Instructions for use Limenda vaginal suppositories blister + 7 fingertip pads No. 7
Composition
active ingredients: metronidazole; miconazole;
1 suppository contains 750 mg of metronidazole and 200 mg of miconazole nitrate;
excipients: Vitepsol S55.
Dosage form
Vaginal suppositories.
Main physicochemical properties: yellowish-white torpedo-shaped suppositories.
Pharmacotherapeutic group
Antimicrobial and antiseptic agents used in gynecology. Combinations of imidazole derivatives. ATX code G01A F20.
Pharmacological properties
Pharmacodynamics
Limenda is a combined antimicrobial drug, the effect of which is due to metronidazole and miconazole, which are part of its composition.
Miconazole provides antifungal activity, and metronidazole provides antibacterial and antitrichomonas effects of the drug. Miconazole nitrate has a broad spectrum of activity and is particularly effective against pathogenic fungi, including C. albicans. In addition, miconazole nitrate is effective against gram-positive bacteria. Metronidazole is an antibacterial and antiprotozoal agent. It is effective against Gardnerella vaginalis and anaerobic bacteria, including anaerobic streptococci and Trichomonas vaginalis.
Pharmacokinetics
Absorption of miconazole nitrate through the vaginal walls is insignificant (approximately 1.4% of the dose). The bioavailability of metronidazole when administered vaginally is 20% compared to its bioavailability when administered orally. Miconazole nitrate is not detected in the blood plasma when Limenda suppositories are administered vaginally. The equilibrium concentration of metronidazole in the blood plasma is 1.6-7.2 mg/ml. Metronidazole is metabolized in the liver. The hydroxymetabolite is the active substance. The half-life of metronidazole is 6-11 hours. Approximately 20% of the dose is excreted in the urine unchanged.
Indication
For the local treatment of vaginal candidiasis, bacterial and trichomonas vaginitis and vaginitis caused by mixed infections.
Contraindication
Hypersensitivity to any of the active ingredients of the drug or to their derivatives, porphyria, epilepsy, severe liver dysfunction.
Interaction with other medicinal products and other types of interactions
Due to the absorption of metronidazole, drug interaction reactions may occur when used simultaneously with certain substances and medications:
Alcohol: The interaction of metronidazole with alcohol may cause a reaction similar to the interaction with disulfiram.
Oral anticoagulants: anticoagulant effect may be enhanced.
Phenytoin: phenytoin blood concentration may increase, metronidazole blood concentration may decrease.
Phenobarbital: decreased concentration of metronidazole in the blood.
Disulfiram: Central nervous system effects (psychotic reactions) may occur.
Cimetidine: may increase the blood concentration of metronidazole and increase the risk of neurotic symptoms.
Lithium: Increased toxic effects of lithium may occur.
Astemizole and terfenadine: metronidazole and miconazole slow down the metabolism of these drugs and increase their concentration in blood plasma.
Effects on blood concentrations of liver enzymes, glucose (hexokinase method), theophylline, and procainamide were also observed.
Acenocoumarol, anisindione, dicumarol, phenindione, phenprocoumon, warfarin: increase the risk of bleeding.
Amiodarone: increased risk of cardiotoxicity (QT prolongation, torsades de pointes, cardiac arrest).
Fluorouracil: increased blood levels of fluorouracil and increased toxicity. Carbamazepine: increased blood concentrations of carbamazepine.
Cyclosporine: increased toxicity of cyclosporine.
Metronidazole may increase busulfan plasma levels, which may lead to significant busulfan toxicity. More frequent monitoring of prothrombin time and INR (international normalized ratio) is necessary when oral anticoagulants are used concomitantly. Adjustment of the oral anticoagulant dose is recommended during metronidazole use and for 8 days after its discontinuation.
Due to the absorption of miconazole nitrate, drug interaction reactions may occur when used simultaneously with certain substances and medications.
Acenocoumarol, anisindione, dicumarol, phenindione, phenprocoumon, warfarin: increased risk of bleeding.
Astemizole, cisapride and terfenadine: miconazole slows down the metabolism of these drugs and increases their plasma concentrations.
Cyclosporine: increased risk of cyclosporine toxicity (renal dysfunction, cholestasis, paresthesia).
Fentanyl: potentiation or prolongation of the effects of opioids (central nervous system depression, respiratory depression).
Phenytoin and fosphenytoin: increased risk of phenytoin toxicity (ataxia, hyperreflexia, nystagmus, tremor).
Carbamazepine: decreased metabolism of carbamazepine.
Glimepiride: increased hypoglycemic effect.
Oxybutynin: increased plasma concentrations of oxybutynin and increased effects (dry mouth, constipation, headache).
Oxycodone: increased plasma concentrations of oxycodone and decreased clearance.
Tolterodine: increased bioavailability of tolterodine in individuals with cytochrome P450 2D6 activity deficiency.
Trimetrexate: increased toxicity of trimetrexate (bone marrow suppression, renal and hepatic dysfunction, gastrointestinal ulcers).
Application features
The patient should be warned not to drink alcohol during therapy and for 2 days after the end of the course of treatment due to the possibility of central nervous system reactions similar to the effects of disulfiram.
