Trichopol (Tablets) Instructions for Use

ATC Code

J01XD01 (Metronidazole)

Active Substance

Metronidazole (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antiprotozoal drug with antibacterial activity

Pharmacotherapeutic Group

Systemic antibacterial agents; other antibacterial agents; imidazole derivatives

Pharmacological Action

An antiprotozoal drug with antibacterial activity, a derivative of 5-nitroimidazole. The mechanism of action involves the biochemical reduction of the 5-nitro group of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group of metronidazole interacts with the DNA of the microbial cell, inhibiting the synthesis of their nucleic acids, which leads to the death of the microorganisms.

Metronidazole is active againstTrichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp.; as well as obligate anaerobesBacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella spp. (Prevotella bivia, Prevotella buccae, Prevotella disiens); some gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.). The MIC for these strains is 0.125-6.25 µg/ml.

In combination with amoxicillin, it is active against Helicobacter pylori (amoxicillin suppresses the development of resistance to metronidazole).

Metronidazole does not have a bactericidal effect against most bacteria and facultative anaerobes, fungi, and viruses. In the presence of mixed flora (aerobes and anaerobes), Metronidazole exhibits synergism with antibiotics effective against common aerobes.

Metronidazole increases the sensitivity of tumors to radiation, causes sensitization to ethanol (disulfiram-like effect), and stimulates reparative processes.

Pharmacokinetics

Absorption

After oral administration, Metronidazole is rapidly and almost completely absorbed from the gastrointestinal tract. Bioavailability is at least 80%. C_max of metronidazole in blood plasma is reached in 1-3 hours. Food intake reduces the rate of absorption and C_max of metronidazole in blood serum.

Distribution

The binding of metronidazole to plasma proteins is less than 20%.

Metronidazole penetrates into most tissues and body fluids, including the lungs, kidneys, liver, skin, cerebrospinal fluid, brain, bile, saliva, amniotic fluid, abscess cavities, vaginal secretions, seminal fluid, breast milk, crosses the blood-brain barrier and the placental barrier. V_d in adults is about 0.55 L/kg, in newborns – 0.54-0.81 L/kg.

Metabolism

About 30-60% of metronidazole is metabolized in the liver by hydroxylation, oxidation, and conjugation with glucuronic acid. The main metabolite (2-hydroxymetronidazole) also has antiprotozoal and antibacterial activity.

Excretion

T_1/2 with normal liver function averages 8 hours (from 6 hours to 12 hours).

Metronidazole is excreted by the kidneys – 60-80% (20% unchanged), through the intestines – 6-15%. The renal clearance of metronidazole is 10.2 ml/min.

Pharmacokinetics in special clinical cases

T_1/2 in alcoholic liver disease is 18 hours (from 10 hours to 29 hours); in newborns born at 28-30 weeks of gestation – about 75 hours; at 32-35 weeks – 35 hours, at 36-40 weeks – 25 hours, respectively.

Metronidazole and its main metabolites are rapidly removed from the blood during hemodialysis (T_1/2 decreases to 2.6 hours). During peritoneal dialysis, they are excreted in insignificant amounts.

In patients with impaired renal function, accumulation of metronidazole in the blood serum is possible after repeated administration (therefore, in patients with severe renal failure, the frequency of drug administration should be reduced).

In elderly patients, the renal excretion of metronidazole is reduced.

Indications

• Trichomoniasis;
• Bacterial vaginosis;
• All forms of amebiasis (intestinal and extraintestinal diseases, including amoebic liver abscess, amoebic dysentery, as well as asymptomatic amebiasis);
• Giardiasis;
• Periodontal infections (including acute ulcerative gingivitis, acute odontogenic infections);
• Anaerobic bacterial infections (gynecological and abdominal infections, CNS infections, bacteremia, sepsis, endocarditis, bone and joint infections, skin and soft tissue infections, respiratory tract infections) caused by Bacteroides spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp. and other anaerobes sensitive to metronidazole;
• Treatment of Helicobacter pylori infections in gastric or duodenal ulcer in combination with bismuth preparations and an antibiotic, for example, amoxicillin;
• Prophylactic use before surgical interventions on the gastrointestinal tract and reproductive organs.

ICD codes

Dosage Regimen

Tablets

The drug is administered orally, during or after meals; the tablets should be swallowed without chewing.

Trichomoniasis

Adults and children over 10 years are prescribed 250 mg (1 tablet) 3 times/day or 500 mg (2 tablets) 2 times/day for 7 days. Women additionally need to be prescribed Metronidazole in the form of vaginal suppositories or tablets. If necessary, the course of treatment can be repeated. A break of 3-4 weeks should be taken between courses with repeated control laboratory tests.

An alternative treatment regimen is the administration of 750 mg (3 tablets) in the morning and 1250 mg (5 tablets) in the evening or 2000 mg (8 tablets)/day as a single dose. The duration of treatment is 2 days. Treatment is carried out simultaneously for both sexual partners.

