Norbactin

INSTRUCTIONS for medical use of the medicinal product NORBACTIN (NORBACTIN)

Composition:

Active substance: norfloxacin;

1 tablet contains 400 mg of norfloxacin;

Excipients: microcrystalline cellulose, sodium croscarmellose, sodium lauryl sulfate, maize starch, colloidal anhydrous silicon dioxide, magnesium stearate, talc, hydroxypropylmethylcellulose, macrogol, titanium dioxide (E 171).

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties: white or almost white, oblong film-coated tablets, with "NBT 400" embossed on one side and a score line on the other; both sides of the tablet have characteristic bevelled edges and shape.

Pharmacotherapeutic group. Antibacterial agents for systemic use. Fluoroquinolones. ATC code J01MA06.

Pharmacological properties.

Pharmacodynamics.

Norfloxacin inhibits bacterial deoxyribonucleic acid (DNA) synthesis by affecting the enzyme DNA gyrase, thereby exerting a bactericidal effect.

The primary spectrum of activity of norfloxacin, with possible geographical variations in susceptibility, includes activity against Neisseria gonorrhoeae (including penicillinase-producing strains).

Norfloxacin is generally effective against pathogenic microorganisms causing urinary tract infections, such as E. coli, Enterobacter spp., Klebsiella, Proteus spp., Pseudomonas aeruginosa, and Serratia marcescens. Additionally, norfloxacin may be effective against pathogenic microorganisms causing enteritis, such as E. coli, Salmonella enteritis, and Campylobacter spp.

Norfloxacin shows moderate activity against certain strains of Ureaplasma urealyticum. Higher levels of resistance are expected against Enterococcus faecalis and Enterococcus faecium.

Norfloxacin is ineffective against obligate anaerobic pathogenic microorganisms such as Actinomyces spp., Bacteroides spp., Clostridium spp. (except for certain strains of C. perfringens) and Peptostreptococcus spp., as well as against Stenotrophomonas maltophilia and Chlamydia trachomatis. There is partial cross-resistance between norfloxacin and other fluoroquinolones. There is no cross-resistance with structurally unrelated substances such as penicillins, cephalosporins, tetracyclines, macrolide antibiotics, aminoglycosides, sulfonamides, 2,4-dihydroxypyrimidines, or combinations of these substances (e.g., co-trimoxazole).

Methicillin-resistant staphylococci are generally resistant to fluoroquinolones.

Pharmacokinetics.

Norfloxacin is rapidly absorbed in the gastrointestinal tract after oral administration, with an absolute bioavailability of 30–40%. Food intake slows absorption. Peak plasma concentrations are reached within 1–2 hours after dosing. The elimination half-life of norfloxacin is approximately 4 hours; it may be prolonged in patients with renal impairment. About 14% of the administered dose is protein-bound in plasma. Norfloxacin achieves high concentrations in tissues of the urogenital tract, urine, and bile. Nearly 30% of the administered dose is excreted unchanged in urine within 24 hours. Approximately 30% of the administered dose of norfloxacin is eliminated via the gastrointestinal tract.

Clinical characteristics.

Indications.

Acute and chronic (complicated or uncomplicated) infections of the upper and lower urinary tract (cystitis, pyelitis, cystopyelitis, pyelonephritis); urinary tract infections associated with surgical interventions, urological procedures, or urolithiasis.

Prophylaxis of infections caused by Gram-negative bacteria in patients with impaired immunity and severe neutropenia.

Contraindications.

Hypersensitivity to norfloxacin or other quinolone derivatives, as well as in case of hypersensitivity to any of the other ingredients contained in the formulation.

Patients with a history of tendinitis or tendon rupture associated with quinolone therapy.

Interaction with other medicinal products and other forms of interaction.

Norfloxacin inhibits the CYP1A2 isoenzyme, which may lead to interactions with other medicinal products metabolized by this isoenzyme.

Nitrofurantoin. In vitro antagonism between norfloxacin and nitrofurantoin has been demonstrated; therefore, concomitant use should be avoided.

Probenecid. Probenecid reduces the urinary excretion of norfloxacin but does not affect its normal serum concentration.

