Metronidazole, tablets 250 mg 20 pcs

Pharmacotherapeutic group: antimicrobial and antiprotozoal agent

ATX code: J01XD01

Pharmacological properties

Pharmacodynamics

Metronidazole is a 5-nitroimidazole derivative. The mechanism of action of metronidazole consists in biochemical reduction of the 5-nitrogroup of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitrogroup of metronidazole interacts with the deoxyribonucleic acid (DNA) of the microbial cell, inhibiting the synthesis of their nucleic acids, which leads to the death of the microorganisms.

Active against Trichomonas vaginalis, Entamoeba histolytica, as well as Gram-negative anaerobes Bacteroides spp. (including B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus), Fusobacterium spp, and some gram-positive anaerobes (sensitive strains of Eubacterium spp., Clostridium spp., Peptococcus niger., Peptostreptococcus spp.). The minimum suppressive concentration for these strains is 0.125-6.25 µg/ml. In combination with amoxicillin it shows activity against Helicobacter pylori (amoxicillin suppresses development of resistance to metronidazole).

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

Pharmacokinetics

Metronidazole is rapidly and almost completely absorbed when ingested (about 80% in 1 hour). Food intake has no effect on absorption of metronidazole. Bioavailability is at least 80%. After oral administration of metronidazole in a dose of 500 mg, its concentration in blood plasma is 10 µg/ml after 1 hour, 13.5 µg/ml after – 3 hours. Binding to blood proteins is insignificant and does not exceed 10-20%. Metronidazole quickly penetrates into tissues (lungs, kidneys, liver, skin, bile, cerebrospinal fluid, saliva, seminal fluid, vaginal secretion), into breast milk and passes through the placental barrier. About 30-60% of metronidazole is metabolized by hydroxylation, oxidation and glucuronidation. The main metabolite (2-oxymetronidazole) also has antiprotozoal and antimicrobial effects.

40-70% of metronidazole is excreted by the kidneys (unchanged – about 35% of the taken dose). The elimination half-life is 8-10 hours.

In patients with impaired renal function when taking metronidazole during a course of treatment, its concentration in serum may increase.

Indications

Protozoal infections: extraintestinal amebiasis (including amebic liver abscess), intestinal amebiasis (amebic dysentery), trichomoniasis.

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

Infections caused by Clostridium spp., Peptococcus niger and Peptostreptococcus spp.: abdominal infections (peritonitis, liver abscess), pelvic infections (endometritis, fallopian tube and ovarian abscess, vaginal abscess infections).

Pseudomembranous colitis associated with the use of antibiotics.

Gastritis or duodenal ulcer associated with Helicobacter pylori (as part of complex therapy).

Prevention of postoperative complications (especially after operations on the colon, in the pararectal area, appendectomy, gynecological operations).

Active ingredient

Metronidazole

Composition

In one tablet:

The active ingredient: metronidazole – 250 mg.

Auxiliary substances: potato starch, stearic acid, povidone (polyvinylpyrrolidone low molecular weight medical 12600±2700, plasdon K-17), sucrose (sugar powder).

How to take, the dosage

Metronidazole is taken orally, before or after meals, with plenty of water.

In intestinal amebiasis, metronidazole is taken in a daily dose of 1500 mg (divided into 3 doses) for 7 days.

In acute amebic dysentery, the daily dose is 2250 mg (divided into 3 doses). In children from 6 to 15 years old a daily dose of 500 mg (divided into 2 doses) is prescribed. In liver abscess and other extraintestinal forms of amebiasis, the maximum daily dose is 2500 mg (divided into 3 doses) for 3-5 days, in combination with tetracycline antibiotics and other therapies. Children from 6 to 15 years of age are prescribed a daily dose of 500 mg (divided into 2 doses).

In case of trichomoniasis in women (urethritis and vaginitis) metronidazole is indicated as a single dose of 2 g or as a course treatment of 250 mg 2 times a day for 10 days.

In case of trichomoniasis in men (urethritis) metronidazole is indicated as a single dose of 2 g or as a course treatment of 250 mg 2 times daily for 10 days.

The treatment of anaerobic infections usually begins with intravenous infusions followed by conversion to tablets. For adults, the dose of the drug is 500 mg 3 times a day.

