
Miconazole nitrate and metronidazole do not have synergistic or antagonistic effects.
The rate of clinical cure that has been achieved in an open, multicenter, uncontrolled clinical trial efficacy and safety of the drug Neo-Penotran® Forte, with a 7-day treatment of 104 patients with a clinical / microbiological diagnosis of vaginitis was 96.6% for vulvovaginal candidiasis, 98.1% for bacterial vaginosis, 97.3% for trichomonas vaginitis and 98. 5% for mixed vaginal infections. The frequency of microbiological cure was 89.8%, 96.2% 100%, 91.7% for each type of infection, respectively.
In a randomized open comparative study of the efficacy, safety and tolerability of Neo-Penotran® Forte, the frequency of clinical and microbiological cure was 84% and 76%, respectively.
Pharmacokinetics.
Absorption.
miconazole nitrate. The absorption of miconazole nitrate when administered intravaginally is very low (about 1.4% of the dose). After intravaginal administration of NEO-PENOTRAN® FORTE, miconazole nitrate was not detected in blood plasma.
Metronidazole: The bioavailability of metronidazole with this route of administration is 20% compared with the oral route of administration. The constant level of metronidazole in blood plasma ranged from 1.1 to 5 µg/ml after daily intravaginal administration of Neo-Penotran® Forte.
Distribution.
miconazole nitrate. Plasma protein binding is 90% -93%. Its penetration into the cerebrospinal fluid is low, but it is widely distributed to other tissues. The volume of distribution is 1400 liters.
Metronidazole. Penetrates into tissues and body fluids, including bile, bones, mammary glands, breast milk, cerebral abscesses, cerebrospinal fluid, liver and hepatic abscesses, saliva, seminal fluid and vaginal secretions, and reaches concentrations similar to those in plasma. It crosses the placental barrier and quickly enters the fetal circulation. No more than 20% binds to plasma proteins. The volume of distribution is 0.25-0.85 l/kg.
Metabolism.
miconazole nitrate. Metabolized in the liver. Two inactive metabolites are identified (2,4-dichlorophenyl-1H imidazole ethanol and 2,4-dichloromygdalic acid).
Metronidazole. Metabolized in the liver by oxidation, the hydroxyl metabolite is active. The main metabolites of metronidazole, hydroxyl and acetic acid metabolites, are excreted in the urine. The hydroxyl metabolite has 30% of the biological activity of metronidazole.
Conclusion.
miconazole nitrate. The half-life is 24 hours. Less than 1% is excreted in the urine. Approximately 50% is excreted in the feces, usually unchanged.
Metronidazole. The half-life is 6-11 hours. Approximately 6-15% of the dose of metronidazole is excreted in the feces, 60-80% does not change and is excreted in the urine, like its metabolites. Approximately 20% of metronidazole is excreted in the urine as unchanged drug.
Data from preclinical studies.
The results of standard preclinical studies of toxicity after repeated use, genotoxicity, carcinogenicity and reproductive toxicity do not indicate the existence of a specific risk to the human body.
In an in vitro microbiological study, no synergistic or antagonistic interaction was found between the active substances that make up the drug, action against Candida albicans, Streptococcus (gram B according to Lancefield), Gardnerella vajinalis and Trichomonas vaginalis.
Preclinical studies of the combination of 750 mg metronidazole and 200 mg miconazole nitrate have shown that there is no enhancement or synergy of the lethal or toxic effects of both compounds in female rats.
In a study of vaginal mucosal irritation in female beagle dogs, the same combination of drugs was found to not cause irritation of the vaginal mucosa and did not lead to clinical, biochemical or hematological abnormalities. In the same study, local and systemic toxic effects were not detected.
Indications
For the treatment of vulvovaginal candidiasis caused by Candida albicans, bacterial vaginosis caused by anaerobic bacteria and Gardnerella vaginalis, trichomonas vaginitis caused by Trichomonas vaginalis, and mixed vaginal infections.
Contraindications
- Hypersensitivity to any of the active ingredients of the drug or to their derivatives.
- Drinking alcoholic beverages during treatment or within 3 days after treatment.
- Taking disulfiram during treatment or within 2 weeks after treatment.
- Porfiry.
- Epilepsy.
- Severe liver dysfunction.
