Flagyl

Flagyl contains the active ingredient metronidazole; the drug belongs to the subgroup of nitro-5-imidazoles and has a therapeutic effect on the biochemical reduction of the 5-nitro group of metronidazoles using transport proteins of protozoan and anaerobic cells.

After restoration, the specified group, interacting with the DNA of the microbial cells, suppresses the binding of nucleic acids, causing lysis of the pathogenic bacterium cell. [ 1 ]

2-oxymetronidazole (the main metabolic unit of metronidazole) also has antiprotozoal and antimicrobial effects.[ 2 ]

Indications Flagyl

It is used (in tablets) for the following diseases:

• protozoal infections (including the extraintestinal form of amebiasis (also amebic liver abscess) and its intestinal form, balantidiasis, giardiasis, vaginitis or urethritis of trichomonas origin, epidermal leishmaniasis and trichomoniasis);
• lesions associated with the influence of bacteroids (these include infections of bones and joints or the central nervous system ( meningitis or brain abscess), bacterial endocarditis, pulmonary empyema or abscess, pneumonia and sepsis);
• infections caused by strains of clostridia, peptostreptococci and peptococci (including infections affecting the pelvic organs (abscess in the fallopian tubes and ovaries, endometritis and vaginal vault infections) and intraperitoneal lesions (peritonitis or liver abscess));
• gastritis or ulcers in the duodenum associated with the influence of Helicobacter pylori (combination treatment);
• pseudomembranous colitis (associated with antibiotic use);
• prevention of complications during the postoperative period (this especially concerns operations in the colon area, appendectomy, pararectal procedures and gynecological interventions).

Suppositories are prescribed in the following cases:

• local treatment for vaginitis (this includes its trichomonas and non-specific forms);
• prevention of the formation of anaerobic infections that may occur when performing operations in the peritoneum and pelvic organs.

Release form

The drug is available in the form of tablets for oral administration (20 pieces) and vaginal suppositories (10 pieces).

Pharmacodynamics

The antiprotozoal and antimicrobial effect of metronidazole develops in relation to most pathogenic bacteria, including: Trichomonas, peptostreptococci with dysenteric amoeba, peptococci, fusobacteria with intestinal lamblia and clostridia, and in addition to this, anaerobic bacteroid strains of obligate spore-forming and non-spore-forming types, as well as individual eubacterial strains.

Resistance to metronidazole is found in facultative and aerobic strains of anaerobic bacteria. [ 3 ]

Pharmacokinetics

After oral administration, metronidazole is almost completely and rapidly absorbed in the gastrointestinal tract (approximately 80% in 1 hour). Food intake does not change the absorption of the drug. The bioavailability level is 100%. After oral administration of 0.5 g of metronidazole, after 1 hour its plasma level is 10 mcg/ml, and after 3 hours – 13.5 mcg/ml.

The half-life is within 8-10 hours. Synthesis with serum protein is no more than 10-20% of the applied dosage.

Metronidazole rapidly passes into tissue fluids (including kidneys, liver, bile, lungs, skin, vaginal secretions, saliva, cerebrospinal fluid and seminal fluid) and breast milk, and also crosses the placenta.

About 30-60% of the drug undergoes changes during metabolic processes through hydroxylation, oxidation and glucuronidation.

Metronidazole is 40-70% excreted through the kidneys (35% is unchanged).

In case of kidney disease, repeated use of metronidazole may result in its accumulation in the serum.

When the drug is administered vaginally in a 0.5 g dose, systemic absorption is approximately 20%; intraplasmic values are approximately 12%, compared with the same single dose taken orally.

Less than 20% of the drug undergoes protein synthesis. The half-life term with systemic use and healthy liver function is 8-10 hours.

Dosing and administration

Schemes for using tablets.

The tablets are taken orally.

For amebiasis, adults should take 1.5 g of the medicine per day (divide the dose into 3 doses). Therapy lasts 7 days.

In case of giardiasis, a child aged 6-10 years should take 375 mg of the substance per day, a child aged 10-15 years – 0.5 g, and an adult – 0.75-1 g. Treatment continues for 5 days.

Trichomoniasis (urethritis or vaginitis in women and urethritis in men) requires a single dose of 2 g or a course of treatment - with a daily dosage of 0.5 g (divided into 2 doses) and a duration of therapy of 10 days.

