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

The drug shows a high activity in a relationship Trichomonas vaginalis, Entamoeba histolytica, as well as in respect of obligate anaerobes (sporo- and spore-forming) Bacteroides spp. (AT. fragilis, AT. distasonis, AT. ovatus, AT. thetaiotaomicron, AT. vulgatus), Fusobacterium spp., Clostridium spp, Peptostreptococcus spp,, Peptococcus spp., sensitive strains Eubacterium spp.

To Metronidazole 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.

Pharmacodynamics

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 reacts with the DNA of a cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Pharmacokinetics:

With intravenous administration of 500 mg of metronidazole for 20 minutes to patients with anaerobic infection, the concentration of the drug in the blood serum in an hour is 35.2 μg / ml, after 4 hours - 33.9 μg / ml, after 8 hours - 25.7 μg / ml. Metronidazole 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.

Binding to blood proteins is weak and does not exceed 10-20%. With normal bile formation, the concentration of metronidazole in the bile after intravenous administration may significantly exceed the concentration of metronidazole in the blood plasma.

It is excreted by the kidneys 60-80% (20% unchanged), through the intestine - 6-15%. The half-life of metronidazole is 6-7 hours. The renal clearance is 10.2 ml / min.

In patients with impaired renal function After repeated administration of metronidazole, cumulation of the drug in serum can be observed. Therefore, in patients with severe renal failure, the frequency of metronidazole should be reduced.

Metronidazole and major metabolites are rapidly removed from the blood during hemodialysis (the elimination half-life is reduced to 2.6 h). When peritoneal dialysis is withdrawn in small quantities.

Indications:

Metronidazole infusion solution is indicated for the treatment of infections caused by drug-susceptible microorganisms:

- prevention and treatment of anaerobic infections in surgical interventions, mainly on the organs of the abdominal cavity, pelvic organs and urinary tract;

- 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 in the anamnesis);

- hepatic failure (in the case of the appointment of large doses);

- I trimester of pregnancy;

- lactation period.

Carefully:

- Pregnancy II - III trimesters (only for life indications);

- renal and / or liver failure.

Pregnancy and lactation:

Metronidazole penetrates the placenta, so do not prescribe the drug in the first trimester of pregnancy, then should be used only if the potential benefit of using the drug for the mother exceeds the possible risk to the fetus.

Because the metronidazole penetrates into breast milk, reaching in it concentrations close to the concentrations in the blood plasma, it is recommended to stop breastfeeding during treatment with the drug.

Dosing and Administration:

Intravenously.

Intravenous administration of metronidazole is indicated for severe infections, also when the drug is not available 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 duration of treatment is determined individually. The maximum daily dose is no more than 4 g. According to the indications, depending on the nature of the infection, a transition to maintenance therapy with oral forms of metronidazole is carried out.

Children under the age of 12 years metronidazole 7.5 mg / kg of body weight is administered in 3 divided doses at a rate of 5 ml per minute.

For the prevention of anaerobic infection before the planned operation on the organs of the abdominal cavity, pelvic organs and urinary tract adults and children over 12 years Metronidazole is prescribed in the form of infusions in a dose of 500-1000 mg, on the day of the operation and the next day - in doses of 1500 mg / day (500 mg every 8 hours). After 1-2 days usually go to maintenance therapy with oral forms of metronidazole.

For patients with severe renal dysfunction (creatinine clearance less than 30 ml / min) and / or liver daily dose of metronidazole is 1000 mg, the frequency of administration is 2 times.

Metronidazole solution for infusion is not recommended to mix with other medicines!

Side effects:

From the gastrointestinal tract: epigastric pain, nausea, vomiting, diarrhea, constipation, intestinal colic, decreased appetite, anorexia, a taste disorder, an unpleasant "metallic" taste in the mouth, dry mouth, glossitis, stomatitis; very rarely - a deviation from the norm of functional liver samples, 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 genitourinary system: dysuria, cystitis, polyuria, urinary incontinence, vulvovaginal candidiasis, pain in the vagina, staining the urine in a red-brown color.

Allergic reactions: skin rash, itching, urticaria, multi-form exudative erythema, nasal congestion, fever.

From the side of the musculoskeletal system: myalgia, arthralgia.

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

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

Other: flattening of the T wave on the electrocardiogram; extremely rarely - ototoxicity, pustular eruptions, gynecomastia.

Overdose:

Too high doses can cause increased side effects, mainly nausea, vomiting,and dizziness; in more severe cases, there may be ataxia, paresthesia and seizures.

Treatment: symptomatic. There is no specific antidote.

Interaction:

Care should be taken when concomitant administration with certain medicines.

Warfarin and other indirect anticoagulants. Metronidazole increases the effect of indirect anticoagulants, which leads to an increase in prothrombin time.

Disulfiram. Simultaneous application can lead to the development of various neurological symptoms, so one should not prescribe metronidazole patients who took disulfiram in the last two weeks. Similarly, disulfiram causes intolerance to ethanol.

Cimetidine inhibits metronidazole metabolism, which can lead to increase its concentration in the blood serum and increase the 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 additional 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.

Sulfonamides enhance antimicrobial action.

With combined intake metronidazole and cyclosporine there may be an increase in the concentration of cyclosporine in the blood plasma.

Metronidazole reduces ground clearance fluorouracil, which can cause an increase in the toxicity of the latter.

With simultaneous application metronidazole can increase plasma concentrations busulfan.

It is not recommended to combine with nondepolarizing muscle relaxants (vecuronium bromide).

Special instructions:

With caution appoint for diseases of the kidneys, liver.

During the treatment period, ethanol intake is contraindicated (development of disulfiram-like reactions is possible: abdominal pain of spastic nature, nausea, vomiting, headache, sudden rush of blood to the face).

In combination with amoxicillin it is not recommended to use in patients younger than 18 years.

With prolonged therapy, it is necessary to control the picture of blood,

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.

Can immobilize treponema and lead to Nelson's false positive test.

During the administration of metronidazole, a red-brown staining of urine can be observed.

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Form release / dosage:

Solution for infusion, 5 mg / ml.

Packaging:

For 100 ml in bottles of glass for blood, transfusion and infusion preparations, ukuporennyh stoppers made of rubber and crimped with aluminum caps.

A bottle with instructions for use is placed in a pack of cardboard.

For hospitals: 35 bottles together with an equal number of instructions for use are placed in boxes of corrugated cardboard with gaskets, with baffles or with grids ("sockets") without preliminary stacking.

Storage conditions:

In a dry, dark place at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LSR-009875/09

Date of registration:04.12.2009

Expiration Date:Unlimited

The owner of the registration certificate:DALHIMFARM, OJSC DALHIMFARM, OJSC Russia

Manufacturer: & nbsp

DALHIMFARM, OJSC Russia

Representation: & nbspDALHIMFARM, OJSCDALHIMFARM, OJSC

Information update date: & nbsp12.09.2016

Illustrated instructions

Instructions

Metronidazole (Metronidazole)