Metronidazole Reneval, tablets 250 mg 24 pcs

Pharmacotherapeutic group:

an antimicrobial and antiprotozoal agent.

The ATX code: J01XD01

Pharmacological properties

Antiprotozoal and antimicrobial drug, a 5-nitroimidazole derivative. Its mechanism of action consists in biochemical reduction of 5-nitrogroup by intracellular transport proteins of anaerobic microorganisms and protozoa.

The reduced 5-nitrogroup interacts with the deoxyribonucleic acid (DNA) of the microbial cell, inhibiting the synthesis of their nucleic acids, which leads to the death of the bacteria.

Active against Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp, as well as obligate anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp, Veillonela spp., Prevotella (P.bivia, P.buccae, P.disiens), and some gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.). The minimum suppressive concentration for these strains is 0.125-6.25 µg/ml.

In combination with amoxicillin it shows activity against Helicobacter pylori (amoxicillin suppresses development of resistance to metronidazole). Aerobic microorganisms and facultative anaerobes are not sensitive to metronidazole, but in the presence of mixed flora (aerobes and anaerobes) metronidazole acts synergistically with antibiotics effective against common aerobes. It increases the sensitivity of tumors to radiation, causes sensitization to alcohol (disulfiram-like effect), stimulates reparative processes.

Indications

Protozoal infections: extraintestinal amebiasis (including amoebic liver abscess), intestinal amebiasis (amoebic dysentery), trichomoniasis.
Infections caused by Bacteroides spp. (including B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus); bone and joint infections; infections of the central nervous system (CNS), 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), infections of the pelvic organs (endometritis, abscess of the fallopian tubes and ovaries, infections of the vaginal vault).
Antibiotic-associated pseudomembranous colitis.
Gastritis or duodenal ulcer associated with Helicobacter pylori (as part of complex therapy).
Prevention of postoperative complications (especially after operations on the colon, in the pararectal area, appendectomy, gynecological operations).

Pharmacological effect

Pharmacotherapeutic group: systemic antibacterial agents; other antibacterial agents; imidazole derivatives.

ATX code: J01XD01

Pharmacological properties

Pharmacodynamics

Metronidazole is a derivative of 5-nitroimidazole. The mechanism of action of metronidazole is 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 cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of microorganisms.

Active against Trichomonas vaginalis, Entamoeba histolytica, as well as gram-negative anaerobes Bacteroides spp. (including B. fragilis,
B. ovatus, B. distasonis, B. thetaiotaomicron, B. vulgatus), Fusobacterium spp. and some gram-positive anaerobes (susceptible strains of Eubacterium spp., Clostridium spp., Peptococcus niger, Peptostreptococcus spp.). The minimum inhibitory concentration (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 sensitive 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% in 1 hour). Eating does not affect the absorption of metronidazole.

Bioavailability is at least 80%. After oral administration of metronidazole at a dose of 500 mg, its concentration is
blood plasma is 10 mcg/ml after 1 hour, 13.5 mcg/ml after 3 hours. Binding to blood proteins is insignificant and does not exceed 10-20%. Metronidazole quickly penetrates into tissues (lungs, kidneys, liver, skin, bile, cerebrospinal fluid, saliva, seminal fluid, vaginal secretions), into breast milk and passes through the placental barrier. About 30-60% of metronidazole is metabolized by hydroxylation, oxidation and
glucuronidation. The main metabolite (2-oxymetronidazole) also has antiprotozoal and antimicrobial effects.
40-70% of metronidazole is excreted by the kidneys (unchanged – about 35% of the dose taken). The half-life is 8-10 hours.

In patients with impaired renal function, a course of taking metronidazole may increase its concentration in the blood serum

Special instructions

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

You should carefully weigh the indications for long-term use of the drug (more than 10 days) and, in the absence of strict indications, avoid its long-term use. If, in the presence of strict indications (carefully weighing the relationship between the expected effect and the potential risk of complications), the drug is used for a longer period than is usually recommended, then treatment should be carried out under the control of hematological indicators (especially leukocytes) and adverse reactions, such as peripheral or central neuropathy, manifested by paresthesia, ataxia, dizziness, convulsions, upon the occurrence of which treatment should be discontinued.

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

Severe hepatotoxicity/acute liver failure (including fatal cases) has been reported in patients with Cockayne syndrome. Metronidazole should be used with caution and only in the absence of alternative treatment in this category of patients. Liver function tests should be performed at the beginning of treatment, during treatment and for 2 weeks after the end of treatment. Patients with Cockayne syndrome should be advised to immediately inform their doctor about
development of any symptoms of potential liver damage (such as new onset persistent abdominal pain, anorexia, nausea, vomiting, fever, malaise, jaundice, dark urine, or itching).

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

Impact on the ability to drive vehicles and machinery

Considering the risk of developing such adverse reactions as confusion, dizziness, hallucinations, visual disturbances, it is recommended during treatment

Active ingredient

Metronidazole

Composition

Active ingredient: metronidazole – 250.0 mg;

excipients: potato starch, stearic acid, talc.

