Tiflox

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TIFLOX (TIFLOX)

Composition:

Active substances: 1 tablet contains ofloxacin 200 mg and ornidazole 500 mg;

Excipients: maize starch, microcrystalline cellulose, sodium methylparaben (E 219), sodium propylparaben (E 217), magnesium stearate, talc, colloidal anhydrous silicon dioxide, sodium starch glycolate (type A), hydroxypropylmethylcellulose, titanium dioxide (E 171), polyethylene glycol 6000.

Pharmaceutical form. Film-coated tablets.

Main physico-chemical characteristics: white or almost white, elongated, biconvex, film-coated tablets with the inscription "TIFLOX" on one side.

Pharmacotherapeutic group.

Antibacterials for systemic use.

ATC code J01RA.

Pharmacological Properties

Pharmacodynamics

In many mixed infections where more than one pathogen is present, combination therapy is required for effective treatment. In such cases, the most effective combination is ofloxacin and ornidazole.

Ofloxacin belongs to the group of fluoroquinolones and has a broad spectrum of activity. The bactericidal action of ofloxacin, as with other fluoroquinolones, is due to its ability to inhibit the bacterial enzyme DNA gyrase.

Ofloxacin demonstrates broad-spectrum activity against microorganisms resistant to penicillins, aminoglycosides, and cephalosporins, as well as against microorganisms with multiple resistance patterns.

The antimicrobial spectrum of ofloxacin includes the following microorganisms:

• Aerobic gram-negative bacteria – E. coli, Klebsiella spp., Salmonella spp., Proteus spp., Shigella spp., Yersinia spp., Enterobacter spp., Morganella morganii, Providencia spp., Vibrio spp., Citrobacter spp., Campylobacter spp., Ps. cepacia, Neisseria gonorrhoeae, N. meningitidis, Haemophilus influenzae, Acinetobacter spp., Moraxella catarrhalis;
• Aerobic gram-positive bacteria – staphylococci, including strains producing and non-producing penicillinase, Streptococcus spp. (particularly beta-hemolytic);
• Moderately susceptible microorganisms – Enterococcus faecalis, Streptococcus pneumoniae, Pseudomonas spp., Legionella spp., Serratia spp., Bacteroides spp., Fusobacterium spp., Gardnerella vaginalis, Ureaplasma urealyticum, Brucella spp., M. tuberculosis.

The drug is not active against anaerobic bacteria (except B. urealyticum), Treponema pallidum, viruses, fungi, and protozoa.

Ornidazole is an antiprotozoal and antibacterial agent, a derivative of 5-nitroimidazole. It is active against Trichomonas vaginalis, Entamoeba histolytica, Giardia lamblia (Giardia intestinalis), and certain anaerobic bacteria such as Bacteroides, Clostridium spp., Fusobacterium spp., and anaerobic cocci. Mechanistically, ornidazole is a DNA-targeting agent with selective activity against microorganisms possessing enzymatic systems capable of reducing the nitro group and catalyzing interactions between ferredoxin-like proteins and nitro compounds. After entering the microbial cell, the drug's mechanism of action involves reduction of the nitro group by microbial nitroreductases, leading to the formation of active reduced metabolites of nitroimidazole. These reduced products form complexes with DNA, causing DNA degradation and disrupting DNA replication and transcription processes. Additionally, metabolites of the drug exhibit cytotoxic properties and interfere with cellular respiration.

Pharmacokinetics

Not studied.

Clinical characteristics.

Indications.

To be used for the treatment of mixed infections caused by pathogens (microorganisms and protozoa) sensitive to the components of the medicinal product:

• complicated urinary tract infections: cystitis, acute pyelonephritis, bacterial prostatitis, epididymitis;
• sexually transmitted diseases.

Official recommendations regarding the appropriate use of antibacterial agents should be taken into account.

Contraindications.

