Edgil - instructions for use, doses, side effects, contraindications

Antiprotozoal and antimicrobial drug, a derivative of 5-nitroimidazole. The mechanism of action is the biochemical reduction of the 5-nitro group of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa. The restored 5-nitro group of metronidazole interacts with the DNA of a cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of the bacterium.

Active in a relationship Trichomonas vaginalis, Entamoeba histolytica, as well as Gram-negative anaerobes Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp. and some Gram-positive anaerobes (sensitive strains 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 shows activity against Helicobacter pylori.

To metronidazole nsensitive Aerobic microorganisms and facultative anaerobes, but in the presence of mixed flora (aerobes and anaerobes) metronidazole acts synergistically with antibiotics effective against conventional aerobes.Increases the sensitivity of tumors to irradiation, causes disulfiram-like reactions.

Pharmacokinetics:

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 the blood-brain barrier and placental barrier. The volume of distribution: adults - about 0.55 l / kg, newborns - 0.54-0.81 l / kg.

The connection with plasma proteins is 10-20%.

When intravenous (iv) 500 mg for 20 minutes, the maximum concentration (C_m_Oh) in the blood serum after 1 hour - 35.2 μg / ml, after 4 hours - 33.9 μg / ml, after 8 hours 25.7 μg / ml. Time to reach the maximum concentration (TC_m_Oh) - 30-60 minutes. the therapeutic concentration persists for 6-8 hours. With normal bile formation, the concentration of metronidazole in the bile after IV injection can significantly exceed the concentration in the plasma.

In the body, about 30-60% of metronidazole is metabolized by hydroxylation, oxidation and glucuronation.The main metabolite (2-oxpmstronndazole) also has antiprotozoal and antimicrobial effects.

Half-life (T_1/2) with normal liver function -8 hours (from 6 to 12 hours), with alcoholic liver damage - 18 hours (from 10 to 29 hours), in newborns: those born at the time of pregnancy - 28-30 weeks - about 75 hours, 32-35 35 h, 36-40 weeks - 25 h. It is excreted by the kidneys 60-80% (20% unchanged), the intestine - 6-15%. Kidney clearance - 10.2 ml / min. In patients with impaired renal function after repeated administration, cumulation of metronidazole in serum can be observed (therefore, the frequency of administration should be reduced in patients with severe renal insufficiency).

Metronidazole and major metabolites are rapidly removed from the blood during hemodialysis (T_1/2is reduced to 2.6 hours). When peritoneal dialysis is withdrawn in minor quantities.

Indications:

- Protozoal infections: extraintestinal amoebiasis. including amoebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis (including trichomonas vaginitis, trichomonas urethritis).

- Infections caused by Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis. Bacteroides ovatus. Bacteroides thetaiotaomicron, Bacteroides vulgatus): infection of bones and joints, infections of the central nervous system (CNS), incl. meningitis, brain abscess, bacterial endocarditis, pneumonia, pleural empyema, lung abscess, sepsis.

- Infections caused by the species Clostridium spp., Peptococcus niger and Peptostreptococcus spp.: infection of the abdominal cavity (peritonitis, liver abscess), pelvic infection (endometritis, abscess of fallopian tubes and ovaries, vaginal vaginal infection).

- Prevention of postoperative complications (especially interference on the colon, paraectal area, appendectomy, gynecological operations).

- Radiation therapy of patients with tumors - as a radiosensitizing drug in cases where tumor resistance is caused by hypoxia in tumor cells.

Contraindications:

- Hypersensitivity to metronidazole and / or other components of the drug, another derivative of nitro imidazole;

- I trimester of pregnancy;

- lactation period (breastfeeding);

- organic lesions of the central nervous system (including epilepsy), leukopenia (including in the anamnesis), hypothyroidism or hypofunction of the adrenal gland, liver failure (in the case of high doses).

Carefully:

Pregnancy (II-III trimesters), renal / hepatic insufficiency, acute and chronic diseases of the peripheral and central nervous system (risk of weighty neurological symptoms).

Pregnancy and lactation:

Contraindicated use of the drug in the I trimester of pregnancy. Application of the drug during II and III trimester of pregnancy is possible only in cases where the intended benefit to the mother exceeds the potential risk to the fetus. If you need to use the drug during lactation, you should decide whether to stop breastfeeding.

Dosing and Administration:

Intravenous infusion:

Adults and children over 12 years of age in the initial dose of 0.5-1 g IV in the drip (the duration of the infusion is 30-40 minutes), and then every 8 hours at 500 mg at a rate of 5 ml / min. With good tolerability after the first 2-3 infusions pass to a jet injection.

