Bacimex (Solution) Instructions for Use

Marketing Authorization Holder

Otsuka Pharmaceutical India, Private Limited (India)

ATC Code

J01XD01 (Metronidazole)

Active Substance

Metronidazole (Rec.INN registered by WHO)

Dosage Form

Bacimex

Solution for infusion 500 mg/100 ml: vial 1 pc.

Dosage Form, Packaging, and Composition

Solution for infusion transparent, from colorless to pale yellow.

Excipients: sodium chloride – 790 mg, citric acid monohydrate – 22.9 mg, anhydrous sodium hydrogen phosphate – 47.6 mg, water for injections – up to 100 ml.

100 ml – polyethylene vials (1) – cardboard packs.

Clinical-Pharmacological Group

Antiprotozoal drug with antibacterial activity

Pharmacotherapeutic Group

Antimicrobial and antiprotozoal agent

Pharmacological Action

An antiprotozoal agent with antibacterial activity, a derivative of 5-nitroimidazole. The mechanism of action involves 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 interacts with the DNA of microbial cells, inhibiting the synthesis of nucleic acids, which leads to the death of microorganisms.

Active against Trichomonas vaginalis, Entamoeba hystolitica, as well as gram-negative anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides ovatus, Bacteroides distasonis, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp. and some gram-positive anaerobes (susceptible strains of Eubacterium spp., Clostridium spp., Peptococcus niger, Peptostreptococcus spp.). The MIC for these strains is 0.125-6.25 µg/ml. In combination with amoxicillin, it is active against Helicobacter pylori (amoxicillin suppresses the development of resistance to metronidazole).

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

Pharmacokinetics

After IV administration of 500 mg over 20 minutes, the C_max in blood serum after 1 hour is 35.2 µg/ml. The concentration of metronidazole in blood serum after 4 hours is 33.9 µg/ml, after 8 hours is 25.7 µg/ml; C_min during subsequent administration is 18 µg/ml. T_max is 30-60 minutes, the therapeutic concentration is maintained for 6-8 hours.

With normal bile formation, the concentration of metronidazole in bile after IV administration can significantly exceed the concentration in plasma.

Binding to blood proteins is insignificant and does not exceed 10-20%. Metronidazole rapidly penetrates into tissues (lungs, kidneys, liver, skin, bile, cerebrospinal fluid, saliva, seminal fluid, vaginal secretions), breast milk and crosses the placental barrier.

About 30-60% of metronidazole is metabolized by hydroxylation, oxidation and glucuronidation. The main metabolite (2-hydroxymetronidazole) also has antiprotozoal and antimicrobial effects.

40-70% of metronidazole is excreted by the kidneys (unchanged – about 35% of the administered dose). T_1/2 is 8-10 hours.

Indications

Protozoal infections: extraintestinal amebiasis (including amoebic liver abscess), intestinal amebiasis (amoebic dysentery), trichomoniasis; infections caused by Bacteroides spp. (including Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides distasonis, Bacteroides vulgatus): bone and joint infections, CNS infections (including meningitis, brain abscess), bacterial endocarditis, pneumonia, empyema and lung abscess, sepsis; infections caused by Clostridium spp., Peptococcus niger, Peptostreptococcus spp.: abdominal infections (peritonitis, liver abscess), pelvic infections (endometritis, abscess of the fallopian tubes and ovaries, vaginal vault infections); pseudomembranous colitis associated with antibiotic use; gastritis or duodenal ulcer associated with Helicobacter pylori (as part of combination therapy); prevention of postoperative complications (especially after interventions on the colon, pararectal area, appendectomy, as well as after gynecological operations).

ICD codes

Dosage Regimen

Administer intravenously by slow infusion. Do not administer by rapid IV injection.

For adult patients, the standard dose is 500 mg every 8 hours. Infuse each 500 mg/100 ml vial over 20 to 30 minutes.