Theophylline. Concurrent administration of norfloxacin and theophylline may increase the plasma levels of theophylline and enhance the development of adverse effects caused by norfloxacin. Therefore, when norfloxacin and theophylline are used concomitantly, plasma theophylline concentrations should be monitored and dosage adjusted if necessary.

Caffeine. Norfloxacin, like other quinolones, inhibits caffeine demethylation, which may lead to reduced elimination and prolonged plasma half-life of caffeine. This should be taken into account when consuming coffee or using medicinal products containing caffeine (e.g., analgesics).

Cyclosporine. Concurrent use with norfloxacin may increase cyclosporine serum concentrations. Therefore, cyclosporine serum levels should be monitored and dosage adjusted accordingly if necessary.

Warfarin. Norfloxacin, like other quinolones, may potentiate the effect of the oral anticoagulant warfarin or its derivatives (e.g., phenprocoumon, acenocoumarol). Therefore, when these medicinal products are used concomitantly, prothrombin time or other coagulation parameters should be closely monitored.

Hormonal contraceptives. The contraceptive effect of oral contraceptives may be compromised in individual cases during antibiotic therapy. Therefore, when norfloxacin is used concomitantly with oral contraceptives, additional use of non-hormonal contraceptive methods is recommended.

Phenylbutazone. Experimental evidence has shown that concomitant use of quinolones with phenylbutazone may cause epileptic seizures; therefore, concomitant use of quinolones with phenylbutazone should be avoided.

Clozapine, ropinirole. Dose adjustment of clozapine or ropinirole may be required when initiating or discontinuing norfloxacin in patients already receiving these agents.

Tizanidine. Concomitant use of tizanidine and norfloxacin is not recommended.

Glibenclamide. Concomitant use of quinolones, including norfloxacin, with glibenclamide (a sulfonylurea derivative) may cause severe hypoglycemia. Therefore, blood glucose monitoring is recommended when these agents are used concomitantly.

Didanosine. Medicinal products containing didanosine should not be administered together with norfloxacin or within 2 hours after administration of norfloxacin, as they may interfere with each other's absorption, leading to reduced serum and urinary concentrations of norfloxacin.

Non-steroidal anti-inflammatory drugs (NSAIDs). Concomitant use of NSAIDs with quinolones, including norfloxacin, may increase the risk of central nervous system stimulation and convulsive seizures. Therefore, norfloxacin should be used with caution in patients receiving concomitant NSAID therapy.

Various agents (iron preparations, antacids, and agents containing magnesium, aluminum, calcium, or zinc). Calcium-containing preparations, multivitamin preparations containing calcium, should not be administered concomitantly with norfloxacin, as they may reduce the absorption of norfloxacin, resulting in lower serum and urinary concentrations. This also applies to enteral nutritional formulations and most dairy products (milk or natural dairy products such as yogurt).

Norfloxacin should be administered at least 2 hours before or 4 hours after administration of such agents.

Norfloxacin should be used with caution when administered concomitantly with agents that prolong the QT interval (e.g., Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, neuroleptics).

Special precautions for use.

When using this drug, as with other drugs of the quinolone group, increased photosensitivity is possible; therefore, during treatment, prolonged and intense exposure to sunlight should be avoided. Use of solariums is also contraindicated during this period. If signs of photosensitization occur, treatment should be discontinued.

When using norfloxacin, as with other quinolones, rare cases of tendinitis and/or tendon rupture (especially of the Achilles tendon) may occur. Elderly patients and patients receiving corticosteroid therapy are particularly susceptible. Therefore, if early signs of joint pain or inflammation occur, the patient should immobilize the affected joints and consult a physician. If the development of tendinitis or tendon rupture cannot be ruled out, treatment with norfloxacin should be discontinued.

When using this drug, latent myasthenia gravis (undiagnosed prior to the start of treatment) may manifest, potentially leading to life-threatening respiratory muscle insufficiency.

If dyspnea occurs during treatment with norfloxacin, appropriate emergency measures should be taken immediately.

When using norfloxacin, as with other quinolones, hemolytic reactions may occur in patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency.