The duration of treatment is up to 7 days. For treatment of pseudomembranous colitis metronidazole is prescribed 500 mg 3-4 times a day. The duration of treatment is determined by the doctor.

For eradication of Helicobacter pylori metronidazole is indicated at 500 mg 3 times daily in combination therapy (for example, with amoxicillin).

To prevent postoperative complications, metronidazole is prescribed in a daily dose of 750-1500 mg (divided into 3 doses) 3-4 days before surgery. One to two days after surgery (when oral administration is already allowed), metronidazole is prescribed at 750 mg per day for 7 days.

Interaction

With disulfiram

Psychotic reactions have been reported in patients receiving metronidazole and disulfiram concomitantly (the interval between the use of these drugs should be at least 2 weeks).

With ethanol

There may be disulfiram-like reactions (skin hyperemia, blood rush to the skin, vomiting, tachycardia).

With indirect anticoagulants (warfarin)

Increased anticoagulant effect and increased risk of bleeding associated with decreased hepatic metabolism of indirect anticoagulants, which may lead to prolongation of prothrombin time. In case of concomitant use of metronidazole and indirect anticoagulants, more frequent monitoring of prothrombin time and, if necessary, adjustment of anticoagulant doses is required.

With lithium preparations

Concomitant use of metronidazole with lithium preparations may increase the concentration of the latter in blood plasma. Concentrations of lithium, creatinine and electrolytes in plasma should be monitored during concomitant use.

With cyclosporine

Concomitant use of metronidazole with cyclosporine may increase the plasma concentration of cyclosporine. If simultaneous use of metronidazole and cyclosporine is necessary, plasma concentrations of cyclosporine and creatinine should be monitored.

With cimetidine

Cimetidine inhibits the metabolism of metronidazole, which may increase its plasma concentrations and increase the risk of side effects.

With drugs that induce microsomal oxidation isoenzymes in the liver (phenobarbital, phenytoin)

Concomitant use of metronidazole Concomitant use of metronidazole with drugs that induce isoenzymes of microsomal oxidation in the liver (phenobarbital, phenytoin) may accelerate excretion of metronidazole, resulting in lower plasma concentrations.

With fluorouracil

Metronidazole decreases clearance of fluorouracil, leading to increased toxicity.

With busulfan

Metronidazole increases the plasma concentration of busulfan, which can lead to severe toxic effects of busulfan.

With non-depolarizing myorelaxants (vecuronium bromide)

The use with non-depolarizing myorelaxants (vecuronium bromide) is not recommended.

With sulfonamides

Sulfonamides increase the antimicrobial effects of metronidazole.

Special Instructions

Since concomitant administration of metronidazole with alcohol (ethanol) may have effects similar to those of disulfiram (skin flushing, blood rush to the skin, vomiting, tachycardia), patients should be warned not to consume alcoholic beverages or drugs containing ethanol during treatment and for at least one day after completion of the drug.

The indications for long-term use should be carefully weighed and long-term use should be avoided in the absence of a strong indication. If in strict indications the drug is used longer than normally recommended, treatment should be monitored for hematologic parameters (especially leukocytes) and adverse reactions such as peripheral or central neuropathy manifested (paresthesias, ataxia, dizziness, seizures), if they occur, treatment should be discontinued.

When treating trichomonad vaginitis in women and trichomonad urethritis in men it is necessary to refrain from sexual contacts. Simultaneous treatment of sexual partners is mandatory. You should not stop treatment during menstruation. After the therapy of trichomoniasis, control tests should be carried out for 3 consecutive cycles before and after menstruation.

The development of severe hepatotoxicity/acute hepatic failure (including fatalities that developed very rapidly after initiation of treatment) has been reported in patients with Cockayne syndrome when treated with metronidazole for systemic use. Metronidazole should be administered to this category of patients only after careful assessment of the benefit/risk ratio and only if no alternative treatment is available.

Liver function tests should be performed before initiation of therapy, during therapy and after therapy until liver function values reach normal values or until baseline values are reached. If liver function values are significantly exceeded during treatment, the drug should be discontinued.

