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

Metronidazole is a effective antiprotozoal and antimicrobial agents of a wide spectrum of action. The drug exhibits high activity with respect to Trichomonas vaginalis, Giardia intestinalis, Entamoeba histolytica, Lamblia intestinalis, as well as in respect of obligate anaerobes (sporo- and non-spore forming) Bacteroides spp. (AT. fragilis, AT. ovatus, AT. distasonis, AT. thetaiotaomicron,,B. vulgatus), Fusobacterium spp., Clostridium spp., Peptostreptococcus spp., Peptococcus spp., sensitive strains Eubacterium.

To Metronidazole insensitive 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 the intravenous administration of 500 mg of metronidazole for 20 minutes to patients with anaerobic infection, the concentration of the drug in the blood serum was 35.2 μg / ml in an hour, 33.9 μg / ml in 4 hours, 25.7 μg / ml after 8 hours . The drug penetrates well into organs and tissues, 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 bile after intravenous administration may significantly exceed the concentration of metronidazole in blood plasma.

Metronidazole is excreted mainly by the kidneys - 63% dose (20% the drug is withdrawn unchanged). 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 the drug cumulation of metronidazole in serum can be observed. Therefore, in patients with severe renal failure, the frequency of metronidazole should be reduced.

Indications:

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

- prevention and treatment of anaerobic infections during surgical interventions, mainly on the organs of the abdominal cavity 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;

- infection of skin and soft tissues, bones and joints.

Contraindications:

- Hypersensitivity to metronidazole or other nitroimidazole derivatives;

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

- leukopenia (including in the anamnesis);

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

- I trimester of pregnancy, lactation.

Carefully:

II and III trimesters of pregnancy, renal / hepatic insufficiency.

Pregnancy and lactation:

The drug is contraindicated in the first trimester of pregnancy; Later, he can be appointed only if the benefit to the mother exceeds the possible risk to the fetus.

During treatment with metronidazole, breastfeeding should be discontinued.

Dosing and Administration:

Intravenously. Intravenous management 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 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 is administered 7.5 mg / kg body weight 3 times a day at a rate of 5 ml per minute.

For the prevention of anaerobic infection before the planned operation on pelvic organs and urinary tract adults and children over 12 years Metronidazole is administered in the form of infusions in a dose of 500-1000 mg, on the day of surgery 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 that intravenous metronidazole be injected intravenously in the same manner in a single dose of 7.5 mg / kg body weight. The maximum daily dose in children under 12 years of age is 22.5 mg / kg body weight. /)

For patients with severe renal dysfunction (SC less than 30 ml / min) and / or liver daily dose of metronidazole 1000 mg; multiplicity of administration 2 times.

Side effects:

Violations of the blood and lymphatic system: agranulocytosis, leukopenia, neutropenia, thrombocytopenia.

Immune system disorders: angioedema, anaphylactic shock.

Disorders of the psyche: psychotic disorders, including confusion, hallucinations, depression, insomnia, irritability, increased excitability.

Disturbances from the nervous system: peripheral sensory neuropathy, headache, convulsions, dizziness, reported on the development of encephalopathy and subacute cerebellar syndrome (impaired coordination and synergy of movements, ataxia, dysarthria, gait disturbance, nystagmus, tremor) that are reversible after metronidazole withdrawal, aseptic meningitis.

Disturbances on the part of the organ of sight: transient visual impairments, such as diplopia, myopia, vagueness of the contours of objects, reduced visual acuity, impaired color perception, neuropathy / optic neuritis.

Disorders from the digestive system: epigastric pain, nausea, vomiting, diarrhea, glossitis, stomatitis, "metallic" aftertaste in pty, decreased appetite, anorexia, dryness of the oral mucosa, constipation, pancreatitis (reversible cases), discoloration of the tongue / "lipped tongue" ( because of the growth of fungal microflora).

Disturbances from the liver and bile ducts: increased activity of "hepatic" enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), development of cholestatic or mixed hepatitis and hepatocellular liver damage, sometimes accompanied by jaundice.

In patients treated with metronidazole in combination with other antibacterial agents, cases of hepatic insufficiency that required liver transplantation were observed.

Disturbances from the skin and subcutaneous tissues: skin rash, skin itching, skin hyperemia, urticaria, pustular skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Disorders from the kidneys and urinary tract: staining urine in a brownish-reddish color, due to the presence in the urine of a water-soluble metronidazole metabolite, dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

General disorders and disorders in place of introduction: fever, nasal congestion, arthralgia, weakness, thrombophlebitis (pain, hyperemia or swelling at the injection site).

Laboratory and instrumental data: flattening of the T wave on the electrocardiogram.

Overdose:

Too high doses can cause 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:

With metronidazole, injection for injection, interaction with other drugs is negligible, but caution should be exercised when concomitant administration with certain medicines:

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

Disulfiram (esperal). 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.

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

Simultaneous administration of drugs stimulating enzymes of microsomal oxidation in the liver (phenobarbital, phenytoin), can accelerate the elimination of metronidazole, as a result of which its concentration in the plasma decreases.

In patients receiving long-term treatment with drugs lithium in high doses,when taking Metronidazole may increase the concentration of lithium in blood plasma and the development of symptoms of intoxication

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

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

Metronidazole, a solution for injection, is not recommended to be mixed with other medicinal products!

Special instructions:

With caution appoint for diseases of the kidneys, liver.

Do not drink alcohol while taking the drug, since metronidazole has the ability to cause aversion to alcoholic beverages.

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

Form release / dosage:Solution for infusion, 5 mg / ml.

Packaging:

For 100 ml of the preparation in a transparent vial (glass type I), closed by a rubber lid, rounded with an aluminum cap on top with a closed plastic polypropylene lid. The aluminum cap is applied internal production code of the preparation.

On 1 bottle together with the instruction on application place in a pack a cardboard.

Storage conditions:

AT protected from light, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014472 / 01

Date of registration:07.07.2008 / 22.01.2014

Expiration Date:Unlimited

Date of cancellation:2018-02-09

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp09.02.2018

Illustrated instructions

Instructions

Efloran (Efloran®)