Very rarely, some quinolones may cause QT interval prolongation on electrocardiogram and infrequent cases of arrhythmias (including extremely rare cases of ventricular fibrillation/flutter). As with other drugs capable of prolonging the QT interval, norfloxacin should be used with caution in patients with hypokalemia, severe bradycardia, or those receiving concomitant treatment with Class Ia or Class III antiarrhythmic agents.

Some quinolones, including norfloxacin, should be used with caution in patients taking cisapride, erythromycin, antipsychotic agents, tricyclic antidepressants, or in patients with personal or family history of QT interval prolongation.

Norbaktin should be used in patients with epilepsy and other CNS disorders that lower the seizure threshold only in cases of extreme clinical necessity. Seizures have been reported in isolated cases in patients treated with norfloxacin. If seizures occur, treatment with norfloxacin should be discontinued.

Norfloxacin may lead to exacerbation and intensification of symptoms in patients with existing or suspected psychiatric disorders, hallucinations, and/or confusion.

Use in patients with myasthenia gravis.

Norbaktin may worsen symptoms of myasthenia, potentially leading to life-threatening respiratory muscle weakness. Appropriate preventive measures should be taken at any signs of respiratory distress syndrome.

Use in renal impairment.

In patients with severe renal impairment, the risk-benefit ratio of using norfloxacin 400 mg tablets should be carefully and individually evaluated. The concentration of norfloxacin in urine may be reduced in patients with severe renal dysfunction, as norfloxacin is primarily excreted via the kidneys.

Crystalluria.

During prolonged treatment, crystalluria should be monitored. Although crystalluria is not typically observed under normal conditions when using norfloxacin 400 mg twice daily, as a precautionary measure, the recommended daily dose should not be exceeded, and patients should drink sufficient fluids to ensure adequate hydration and proper urine output.

Cholestatic hepatitis.

Patients receiving norfloxacin who develop symptoms of cholestatic hepatitis, such as anorexia, jaundice, dark urine, pruritus, or increased abdominal wall tone, should be advised to discontinue treatment and consult their physician.

Use of the drug in patients with cardiovascular disorders.

Caution should be exercised when using fluoroquinolones, including norfloxacin, in patients with risk factors for QT interval prolongation, such as:

• congenital long QT syndrome
• concomitant use of drugs that prolong the QT interval (e.g., Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, neuroleptics)
• uncorrected electrolyte imbalances (e.g., hypokalemia, hypomagnesemia)
• cardiovascular diseases (e.g., heart failure, myocardial infarction, bradycardia)
• elderly patients and women may be more sensitive to drugs that prolong the QT interval. Therefore, caution should be exercised when using fluoroquinolones, including norfloxacin, in these patient groups.

The drug contains lactose and therefore should not be administered to patients with hereditary galactose intolerance, lactase deficiency, or glucose/galactose malabsorption syndrome.

Norfloxacin should be administered at least 2 hours before or 4 hours after calcium-containing products, multivitamin preparations containing calcium, enteral nutritional solutions, and dairy products.

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy.

Norfloxacin, like other quinolones, is excreted in breast milk; therefore, if treatment is necessary, breastfeeding should be discontinued.

Ability to affect reaction speed when driving or operating machinery.

During treatment with this drug, patients should refrain from driving or operating machinery.

Method of Administration and Dosage.

Norbactin is intended for use in adults.

The medication should be taken with liquid on an empty stomach or together with food. It is preferable to take it twice daily (in the morning and evening), but it may also be taken once daily (at the same time each day).

The dosage depends on the sensitivity of the pathogenic microorganisms and the severity of the infection. Therefore, prior to initiating treatment, it is necessary to determine the sensitivity of the causative microorganism to norfloxacin. However, treatment may be started before the sensitivity test results are available. In such cases, specimens for laboratory diagnosis must be collected before the planned therapy begins, so that the treatment can be adjusted if the pathogens are found to be resistant to norfloxacin.

Dosage.

* Some symptoms of urinary tract infections (burning during urination, elevated temperature, pain) improve within 1–2 days, but treatment should be continued for the recommended duration.

** If the desired therapeutic effect is achieved within the first 4 weeks, the dose of Norbactin may be reduced to 1 tablet per day.

*** Currently, there are no data available regarding treatment duration beyond 8 weeks.

Dosing in patients with renal impairment.

