Trichobrol (Tablets) Instructions for Use

Marketing Authorization Holder

Bryntsalov-A, JSC (Russia)

ATC Code

J01XD01 (Metronidazole)

Active Substance

Metronidazole (Rec.INN registered by WHO)

Dosage Form

Trichobrol

Tablets 250 mg: 10, 20, 40, or 60 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blister packs (1) – cardboard packs.
10 pcs. – blister packs (2) – cardboard packs.
10 pcs. – blister packs (4) – cardboard packs.
10 pcs. – non-blister contour packs (4) – cardboard packs.
10 pcs. – non-blister contour packs (1) – cardboard packs.
10 pcs. – non-blister contour packs (2) – cardboard packs.
20 pcs. – jars (1) – cardboard packs.
20 pcs. – bottles (1) – cardboard packs.
20 pcs. – plastic containers (1) – cardboard packs.
40 pcs. – plastic containers (1) – cardboard packs.
40 pcs. – jars (1) – cardboard packs.
40 pcs. – bottles (1) – cardboard packs.
60 pcs. – bottles (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
60 pcs. – plastic containers (1) – cardboard packs.

Clinical-Pharmacological Group

Antiprotozoal drug with antibacterial activity

Pharmacotherapeutic Group

Antimicrobial and antiprotozoal agent

Pharmacological Action

An antiprotozoal agent 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 microbial cells, inhibiting the synthesis of nucleic acids, which leads to the death of microorganisms.

Active against Trichomonas vaginalis, Entamoeba hystolitica, as well as gram-negative anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides ovatus, Bacteroides distasonis, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp. and some gram-positive anaerobes (susceptible strains of Eubacterium spp., Clostridium spp., Peptococcus niger, 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).

Aerobic microorganisms and facultative anaerobes are not susceptible to metronidazole, but in the presence of mixed flora (aerobes and anaerobes), Metronidazole acts synergistically with antibiotics effective against common aerobes.

Pharmacokinetics

When taken orally, Metronidazole is rapidly and almost completely absorbed (approximately 80% within 1 hour). Food intake does not affect the absorption of metronidazole. Bioavailability is at least 80%.

After oral administration of metronidazole at a dose of 500 mg, its plasma concentration is 10 µg/ml after 1 hour, 13.5 µg/ml after 3 hours.

Binding to blood proteins is insignificant and does not exceed 10-20%. Metronidazole rapidly penetrates into tissues (lungs, kidneys, liver, skin, bile, cerebrospinal fluid, saliva, seminal fluid, vaginal secretions), breast milk and crosses the placental barrier.

About 30-60% of metronidazole is metabolized by hydroxylation, oxidation and glucuronidation. The main metabolite (2-hydroxymetronidazole) also has antiprotozoal and antimicrobial activity.

40-70% of metronidazole is excreted by the kidneys (unchanged – about 35% of the administered dose). T_1/2 is 8-10 hours.

Indications

Protozoal infections: extraintestinal amebiasis (including amoebic liver abscess), intestinal amebiasis (amoebic dysentery), trichomoniasis; infections caused by Bacteroides spp. (including Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides distasonis, Bacteroides vulgatus): bone and joint infections, CNS infections (including meningitis, brain abscess), bacterial endocarditis, pneumonia, empyema and lung abscess, sepsis; infections caused by Clostridium spp., Peptococcus niger, Peptostreptococcus spp.: abdominal infections (peritonitis, liver abscess), pelvic infections (endometritis, abscess of the fallopian tubes and ovaries, vaginal vault infections); pseudomembranous colitis associated with antibiotic use; gastritis or duodenal ulcer associated with Helicobacter pylori (as part of combination therapy); prevention of postoperative complications (especially after interventions on the colon, pararectal area, appendectomy, and after gynecological operations).

ICD codes

Dosage Regimen

Set the dosage regimen individually based on the indication, clinical situation, and patient age.

Administer orally during or after a meal. Swallow the tablets whole with water.