Hypersensitivity to ofloxacin, ornidazole, other derivatives of fluoroquinolones or nitroimidazoles, or to any other component of the drug. The drug should be avoided in patients who previously experienced serious adverse reactions during treatment with fluoroquinolone or quinolone antibiotics.

Central nervous system disorders with lowered seizure threshold (following head trauma, stroke, inflammatory processes of the brain and meninges); multiple sclerosis; epilepsy; glucose-6-phosphate dehydrogenase deficiency; tendinitis in medical history; blood disorders or other hematological abnormalities; QT interval prolongation; uncompensated hypoglycemia.

The medicinal product is contraindicated in patients taking class IA (quinidine, procainamide) or class III (amiodarone, sotalol) antiarrhythmic agents, tricyclic antidepressants, or macrolides; and in patients with tendon ruptures after prior use of fluoroquinolones.

Interaction with other medicinal products and other types of interactions.

Interactions associated with ofloxacin.

Concomitant use of ofloxacin with antihypertensive agents may lead to sudden drop in arterial blood pressure. In such cases, or when anesthesia with barbiturates is performed, monitoring of cardiovascular function is required.

Concomitant use of ofloxacin with drugs that prolong the QT interval (class IA antiarrhythmics: quinidine, procainamide; class III antiarrhythmics: amiodarone, sotalol; tricyclic antidepressants, macrolides) is contraindicated.

Concomitant use of ofloxacin with nonsteroidal anti-inflammatory drugs (including phenylpropionic acid derivatives), nitroimidazole derivatives, and methylxanthines increases the risk of nephrotoxic effects and lowering of the seizure threshold, which may lead to seizures. If seizures occur, the drug should be discontinued.

Nonsteroidal anti-inflammatory drugs may enhance the stimulatory effect of the drug on the central nervous system. Additional lowering of the seizure threshold may also occur when used concomitantly with certain nonsteroidal anti-inflammatory drugs.

Concomitant administration of high-dose ofloxacin with drugs excreted via tubular secretion may lead to increased plasma concentrations due to reduced elimination.

Since concomitant use of most quinolones, including ofloxacin, inhibits the enzymatic activity of cytochrome P450, concomitant use of ofloxacin with drugs metabolized by this system (cyclosporine, theophylline, methylxanthine, caffeine, warfarin) prolongs the half-life of these medicinal products.

The steady-state concentration of theophylline in serum, its elimination half-life, and the risk of theophylline-related adverse reactions may increase when used concomitantly with Tiflox. Serum theophylline levels should be carefully monitored and the dosage adjusted accordingly when used concomitantly with Tiflox. Adverse reactions (including seizures) may occur with or without elevated serum theophylline levels.

If Tiflox is used together with warfarin or its derivatives, prothrombin time or appropriate coagulation tests should be closely monitored.

When quinolones are used concomitantly with other drugs that lower the seizure threshold, such as theophylline, an additive reduction in the central nervous system seizure threshold may occur, although ofloxacin is considered not to engage in pharmacokinetic interactions with theophylline, unlike some other fluoroquinolones.

Concomitant use of ofloxacin with vitamin K antagonists requires continuous monitoring of the blood coagulation system.

Concomitant use of the drug with antacids containing calcium, magnesium, or aluminum, sucralfate, divalent or trivalent iron, multivitamins containing zinc, reduces the absorption of ofloxacin. Therefore, the interval between administration of these agents should be at least 4 hours.

Concomitant use of ofloxacin with oral antidiabetic agents and insulin may result in hypoglycemia or hyperglycemia; therefore, monitoring of parameters for compensation is necessary. When used concomitantly with glyburide, an increase in serum glyburide levels may occur.

The risk of crystalluria and nephrotoxic effects increases when ofloxacin is used concomitantly with urine-alkalinizing agents (carbonic anhydrase inhibitors, citrates, sodium bicarbonate).

Concomitant use of ofloxacin with probenecid, cimetidine, furosemide, or methotrexate leads to increased plasma concentrations of ofloxacin and an increased risk of its toxic effects.

