Instructions for Gainex forte vaginal suppositories strip No. 7
Composition
active ingredients: metronidazole, miconazole nitrate;
1 suppository contains metronidazole 750 mg, miconazole nitrate 200 mg;
excipients: solid fat.
Dosage form
Vaginal suppositories.
Main physicochemical properties: suppositories from white to light yellow in color, torpedo-shaped.
Pharmacotherapeutic group
Antimicrobial, antiprotozoal, antifungal agents.
ATX code G01A F20.
Pharmacological properties
Pharmacodynamics
Gainex® Forte is a combined antimicrobial drug, the effect of which is due to metronidazole and miconazole, which are part of its composition.
Miconazole nitrate is a local antifungal and antibacterial agent of a broad spectrum of action of the imidazole group. Miconazole inhibits the biosynthesis of ergosterol and changes the lipid composition of the membrane, causing the death of the fungal cell. It has a fungicidal effect on dermatophytes (Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum canis), yeast and yeast-like fungi (Candida albicans, Candida glabrata and other Candida species), as well as on other pathogenic fungi (Malassezia furtur, Aspergilus niger, Penicillium crustaceum). Miconazole nitrate has an antibacterial effect, more pronounced against gram-positive bacteria.
Metronidazole, a 5-nitroimidazole derivative, is an antibacterial and antiprotozoal agent. It is effective against infections caused by anaerobic bacteria and protozoa, including Trichomonas vaginalis, Gardnerella vaginalis, and anaerobic streptococci.
Miconazole nitrate and metronidazole do not have synergistic or antagonistic effects.
Pharmacokinetics
Absorption.
Miconazole nitrate. Absorption of miconazole nitrate through the vaginal walls is negligible (approximately 1.4% of the dose). Miconazole nitrate is not detected in blood plasma after intravaginal administration.
Metronidazole
The bioavailability of metronidazole when administered vaginally is 20% compared to its bioavailability when administered orally. The equilibrium concentration of metronidazole in blood plasma is 1.1–5.0 μg/ml after intravaginal administration of a daily dose of the drug Gainex® Forte.
Distribution.
Miconazole nitrate. Plasma protein binding is 90–93%. Its penetration into cerebrospinal fluid is low, but it is widely distributed in other tissues. The volume of distribution is 1400 l.
Metronidazole. Penetrates into tissues and body fluids, including bile, bone, breast, milk, cerebral abscesses, cerebrospinal fluid, liver and liver abscesses, saliva, seminal fluid, and vaginal secretions, reaching concentrations similar to those found in plasma. It crosses the placental barrier and rapidly enters the fetal bloodstream. Plasma protein binding is less than 20%. The volume of distribution is 0.25–0.85 L/kg.
Biotransformation.
Miconazole nitrate. Metabolized in the liver. Two inactive metabolites (2,4-dichlorophenyl-1H-imidazole-ethanol and 2,4-dichloromandelic acid) are identified.
Metronidazole. Metabolized in the liver by oxidation, the hydroxy metabolite is active. The main metabolites of metronidazole - hydroxy derivatives and acetic acid derivatives - are excreted in the urine. The hydroxy metabolite exhibits 30% of the biological activity of metronidazole.
Breeding.
Miconazole nitrate. The half-life is 24 hours. Less than 1% is excreted in the urine. Approximately 50%, mainly unchanged, is excreted in the feces.
Metronidazole. The half-life is 6–11 hours. Approximately 6–15% of a metronidazole dose is excreted in the feces. Approximately 60–80% of metronidazole is excreted in the urine as unchanged drug and as metabolites. Approximately 20% of metronidazole is excreted in the urine as unchanged drug.
Preclinical data.
The results of standard non-clinical studies of repeated dose toxicity, genotoxicity, carcinogenicity and reproductive toxicity do not indicate the existence of a specific risk for humans.
In an in vitro microbiological study, no synergistic or antagonistic interaction was detected between the active substances included in the preparation when acting against Candida albicans, Streptococcus (Gram B according to Lancefield), Gardnerella vaginalis and Trichomonas vaginalis.
Indication
For the treatment of candidal vulvovaginitis caused by Candida albicans, bacterial vaginosis caused by anaerobic bacteria and Gardnerella vaginalis, trichomonas vaginitis caused by Trichomonas vaginalis, and mixed vaginal infections.
Contraindication
Hypersensitivity to any of the active ingredients of the drug or to their derivatives. Drinking alcoholic beverages during treatment or within 3 days after the end of treatment. Taking disulfiram during treatment or within 2 weeks after the end of treatment. First trimester of pregnancy. Porphyria. Epilepsy. Severe liver dysfunction.
Interaction with other medicinal products and other types of interactions
Associated with metronidazole (due to its absorption).
