Instructions for use Trichopol tablets 250 mg blister No. 20
Composition
active ingredient: metronidazole;
1 tablet contains metronidazole 250 mg;
excipients: potato starch, gelatin, glucose solution, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white with a yellow tint tablets, turn yellow under the influence of light, round, flat, with a dividing line on one side.
Pharmacotherapeutic group
Antibacterials for systemic use. Imidazole derivatives. ATX code J01X D01.
Pharmacological properties
Pharmacodynamics.
Metronidazole belongs to the nitro-5-imidazoles and has a broad spectrum of activity. The cut-off concentrations that allow differentiation of susceptible strains (S) from strains with moderate sensitivity, and strains with moderate sensitivity from resistant strains (R), are as follows: S ≤ 4 mg/l and R > 4 mg/l.
The prevalence of acquired resistance in certain species of microorganisms may vary geographically and over time. Therefore, it is useful to have information on the local prevalence of resistance, especially when treating severe infections. These data are only a general guide to the likelihood of susceptibility of a particular bacterial strain to this antibiotic.
Sensitive to the drug: Peptostreptococcus spp., Clostridium spp., Bacteroides spp., Fusobacterium spp., Porphyromonas, Bilophila, Helicobacter pylori, Prevotella spp., Veilonella. Metronidazole inhibits the development of protozoa - Trichomonas vaginalis, Giardia intestinalis (Lamblia intestinalis), Entamoeba histolytica. Unstable sensitive to the drug: Bifidobacterium spp., Eubacterium spp. Insensitive strains of microorganisms: Propionibacterium, Actinomyces, Mobiluncus.
Pharmacokinetics.
Absorption: Metronidazole is rapidly and almost completely absorbed after oral administration (at least 80% per hour). Peak serum concentrations achieved after oral administration are similar to those achieved after intravenous administration of equivalent doses.
Oral bioavailability is 100%. It is not significantly reduced by concomitant food intake.
Distribution: Approximately 1 hour after a single 500 mg dose, the mean peak plasma concentration is 10 μg/mL. After 3 hours, the mean plasma concentration is 13.5 μg/mL.
The half-life is 8-10 hours, binding to blood proteins is insignificant - no more than 20%. The apparent volume of distribution is high (approximately 40 liters, i.e. 0.65 liters/kg).
Distribution is rapid and extensive, with concentrations reaching levels close to those in plasma, lungs, kidneys, liver, skin, bile, cerebrospinal fluid, saliva, seminal fluid, and vaginal secretions.
Metronidazole crosses the placental barrier and enters breast milk.
Biotransformation. Metronidazole is metabolized by oxidation in the liver. Two metabolites are formed:
- the main "alcohol" metabolite, which provides approximately 30% of the antibacterial activity of metronidazole against anaerobic bacteria, has a half-life of approximately 11 hours;
- an "acidic" metabolite, which is present in smaller quantities and provides approximately 5% of the antibacterial activity of metronidazole.
Excretion. Significant concentration in the liver and bile; low concentration in the colon; insignificant elimination with feces. Excretion of the drug is carried out by 35-65% by the kidneys (in the form of metronidazole and oxidized metabolites).
Indication
Infections caused by microorganisms sensitive to the drug: amebiasis; urogenital trichomoniasis; nonspecific vaginitis; giardiasis; surgical infections caused by anaerobic microorganisms sensitive to metronidazole; replacement of intravenous treatment of infections caused by anaerobic microorganisms sensitive to metronidazole.
Contraindication
Hypersensitivity to metronidazole, imidazole derivatives or other components of the drug.
First trimester of pregnancy.
Simultaneous use of the drug in combination with disulfiram or alcohol.
Children under 6 years of age (due to the dosage form).
Cocaine (see section "Adverse reactions").
Interaction with other medicinal products and other types of interactions
Combinations that are not recommended.
Alcohol. Metronidazole increases the toxic effects of alcohol. Drinking alcohol while taking metronidazole can cause side effects such as hot flashes, sweating, headache, nausea, vomiting, and abdominal pain. Alcohol should be avoided during treatment with metronidazole and for at least 48 hours after the end of treatment, as the Antabuse effect (hot flashes, erythema, vomiting, tachycardia) may develop.
Disulfiram: There is a risk of acute psychotic episodes or confusion in patients taking metronidazole and disulfiram concomitantly. Metronidazole should not be used for 2 weeks after disulfiram discontinuation.
Busulfan: When using busulfan in high doses: a doubling of busulfan concentrations in patients receiving metronidazole, which may lead to severe busulfan toxicity.