Ofloxacin may inhibit the growth of Mycobacterium tuberculosis, leading to false-negative results in bacteriological testing for tuberculosis diagnosis.

Laboratory tests. During ofloxacin therapy, pseudopositive results may occur in urine tests for opiates or porphyrins. Therefore, more specific methods should be used.

Interactions associated with ornidazole.

Unlike other nitroimidazole derivatives, ornidazole does not inhibit aldehyde dehydrogenase; however, Tiflox should not be used concomitantly with alcohol. Ornidazole enhances the effect of oral anticoagulants of the coumarin group, increasing the risk of bleeding; therefore, appropriate dose adjustment is required.

Ornidazole prolongs the muscle-relaxant effect of vecuronium bromide.

Concomitant use of phenobarbital and other enzyme inducers reduces the serum circulation time of ornidazole, whereas enzyme inhibitors (e.g., cimetidine) increase it.

Special precautions for use.

Central and peripheral nervous system disorders. The medicinal product should be used with caution in patients with disorders of the central nervous system that lead to a reduced seizure threshold (e.g., epilepsy).

If seizures occur, the drug should be discontinued.

Exacerbation of central or peripheral nervous system disorders may occur during treatment with the drug. If peripheral neuropathy, impaired motor coordination (ataxia), dizziness, or altered consciousness develops, treatment should be discontinued.

The medicinal product should be used with caution in patients with cerebral vascular atherosclerosis.

Renal function impairment. Adequate hydration (patients should consume sufficient amounts of water) should be maintained during treatment with Tiflox to prevent crystalluria.

The drug should be administered with caution to patients with impaired renal function (do not exceed the average daily dose), and laboratory monitoring of renal function parameters is required. The dose of ofloxacin should be adjusted in patients with reduced renal function due to delayed elimination.

Dosage and timing of administration should be adjusted in patients with renal insufficiency and in elderly patients to compensate for delayed elimination.

Hemodialysis. In patients undergoing hemodialysis, the shortened elimination half-life should be taken into account, and additional doses of the drug should be administered before or after hemodialysis.

Hepatic function impairment. The drug should be administered with caution to patients with hepatic impairment (due to the potential for worsening liver function), and laboratory monitoring of liver function parameters is required. Fulminant hepatitis and liver failure (including fatal outcomes) may occur during treatment with fluoroquinolones. Patients should discontinue treatment and consult a physician if symptoms or signs of liver disease develop, such as anorexia, jaundice, darkening of urine, pruritus, or abdominal tenderness on palpation (see section "Adverse reactions").

Patients with severe hepatic impairment (cirrhosis) should not exceed the average daily dose.

The drug should be avoided in patients who previously experienced serious adverse reactions to quinolones or fluoroquinolones. Treatment in such patients should be initiated only if no alternative treatment options are available and after careful benefit-risk assessment.

Prolonged, disabling, and potentially irreversible serious adverse reactions

Very rarely, in patients receiving quinolones and fluoroquinolones, regardless of age and existing risk factors, prolonged (lasting weeks or years), disabling, and potentially irreversible serious adverse reactions affecting various systems of the body (including musculoskeletal, nervous, psychiatric, and sensory systems), sometimes involving multiple systems simultaneously, have been reported. The drug should be discontinued immediately upon the first signs or symptoms of any serious adverse reaction, and medical advice should be sought.

Clostridium difficile-associated disease. Diarrhea, particularly severe, persistent, or bloody diarrhea, during or after treatment with Tiflox may be a symptom of pseudomembranous colitis.

If pseudomembranous colitis is suspected, Tiflox should be discontinued immediately and appropriate symptomatic antibiotic therapy (e.g., vancomycin, teicoplanin, or metronidazole) should be initiated without delay. Medicinal products that inhibit intestinal peristalsis are contraindicated in this situation.