Children aged 3 to 7 years are prescribed 125 mg (1/2 tablet) 2 times/day; aged 7 to 10 years – 125 mg (1/2 tablet) 3 times/day. The course of treatment is 7 days.

Bacterial vaginosis

Adults are prescribed 500 mg (2 tablets) 2 times/day for 7 days or 2000 mg (8 tablets)/day as a single dose. Simultaneous treatment of the sexual partner is not required.

Amebiasis

For invasive forms of intestinal amebiasis in susceptible patients (including amoebic dysentery)adults and children over 10 years are prescribed 750 mg (3 tablets) 3 times/day. Children aged 3 to 7 years – 250 mg (1 tablet) 4 times/day; aged 7 to 10 years – 375 mg (1.5 tablets) 3 times/day. The course of treatment is usually 5 days.

For intestinal amebiasis in less susceptible patients and for chronic amoebic hepatitisadults and children over 10 years are prescribed 375 mg (1.5 tablets) 3 times/day. Children aged 3 to 7 years – 125 mg (1/2 tablet) 4 times/day; aged 7 to 10 years – 250 mg (1 tablet) 3 times/day. The duration of the course of treatment is 5-10 days.

For amoebic liver abscess and other forms of extraintestinal amebiasisadults and children over 10 years are prescribed 375 mg (1.5 tablets) 3 times/day. Children aged 3 to 7 years – 125 mg (1/2 tablet) 4 times/day; aged 7 to 10 years – 250 mg (1 tablet) 3 times/day. The course of treatment is 5 days.

For asymptomatic cyst carriageadults and children over 10 years are prescribed 375-750 mg (1.5-3 tablets) 3 times/day. Children aged 3 to 7 years – 125 mg (1/2 tablet) 4 times/day; aged 7 to 10 years – 250 mg (1 tablet) 3 times/day. The duration of the course of treatment is 5-10 days.

Giardiasis

Adults and children over 10 years are prescribed 500 mg (2 tablets) 2 times/day for 5-7 days; or 2000 mg (8 tablets) once/day for 3 days.

Children aged 3 to 7 years – 250-375 mg (1-1.5 tablets) once/day for 5 days, or 500-750 mg (2-3 tablets) once/day for 3 days. Children aged 7 to 10 years – 250 mg (1 tablet) 2 times/day for 5 days, or 1000 mg (4 tablets) once/day for 3 days.

Periodontal infections

For acute ulcerative gingivitisadults and children over 10 years are prescribed 250 mg (1 tablet) 3 times/day. Children aged 3 to 7 years – 125 mg (1/2 tablet) 2 times/day; aged 7 to 10 years – 125 mg (1 tablet) 3 times/day. The duration of the course of treatment is 3 days.

For acute odontogenic infectionsadults and children over 10 years are prescribed 250 mg (1 tablet) 3 times/day for 3-7 days.

Infections caused by anaerobic bacteria

Treatment of anaerobic infections usually begins with intravenous infusions. As soon as possible, treatment should be continued with metronidazole in tablet form.

Adults and children over 10 years are prescribed 500 mg (2 tablets) 3-4 times/day. The duration of treatment should not exceed 7 days.

For children under 10 years, the use of metronidazole in the form of infusion solutions is recommended for the treatment of anaerobic infections.

Eradication of Helicobacter pylori

Prescribe 500 mg (2 tablets) 3 times/day for 7 days (as part of combination therapy, for example, with amoxicillin 2.25 g/day).

Prevention of infections caused by anaerobic bacteria (before surgical operations on the abdominal cavity, in gynecology and obstetrics)

Adults and children over 12 years are prescribed 250-500 mg (1-2 tablets) 3 times/day for 3-4 days before surgery. 1-2 days after the operation (when oral intake is already allowed), 250 mg (1 tablet) 3 times/day is prescribed for 7 days.

In severe renal failure (creatinine clearance less than 10 ml/min), the daily dose of Trichopol should be reduced by half.

Adverse Reactions

From the digestive system: epigastric pain, nausea, vomiting, diarrhea, constipation, intestinal colic, decreased appetite, anorexia, taste disturbance, unpleasant metallic taste in the mouth, dry mouth, glossitis, stomatitis; very rarely – abnormal liver function tests, cholestatic hepatitis, jaundice, pancreatitis.

From the central nervous system: with prolonged use – headache, dizziness, impaired coordination of movements, ataxia, peripheral neuropathy, increased excitability, irritability, depression, sleep disturbance, drowsiness, weakness; in some cases – confusion, hallucinations, convulsions; very rarely – encephalopathy.

From the urinary system: dysuria, cystitis, polyuria, urinary incontinence, red-brown discoloration of urine.

From the reproductive system: vaginal pain.

Allergic reactions: skin rash, itching, urticaria, multiforme exudative erythema, nasal congestion, fever.

From the musculoskeletal system: myalgia, arthralgia.

From the hematopoietic system: leukopenia; rarely – agranulocytosis, neutropenia, thrombocytopenia, pancytopenia.

Other: flattening of the T wave on ECG; extremely rarely – ototoxicity; pustular rash.