Oral anticoagulant therapy. In patients receiving antibacterial therapy, an increase in the effects of oral anticoagulants and an increased risk of hemorrhagic complications due to a slowdown in their metabolism in the liver have been reported. Risk factors include the severity of the infection or inflammation, the patient's age and general health. In these circumstances, it is difficult to determine to what extent the MHC imbalance is caused by the infection itself or by its treatment. However, some classes of antibiotics are more likely to be involved in this effect, especially fluoroquinolones, macrolides, cyclines, cotrimoxazole and some cephalosporins. More frequent monitoring of prothrombin levels and monitoring of MHC (international normalized ratio) levels is necessary. It is recommended that the oral anticoagulant dose be adjusted during metronidazole treatment and for 8 days after its discontinuation.
Trichopol® does not interact with heparin.
Fluorouracil (and, by extrapolation, tegafur and capecitabine). Increased toxicity of fluorouracil due to decreased clearance.
Lithium: Increased blood lithium levels, which may be toxic, with signs of lithium overdose. Blood lithium levels should be monitored closely and dosage adjustments may be necessary. Lithium retention, with possible renal damage, has been reported in patients receiving lithium and metronidazole concomitantly; lithium therapy should be discontinued or reduced before metronidazole is administered.
Cyclosporine: Patients receiving cyclosporine are at risk of increased serum cyclosporine levels. Cyclosporine and plasma creatinine levels should be monitored if concomitant use of cyclosporine and metronidazole is necessary.
Phenytoin and phenobarbital: Drugs that activate liver microsomal enzymes, such as phenytoin and phenobarbital, accelerate the elimination of metronidazole by reducing the half-life of metronidazole to 3 hours, which leads to a decrease in its serum concentration.
Effect on paraclinical tests. It should be remembered that metronidazole is able to immobilize treponemas, which causes a false positive result in the Nelson test.
Cimetidine: Drugs that reduce liver enzyme activity (e.g. cimetidine) may prolong the half-life of metronidazole.
Terfenadine and astemizole. Metronidazole may interact with terfenadine and astemizole and cause adverse reactions from the cardiovascular system (prolongation of the QT interval on the ECG, arrhythmias, etc.).
Enzyme-inducing anticonvulsants: Decreased plasma concentrations of metronidazole due to increased hepatic metabolism by the enzyme inducer. Clinical monitoring is indicated and metronidazole dosage adjustment may be necessary during and after treatment with the inducer.
Rifampicin: Decreased plasma concentrations of metronidazole due to increased hepatic metabolism by rifampicin. Clinical monitoring is indicated and metronidazole dosage adjustment may be necessary during and after rifampicin treatment.
Metronidazole belongs to the cytochrome P450 3A4 (CYP 3A4) inhibitors, therefore it may reduce the metabolism of drugs metabolized by this enzyme.
Metronidazole may interact with drugs that prolong the QT interval, such as: amiodarone, ciprofloxacin, levofloxacin, sparfloxacin, erythromycin, clarithromycin, mefloquine, ketoconazole, cisapride, tamoxifen, donepezil, haloperidol, pimozide, thioridazine, mesiridazine.
Application features
Hypersensitivity/skin and skin disorders. Allergic reactions, including anaphylactic shock, which may be life-threatening, may occur (see section 4.8). In such cases, metronidazole treatment should be discontinued and appropriate therapy should be initiated.
If at the beginning of treatment the patient develops generalized erythema and pustular rashes accompanied by fever, acute generalized exanthematous pustulosis should be suspected (see section "Adverse reactions"); in the event of such a reaction, treatment with the drug should be discontinued, and further use of metronidazole, both alone and in combination with other drugs, is contraindicated.
Severe skin reactions, some of which were fatal, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN or Lyell's syndrome), and acute generalized exanthematous pustulosis (AGEP) have been reported with the use of metronidazole. Patients should be informed of the signs and symptoms of these conditions and should be closely monitored for any skin changes.
If any signs or symptoms of SJS, TEN (e.g. progressive skin rash, often with blistering or mucosal involvement) or GHEP occur (see section 4.8), treatment should be discontinued and any further use of metronidazole, either alone or in combination with other drugs, is contraindicated.
Cases of encephalopathy have been reported during post-marketing surveillance. In addition, cases of MRI changes associated with encephalopathy have been observed (see section 4.8). The most common sites of involvement are the cerebellum (particularly the dentate nucleus) and the corpus callosum. In most cases, encephalopathy and MRI changes resolved after discontinuation of treatment. Very rare cases of death have been reported.
Patients should be monitored for possible signs of encephalopathy or for worsening symptoms in patients with central nervous system disorders.
In the event of aseptic meningitis developing during treatment with the drug, re-administration of metronidazole is not recommended, and in patients with a serious infectious disease, a benefit/risk assessment should be performed.
Peripheral nervous system disorders: Patients should be monitored for signs of peripheral neuropathy, especially during long-term treatment or in the presence of severe, chronic, or progressive peripheral neurological disorders.
