Metrogyl^® (Tablets, Solution, Gel) 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

Antimicrobial and antiprotozoal agent

Pharmacological Action

Antiprotozoal and antimicrobial drug, a derivative of 5-nitroimidazole. The mechanism of action consists in 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 their nucleic acids, which leads to the death of bacteria.

It is 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., Veillonella spp., Prevolella spp. (Prevotella bivia, Prevotella buccae, Prevotella disiens) and some gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.).

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

Aerobic microorganisms and facultative anaerobes are insensitive to metronidazole, but in the presence of mixed flora (aerobes and anaerobes), Metronidazole acts synergistically with antibiotics effective against common aerobes.

It increases tumor sensitivity to irradiation, causes disulfiram-like reactions, and stimulates reparative processes.

Pharmacokinetics

After IV administration of 500 mg of Metrogyl^® over 20 minutes, the serum concentration of the drug was 35.2 µg/ml after 1 hour, 33.9 µg/ml after 4 hours, and 25.7 µg/ml after 8 hours.

With normal bile formation, the concentration of metronidazole in the bile after IV administration can significantly exceed the concentration in plasma.

About 30-60% of metronidazole is metabolized in the body by hydroxylation, oxidation, and glucuronidation.

The main metabolite (2-hydroxymetronidazole) also has antiprotozoal and antimicrobial effects.

T_1/2 with normal liver function is 8 hours (from 6 to 12 hours), with alcoholic liver damage – 18 hours (from 10 to 29 hours), in newborns: born at gestational age – 28-30 weeks – approximately 75 hours, 32-35 weeks – 35 hours, 36-40 weeks – 25 hours.

It is excreted by the kidneys 60-80% (20% unchanged), through the intestines – 6-15%. Renal clearance is 10.2 ml/min.

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

Metronidazole and the main metabolites are rapidly removed from the blood during hemodialysis (T_1/2 is reduced to 2.6 hours). It is excreted in insignificant amounts during peritoneal dialysis.

Indications

• Protozoal infections: extraintestinal amebiasis, including amoebic liver abscess, intestinal amebiasis (amoebic dysentery), trichomoniasis, giardiasis, balantidiasis, lambliasis, cutaneous leishmaniasis, trichomonal vaginitis, trichomonal urethritis;
• Infections caused by Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus): infections of bones and joints, CNS infections, including meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess;
• Infections caused by species of Bacteroides spp., including the B. fragilis group, Clostridium spp., Peptococcus spp., and Peptostreptococcus spp.: abdominal infections (peritonitis, liver abscess), pelvic organ infections (endometritis, endomyometritis, abscess of the fallopian tubes and ovaries, infections of the vaginal vault after surgical operations), skin and soft tissue infections;
• Infections caused by species of Bacteroides spp., including the B. fragilis group, Clostridium spp.;
• Sepsis;
• Pseudomembranous colitis (associated with antibiotic use);
• Gastritis or duodenal ulcer associated with Helicobacter pylori;
• Alcoholism;
• Prevention of postoperative complications (especially interventions on the colon, perirectal area, appendectomy, gynecological operations).

ICD codes

Dosage Regimen

Solution

IV administration of the drug is indicated for severe infections, as well as when oral administration is not possible.

Adults and children over 12 years old – initial dose of 0.5-1 g IV drip (infusion duration – 30-40 minutes), then – every 8 hours, 500 mg at a rate of 5 ml/min. With good tolerance after the first 2-3 infusions, switch to jet administration. The course of treatment is 7 days. If necessary, IV administration is continued for a longer time. The maximum daily dose is 4 g. According to indications, switch to maintenance oral administration at a dose of 400 mg 3 times/day.

Children under 12 years old are prescribed according to the same scheme in a single dose of 7.5 mg/kg.

For purulent-septic diseases, usually one course of treatment is conducted.

For prophylactic purposes, adults and children over 12 years old are prescribed IV drip 0.5-1 g the day before surgery, on the day of surgery and the next day – 1.5 g/day (500 mg every 8 hours). After 1-2 days, switch to maintenance therapy orally.

For patients with chronic renal failure and CC less than 30 ml/min and/or hepatic insufficiency, the maximum daily dose is no more than 1 g, frequency of administration – 2 times/day.

Gel

For external use. The gel is applied in a thin layer to previously cleansed affected skin areas 2 times/day, in the morning and evening, for 3-9 weeks.

The duration of treatment is 3-4 months, the therapeutic effect is usually noted after 3 weeks of treatment.

Tablets

Orally during or after meals, without chewing or with milk.

Adults and children over 15 years old – 200-400 mg 2-3 times/day.

The dose of the drug and the course of treatment are determined by the nature of the infection.

Trichomoniasis: 200 mg 3 times for 7 days; women additionally need to be prescribed Metronidazole in the form of vaginal suppositories or vaginal ointments. If necessary, the course of treatment can be repeated or the dose increased to 750-1000 mg/day. A break of 3-4 weeks should be made between courses with repeated control laboratory tests. An alternative therapy regimen is a single dose of 2 g to the patient and their sexual partner.