Interaction with other medicinal products and other forms of interaction
Through the absorption of metronidazole, drug interaction reactions can be observed when used simultaneously with certain substances and drugs:
alcohol: the interaction of metronidazole with alcohol can cause a reaction similar to the interaction with disulfiram. You can not drink alcohol during therapy and within 3 days after the completion of the course;
amiodarone: increased risk of cardiotoxicity (QT interval prolongation, ventricular flutter-fibrillation, cardiac arrest)
astemizole and terfenadine: metronidazole inhibits the metabolism of these drugs and increases their plasma concentrations
carbamazepine: increases the concentration of carbamazepine in the blood
cimetidine: increases the level of metronidazole in the blood and the risk of neurological side effects
cyclosporine: increased risk of cyclosporine toxicity;
disulfiram: effects from the central nervous system(eg, psychotic reactions)
lithium: increased blood levels and toxicity of lithium;
phenytoin: increases the level of phenytoin in the blood, decreases the level of metronidazole in the blood
phenobarbital: the level of metronidazole in the blood decreases
fluorouracil: increased blood levels and toxicity of fluorouracil;
feroral anticoagulants enhances the effect of anticoagulants.
During treatment with the drug, its effect on the blood levels of liver enzymes, glucose (hexokinase method), theophylline and procainamide was observed.
Due to the characteristics of the absorption of miconazole nitrate with the simultaneous use of the lower names medicines The following reactions may occur:
acenocoumarol, anisindione, dicoumarol, phenidion, phenprocoumon warfarin: increased risk of bleeding
astemizole, cisapride and terfenadine: miconazole inhibits the metabolism of these drugs and increases their plasma concentrations
carbamazepine: the metabolism of carbamazepine decreases;
cyclosporine: increased risk of cyclosporine toxicity (kidney dysfunction, cholestasis, paresthesia)
fentanyl: increased or prolonged action of opioids (central nervous system depression, depression, respiratory depression)
phenytoin and fosphenytoin: increased risk of phenytoin toxicity (ataxia, hyperlexia, nystagmus, tremor)
glimepiride: increased hypoglycemic effect;
oxybutynin: plasma concentration or action of oxybutynin increases;
oxycodone: the concentration of oxycodone in plasma increases and its output decreases;
pimozide: increased risk of cardiotoxicity (QT interval prolongation, ventricular flutter-fibrillation, cardiac arrest)
tolterodine: the bioavailability of tolterodine increases in individuals with cytochrome P450 2D6 deficiency;
trimetrexate: increased toxicity of trimetrexate (bone marrow suppression, impaired renal and hepatic function, and formation of ulcers in the stomach and intestines).
Application features
The patient should be warned that alcohol should not be consumed during therapy and within 3 days after completion of the course of treatment due to the possibility of reactions from the central nervous system, similar action disulfiram.
High doses of the drug and a long period of use can cause peripheral neuropathy and convulsions.
The suppository base may interact in an undesirable way with rubber or latex, from which contraceptive diaphragms and condoms are made, therefore their simultaneous use with suppositories is not recommended.
Sexual partners of patients with trichomonas vaginitis should also be treated.
In renal insufficiency, the dose of metronidazole should be reduced.
In severe hepatic impairment, the clearance of metronidazole may be altered. Metronidazole may worsen the symptoms of encephalopathy due to its increased level in blood plasma. Therefore, metronidazole should be used with caution in patients with hepatic encephalopathy. The daily dose for such patients should be reduced to 1/3.
For elderly patients (over 65 years): the same recommendations as for other patients.
Do not swallow suppositories or use the drug by any other route of administration.
Metronidazole may increase plasma levels of bisulfan, which may lead to significant toxic effects of bisulfan. It is necessary to more often monitor the level of prothrombin and INR (international normalized ratio) while using oral anticoagulants when using metronidazole and within 8 days after withdrawal.
Suppositories should not be used with contraceptives - a diaphragm and condoms, since the suppository base may interact with rubber in an undesirable way.
Intravaginal agents (eg, tampons, douches, or spermicides) should not be used concomitantly with treatment.
Sexual partners in whom Trichomonas vaginalis is found should undergo treatment at the same time as the patient.
Use during pregnancy or lactation.
Since the effects of the active ingredients of NEO-PENOTRANE® FORTE on the fetus and development of newborns have not been fully studied, women who need to use this drug should avoid pregnancy using an effective contraceptive method.
Data from preclinical animal studies on pregnancy, embryonic and fetal development, perinatal and/or postnatal development are insufficient. The possible risk to humans is unknown.
