Metronidazole Nycomed - instructions for use, dose, 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 by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group reacts with the deoxyribonucleic acid (DNA) of a cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Active in a relationship Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp., as well as gram-negative anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella (P. bivia, P. buccae, P. disiens), and some Gram-positive anaerobes (sensitive strains Eubacterium spp., Clostridium niger, Peptococcus spp., Peptostreptococcus spp.). The minimum inhibitory concentration for these strains is 0.125-6.25 μg / ml.

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

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.

Increases the sensitivity of tumors to radiation, causes sensitization to alcohol (disulfiram-like action).

Pharmacokinetics:

Absorption is high (bioavailability is not 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 the blood-brain and placental barrier. The volume of distribution: adults - about 0,55 l / kg, newborns-0,54-0,81 l / kg.

The maximum concentration of the drug in the blood (C_max) is from 6 to 40 μg / ml, depending on the dose. Time to reach the maximum concentration (TC_max) - 1-3 hours. Communication with plasma proteins - 10-20%.

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

The half-life (T_1/2) With normal hepatic function - 8 hours (6 to 12 hours), with alcoholic liver disease - 18 h (from 10 to 29 h), in neonates: born at 28-30 weeks gestation - about 75 hr, respectively, 32-35 weeks - 35 h, 36-40 weeks -. 25 hours excreted by the kidneys 60-80% (20% unchanged) through 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 admission 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 small quantities.

Indications:

Prevention and treatment of infections caused by microorganisms that are sensitive to metronidazole ( Bacteroides spp., AT. fragilis, AT. distasonis, AT. ovatus, AT. thetaiotaomicron, AT. Vulgates, Clostridium, Peptococcus and Peptostreptococcus):

protozoal infections: extraintestinal amebiasis, including amebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis, giardiazis,balantidiasis, giardiasis, cutaneous leishmaniasis, trichomonas vaginitis, trichomoniasis urethritis;
infection of bones and joints;
infections of the central nervous system (CNS);
infection of the abdominal cavity;
infections of the pelvic organs;
infections of the skin and soft tissues;
sepsis.

Pseudomembranous colitis (associated with the use of antibiotics).

Gastritis or duodenal ulcer associated with Helicobacter pylori.

Prevention of anaerobic infection during surgical interventions.

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

Crohn's disease.

Contraindications:

Hypersensitivity to any components of the drug, leukopenia (including in the anamnesis), organic lesions of the central nervous system, epilepsy, liver failure (in the case of high doses), pregnancy (I trimester), lactation.

Children's age (up to 3 years).

Carefully:

Pregnancy (M-trimester), renal / hepatic insufficiency.

Diseases of the blood and active stage of CNS diseases

Care should be taken when prescribing metronidazole to people with blood and central nervous system diseases.If the duration of treatment exceeds the recommended time, systematic monitoring of the blood picture (especially the level of leukocytes) and neurological status is necessary in order to avoid the development of side effects from the central and peripheral nervous system (such as paresthesia, ataxia, dizziness, epileptic seizures).

Diseases of the liver

In patients with severe liver disease, a dose reduction is necessary. This is especially true for patients with hepatic encephalopathy, since metronidazole can contribute to increased symptoms.

Alcohol, including alcohol-containing medicines

You can not consume alcohol during the treatment with metronidazole and within three days after its withdrawal due to the risk of developing a disulfiram-like reaction between metronidazole and alcohols. This also applies to alcohol-containing drugs, both in the oral and parenteral forms.

Lithium preparations

When concurrent administration of metronidazole and lithium preparations, and also within 2-3 weeks after the withdrawal of metronidazole, the level of lithium, creatinine and electrolytes of blood serum should be carefully monitored.

Kidney Diseases

At the time of hemodialysis metronidazole should be canceled. The drug should not be prescribed until the completion of the course of hemodialysis.

Taking metronidazole may be accompanied by staining the urine in a dark color.

Metronidazole, film-coated tablets, contain lactose, so the drug should not be administered to patients with congenital galactose intolerance, Lappease lactase deficiency or impaired glucose-galactose absorption.