Alcohol: The interaction of metronidazole with alcohol may cause a reaction similar to that of disulfiram. Alcohol should not be consumed during therapy and for 3 days after the end of the course (see section "Special instructions").
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: central nervous system effects (e.g. psychotic reactions).
Lithium: increased lithium toxicity.
Phenytoin: increases the level of phenytoin in the blood, decreases the level of metronidazole in the blood.
Phenobarbital: decreases the level of metronidazole in the blood.
Fluorouracil: increases blood levels and toxicity of fluorouracil.
Oral anticoagulants: the effect of anticoagulants is enhanced, the risk of bleeding increases (see section "Special warnings and precautions for use").
During treatment with metronidazole, its effect on blood levels of liver enzymes, glucose (hexokinase method), theophylline and procainamide was observed.
Associated with miconazole nitrate (due to the peculiarities of its absorption).
Acenocoumarol, anisindione, dicumarol, phenidione, 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 is reduced.
Cyclosporine: increased risk of cyclosporine toxicity (renal dysfunction, cholestasis, paresthesia).
Fentanyl: increases or prolongs the effects 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: increased plasma concentration or effects of oxybutynin (dry mouth, constipation, headache).
Oxycodone: increases plasma concentrations of oxycodone and decreases its excretion.
Pimozide: increased risk of cardiotoxicity (QT prolongation, ventricular fibrillation, cardiac arrest).
Tolterodine: The bioavailability of tolterodine is increased in individuals with cytochrome P450 2D6 deficiency.
Trimetrexate: increased toxicity of trimetrexate (bone marrow suppression, renal and hepatic dysfunction, and gastric and intestinal ulceration).
Application features
Alcohol
The patient should be warned not to drink alcohol during therapy and for 3 days after the end of the course of treatment, as reactions from the central nervous system similar to the action of disulfiram may occur (see section "Interaction with other medicinal products and other types of interactions").
Long-term use
High doses of the drug and long-term use can cause peripheral neuropathy and seizures.
Simultaneous treatment of sexual partners
Sexual partners of patients with trichomonas vaginitis should also be treated. Sexual partners who are found to have Trichomonas vaginalis should be treated at the same time as the patient.
Renal and hepatic failure
In renal failure, the dose of metronidazole must be reduced.
In severe hepatic insufficiency, the clearance of metronidazole may be altered. Metronidazole may exacerbate symptoms of encephalopathy due to its increased plasma levels. Therefore, metronidazole should be used with caution in patients with hepatic encephalopathy. The daily dose for such patients should be reduced to 1/3.
Application to patients of different age groups
For elderly patients (65 years and older), the recommendations are the same as for other patients.
The drug is not recommended for use in virgin girls and young patients who have not reached puberty.
Concomitant use with oral anticoagulants
Metronidazole may increase plasma levels of bisulfan, which may lead to significant bisulfan toxicity. Prothrombin and INR (international normalized ratio) levels should be monitored more frequently when oral anticoagulants are used concomitantly during metronidazole use and for 8 days after discontinuation.
Other application features
Do not swallow suppositories or administer the drug by any other route of administration.
The suppository base may interact in an undesirable way with rubber or latex, from which contraceptive diaphragms and condoms are made, so their simultaneous use with suppositories is not recommended.
Other intravaginal products (e.g. tampons, douches or spermicides) should not be used concurrently with treatment.
In case of severe vaginal irritation (burning, itching), treatment with Gainex® Forte should be discontinued (see section “Adverse reactions”).
Ability to influence reaction speed when driving vehicles or other mechanisms
Systemic use of metronidazole may affect the ability to drive or operate machinery. Compared to systemic use, the absorption of metronidazole is significantly lower with vaginal administration. There is a possibility of dizziness, ataxia, psychoemotional disorders. In the presence of such symptoms, it is not recommended to drive or operate machinery.
Use during pregnancy or breastfeeding
Pregnancy
Pregnancy – category C.
Since there is insufficient data on the absence of negative effects on the fetus and development of newborns with intravaginal use of suppositories containing metronidazole and miconazole nitrate, women of childbearing age should avoid pregnancy while using the drug Gainex® Forte.
The use of Gainex® Forte in the first trimester of pregnancy is contraindicated.
In the II and III trimesters of pregnancy, the drug should be used only as prescribed by a doctor in cases where the expected benefit to the mother outweighs the potential risk to the fetus.
Breast-feeding.
Breastfeeding should be discontinued during treatment with the drug, as metronidazole passes into breast milk. Breastfeeding can be resumed 1-2 days after the end of treatment.
Fertility
There is no evidence of harmful effects on fertility when metronidazole or miconazole nitrate are used alone.
