Metronidazole - instructions for use, dose, side effects, contraindications

Metronidazole is an antiprotozoal and antimicrobial drug, a derivative of 5-nitroimidazole. The mechanism of action is the biochemical reduction of the 5-nitro group by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group reacts with the deoxyribonuclease of the microorganism cell, inhibiting the synthesis of the nucleic acid, which leads to the death of the bacterium.

Metronidazole is active at respect Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia intestinalis, as well as obligate anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp. and some Gram-positive microorganisms (Eubacterium spp. Clostridium spp. Peptococcus spp .. Peptostreptococcus spp.).

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

Metronidazole is not sensitive Aerobic microorganisms and facultative anaerobes, but in the presence of mixed flora (aerobes and anaerobes) metronidazole acts synergistically with antibiotics effective against conventional aerobes.

Pharmacokinetics:

Bioavailability - Mr.e less than 80%. It has a high penetrating ability, reaching bactericidal concentrations in most tissues and body fluids, including lungs, kidneys, liver, skin, cerebrospinal fluid, brain, bile, saliva, amniotic fluid, abscess cavities, vaginal secretion, seminal fluid, breast milk. Penetrates through blood-brain and placental barriers.

The volume of distribution in adults is approximately 0.55 l / kg, in newborns - 0.54-0.81 l / kg. Concentration in the blood plasma is proportional to the administered dose. Links with plasma proteins do not exceed 10-20%. With normal bile formation, the concentration of metronidazole in the bile after intravenous administration may significantly exceed the concentration and plasma.

AT The organism of 30-60% of metronidazole is metabolized in the liver. The main metabolite, 2-oximetronidazole, also has antiprotozoal and antimicrobial effects.

Are deduced metronidazole and its metabolites are mainly kidneys (20% of the drug is excreted unchanged). From 6 to 15% of the administered dose is excreted with feces.

Half-life (T_1/2) Metronidazole with normal liver function averages 8 hours (6 to 12 hours),with alcoholic liver damage - an average of 18 hours (10 to 29 hours); in newborns born at the gestational age of 28-31 weeks - about 75 hours, 32-35 weeks - about 35 hours, 36-40 weeks - about 25 hours.

Kidney clearance - 10.2 ml / min. In patients with impaired renal function after repeated administration, cumulation of metronidazole in the blood plasma can be observed.

Metronidazole and its metabolites are rapidly removed from the blood during hemodialysis (T_1/2is decreasing up to 2.6 hours). With peritoneal dialysis metronidazole is displayed in minor amounts.

Indications:

Metronidazole, a solution for infusions, is recommended for the treatment of infections caused by microorganisms that are sensitive to the drug:

- prevention and treatment of anaerobic infections in surgical procedures, mostly on the abdomen and urinary organs;

- combined therapy of severe mixed aerobic-anaerobic infections;

- severe form of intestinal and hepatic amebiasis;

- sepsis;

- peritonitis;

- osteomyelitis;

- gynecological infections;

- abscesses of small pelvis and brain;

- abscessed pneumonia;

- gas gangrene;

- infections of the skin and soft tissues, bones and joints.

Contraindications:

- Hypersensitivity to metronidazole or other nitroimidazole derivatives;

- organic lesions of the central nervous system (including epilepsy);

- leukopenia (including at anamnesis);

- hepatic insufficiency (in case of administration of large doses of the drug);

- I trimester of pregnancy and lactation.

Carefully:In the II and III trimester of pregnancy, with renal / hepatic insufficiency.

Pregnancy and lactation:

The drug is contraindicated in the first trimester of pregnancy; It can be appointed later onlyif the benefit to the mother exceeds the possible risk for the fetus.

During treatment with metronidazole, breastfeeding should be discontinued.

Dosing and Administration:

Intravenously. Intravenous administration of metronidazole is indicated in cases of severe infection, and when there is no possibility of taking the drug inside.

For adults and children over 12 years a single dose of 500 mg, the rate of intravenous continuous (jet) or dropwise administration - 5 ml per minute. The interval between administrations is 8 hours. The maximum daily dose is no more than 4 g.