Neo-Penotran® Forte should not be used in the first trimester of pregnancy. In the II and III trimesters, the drug can be used only if necessary, if the doctor decides that the benefits outweigh the risks.
There is no evidence of a harmful effect on human and animal fertility when metronidazole or miconazole nitrate are used alone.
During the use of Neo-Penotran® Forte, breast-feeding should be stopped, since metronidazole, one of the active components of the drug, passes into breast milk. Breastfeeding can be resumed 1-2 days after the end of treatment.
The ability to influence the reaction rate when driving vehicles or operating other mechanisms.
Systemic use of metronidazole may affect the ability to drive or use machines. Compared with systemic administration, the absorption of metronidazole is significantly lower with vaginal administration. There is a possibility of dizziness, ataxia, psycho-emotional disorders. In the presence of such symptoms, it is not recommended to drive vehicles or other mechanisms.
Dosage and administration
1 vaginal suppository should be injected deep into the vagina at night for 7 days.
In case of recurrence of the disease or vaginitis resistant to other treatment, Neo-Penotran® Forte should be used within 14 days.
Children
Overdose
There are no data on an overdose of metronidazole when administered vaginally. When introduced into the vagina, metronidazole can be absorbed in an amount sufficient to cause systemic effects.
If accidentally enters the digestive system a large number of drug, if necessary, apply the appropriate method of gastric lavage. Treatment should be carried out in cases where 12 g of metronidazole has entered the digestive system. There is no specific antidote, symptomatic treatment is recommended. With an overdose of metronidazole, the following symptoms are observed: nausea, vomiting, abdominal pain, diarrhea, itching, metallic taste in the mouth, ataxia, vertigo, paresthesia, convulsions, leukopenia, dark urine.
Symptoms of overdose of miconazole nitrate include nausea, vomiting, sore throat and oral cavity, anorexia, headache, diarrhea.
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Adverse reactions
Frequency listed below side effects is defined as follows:
very often (≥1/10); often (from ≥1/100 to<1/10); нечасто (от ≥1 / 1000 до <1/100), редко (от ≥1 / 10000 до <1/1000); очень редко (<1/10000), неизвестно (нельзя оценить по имеющимся данным).
In some cases, side effects such as hypersensitivity reactions (including skin rashes) and abdominal pain, headache, itching, burning and irritation of the vagina can be observed. The incidence of systemic side effects is very low due to the very low level of metronidazole in blood plasma with vaginal use of the drug (2-12% of the level achieved with oral metronidazole). Another active ingredient of the drug, miconazole nitrate, can cause vaginal irritation (burning, itching), like all other antifungal agents containing imidazole derivatives that are administered vaginally (2-6%). If severe irritation occurs, discontinue use.
Side effects resulting from the systemic action of the active ingredients of Neo-Penotran ® Forte are listed below.
From the blood and lymphatic system:
Very rarely agranulocytosis, neutropenia, thrombocytopenia, pancytopenia
Not known: leukopenia.
From the immune system:
Rarely anaphylactic shock.
Not known: hypersensitivity reactions, allergic reactions, angioedema, urticaria, fever.
From the side of metabolism and digestive tract Not known: anorexia. Psychiatric disorders:
Very rare: disturbances of consciousness, including confusion and hallucinations.
Not known: depression.
From the nervous system:
Common: dizziness, headache,
Very rarely, encephalopathy (eg, confusion, fever, increased sensitivity to light, torticollis, hallucinations, paralysis, visual and movement disorders) and subacute cerebellar syndrome (eg, ataxia, dysarthria, gait disturbance, nystagmus, tremor), which may resolve after discontinuation of the drug.
Not known: fatigue or weakness, convulsions, peripheral neuropathy due to intensive and / or prolonged metronidazole therapy, aseptic meningitis.
From the side of the organs of vision:
Very rarely, temporary visual disturbances such as diplopia, myopia, blurred images, decreased visual acuity, changes in color perception;
Not known: optic neuropathy/neuritis.
Hepatobiliary system:
Very rarely: increased levels of liver enzymes (AST, ALT, alkaline phosphatase), cholestatic or mixed hepatitis and damage to liver cells (hepatocytes), sometimes with jaundice; cases of liver failure have been reported requiring liver transplantation in patients treated with metronidazole and other antibiotics.
From the skin and its derivatives:
Very rare: skin rash, pustular eruptions, hot flushes, itching.