Method of administration and doses
Adults should use 1 suppository intravaginally in the evening before bedtime for 7 days.
For relapses of the disease or vaginitis resistant to other treatments, the drug should be used in the evening before bedtime, 1 suppository per night for 14 days.
It is not recommended to use Gainex® Forte during menstruation due to a decrease in the effectiveness of the drug and the possibility of some complications during administration.
Vaginal suppositories should be inserted in a lying position, deep into the vagina. If possible, do not assume an upright position for at least half an hour after inserting the suppository. Do not use double doses to make up for a missed dose.
Children
The drug is not recommended for use in children.
Overdose
The drug is intended for vaginal use only. There is no data on overdose of metronidazole when administered vaginally. When administered into the vagina, metronidazole can be absorbed in an amount sufficient to cause systemic effects. When using an excessive number of suppositories, systemic effects associated with metronidazole may occur, but when administered intravaginally, metronidazole will not cause life-threatening symptoms.
If a large amount of the drug accidentally enters the digestive system, an appropriate gastric lavage method should be used if necessary. 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. In case of overdose of metronidazole, the following symptoms are observed: nausea, vomiting, abdominal pain, diarrhea, itching, metallic taste in the mouth, ataxia, vertigo, paresthesia, convulsions, leukopenia, darkening of urine. In case of overdose of miconazole nitrate, the following symptoms are observed: nausea, vomiting, inflammation of the throat and mouth, anorexia, headache, diarrhea.
Metronidazole and its metabolites are well eliminated by hemodialysis.
Adverse reactions
The incidence of systemic side effects is low due to the very low plasma levels of metronidazole after vaginal administration (2-12% of the levels achieved with oral metronidazole). Another active ingredient of the drug, miconazole nitrate, can cause vaginal irritation (burning, itching), as do all other antifungal agents containing imidazole derivatives administered intravaginally (2-6%). In vaginitis, the use of the drug can cause inflammation of the vaginal mucosa. Therefore, burning and itching in the vagina can occur from the beginning to the third day of therapy. These symptoms significantly decrease during treatment. In case of severe irritation or other allergic reactions (rash, angioedema of the face, lips, tongue, larynx and bronchospasm), treatment should be discontinued.
Adverse reactions due to the local action of the active ingredients of the drug Gainex® Forte.
Metronidazole: hypersensitivity reactions (including skin rash), abdominal pain, headache, itching, burning and irritation of the vagina.
Miconazole nitrate: vaginal irritation (burning, itching).
Adverse reactions due to the systemic action of the active ingredients of the drug Gainex® Forte.
Blood and lymphatic system disorders: agranulocytosis, neutropenia, thrombocytopenia, pancytopenia, leukopenia.
On the part of the immune system: hypersensitivity reactions, allergic reactions, angioedema, urticaria, fever, anaphylactic shock.
Nervous system: dizziness, headache, fatigue, weakness, ataxia, convulsions, peripheral neuropathy, aseptic meningitis, encephalopathy* (e.g. confusion, fever, increased sensitivity to light, torticollis, hallucinations, paralysis, visual and movement disorders), subacute cerebellar syndrome* (e.g. ataxia, dysarthria, gait disturbance, nystagmus, tremor).
On the part of the organs of vision: temporary visual disturbances such as diplopia, myopia, blurred vision, decreased visual acuity, changes in color perception, optic neuropathy/neuritis.
Hepatobiliary disorders: increased liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), cholestatic or mixed hepatitis and liver cell (hepatocyte) damage, sometimes with jaundice; cases of liver failure requiring liver transplantation have been reported in patients treated with metronidazole and other antibiotics.
Skin and subcutaneous tissue disorders: rash, including those that may be accompanied by fever, flushing, hyperemia, itching, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, contact dermatitis.
Musculoskeletal and connective tissue disorders: myalgia, arthralgia.
On the part of the kidneys and urinary tract: darkening of urine (due to the metabolism of metronidazole).
Gastrointestinal: anorexia, taste disturbance, inflammation of the oral mucosa, metallic taste in the mouth, coated tongue, stomatitis, glossitis, nausea, vomiting, constipation, epigastric pain, diarrhea, dry mouth, decreased appetite, abdominal pain and cramps.
General disorders and administration site conditions: vaginal discharge, vaginitis, vulvovaginal irritation, pelvic discomfort, thirst, vaginal burning sensation, itching, irritation, local irritation and hypersensitivity, hot flashes, increased body temperature.
* May disappear after stopping the drug.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
7 suppositories in a strip. 1 strip in a cardboard box.
Vacation category
According to the recipe.
Producer
Kusum Healthcare Pvt Ltd.
Location of the manufacturer and its business address
SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India/SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.