For severe anaerobic infections, the dose may be increased to a maximum of 4 grams per day, based on clinical severity.

For surgical prophylaxis, administer a single 500 mg dose approximately one hour prior to surgery. A second 500 mg dose may be given 8 hours later for prolonged procedures.

For pediatric patients, administer 7.5 mg/kg body weight every 8 hours. Calculate the dose based on the child’s weight.

Adjust the infusion rate for pediatric patients to achieve an infusion duration of 20 to 30 minutes per dose.

In patients with severe hepatic impairment, reduce the dose. Avoid high-dose regimens.

No specific dosage adjustment is required for renal impairment, including patients on hemodialysis.

The duration of therapy is typically 7 to 10 days, but may be extended based on clinical response.

Do not mix with other intravenous medications or additives in the same infusion container.

Inspect the solution visually for particulate matter and discoloration prior to administration. Do not use if the solution is cloudy or contains precipitates.

Adverse Reactions

From the digestive system epigastric pain, nausea, vomiting, diarrhea; inflammation of the oral mucosa (glossitis, stomatitis), taste disturbances (“metallic” taste in the mouth), decreased appetite, anorexia, dry oral mucosa, constipation; pancreatitis (reversible cases); tongue discoloration/”coated” tongue (due to excessive growth of fungal flora).

From the immune system angioedema, anaphylactic shock.

From the nervous system peripheral sensory neuropathy; headache, seizures, dizziness. Cases of encephalopathy (e.g., confusion) and subacute cerebellar syndrome (impaired coordination and synergy of movements, ataxia, dysarthria, gait disturbances, nystagmus and tremor) have been reported, which are reversible after discontinuation of metronidazole; aseptic meningitis.

From the psyche psychotic disorders, including confusion, hallucinations; depression, insomnia, irritability, increased excitability.

From the organ of vision transient visual disturbances such as diplopia, myopia, blurred vision, decreased visual acuity, impaired color perception; optic neuritis.

From the organ of hearing and labyrinthine disorders hearing impairment/hearing loss (including sensorineural deafness); tinnitus.

From the hematopoietic system agranulocytosis, leukopenia, neutropenia, thrombocytopenia.

From the liver and biliary tract increased activity of liver enzymes (AST and ALT, ALP), development of cholestatic or mixed hepatitis, hepatocellular liver damage, sometimes accompanied by jaundice. Cases of liver failure requiring liver transplantation have been observed in patients treated with metronidazole in combination with other antibiotics.

From the skin and subcutaneous tissues rash, itching, flushing, skin hyperemia, urticaria; pustular skin rash; acute generalized exanthematous pustulosis; fixed drug eruption; Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the urinary system possible brownish-reddish discoloration of urine due to the presence of a water-soluble metabolite of metronidazole in the urine; dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

From laboratory parameters and instrumental studies flattening of the T wave on ECG.

General reactions fever, nasal congestion, arthralgia, weakness.

Contraindications

Hypersensitivity to metronidazole, other nitroimidazole derivatives, imidazoles; organic lesions of the CNS (including epilepsy); leukopenia (including history); hepatic insufficiency (in case of prescribing the drug in high doses); pregnancy, breastfeeding period.

With caution

Hepatic encephalopathy, acute and chronic diseases of the peripheral and central nervous system (risk of worsening neurological symptoms), renal failure.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Contraindicated in high doses in hepatic insufficiency. Should be used with caution in hepatic encephalopathy.

Use in Renal Impairment

Should be used with caution in renal failure.

Pediatric Use

IV use in children is possible according to indications, in doses and regimens recommended for the respective age.

Special Precautions

Since the simultaneous use of metronidazole with alcohol (ethanol) can have an effect similar to that of disulfiram (skin flushing, flushing, vomiting, tachycardia), patients should be warned that during treatment and for at least one day after the end of metronidazole use, they should not consume alcoholic beverages or medicines containing ethanol.