It is better to begin treatment with drop injections.With good tolerability after the first 2-3 infusions pass to a jet injection. The course of treatment is 7 days. If necessary, intravenous administration is continued for a longer time. According to the indications, depending on the nature of the infection, it is possible to switch to maintenance therapy with oral forms of metronidazole.

Children under the age of 12 years metronidazole prescribe the same scheme in a single dose of 7.5 mg / kg body weight.

With purulent-septic diseases usually spend 1 course of treatment.

For the prevention of anaerobic infection before the planned operation on the organs of the abdominal cavity and urinary tract adults and children over 12 years Metronidazole is prescribed on the day of the operation in the form of infusions in a dose of 500-1000 mg and the next day at a dose of 1500 mg / day (500 mg every 8 hours). With the development of postoperative infectious complications, the duration of therapy is extended to 7 days; it is possible to switch to oral therapy.

Children under the age of 12 years it is recommended the administration of metronidazole intravenously drip on the same schedule in a single dose of 7.5 mg / kg body weight. Maximum daily intake in children at the age of 12 years - 22.5 mg / kg body weight.

For patients with severe renal dysfunction (creatinine clearance less than 30 ml / min) and / or liver daily dose of metronidazole - not more than 1000 mg; multiplicity of reception - 2 times.

Side effects:

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

From the digestive system: diarrhea, anorexia, nausea, vomiting, intestinal colic, constipation, "metallic" taste in the mouth, dry mouth, glossitis, stomatitis, pancreatitis, liver failure.

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

From the genitourinary system: dysuria, cystitis, polyuria, urinary incontinence, candidiasis, gynecomastia, staining of urine in red-brown color.

Local Reactions: thrombophlebitis (pain, redness or swelling at the injection site).

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

Overdose:

Symptoms: nausea, vomiting, dizziness; in more severe cases, there may be ataxia, paresthesia and seizures.

Treatment: symptomatic therapy, conducting hemodialysis. Specific antidote absent.

Interaction:

Metronidazole enhances the action warfarin and other indirect anticoagulants, which leads to an increase in the time of prothrombin formation.

Cimetidine inhibits the metabolism of metronidazole, which can lead to an increase in its serum concentration and increased risk of side effects.

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

In patients receiving long-term treatment with drugs lithium in high doses, with the use of metronidazole, an increase in the concentration of lithium in the blood plasma and the development of symptoms of intoxication are possible.

The antimicrobial effect of metronidazole is enhanced in combination with sulfonamides and antibiotics.

Enhances the effect Nondepolarizing muscle relaxants (vecuronium bromide).

Special instructions:

With caution appoint for diseases of the kidneys and liver.

While taking the drug is not recommended to drink alcohol, because metronidazole has the ability to induce aversion to alcoholic beverages.

Long-term use of the drug is desirable to be carried out under the control of peripheral blood.

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

Metronidazole increases the sensitivity of tumors to irradiation.

To avoid the possibility of developing a variety of neurological symptoms metronidazole should be appointed no earlier than 2 weeks after the end of the disulfiram.

Form release / dosage:Solution for infusion, 500 mg / 100 ml.

Packaging:

For 100 ml of the drug is placed in a round or flat polyethylene bottle.

The bottle is placed in a polypropylene bag and then in a cardboard box along with the instructions for use.

Storage conditions:

In the dark place at a temperature of 0 to 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014878 / 01

Date of registration:01.07.2008 / 03.12.2009

Expiration Date:Unlimited

The owner of the registration certificate:Orchid Helsker (a division of Orchid Chemicals and Pharmaceuticals Ltd.)Orchid Helsker (a division of Orchid Chemicals and Pharmaceuticals Ltd.) India

Manufacturer: & nbsp

ORCHID HEALTHCARE India

Representation: & nbspOrchid Chemicals and Pharmaceuticals Co., Ltd.Orchid Chemicals and Pharmaceuticals Co., Ltd.Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)