For non-specific vaginitis, 0.5 g of Flagyl is used per day (divided into 2 doses); therapy lasts 1 week.

To treat anaerobic infections, it is necessary to use 1-1.5 g of the medicine per day.

In case of severe renal dysfunction (CC level below 10 ml per minute), it is necessary to reduce the daily dose by half.

Schemes for the use of suppositories.

Suppositories can only be used by adult women. The suppository must be inserted deep into the vagina.

For trichomonas vaginitis, use 1 suppository (0.5 g) per day, in combination with Flagyl tablets. Therapy continues for 10 days.

For non-specific vaginitis, use 1 suppository 2 times a day (1 g per dose). Treatment lasts 1 week. If necessary, you can also use the oral form of the drug.

It is imperative to carry out the same therapy on the woman’s sexual partner, regardless of whether he has visible signs of the disease.

Flagyl can be used for a maximum of 10 days; the course can be repeated a maximum of 2-3 times per year.

• Application for children

It is prohibited to use tablets in persons under 6 years of age, and suppositories in patients under 18 years of age.

Use Flagyl during pregnancy

Flagyl should not be prescribed during breastfeeding or pregnancy.

Contraindications

Among the contraindications for suppositories and tablets:

• organic lesions of the central nervous system;
• blood diseases (including a history of leukopenia);
• personal intolerance to imidazole;
• liver failure (when large doses are used).

Side effects Flagyl

Side effects for suppositories and tablets:

• leuko- or neutropenia;
• xerostomia, glossitis, vomiting or nausea, metallic taste and loss of appetite, as well as diarrhea or constipation, stomatitis, anorexia and epigastric pain;
• polyuria, cystitis, dysuria, urinary incontinence, urine turning reddish-brown;
• fever, incoordination, headaches, hallucinations, dizziness, confusion, insomnia, convulsions, weakness and polyneuropathy (especially after prolonged use), as well as ataxia, severe excitability, depression and irritability;
• epidermal rashes or hyperemia, urticaria;
• nasal congestion, candidiasis, pancreatitis, flattening of the T-wave in ECG readings and arthralgia.
• Negative effects of candles:
• burning or irritation in the penis area of the patient's sexual partner;
• increased frequency of urination;
• vulvitis;
• vaginal burning;
• vaginal candidiasis (develops after stopping treatment).

Overdose

Metronidazole poisoning causes vomiting or nausea and ataxia, as well as polyneuropathy and convulsions; symptomatic measures are required.

Interactions with other drugs

When used together with ethanol-containing drugs, intolerance to them develops.

The combination of metronidazole and disulfiram can provoke the development of various neurological symptoms, which is why it is necessary to use these drugs with at least a 2-week interval.

Combination with indirect anticoagulants potentiates their activity, which leads to an increase in the level of PT.

Administration simultaneously with cyclosporine or lithium agents may cause an increase in their plasma values.

Cimetidine can inhibit the metabolic transformations of metronidazole, as a result of which its serum level may increase and the risk of developing negative symptoms may increase.

Combination with drugs that stimulate liver microsomal enzymes (phenobarbital or phenytoin) may increase the excretion of metronidazole, resulting in a decrease in its plasma level.

Flagyl reduces the clearance rates of 5-fluorouracil and increases serum levels of busulfan, which increases the toxicity of these drugs.

It is prohibited to combine metronidazole with non-depolarizing muscle relaxants (vecuronium bromide).

Storage conditions

Flagyl must be stored at temperatures no higher than 25°C.

Shelf life

Flagyl tablets can be used within a 5-year period from the date of manufacture of the therapeutic product; the shelf life of suppositories is 4 years.

Analogues

The analogs of the drug are Ginofort, Zalain and Atrican with Tinidazole, and in addition Ginalgin, Livarol and Nitasol, Candid and Ketoconazole with Neo-Penotran. Also on the list are Clotrimazole, Candibene, Funginal and Mikogal.

Reviews

Flagyl receives quite mixed reviews. Some comments note the high therapeutic effectiveness of the drug, but there are also reports in which patients write about the frequent development of intense side effects when using it.

It should be noted that the use of metronidazole often causes various, sometimes severe, negative manifestations (weakness, fever, dizziness, epigastric pain, vomiting or nausea, urticaria, etc.), but, due to the high effectiveness of treatment and the low cost of the drug, they do not prevent it from remaining a fairly popular means of therapy.