Not known: erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis.
From the musculoskeletal system and connective tissue:
Very rarely - myalgia, arthralgia.
From the side of the kidneys and urinary organs Very rarely: darkening of the urine (due to the metabolism of metronidazole). Gastrointestinal disorders:
Not known: taste disturbance, inflammation of the oral mucosa, metallic taste, coated tongue, nausea, vomiting, constipation, gastrointestinal disorders such as epigastric pain, diarrhea, dry mouth, decreased appetite, abdominal pain and cramps.
General disorders and reactions at the injection site:
Very common vaginal discharge
Often vaginitis, vulvovaginal irritation, pelvic discomfort.
Infrequently: feeling of thirst.
Rarely burning in the vagina, itching, irritation, stomach pain, rash.
Not known: local irritation and hypersensitivity, contact dermatitis.
These side effects are rare, since the concentration of metronidazole in the blood after intravaginal administration is low.
pharmachologic effect
Neo-Penotran Forte-L suppositories contain miconazole, which has an antifungal effect, metronidazole, which has an antibacterial and antitrichomonal effect, and lidocaine, which gives a local anesthetic effect.
Miconazole, which is a synthetic derivative of imidazole, has antifungal activity and has a wide spectrum of action. Particularly effective against pathogenic fungi, including Candida albicans. In addition, miconazole is effective against gram-positive bacteria. The action of miconazole is the synthesis of ergosterol in the cytoplasmic membrane. Miconazole modifies the permeability of Candida species mycotic cells and inhibits glucose uptake in vitro.
Metronidazole, which is a derivative of 5-nitroimidazole, is an antiprotozoal and antibacterial agent effective against several infections caused by anaerobic bacteria and protozoa, such as Trichomonas vaginalis, Gardnerella vaginalis and anaerobic bacteria, incl. anaerobic streptococci.
Miconazole and metronidazole do not have a synergistic or antagonistic effect when taken simultaneously.
Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes necessary for the occurrence and conduction of impulses, thereby providing a local anesthetic effect.
Pharmacokinetics
Miconazole nitrate: absorption of miconazole nitrate when administered intravaginally is very small (approximately 1.4% of the dose). Miconazole nitrate can be determined in plasma within three days after intravaginal administration of Neo-Penotran Forte-L suppositories.
Metronidazole: the bioavailability of metronidazole with intravaginal administration is 20% compared with oral administration. The equilibrium concentration of metronidazole in plasma is 1.1-5.0 μg / ml after daily intravaginal administration of Neo-Penotran Forte-L suppositories for 3 days. Metronidazole is metabolized in the liver by oxidation. The main metabolites of metronidazole are hydroxy derivatives and acetic acid compounds, which are excreted by the kidneys. The biological activity of hydroxy metabolites is 30% of the biological activity of metronidazole. T 1/2 of metronidazole is 6-11 hours. After oral or intravenous administration of metronidazole, 60-80% of the dose is excreted by the kidneys (about 20% - unchanged, and in the form of metabolites).
Lidocaine: action begins in 3-5 minutes. Lidocaine is absorbed when applied superficially to damaged skin and mucous membranes and is rapidly metabolized in the liver. Metabolites and the drug unchanged (10% of the administered dose) are excreted through the kidneys. After daily intravaginal administration of Neo-Penotran Forte-L suppositories for 3 days, lidocaine is absorbed in a minimal amount, and its plasma levels are 0.04-1 μg / ml.
Indications
- vaginal candidiasis caused by Candida albicans;
- bacterial vaginitis caused by anaerobic bacteria and Gardnerella vaginalis, Trichomonas vaginitis caused by Trichomonas vaginalis;
- mixed vaginal infections.
At recurrent disease or vaginitis resistant to other treatment it is recommended to extend the course of treatment up to 14 days.
Suppositories should be inserted in the supine position deep into the vagina using the supplied disposable fingertips.
Side effect
IN rare cases hypersensitivity reactions (skin rashes) and side effects such as abdominal pain, headache, vaginal itching, burning and irritation of the vagina are observed.
The incidence of systemic side effects is very low, since with vaginal use of metronidazole contained in Neo-Penotran Forte-L vaginal suppositories, the plasma concentration of metronidazole is very low (2-12% compared with oral administration).
miconazole nitrate, like all other antifungal agents based on imidazole derivatives that are injected into the vagina, can cause vaginal irritation (burning, itching) (2-6%). Such symptoms can be eliminated by the local anesthetic action of lidocaine. In case of severe irritation, treatment should be discontinued.