Contraindications

• Leukopenia (including history);
• Organic lesions of the central nervous system (including epilepsy);
• Hepatic insufficiency (in case of prescribing the drug in high doses);
• First trimester of pregnancy;
• Lactation period (breastfeeding);
• Children under 3 years of age;
• Hypersensitivity to metronidazole or other nitroimidazole derivatives, as well as to any other component of the drug.

Use with caution in patients with renal and/or hepatic insufficiency, in the second and third trimesters of pregnancy.

Use in Pregnancy and Lactation

Metronidazole crosses the placental barrier, therefore Trichopol^® is contraindicated for use in the first trimester of pregnancy. The use of the drug in the second and third trimesters is possible only in cases where the intended benefit to the mother outweighs the potential risk to the fetus.

Since Metronidazole is excreted in breast milk, reaching concentrations close to those in blood plasma, if it is necessary to use Trichopol during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

Trichopol^® should be prescribed with caution to patients with severe hepatic insufficiency, because as a result of slowed metabolism, the concentration of metronidazole and its metabolites in plasma increases.

Use in Renal Impairment

The drug should be prescribed with caution to patients with renal insufficiency.

In severe renal failure (creatinine clearance less than 10 ml/min), the daily dose of Trichopol should be reduced by half.

Pediatric Use

The drug is contraindicated for use in children under 3 years of age.

In combination with amoxicillin, Trichopol^® is not recommended for use in children and adolescents under 18 years of age.

Geriatric Use

In elderly patients, the renal excretion of metronidazole is reduced.

Special Precautions

Trichopol^® should be prescribed with caution to patients with severe hepatic insufficiency, because as a result of slowed metabolism, the concentration of metronidazole and its metabolites in plasma increases.

Due to slowed excretion, caution should be exercised when choosing the dose of metronidazole in patients with renal insufficiency.

Caution is required when prescribing Trichopol to patients with suppressed bone marrow hematopoiesis and CNS functions, as well as to elderly patients. The appearance of ataxia, dizziness, and any other deterioration in the neurological status of patients requires discontinuation of treatment.

During long-term therapy with metronidazole (more than 10 days), the peripheral blood picture and liver function should be monitored.

In case of leukopenia, the possibility of continuing treatment depends on the risk of developing an infectious process.

The use of metronidazole should be avoided in patients with porphyria.

Trichopol^® may cause immobilization of treponemes, leading to a false-positive Nelson test.

When treating trichomonal vaginitis in women and trichomonal urethritis in men, it is necessary to refrain from sexual activity. Simultaneous treatment of sexual partners is mandatory. After therapy for trichomoniasis, follow-up tests should be performed over three consecutive cycles before and after menstruation.

After treatment of giardiasis, if symptoms persist, three stool tests should be performed after 3-4 weeks at intervals of several days (in some successfully treated patients, lactose intolerance caused by the invasion may persist for several weeks or months, resembling the symptoms of giardiasis).

Patients must refrain from consuming alcohol during metronidazole therapy and for at least 48 hours after completion of treatment due to the possibility of developing disulfiram-like reactions: cramping abdominal pain, nausea, vomiting, headache, sudden flushing of the face.

During treatment with metronidazole, urine may turn dark or reddish-brown due to the presence of water-soluble pigments.

Use in Pediatrics

In combination with amoxicillin, Trichopol^® is not recommended for use in children and adolescents under 18 years of age.

Effect on the Ability to Drive Vehicles and Operate Machinery

When taking the drug, potentially hazardous activities requiring increased concentration and speed of psychomotor reactions should be avoided, especially driving vehicles and operating machinery.

Overdose

Symptoms increased side effects, mainly nausea, vomiting, and dizziness; in more severe cases, ataxia, paresthesia, and seizures are possible. The lethal dose for humans is unknown.

Treatment symptomatic and supportive therapy should be performed. There is no specific antidote.

Drug Interactions

Metronidazole enhances the effect of warfarin and other coumarin anticoagulants (with this combination, a reduction in the doses of both drugs is required).

Similar to disulfiram, Metronidazole causes ethanol intolerance. Concurrent use of Trichopol with disulfiram may lead to the development of various neurological symptoms (the interval between the use of these drugs should be at least 2 weeks).

Cimetidine inhibits the metabolism of metronidazole, which may lead to an increase in its plasma concentration and an increased risk of adverse reactions.

Concomitant administration of drugs that stimulate the activity of liver microsomal enzymes (phenobarbital, phenytoin) may accelerate the elimination of metronidazole, leading to a decrease in its plasma concentration.

In patients receiving long-term treatment with high doses of lithium preparations, metronidazole intake may lead to an increase in plasma lithium concentration and the development of symptoms of intoxication.

It is not recommended to combine Metronidazole with non-depolarizing muscle relaxants (vecuronium bromide).

With combined use of metronidazole and cyclosporine, an increase in the plasma concentration of cyclosporine may be observed.

Metronidazole reduces the clearance of fluorouracil, which may increase the toxicity of the latter.

Sulfonamides enhance the antimicrobial effect of metronidazole.

Storage Conditions

The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life is 5 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.