High doses of the drug and long-term use can cause peripheral neuropathy and seizures.
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.
Sexual partners of patients with trichomonas vaginitis should also undergo treatment.
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.
For elderly patients (over 65 years of age): same recommendations as for other patients.
The drug is not recommended for use in virgin girls.
Do not swallow suppositories or apply the drug by any route other than vaginally.
Use during pregnancy or breastfeeding
Use in the first trimester of pregnancy is contraindicated. After the first trimester of pregnancy, Limenda may be used only after weighing the risk/benefit ratio, as prescribed and under the supervision of a physician.
Breastfeeding should be discontinued during treatment with metronidazole, as metronidazole passes into breast milk. Breastfeeding can be resumed 1-2 days after the end of treatment.
The ability to influence the speed of reactions when driving vehicles or other mechanisms
Compared to systemic use, vaginal administration results in significantly lower absorption of metronidazole. Dizziness, ataxia, and psychoemotional disorders may occur. In the presence of such symptoms, it is not recommended to drive or operate other machinery.
Method of administration and doses
1 vaginal suppository should be inserted deep into the vagina at night for 7 days.
For relapses of the disease or vaginitis resistant to other treatment, the drug Limenda should be used for 14 days.
Vaginal suppositories should be inserted deep into the vagina using the disposable fingers included in the package.
For elderly patients (over 65 years of age), dosage adjustment is not required.
Children
The drug is not recommended for use in children.
Overdose
There are no data on overdose of metronidazole when administered vaginally in humans. When administered into the vagina, metronidazole may be absorbed in sufficient quantities to cause systemic effects.
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. The following symptoms are observed in case of an overdose of metronidazole: nausea, vomiting, abdominal pain, diarrhea, itching, metallic taste in the mouth, ataxia, vertigo, paresthesia, convulsions, leukopenia, darkening of urine.
In case of an overdose of miconazole nitrate, the following symptoms are observed: nausea, vomiting, inflammation of the throat and mouth, anorexia, headache, diarrhea.
Adverse reactions
The incidence of systemic adverse reactions is low due to the very low plasma levels of metronidazole after vaginal administration (2-12% compared to oral administration). Miconazole nitrate may cause vaginal irritation (burning, itching), as do all other antifungal agents containing imidazole derivatives administered vaginally (2-6%). These complaints quickly disappear with continued treatment. In case of severe irritation, treatment should be discontinued.
Adverse reactions that have been reported with systemic use of the active ingredients of the drug are listed below.
Blood and lymphatic system disorders
Frequency unknown: leukopenia.
Blood and immune system disorders
Frequency unknown: hypersensitivity reactions.
Mental disorders
Uncommon: depression.
Rare: mental disorders.
Blood and nervous system disorders
Rare: ataxia, convulsions, dizziness, headache.
Frequency unknown: fatigue or weakness, peripheral neuropathy due to active and/or prolonged metronidazole therapy.
Blood and gastrointestinal tract
Frequency unknown: taste changes, metallic taste, nausea, vomiting, constipation, dry mouth, diarrhea, loss of appetite, abdominal pain or cramps.
General and injection site conditions
Common: vaginitis, vulvovaginal irritation, pelvic discomfort.
Uncommon: feeling thirsty.
Rare: vaginal burning sensation, itching, irritation, rash.
Frequency unknown: local irritation and hypersensitivity, contact dermatitis.
Side effects such as:
inflammation of the oral mucosa, stomatitis, glossitis, pancreatitis, flushing; rashes, which may be accompanied by fever; urticaria, angioedema, anaphylactic shock; pustular rash; encephalopathy (e.g. confusion) and subacute cerebellar syndrome (e.g. ataxia, dysarthria, gait disturbance, nystagmus, tremor), which may resolve after discontinuation of the drug, aseptic meningitis; psychotic disorders, confusion, hallucinations; diplopia, myopia, blurred vision, decreased visual acuity, changes in color perception, optic neuropathy/neuritis; agranulocytosis, neutropenia and thrombocytopenia; increased levels of liver enzymes (ACT, ALT, alkaline phosphatase), cholestatic or mixed hepatitis and hepatocellular liver damage, sometimes with jaundice; Cases of liver failure requiring liver transplantation have been reported in patients treated with metronidazole and other antibiotics; fever.
These side effects are rare because the concentration of metronidazole in the blood is much lower when administered vaginally.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in a place protected from light and out of the reach of children.
Packaging
7 vaginal suppositories in a blister; 1 blister complete with 7 disposable fingers or 2 blisters complete with 14 disposable fingers in a cardboard box.
Vacation category
According to the recipe.
Producer
Zentiva Saglyk Urunleri San. in Tij. A.Sh./Zentiva Saglik Urunleri San. ve Tic. AS
Location of the manufacturer and its business address
Kucukkaristiran Mahallesi, Merkez Sokak, No: 223/A 39780 Buyukkaristiran/Luleburgaz-Kirklareli, Turkey
Applicant
ROTAPHARM ILACLARI LTD. STI., Turkey/ROTAPHARM ILACLARI LTD. STI., Turkey.