For intestinal amebiasis, adults take 750 mg three times daily for 5-10 days. Children aged 6-15 years take 30-40 mg/kg/day in three divided doses for 5-10 days.

For amebic liver abscess, adults take 500-750 mg three times daily for 5-10 days. Children aged 6-15 years take 30-40 mg/kg/day in three divided doses for 5-10 days.

For trichomoniasis, adults take 250 mg twice daily for 10 days or a single 2 g dose. Treat sexual partners simultaneously. For children aged 6-15 years, use 30-40 mg/kg/day in two divided doses for 7 days.

For anaerobic bacterial infections, the usual adult dose is 500 mg three times daily. The maximum daily dose should not exceed 4 g.

For pseudomembranous colitis caused by *C. difficile*, adults take 500 mg three times daily for 10-14 days.

For *H. pylori* eradication, use as part of combination therapy. A common regimen is 500 mg two to three times daily for 10-14 days alongside other agents.

For surgical prophylaxis against anaerobic infections, administer 500-750 mg preoperatively and continue postoperatively for up to 7 days.

Adjust the dose in patients with severe hepatic impairment. Do not use in children under 6 years of age.

Complete the full prescribed course of therapy. Do not consume alcohol during treatment and for at least 48 hours after completion.

Adverse Reactions

From the digestive system epigastric pain, nausea, vomiting, diarrhea; inflammation of the oral mucosa (glossitis, stomatitis), taste disorders ( “metallic” taste in the mouth), decreased appetite, anorexia, dry oral mucosa, constipation; pancreatitis (reversible cases); tongue discoloration/ “coated” tongue (due to excessive growth of fungal flora).

From the immune system angioedema, anaphylactic shock.

From the nervous system peripheral sensory neuropathy; headache, seizures, dizziness. Encephalopathy (e.g., confusion) and subacute cerebellar syndrome (impaired coordination and synergy of movements, ataxia, dysarthria, gait disturbances, nystagmus and tremor) have been reported, which are reversible after discontinuation of metronidazole; aseptic meningitis.

From the psyche psychotic disorders, including confusion, hallucinations; depression, insomnia, irritability, increased excitability.

From the organ of vision transient visual disturbances such as diplopia, myopia, blurred vision, decreased visual acuity, impaired color perception; optic neuritis.

From the organ of hearing and labyrinthine disorders hearing impairment/hearing loss (including sensorineural deafness); tinnitus.

From the hematopoietic system agranulocytosis, leukopenia, neutropenia, thrombocytopenia.

From the liver and biliary tract increased activity of liver enzymes (AST and ALT, ALP), development of cholestatic or mixed hepatitis, hepatocellular liver damage, sometimes accompanied by jaundice. In patients treated with metronidazole in combination with other antibiotics, cases of liver failure requiring liver transplantation have been observed.

From the skin and subcutaneous tissues rash, itching, flushing, skin hyperemia, urticaria; pustular skin rash; acute generalized exanthematous pustulosis; fixed drug eruption; Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the urinary system possible brownish-reddish discoloration of urine due to the presence of a water-soluble metabolite of metronidazole in the urine; dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

From laboratory parameters and instrumental studies flattening of the T wave on ECG.

General reactions fever, nasal congestion, arthralgia, weakness.

Contraindications

Hypersensitivity to metronidazole, other nitroimidazole derivatives, imidazoles; organic lesions of the CNS (including epilepsy); leukopenia (including history); hepatic insufficiency (when prescribing the drug in high doses); pregnancy, breastfeeding period; children under 6 years of age.

With caution

Hepatic encephalopathy, acute and chronic diseases of the peripheral and central nervous system (risk of worsening neurological symptoms), renal failure.

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is contraindicated.

Use in Hepatic Impairment

Contraindicated in high doses in hepatic insufficiency. Should be used with caution in hepatic encephalopathy.

Use in Renal Impairment

Should be used with caution in renal failure.

Pediatric Use

Contraindicated in children under 6 years of age.