Norbactin can be used in patients with renal impairment. In patients with creatinine clearance less than or equal to 30 mL/min × 1.73 m², the recommended dose of Norbactin should not exceed 1 tablet per day.

Dosing in elderly patients.

In the absence of renal impairment, there is no need to adjust the dose of Norbactin in elderly patients.

Children.

Contraindicated in children.

Overdose.

Symptoms: elevated body temperature, dyspnea, fever, leukopenia, thrombocytopenia, acute hemolytic anemia, QT interval prolongation, gastrointestinal disturbances, renal failure.

Treatment. In case of acute overdose, the patient should immediately take a solution containing calcium to form a calcium-norfloxacin complex, which is poorly absorbed from the gastrointestinal tract, followed by induction of vomiting or gastric lavage.

The patient must be carefully monitored (including ECG monitoring), and symptomatic and supportive treatment should be administered as needed. Adequate fluid replacement should be ensured.

Side effects.

Cardiac disorders: tachycardia, arrhythmia; very rarely with the use of some drugs in the quinolone group, including norfloxacin, QT interval prolongation and ventricular arrhythmia (including torsade de pointes) may occur.

Blood and lymphatic system disorders: leukopenia, eosinophilia, neutropenia, decreased hematocrit, hemolytic anemia, thrombocytopenia.

Nervous system disorders: headache, dizziness, drowsiness, hallucinations, fatigue, mood changes, paresthesia, insomnia, depression, anxiety, irritability, euphoria, disorientation, confusion, polyneuropathy including Guillain-Barré syndrome, epileptiform seizures, hypesthesia, psychiatric disorders including psychotic reactions, tremor, myoclonia, myasthenia gravis, confusion.

Gastrointestinal disorders: anorexia, bitter taste in mouth, nausea, vomiting, abdominal pain, diarrhea, pseudomembranous enterocolitis (with prolonged use), mild gastralgia, heartburn, pancreatitis.

Renal and urinary system disorders: crystalluria, glomerulonephritis, interstitial nephritis, dysuria, polyuria, albuminuria, urethral hemorrhage, hypercreatininemia, renal failure.

Skin and subcutaneous tissue disorders: pruritus, edema, exanthema, petechiae, hemorrhagic bullae and papules with crusting as manifestations of vascular involvement (vasculitis), rash.

Musculoskeletal and connective tissue disorders: arthralgia, tendinitis, tenosynovitis, tendon ruptures, myalgia, arthritis, inflammation of the Achilles tendon which may lead to Achilles tendon rupture, rhabdomyolysis.

Vascular disorders: decreased blood pressure, syncope, vasculitis.

Immune system disorders: urticaria, anaphylaxis, angioneurotic edema; in isolated cases – exfoliative dermatitis, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), erythema multiforme exudativum, photosensitization.

Hepatobiliary disorders: hepatitis, increased liver transaminase activity, jaundice.

Laboratory test abnormalities: increased serum levels of glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, and alkaline phosphatase.

Other: vaginal candidiasis, diplopia, increased lacrimation, tinnitus, hearing loss, dyspnea, dysgeusia.

Pseudomembranous colitis. In case of pseudomembranous colitis, the physician should consider discontinuing norfloxacin therapy depending on clinical indications and immediately initiate appropriate treatment for this adverse reaction (e.g., administration of antibiotics/chemotherapeutic agents with clinically proven efficacy). Medicinal products that inhibit intestinal peristalsis should not be used.

Severe hypersensitivity reactions (e.g., anaphylaxis). If such reactions occur, norfloxacin therapy should be discontinued immediately and appropriate emergency measures should be taken (e.g., administration of antihistamines, corticosteroids, sympathomimetics, and, if necessary, artificial ventilation of the lungs).

Occurrence of epileptiform seizures. In such cases, standard appropriate emergency measures should be taken (e.g., maintaining airway patency, administration of anticonvulsant drugs, particularly diazepam or barbiturates).

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C, in a place inaccessible to children.

Packaging. 10 tablets per blister; 1 or 10 blisters per cardboard box.

Prescription category. Prescription only.

Manufacturer.

San Pharmaceutical Industries Limited.

Manufacturer's address and site of operation.

Plot No. B-2, Madkai Industrial Estate, Ponda, Goa - 403404, India