Indications for long-term use of metronidazole should be carefully weighed and, in the absence of strict indications, its long-term use should be avoided.

If, in the presence of strict indications, Metronidazole is used for longer than is usually recommended, treatment should be carried out under the control of hematological parameters (especially leukocytes) and adverse reactions such as peripheral or central neuropathy (paresthesia, ataxia, dizziness, seizures), upon the appearance of which treatment should be discontinued.

When treating trichomonas vaginitis in women and trichomonas urethritis in men, it is necessary to refrain from sexual intercourse. Simultaneous treatment of sexual partners is mandatory. Treatment should not be interrupted during menstruation. After therapy for trichomoniasis, control tests should be performed during 3 subsequent cycles before and after menstruation.

Metronidazole should be used with caution in patients with hepatic encephalopathy, as well as in patients with acute or chronic diseases of the central or peripheral nervous system due to the possible risk of neurological deterioration.

Cases of severe hepatotoxicity/acute liver failure (including fatal cases that developed very rapidly after the start of treatment) have been reported in patients with Cockayne syndrome when treated with systemic metronidazole. Metronidazole should be prescribed to this category of patients only after a careful benefit/risk assessment and only in the absence of alternative treatment.

Liver function tests should be performed before starting treatment, during therapy and after its completion until liver function parameters return to normal values, or until baseline values of these parameters are reached. If liver function parameters are significantly exceeded during treatment, the drug should be discontinued.

Patients with Cockayne syndrome should be advised to immediately report any symptoms of potential liver damage to their doctor and to discontinue metronidazole.

Cases of severe bullous skin reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis or acute generalized exanthematous pustulosis, have been reported after the use of metronidazole. If symptoms or signs of these diseases develop, treatment with the drug should be stopped immediately.

It should be taken into account that Metronidazole can immobilize treponemes, which leads to a false-positive Nelson test.

Long-term use of metronidazole should be carefully justified due to possible mutagenicity and carcinogenicity.

Effect on ability to drive vehicles and mechanisms

During the use of metronidazole, it is advisable to refrain from performing potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

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

When used concomitantly with ethanol, disulfiram-like reactions may occur (skin flushing, flushing, vomiting, tachycardia).

When used concomitantly with indirect anticoagulants (warfarin) – enhancement of the anticoagulant effect and increased risk of bleeding, associated with a decrease in the hepatic metabolism of indirect anticoagulants, which may lead to prolongation of prothrombin time. In case of simultaneous use of metronidazole and indirect anticoagulants, more frequent monitoring of prothrombin time and, if necessary, adjustment of anticoagulant doses is required.

When metronidazole is used concomitantly with lithium preparations, the concentration of the latter in blood plasma may increase. When used concomitantly, plasma concentrations of lithium, creatinine and electrolytes should be monitored.

When metronidazole is used concomitantly with cyclosporine, the concentration of cyclosporine in blood plasma may increase. If simultaneous use of metronidazole and cyclosporine is necessary, plasma concentrations of cyclosporine and creatinine should be monitored.

Cimetidine inhibits the metabolism of metronidazole, which may lead to an increase in its plasma concentration and an increased risk of adverse events.

Concomitant use of metronidazole with drugs that induce microsomal oxidation isoenzymes in the liver (phenobarbital, phenytoin) may accelerate the elimination of metronidazole, resulting in a decrease in its plasma concentration.

Metronidazole reduces the clearance of fluorouracil, leading to increased toxicity.

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

It is not recommended to use Metronidazole with non-depolarizing muscle relaxants (vecuronium bromide).

Sulfonamides enhance the antimicrobial effect of metronidazole.

Concomitant use of mebendazole and metronidazole should be avoided.

Simultaneous administration of metronidazole with other solutions containing sodium salts may lead to sodium retention in the body.

During laboratory tests while using metronidazole, difficulties may arise in determining the activity of AST, ALT, LDH, and the concentration of triglycerides.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.