Pregnancy

Since metronidazole crosses the placental barrier and its effect on human fetal organogenesis is unknown, the use of Metronidazole Renewal during pregnancy is contraindicated. Metronidazole passes into breast milk, so the use of the drug during breastfeeding is contraindicated

Contraindications

Hypersensitivity to metronidazole, to other nitroimidazole derivatives, to imidazoles and to other components of the drug; organic lesions of the central nervous system (including epilepsy); leukopenia (including history); liver failure (if large doses are prescribed); pregnancy, lactation 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.

Side Effects

Gastrointestinal disorders

•Epigastric pain, nausea, vomiting, diarrhea.
•Inflammation of the oral mucosa (glossitis, stomatitis), taste disturbances (“metallic” taste in the mouth), decreased appetite, anorexia, dry oral mucosa, constipation.
•Pancreatitis (reversible cases).
•Change in tongue color/coated tongue (due to excessive growth of fungal microflora).

Immune system disorders

•Angioedema, anaphylactic shock.

Nervous system disorders

•Peripheral sensory neuropathy.
•Headache, cramps, dizziness.
•Encephalopathy (eg, confusion) and subacute cerebellar syndrome (impaired coordination and synergism of movements, ataxia, dysarthria, gait disturbances, nystagmus and tremor) have been reported, which reverse after discontinuation of metronidazole.
•Aseptic meningitis.

Mental disorders

•Psychotic disorders, including confusion, hallucinations.
•Depression, insomnia, irritability, increased excitability.

Visual disorders

•Transient visual impairments such as diplopia, myopia, blurred vision, decreased visual acuity, impaired color perception.
•Neuropathy/optic neuritis.

Hearing and labyrinth disorders

• Hearing impairment/hearing loss (including sensorineural deafness).
• Tinnitus.

Blood and lymphatic system disorders

• Agranulocytosis, leukopenia, neutropenia and thrombocytopenia.

Disorders of the liver and biliary tract

• Increased activity of “liver” enzymes (aspartate aminotransferase (AST) and alanine aminotransferase (ALT), alkaline phosphatase), development of cholestatic or mixed hepatitis, hepatocellular liver damage, sometimes accompanied by jaundice.
• Cases of liver failure requiring liver transplantation have been observed in patients treated with metronidazole in combination with other antibiotics.

Disorders of the skin and subcutaneous tissues

• Rash, itching, flushing of the skin, skin hyperemia, urticaria.
• Pustular skin rash.
• Fixed drug rash.
• Stevens-Johnson syndrome, toxic epidermal necrolysis.

Renal and urinary tract disorders

• Urine may be brownish-reddish in color, due to the presence of a water-soluble metabolite of metronidazole in the urine.
• Dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

General disorders

• Fever, nasal congestion, arthralgia, weakness.

Laboratory and instrumental data

• Flattening of the T wave on the ECG.

Interaction

With disulfiram

The development of psychotic reactions has been reported in patients receiving concomitant metronidazole and disulfiram (the interval between the use of these drugs should be at least 2 weeks).

With ethanol

Disulfiram-like reactions may occur (hyperemia of the skin, flushing of the skin, vomiting, tachycardia).

With indirect anticoagulants (warfarin)

Increased anticoagulant effect and increased risk of bleeding associated with decreased hepatic metabolism of indirect anticoagulants, which can lead to prolongation of prothrombin time. In the case of simultaneous use of metronidazole and indirect anticoagulants, more frequent monitoring of prothrombin time is required and, if necessary, dose adjustment of anticoagulants.

With lithium preparations

With the simultaneous use of metronidazole with lithium preparations, the concentration of the latter in the blood plasma may increase. With simultaneous use, the concentrations of lithium, creatinine and electrolytes in the blood plasma should be monitored.

With cyclosporine

With simultaneous use of metronidazole with cyclosporine, the concentration of cyclosporine in the blood plasma may increase. If simultaneous use of metronidazole and cyclosporine is necessary, the concentrations of cyclosporine and creatinine in the blood plasma should be monitored.

With cimetidine

Cimetidine inhibits the metabolism of metronidazole, which may lead to an increase in its concentration in the blood plasma and an increased risk of side effects. With drugs that induce isoenzymes of microsomal oxidation in the liver (phenobarbital, phenytoin) The simultaneous use of metronidazole with drugs that induce isoenzymes of microsomal oxidation in the liver (phenobarbital, phenytoin) can accelerate the elimination of metronidazole, resulting in a decrease in its concentration in the blood plasma.

With fluorouracil

Metronidazole reduces the clearance of fluorouracil, leading to increased toxicity.

With busulfan

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

With non-depolarizing muscle relaxants (vecuronium bromide)

Not recommended for use with non-depolarizing muscle relaxants (vecuronium bromide).

With sulfonamides

Sulfonamides enhance the antimicrobial effect of metronidazole

Overdose

Ingestion of single doses of metronidazole up to 12 g has been reported in suicide attempts and accidental overdoses.

Symptoms: vomiting, ataxia, slight disorientation.

Treatment: There is no specific antidote for metronidazole overdose. If a significant dose overdose is suspected, symptomatic and supportive therapy should be provided.

Storage conditions

In the original packaging (blister packaging in a pack) at a temperature not exceeding 30 ºС.

Keep out of reach of children

Shelf life

3 years.

Do not use after the expiration date stated on the package.

Manufacturer

Update of PFC JSC, Russia