Special Precautions

Since the simultaneous use of metronidazole with alcohol (ethanol) can have an effect similar to that of disulfiram (skin flushing, flushing, vomiting, tachycardia), patients should be warned not to consume alcoholic beverages or medications containing ethanol during treatment and for at least one day after the end of metronidazole use.

Indications for long-term use of metronidazole should be carefully weighed and, in the absence of strict indications, its long-term use should be avoided. If, in the presence of strict indications, Metronidazole is used for longer than is usually recommended, treatment should be carried out under the control of hematological parameters (especially leukocytes) and adverse reactions such as peripheral or central neuropathy (paresthesia, ataxia, dizziness, seizures), upon the appearance of which treatment should be discontinued.

When treating trichomonal vaginitis in women and trichomonal urethritis in men, it is necessary to refrain from sexual intercourse. Simultaneous treatment of sexual partners is mandatory. Treatment should not be interrupted during menstruation. After therapy for trichomoniasis, control tests should be carried out for 3 consecutive cycles before and after menstruation.

Metronidazole should be used with caution in patients with hepatic encephalopathy, as well as in patients with acute or chronic diseases of the central or peripheral nervous system due to the possible risk of neurological deterioration.

The development of severe hepatotoxicity/acute liver failure (including fatal cases that developed very rapidly after the start of treatment) has been reported in patients with Cockayne syndrome when treated with systemic metronidazole. Metronidazole should be prescribed to this category of patients only after a careful benefit/risk assessment and only in the absence of alternative treatment.

Liver function tests should be performed before starting treatment, during therapy and after its completion until liver function parameters return to normal values, or until baseline values of these parameters are reached. If liver function parameters are significantly exceeded during treatment, then the use of the agent should be discontinued.

Patients with Cockayne syndrome should be advised to immediately report any symptoms of potential liver damage to their doctor and to discontinue metronidazole.

Cases of severe bullous skin reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis or acute generalized exanthematous pustulosis, have been reported after the use of metronidazole. If symptoms or signs of these diseases develop, treatment with the agent should be stopped immediately.

It should be taken into account that Metronidazole can immobilize treponemes, which leads to a false-positive Nelson test.

Long-term use of metronidazole should be carefully justified due to possible mutagenicity and carcinogenicity.

Effect on ability to drive vehicles and mechanisms

During the use of metronidazole, it is advisable to refrain from performing potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Psychotic reactions have been reported in patients receiving Metronidazole and disulfiram simultaneously (the interval between the use of these drugs should be at least 2 weeks).

When used concomitantly with ethanol, disulfiram-like reactions may occur (skin flushing, flushing, vomiting, tachycardia).

When used concomitantly with indirect anticoagulants (warfarin) – enhancement of the anticoagulant effect and an increased risk of bleeding associated with a decrease in the hepatic metabolism of indirect anticoagulants, which may lead to an increase in prothrombin time. In case of simultaneous use of metronidazole and indirect anticoagulants, more frequent monitoring of prothrombin time and, if necessary, adjustment of anticoagulant doses is required.

When metronidazole is used concomitantly with lithium preparations, the plasma concentration of the latter may increase. When used concomitantly, plasma concentrations of lithium, creatinine and electrolytes should be monitored.

When metronidazole is used concomitantly with cyclosporine, the plasma concentration of cyclosporine may increase. If simultaneous use of metronidazole and cyclosporine is necessary, plasma concentrations of cyclosporine and creatinine should be monitored.

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

Concomitant use of metronidazole with drugs that induce microsomal oxidation isoenzymes in the liver (phenobarbital, phenytoin) may accelerate the elimination of metronidazole, resulting in a decrease in its plasma concentration.

Metronidazole reduces the clearance of fluorouracil, leading to an increase in its toxicity.

Metronidazole increases the plasma concentration of busulfan, which may lead to the development of severe toxic effects of busulfan.

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

Sulfonamides enhance the antimicrobial effect of metronidazole.

Concomitant use of mebendazole and metronidazole should be avoided.

During laboratory tests while using metronidazole, difficulties may arise in determining the activity of AST, ALT, LDH, and the concentration of triglycerides.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.