Patients with Cockayne syndrome should be advised to inform their physician immediately if they develop any symptoms of potential liver damage and discontinue metronidazole.

It should be taken into account that metronidazole may immobilize treponemes, resulting in a false-positive Nelson’s test.

Effect on driving, operating machinery

Given the risk of adverse reactions such as confusion, dizziness, hallucinations, visual disturbances, it is recommended to refrain during treatment from driving and from other potentially dangerous activities requiring increased concentration and rapid psychomotor reactions.

Synopsis

Round flat cylindrical white to white to white with a yellowish-greenish tinge with a rib and bevel.

Contraindications

– hypersensitivity to metronidazole, to other nitroimidazole derivatives, to imidazoles or to other components of the drug;

– organic CNS lesions (including epilepsy);

– leukopenia (including history);

– hepatic impairment (in case of high doses);

– pregnancy;

– breastfeeding period; <

– childhood under 6 years of age;

– sucrose/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption.

With caution

– hepatic encephalopathy;

– acute and chronic peripheral and central nervous system disorders (risk of worsening of neurologic symptoms);

– renal failure.

Side effects

Gastrointestinal disorders

Pain in the epigastrium, nausea, vomiting, diarrhea.

– Inflammation of the oral mucosa (glossitis, stomatitis), taste disorders (“metallic” taste in the mouth), decreased appetite, anorexia, dry oral mucosa, constipation.

– Pancreatitis (reversible cases).

– Discoloration of the tongue/”encrusted” tongue (due to excessive growth of fungal microflora).

Immune system disorders

– Angioneurotic edema, anaphylactic shock.

Nervous system disorders

– Peripheral sensory neuropathy.

– Headache, seizures, dizziness.

– The development of encephalopathy (e.g., confusion) and subacute cerebellar syndrome (impaired coordination and synergism of movements, ataxia, dysarthria, gait disturbances, nystagmus and tremor) have been reported and are reversed after withdrawal of metronidazole.

– Aseptic meningitis.

Psychiatric disorders

– Psychotic disorders, including confusion, hallucinations.

– Depression, insomnia, irritability, increased excitability.

Visual disorders

– Transient visual disturbances such as diplopia, myopia, blurred vision, decreased visual acuity, impaired color perception.

– Neuropathy/neuritis of the optic nerve.

Hearing and labyrinth disorders

– Hearing disorders/hearing loss (including neurosensory deafness).

– Tinnitus.

Blood and lymphatic system disorders

– Agranulocytosis, leukopenia, neutropenia and thrombocytopenia.

Liver and biliary tract disorders

. – Increased activity of “liver” enzymes (aspartate aminotransferase (AST) and alanine aminotransferase (ALT), alkaline phosphatase), development of cholestatic or mixed hepatitis, hepatocellular liver damage, sometimes accompanied by jaundice.

In patients treated with metronidazole in combination with other antibiotics, there have been cases of liver failure requiring liver transplantation.

Skin and subcutaneous tissue disorders

– Rash, itching, skin rash, skin flushing, skin hyperemia, urticaria.

– Pustular skin rash.

– Fixed drug rash.

– Stevens-Johnson syndrome, toxic epidermal necrolysis.

Renal and urinary tract disorders

– Possible staining of urine with brownish-reddish color due to the presence of water-soluble metabolite of metronidazole in urine.

– Dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

General disorders and disorders at the site of administration

Fever, nasal congestion, arthralgia, weakness.

Laboratory and instrumental findings

Smoothing of the T wave on the ECG.

Overdose

Ingestion of single doses of metronidazole up to 12 g has been reported in suicide attempts and accidental overdoses.

Symptoms: vomiting, ataxia, slight disorientation.

Treatment: there is no specific antidote for metronidazole overdose. If a significant overdose is suspected, symptomatic and supportive therapy should be given.

Pregnancy use

Since metronidazole passes through the placental barrier and its effect on human fetal organogenesis is unknown, use of the drug during pregnancy is contraindicated.

Metronidazole penetrates into breast milk, so the use of the drug during breastfeeding is contraindicated.

Similarities

Flagil, Metrogil, Trichopol, Metronidazole, Rosamet, Metronidazole-Acos, Metronidazole Renewal