To side effects due to systemic use metronidazole, include hypersensitivity reactions (rarely), leukopenia, ataxia, psycho-emotional disorders, peripheral neuropathy in overdose and prolonged use, convulsions; diarrhea (rare), constipation, dizziness, headache, loss of appetite, nausea, vomiting, abdominal pain or cramps, change in taste (rare), dry mouth, metallic or unpleasant taste, increased fatigue. These side effects occur in extremely rare cases, since blood levels of metronidazole with intravaginal use are very low.
Contraindications for use
- I trimester of pregnancy;
- porphyria;
- epilepsy;
- severe liver dysfunction;
- Hypersensitivity to the components of the drug.
Use during pregnancy and lactation
Metronidazole and lidocaine belong to category B, miconazole - to category C. After the first trimester of pregnancy, Neo-Penotran Forte-L can be used under medical supervision in cases where the intended benefit outweighs the potential risk to the fetus.
Breastfeeding should be stopped, because. metronidazole passes into breast milk. Feeding can be resumed 24-48 hours after the end of treatment. It is not known whether lidocaine passes into breast milk. A lactating woman should take lidocaine with caution.
Overdose
Symptoms: nausea, vomiting, abdominal pain, diarrhea, itching, metallic taste in the mouth, ataxia, paresthesia, convulsions, leukopenia, dark urine. Symptoms of an overdose of miconazole nitrate are nausea, vomiting, dryness in the larynx and mouth, anorexia, headache, diarrhea.
Treatment: in case of accidental ingestion of a large dose of the drug, if necessary, gastric lavage can be done. There is no specific antidote; symptomatic treatment is applied. Treatment should be administered to persons who have taken a dose of 12 g of metronidazole.
drug interaction
As a result of the absorption of metronidazole, the following interactions may occur:
Alcohol: disulfiram-like reactions.
Oral anticoagulants: enhancement of the anticoagulant effect.
Phenytoin: an increase in phenytoin levels and a decrease in the level of metronidazole in the blood.
Phenobarbital: decrease in the level of metronidazole in the blood.
Disulfiram: changes from the side of the central nervous system are possible (for example, mental reactions).
Cimetidine: it is possible to increase the level of metronidazole in the blood and, therefore, increase the risk of neurological side effects. Lithium: Lithium toxicity may increase.
Astemizole and terfenadine: Metronidazole and miconazole inhibit the metabolism of these compounds and increase their plasma concentration.
There is an effect on blood levels of liver enzymes, glucose (when determined by the hexokinase method), theophylline and procainamide.
Terms of dispensing from pharmacies
The drug is dispensed by prescription.
Terms and conditions of storage
Store the drug at a temperature not exceeding 25°C. Do not store in refrigerator. Store in original packaging.
Keep out of the reach of children.
Shelf life - 2 years. Do not use after the expiration date
Application for violations of liver function
Contraindicated in severe liver failure.
In patients with reduced liver function, the half-life of lidocaine may increase by a factor of two or more.
Application for violations of kidney function
It is necessary to avoid alcohol during treatment and at least for 24-48 hours after the end of the course due to possible disulfiram-like reactions. Large doses and prolonged systematic use of the drug can cause peripheral neuropathy and convulsions. Caution should be exercised when using suppositories simultaneously with contraceptive diaphragms and condoms due to the possible interaction of rubber with the suppository base.
In patients diagnosed with trichomonas vaginitis, simultaneous treatment of the sexual partner is necessary.
In renal insufficiency, the dose of metronidazole should be reduced.
In severe hepatic impairment, the clearance of metronidazole may be impaired.
Metronidazole may cause symptoms of encephalopathy due to elevated plasma levels and should therefore be used with caution in patients with hepatic encephalopathy.
In patients suffering from hepatic encephalopathy, the daily dose of metronidazole should be reduced to 1/3.
In patients with reduced liver function, the half-life of lidocaine may increase two or more times.
Decreased renal function does not affect the pharmacokinetics of lidocaine, but may cause accumulation of metabolites.
Influence on the ability to drive vehicles and control mechanisms
Suppositories Neo-Penotran Forte-L do not affect the ability to drive a car and work with mechanisms.
Preclinical safety data
Preclinical studies of safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, reproductive toxicity have not identified a potential risk to humans.