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 the indications, a transition to oral administration in the appropriate dosage form is performed.

Children under the age of 12 years injected at a dose of 7.5 mg / kg body weight 3 times a day at a rate of 5 ml / min. The maximum daily dose is 22.5 mg / kg of body weight.

For preventive purposes, adults and children over 12 years of age injected in / in a drop of 0.5-1 g on the eve of surgery, on the day of surgery and the next day - 1.5 g / day (500 mg every 8 h). After 1-2 days, they switch to maintenance therapy inside. 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.

Patients with chronic renal insufficiency and creatinine clearance less than 30 ml / min and / or liver failure the maximum daily dose - no more than 1 g, the frequency of administration - 2 times a day.

As a radiosensitizing drug the drug is injected / drip at a rate of 160 mg / kg or 4-6 g / m² body surface for 0.5-1 hour before the start of irradiation. Apply before each irradiation session for 1-2 weeks. In the remaining period of radiation treatment metronidazole do not apply. The maximum single dose should not exceed 10 grams, the course dose should be 60 g. To remove intoxication caused by irradiation, a dropwise injection of 5% dextrose solution or 0.9% sodium chloride solution is used.

Side effects:

Disorders from the gastrointestinal tract: epigastric pain, nausea, vomiting, diarrhea, glossitis, stomatitis, metallic taste in the mouth, 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).

Immune system disorders: angioedema, anaphylactic shock.

Impaired 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 disorders, nystagmus, tremor) that are reversible after metronidazole withdrawal, aseptic meningitis.

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

Disorders from the side of the organ of vision: transient visual impairments, such as diplopia, myopia, vagueness of contours of subjects, reduced visual acuity, violation of color perception; Neuropathy / optic neuritis.

Disturbances from the blood of the lymphatic systems: agranulocytosis, leukopenia, neutropenia, thrombocytopenia.

Disturbances from the liver and bile ducts: an increase in the 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.

Disruptedand I from the skin and subcutaneous tissues: rash, 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 at the site of administration: fever, nasal congestion, arthralgia, weakness (for oral and parenteral dosage forms), thrombophlebitis (pain, hyperemia or swelling at the injection site) (for parenteral dosage forms).

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

Overdose:

Symptoms: nausea, vomiting, ataxia; when receiving as a radiosensitizing agent - convulsions, peripheral neuropathy.

Treatment: there is no specific antidote, symptomatic and supportive therapy.

Interaction:

Increases the effect of indirect anticoagulants, which leads to an increase in prothrombin time.

Similarly, disulfiram causes intolerance to ethanol.

Simultaneous use with disulfiram can lead to the development of various neurologic symptoms (the interval between appointments is at least 2 weeks).

Metronidazole for intravenous administration is not recommended to be mixed with other drugs.

Cimetidine suppresses 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 use of drugs that induce 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.

With simultaneous use with lithium preparations, the concentration of the latter in the plasma may increase and symptoms of intoxication may develop.

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

Sulfonamides increase the antimicrobial effect of metronidazole.

With simultaneous application with cyclosporine, an increase in the concentration of cyclosporine in the blood plasma can be observed.

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

With simultaneous application metronidazole can increase the plasma concentrations of busulfan.

Special instructions:

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).

With prolonged 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.

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

Stains urine in a dark color.

When treating trichomonadal vaginitis in women and trichomoniasis in men, it is necessary to abstain from sexual activity. It is necessary to simultaneously treat sexual partners. After therapy with trichomoniasis, control tests should be performed for 3 consecutive cycles before and after menstruation.

Effect on the ability to drive transp. cf. and fur:

In connection with the possibility of dizziness and other side effects associated with the drug, it is recommended to refrain from driving and other machinery and mechanisms.

Form release / dosage:

Solution for infusion, 5 mg / ml.

Packaging:

Infusion bottle of low density polyethylene with polymer suspension, capacity 100 ml, with a cap of opening control.

One bottle of low-density polyethylene containing 100 ml of the preparation is sealed in a cellophane bag, placed along with the instruction for medical use in a cardboard pack.

Storage conditions:

In a sheltered spot, at a temperature of no higher than 25 ° 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:LP-002887

Date of registration:03.03.2015

Expiration Date:03.03.2020

The owner of the registration certificate:Edge Pharma Private LimitedEdge Pharma Private Limited India

Manufacturer: & nbsp

EDGE PHARMA PRIVATE, Limited India

Representation: & nbspEdge Pharma Private Limited Edge Pharma Private Limited India

Information update date: & nbsp09.09.2016

Illustrated instructions

Instructions

Edgil (EDGIL)