Psychiatric disorders: After receiving the first dose of the drug, patients may experience psychotic reactions, including self-destructive behavior (in isolated cases, suicidal thoughts or suicide attempts are possible), especially if they have a history of psychiatric disorders (see section "Adverse reactions"). If this occurs, metronidazole should be discontinued, a doctor should be informed and appropriate therapeutic measures should be taken immediately.
Hematological effects.
If there is a history of hematological disorders or treatment is carried out with high doses of metronidazole and/or for a long time, regular monitoring of the white blood cell count is recommended.
If leukopenia develops, it is important to carefully weigh the expected benefits of continued treatment against the potential risks. In the case of long-term treatment, one should be monitored for signs of side effects such as central and peripheral neuropathy (paresthesia, ataxia, dizziness or convulsive crisis).
Patients who have changes in blood parameters before and after treatment with metronidazole should be under medical supervision if metronidazole needs to be re-administered.
Pediatric patients. Tablets are contraindicated in children under 6 years of age due to the risk of aspiration. Other metronidazole formulations are available for young children.
Interaction with other drugs. The simultaneous use of metronidazole and alcohol is contraindicated due to the possibility of a disulfiram-like reaction (Antabuse effect) (hot flashes, erythema, vomiting, tachycardia) (see section "Interaction with other drugs and other types of interactions").
The simultaneous use of metronidazole and busulfan is not recommended (see section “Interaction with other medicinal products and other types of interactions”).
The simultaneous use of metronidazole and disulfiram is not recommended (see section "Interaction with other medicinal products and other types of interactions").
Effect on laboratory test results: Metronidazole may immobilize treponema, thereby causing false-positive results in the Nelson test.
Cases of severe hepatotoxicity/acute hepatic failure, including fatalities, have been reported shortly after initiation of treatment in patients with Cockayne syndrome with systemic metronidazole-containing medicinal products. In view of the above, metronidazole should be used in this patient population only after careful risk/benefit assessment and only if no alternative treatment is available. Liver function tests should be performed immediately before, during and after treatment until liver function tests return to normal or to baseline values. If significant increases in liver function tests occur during treatment, this medicinal product should be discontinued.
Patients with Cockayne syndrome should be advised to immediately report to their physician any symptoms that could potentially be caused by liver damage and to discontinue metronidazole in such cases.
Metronidazole may alter some laboratory test values (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase, triglycerides, glucose).
There is a possibility of persistence of gonococcal infection after elimination of Trichomonas vaginalis.
In the presence of renal failure, the half-life of metronidazole does not change. Accordingly, there is no need to reduce the dose of metronidazole. At the same time, metabolites of metronidazole are retained in the body of such patients. The clinical significance of this phenomenon is currently unknown.
In patients undergoing hemodialysis, metronidazole and its metabolites are effectively removed from the bloodstream within 8 hours of the procedure. Accordingly, a repeat dose of metronidazole should be administered immediately after completion of the hemodialysis procedure.
Metronidazole is metabolized mainly by oxidation in the liver. In the presence of severe hepatic insufficiency, a significant decrease in metronidazole clearance may be observed. In patients with hepatic encephalopathy, significant accumulation of metronidazole is possible. High plasma concentrations of metronidazole resulting from such accumulation may partially provide symptoms of encephalopathy. Therefore, Trichopol® should be used with caution in patients with hepatic encephalopathy. The daily dose of the drug should be reduced to one third of the usual dose; this reduced dose can be taken once a day.
The drug is not considered to pose any carcinogenic risk to humans, although a carcinogenic effect has been observed in some strains of mice. However, this effect has not been observed in rats or hamsters.
Due to the non-obvious risk of mutagenicity, the appropriateness of long-term use of metronidazole should be carefully assessed.
Metronidazole should be administered with caution to patients who have taken corticosteroids and are prone to edema.
After using metronidazole, candidiasis of the oral cavity, vagina, and gastrointestinal tract may develop, which requires appropriate treatment.
Patients should be warned that metronidazole may cause urine to turn dark (due to the presence of metronidazole metabolites).
Each tablet contains 6.6 g of glucose. It should be used with caution in patients with diabetes.
Use during pregnancy or breastfeeding
Pregnancy.
Data on the use of metronidazole are limited. Metronidazole crosses the placental barrier. Use is contraindicated in the first trimester of pregnancy. The drug can be prescribed during the second and third trimesters only if necessary, when the benefits of using the drug outweigh the potential risks.
Breast-feeding.
Metronidazole passes into breast milk. Trichopol should not be used during breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
Persons who drive vehicles and operate machinery should be aware of the possible occurrence of confusion, dizziness, hallucinations, and seizures while taking this drug and should refrain from driving vehicles and operating machinery during treatment.