Amebiasisadults – 400 mg 3 times/day; children – 30-40 mg/kg/day in 3 divided doses. The course of treatment is 7-10 days.

Amoebic liver abscessadults – 400 mg or 800 mg 3 times/day in combination with antibiotics (tetracyclines or other methods); children – 30-35 mg/kg/day (in 3 divided doses). The course of treatment is 5-10 days.

Anaerobic bacterial infections:adults – 200-400 mg 2-3 times/day; children – 7 mg/kg every 8 hours. The course of treatment is 7-10 days;

For prevention of anaerobic infection before surgical interventions on pelvic organs and large intestine, a single oral dose of 1000 mg is prescribed, then – 200 mg 3 times/day.

In combination with amoxicillin (2.25 g/day), the daily dose of metronidazole is 1.5 g, frequency of administration – 3 times/day.

For patients with severe impairment of liver and kidney function, the daily dose of metronidazole is 1 g, amoxicillin – 1.5 g. Frequency of administration – 2 times/day.

Adverse Reactions

From the digestive system: diarrhea, decreased appetite, nausea, vomiting, intestinal colic, constipation, metallic taste in the mouth, dry mouth, glossitis, stomatitis, pancreatitis.

From the nervous system: dizziness, impaired coordination of movements, ataxia, confusion, irritability, depression, increased excitability, weakness, insomnia, headache, convulsions, hallucinations, peripheral neuropathy.

Allergic reactions: urticaria, skin rash, skin hyperemia, nasal congestion, fever, arthralgia.

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

Local reactions: thrombophlebitis (pain, hyperemia or swelling at the injection site).

Others: neutropenia, leukopenia, flattening of the T wave on ECG.

Contraindications

• Organic lesions of the CNS (including epilepsy);
• Hepatic insufficiency (in case of prescribing large doses);
• Blood diseases;
• Pregnancy (I trimester);
• Lactation period;
• Hypersensitivity to metronidazole or other nitroimidazole derivatives.

With caution: renal failure.

Use in Pregnancy and Lactation

I trimester of pregnancy – contraindicated; II and III trimesters of pregnancy – only for vital indications;

For nursing mothers – according to indications with simultaneous cessation of breastfeeding.

Use in Hepatic Impairment

For patients with hepatic insufficiency, the maximum daily dose is no more than 1 g, frequency of administration – 2 times/day.

Use in Renal Impairment

For patients with chronic renal failure and CC less than 30 ml/min, the maximum daily dose is no more than 1 g, frequency of administration – 2 times/day.

Pediatric Use

Children over 12 years old – initial dose of 0.5-1 g IV drip (infusion duration – 30-40 minutes), then – every 8 hours, 500 mg at a rate of 5 ml/min. With good tolerance after the first 2-3 infusions, switch to jet administration. The course of treatment is 7 days. If necessary, IV administration is continued for a longer time. The maximum daily dose is 4 g. According to indications, switch to maintenance oral administration at a dose of 400 mg 3 times/day.

Children under 12 years old are prescribed according to the same scheme in a single dose of 7.5 mg/kg.

For purulent-septic diseases, usually one course of treatment is conducted.

For prophylactic purposes, children over 12 years old are prescribed IV drip 0.5-1 g the day before surgery, on the day of surgery and the next day – 1.5 g/day (500 mg every 8 hours). After 1-2 days, switch to maintenance therapy orally.

Special Precautions

During treatment, alcohol intake is contraindicated (disulfiram-like reactions may develop: abdominal pain of a spastic nature, nausea, vomiting, headache, sudden flushing of the face).

In combination with amoxicillin, it is not recommended for use in patients under 18 years of age.

With long-term therapy, it is necessary to monitor the blood picture.

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

The appearance of ataxia, dizziness and any other deterioration in the neurological status of patients requires discontinuation of treatment.

It can immobilize treponemes and lead to a false-positive Nelson test.

It colors urine dark.

Drug Interactions

Metrogyl^® for IV administration is not recommended to be mixed with other drugs.

It enhances the effect of indirect anticoagulants, which leads to an increase in prothrombin formation time.

Similar to disulfiram, it causes ethanol intolerance. Simultaneous use with disulfiram may lead to the development of various neurological symptoms (the interval between prescriptions is at least 2 weeks).

Cimetidine suppresses the metabolism of metronidazole, which may lead to an increase in its serum concentration and an increased risk of adverse events.

Simultaneous administration of drugs that stimulate microsomal oxidation enzymes in the liver (phenobarbital, phenytoin) may accelerate the elimination of metronidazole, resulting in a decrease in its plasma concentration.

When taken simultaneously with lithium preparations, the concentration of the latter in plasma may increase and symptoms of intoxication may develop.

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

Sulfonamides enhance the antimicrobial effect of metronidazole.

Storage Conditions

List B. Store in a light-protected place, out of reach of children, at a temperature not exceeding 30°C (86°F). Do not use after the expiration date indicated on the package. Do not freeze.

Shelf Life

Shelf life – 3 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.