Dosing and Administration:

Inside, during or after a meal, (or squeezed milk), without chewing.

Infections caused by anaerobic bacteria

Adults: 500 mg 3 times a day.

Children: 30-50 mg / kg per day in 3 divided doses.

Acute amoebic dysentery, amoebic liver abscess

Adults: 2 g once a day for 3 days or 500-1000 mg 3 times a day for 5-10 days.

Children: 30-50 mg / kg per day in 3 divided doses for 5 days.

Asymptomatic course of amoebic dysentery

Adults: 500 mg 3 times a day.

Children: 25-40 mg / kg per day in 2-4 admission for 5-10 days.

Lambliasis

Adults: 2 g once a day for 2-3 days or 500 mg 2 times a day for 5-7 days.

Children: 25-40 mg / kg per day in 2-4 admission for 7 days.

Trichomoniasis

Adults: 500 mg twice daily for 6 days or 2 g once.

Ulcerative gingivitis

Adults: 500 mg 3 times a day for 3 days.

Nonspecific vaginitis

Adults: 2 g on the first and third day or 500 mg 2 times a day for 7 days.

Crohn's disease

Adults: 500 mg twice a day.

Children: 15 mg / kg per day in 2 divided doses.

Prevention of anaerobic infection in surgical interventions

Adults: 1 g once.

Children: 25 mg / kg.

Postoperative treatment

Adults: 500 mg 3 times a day.

Children: 30-50 mg / kg per day in 3 divided doses.

Liver failure

For patients with severe hepatic insufficiency, there is a risk of accumulation of metronidazole and its metabolites. In such patients metronidazole use with caution. The recommended daily dose should be reduced three-fold, taking once daily.

Renal insufficiency

No dose reduction is required.

Older and older patients

No dose reduction is required.

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),change in the color of the tongue / "lined tongue" (due to the growth of fungal microflora).

Immune system disorders: angioedema, anaphylactic shock.

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 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.

Disturbances on the part of the organ of sight: transient visual impairments, such as diplopia and myopia, vagueness of contours of subjects, reduced visual acuity, violation of color perception; Neuropathy / optic neuritis.

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

Disturbances from the side of baked 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 and combinations with other antibacterial agents, there were cases of liver failure that required liver transplantation.

Disturbances 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 of urine in a brownish-reddish color due to the presence in the urine of a water-soluble metabolite of metronidazole, dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

General disorders and disorders at the site of administration: fever, nasal congestion, arthralgia, weakness.

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

Overdose:

Symptoms

The most common symptoms of overdose are nausea, vomiting, food aversion, metallic taste in the mouth, headache and dizziness.Seldom symptoms include insomnia, drowsiness, CNS depression, oliguria and staining of urine in a dark color. In some cases, there is a development of ototoxic effect and epileptic seizures.

Treatment of complications

In connection with the absence of a specific antidote, symptomatic and supportive therapy is performed. Metronidazole can be removed from the blood with hemodialysis, however, this rarely occurs.

Interaction:

It is not recommended simultaneous use of metronidazole with the following drugs:

Alcohol, including alcohol-containing medicines

Possible mechanism: Metronidazole inhibits the metabolism of acetaldehyde.

Result: disulfiram-like reaction (reddening of the skin, vomiting, a feeling of heat, rapid breathing and tachycardia). Simultaneous reception should be avoided.

Amiodarone

Possible mechanism: Metronidazole suppresses the metabolism of amiodarone.

Result: Increased risk of cardiotoxic effect (lengthening of the interval QT, bidirectional spindle ventricular (pirouette) tachycardia, cardiac arrest).

Busulfan

Metronidazole can help increase the concentration of busulfan in the blood plasma, and, consequently, increase its toxicity.

Disulfiram

Possible mechanism: unknown.

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

The simultaneous administration of metronidazole with the following drugs should be done with caution:

Ergot alkaloids (eg, ergotamine)

Possible mechanism: Metronidazole inhibits the activity of cytochrome P450 3A4 and, as a result, slows the metabolism of ergot alkaloids.