Method of administration and doses
For amebiasis, take Trichopol® for 7 days. Adults: 1.5 g per day (in 3 doses); children (with a body weight ≥ 20 kg): 30–40 mg/kg per day, divided into 3 doses.
In the case of a liver abscess due to amebiasis, drainage or aspiration of pus is performed simultaneously with metronidazole therapy.
Treat giardiasis for 5 days. Adults should be prescribed 750–1000 mg of Trichopol® per day; children aged 10–15 years – 500 mg per day in two divided doses.
For trichomoniasis in women (urethritis and vaginitis caused by Trichomonas), Trichopol® should be prescribed for a course of treatment for 10 days, combining 1 tablet 2 times a day and 1 vaginal suppository (500 mg) per day. The sexual partner should be treated at the same time, regardless of the presence or absence of clinical signs of Trichomonas infection, even if the result of laboratory tests is negative.
For trichomoniasis in men (urethritis caused by Trichomonas), Trichopol® should be prescribed for a course of treatment for 10 days: 1 tablet 2 times a day.
In exceptional cases, it may be necessary to increase the daily dose to 0.750 g or 1 g.
For nonspecific vaginitis, prescribe 500 mg of Trichopol® 2 times a day for 7 days. The partner should be treated at the same time.
For the treatment of anaerobic infections (first-line therapy or replacement therapy), adults should be prescribed 1.0–1.5 g of Trichopol® per day, and children over 6 years of age (with a body weight ≥ 16 kg) should be prescribed 20–30 mg/kg per day.
Children
The drug in the form of 250 mg tablets can be used in children aged 6 years and older.
Overdose
The lethal dose of metronidazole for humans is unknown. In isolated cases, symptoms of neurotoxicity have been observed after oral administration of metronidazole at doses of 6-10.4 mg per day for 5-7 days, including convulsions and peripheral neuropathy.
There have been reports of a single dose of up to 15 g taken during suicide attempts and accidental overdose. Symptoms included vomiting, ataxia and mild disorientation.
There is no specific antidote. In case of significant overdose, symptomatic therapy should be carried out.
Side effects
From the gastrointestinal tract:
epigastric pain, nausea, vomiting, diarrhea;
inflammation of the oral mucosa with a feeling of dryness, stomatitis, taste disorders, metallic taste in the mouth, anorexia;
cases of pancreatitis that are reversible;
discoloration or change in appearance of the tongue (mycosis).
On the part of the skin and its derivatives:
prolonged hyperemia, itching of the skin, hot flashes, rashes (in rare cases - pustular rash); sometimes - febrile manifestations;
urticaria, angioedema, exceptional cases of anaphylactic shock (see section "Special warnings and precautions for use");
Stevens–Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, fixed toxicoderma.
From the nervous system:
peripheral sensory neuropathy;
headache;
dizziness;
confusion of consciousness;
cramps;
transient epileptic seizures;
ataxia, fever, drowsiness.
subacute cerebellar syndrome (ataxia, dysarthria, gait disturbance, nystagmus, tremor), which may resolve after discontinuation of the drug (see section "Special instructions for use");
encephalopathy (e.g. fever, headache, sensitivity to light, stiff neck, hallucinations, paralysis, visual and motor disturbances), which may be accompanied by MRI changes, which usually disappear after discontinuation of treatment with the drug. Very rare cases of death have been reported (see section "Special warnings and precautions for use");
aseptic meningitis (see section "Special instructions").
On the part of the organs of vision:
temporary visual impairments, such as diplopia, myopia, blurred vision, decreased visual acuity, changes in color vision;
neuropathy/optic neuritis.
From the psyche:
hallucinations;
psychotic reactions with paranoia and/or delirium, which in some cases may be accompanied by suicidal thoughts or suicide attempts (see section "Special warnings and precautions for use");
depressed mood.
Blood and lymphatic system disorders:
in rare cases - agranulocytosis, neutropenia, thrombocytopenia, pancytopenia, leukopenia.
From the hepatobiliary system:
increased activity of liver enzymes (AST, 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 in combination with other antibiotics;
Cases of severe hepatotoxicity/acute hepatic failure, including fatal outcomes, have been reported shortly after initiation of treatment with systemic metronidazole-containing products in patients with Cockayne syndrome (see section 4.3).
On the part of the musculoskeletal system:
arthralgia, myalgia.
From the reproductive system:
vaginal pain, candidiasis.
Other: During treatment, urine may become reddish-brown in color, which is due to the presence of water-soluble pigments that are a product of metronidazole metabolism.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
10 tablets in a blister; 2 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Pharmaceutical Works «Polpharma» SA, Poland.
Location of the manufacturer and its business address
19, Pelplinska Str., 83-200 Starogard Gdanski, Poland.