Result: Increased risk of ergotism (nausea, vomiting, vasospastic ischemia).

Warfarin

Possible mechanism: Metronidazole inhibits the metabolism of warfarin.

Result: Increased effects of warfarin and, as a result, risk of bleeding.

With the simultaneous use of both drugs, the prothrombin time should be determined at short intervals and the dose of warfarin should be adjusted, if necessary.

Vecuronium

Result: Metronidazole strengthens the action of vecuronium.

Carbamazepine

Possible mechanism: Unknown. It is possible to slow the metabolism of carbamazepine under the influence of metronidazole.

Result: Metronidazole can increase the concentration of carbamazepine in the blood serum and, consequently, increase its toxicity.

Lithium preparations

Possible mechanism: Decreased renal clearance of lithium.

Result: Increase in the concentration of lithium in blood plasma and the risk of toxic effects of lithium (weakness, tremor, severe thirst, confusion).

Tacrolimus

Possible mechanism: Metronidazole suppresses metabolism and excretion of tacrolimus.

Result: Metronidazole can increase the concentration of tacrolimus in the blood plasma and, as a consequence, increase the risk of its toxic effects (nephrotoxicity, hyperglycemia, hypercalcemia).

Phenytoin

Possible mechanism: Suppression of the metabolism of phenytoin or enhancement of microsomal metabolism of metronidazole.

Result: Increased risk of toxic effects of phenytoin and a decrease in the concentration of metronidazole in the blood plasma.

Phenobarbital

Possible mechanism: Metronidazole metabolism acceleration in the liver.

Result: Decreased concentration of metronidazole in plasma.

Fluorouracil

Possible mechanism: Reducing the clearance of fluorouracil.

Result: Increased concentration of fluorouracil in the blood serum, as well as the risk of its toxic effects (granulocytopenia, anemia, thrombocytopenia, stomatitis, vomiting).

Cholestyramine

Possible mechanism: Decreased absorption of metronidazole.

Result: Decreased efficacy of metronidazole.

Cyclosporin

Possible mechanism: It is possible to increase the concentration of cyclosporine in the blood under the influence of metronidazole. If simultaneous administration of metronidazole and cyclosporine is required, the concentration of cyclosporin and creatinine in serum should be determined at short intervals.

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

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

Sulfonamides increase the antimicrobial effect of metronidazole.

Laboratory research

The use of metronidazole may affect certain blood test parameters, such as activity of aspartate aminotransferase (AcAt), alanine aminotransferase (AlAt), lactate dehydrogenase (LDH), hexokinase, triglyceride level. The values of these parameters can be reduced to zero.

Special instructions:

Adhere to the regionally approved standards for the use of antibiotics.

Metronidazole Nycomed tablets coated with a film coat contain lactose, in this connection the drug should not be administered to patients with congenital intolerance to galactose, deficiency of Lapp lactase or impaired absorption of glucose-galactose.

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

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. Treatment does not stop during menstruation. After trichomoniasis therapy, control tests should be performed for three consecutive cycles before and after menstruation.

After the treatment of giardiasis, if symptoms persist, after 3 to 4 weeks, 3 feces should be analyzed at intervals of several days (in some successfully treated patients lactose intolerance caused by invasion can persist for several weeks or months, recalling the symptoms of giardiasis).

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

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

Form release / dosage:

Tablets, film-coated, 500 mg.

Packaging:

For 20 tablets are placed in bottles of dark glass, sealed with a screw cap made of polyethylene, under which there is a ring for tearing off the sealing gasket, which provides control of the first opening.

One bottle together with the instruction for use is placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N013250 / 01

Date of registration:19.01.2012 / 13.11.2015

Expiration Date:Unlimited

The owner of the registration certificate:Takeda Pharma A / STakeda Pharma A / S Denmark

Manufacturer: & nbsp

Takeda Pharma A / S Denmark

Representation: & nbspTakeda Pharmaceuticals Ltd.Takeda Pharmaceuticals Ltd.

Information update date: & nbsp10.09.2016

Illustrated instructions

Instructions

Metronidazole Nycomed (Metronidazole Nycomed)