Tendinitis and tendon rupture

Tendinitis and tendon rupture (not limited to the Achilles tendon), sometimes bilateral, may occur within 48 hours of starting treatment with quinolones and fluoroquinolones, and have been reported even several months after discontinuation of treatment.

The risk of tendinitis and tendon rupture is increased in elderly patients, patients with renal impairment, patients who have undergone solid organ transplantation, and patients receiving concomitant corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.

If signs of tendinitis (e.g., painful swelling, inflammation) occur, treatment with the drug should be discontinued, and alternative therapy should be considered. The affected limb(s) should be appropriately managed (e.g., immobilization). Corticosteroids should not be used if signs of tendinopathy develop.

In the event of such an adverse reaction as tendinitis, orthopedic consultation is required to determine whether treatment should be continued.

Fluoroquinolones, including ofloxacin, increase the risk of tendinitis and tendon rupture at any age. This adverse effect most commonly affects the Achilles tendon, rupture of which may require surgical intervention. The risk of developing tendinitis and tendon rupture is increased in patients aged 60 years and older, those taking corticosteroid medications, and those who have undergone kidney, heart, or lung transplantation. In addition to age and corticosteroid use, other factors that independently increase the risk of tendon rupture include vigorous physical activity, renal insufficiency, and prior tendon injury, such as rheumatoid arthritis.

QT interval prolongation. Some quinolones, including ofloxacin, may prolong the QT interval on the electrocardiogram and cause isolated cases of arrhythmias. The drug should not be administered to patients with known QT interval prolongation, specifically: elderly patients; patients with uncorrected electrolyte imbalances (hypokalemia, hypomagnesemia); patients with congenital long QT syndrome; patients with acquired QT interval prolongation; patients with cardiac diseases (e.g., heart failure, myocardial infarction, bradycardia).

Clinical and laboratory monitoring is recommended when high doses of the drug are used or when treatment exceeds 10 days.

Aortic aneurysm and dissection, and cardiac valve regurgitation/insufficiency

Epidemiological studies have shown an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and regurgitation of the aortic and mitral valves following fluoroquinolone use. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any cardiac valve have been reported in patients receiving fluoroquinolones (see section "Adverse reactions").

Therefore, fluoroquinolones should be prescribed only after careful benefit-risk assessment and consideration of alternative treatment options in patients with a family history of aortic aneurysm or congenital heart valve defects, patients with a confirmed diagnosis of aortic aneurysm and/or dissection, patients with cardiac valve disease, and patients with other risk factors, namely:

• risk factors for both aortic aneurysm and dissection and cardiac valve regurgitation/insufficiency: connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis;
• risk factors for aortic aneurysm and dissection: vascular disorders such as Takayasu arteritis or giant cell arteritis, atherosclerosis, Sjögren's syndrome;
• risk factors for cardiac valve regurgitation/insufficiency: infective endocarditis.

The risk of aortic aneurysm and dissection and their rupture is also increased in patients receiving systemic corticosteroids concurrently.

Patients should seek immediate medical attention if they experience sudden abdominal, chest, or back pain.

Patients should also be advised to seek immediate medical help if acute shortness of breath, a new episode of palpitations, or development of abdominal or lower limb edema occurs.

Blood disorders. In patients with a history of blood disorders, monitoring of leukocyte levels is recommended, especially during repeated treatment courses.

Vitamin K antagonists. Due to the potential for increased coagulation test parameters (prothrombin time/international normalized ratio) and/or bleeding in patients receiving fluoroquinolones in combination with vitamin K antagonists (e.g., warfarin), monitoring of coagulation test results is required when these two drug groups are used concomitantly (see section "Interaction with other medicinal products and other forms of interaction").

Hypersensitivity to fluoroquinolones. Hypersensitivity and allergic reactions to fluoroquinolones have been reported after the first dose. Anaphylactic and anaphylactoid reactions may progress to life-threatening shock, even after the first dose. In such cases, Tiflox should be discontinued and appropriate treatment initiated.

Photosensitization. Patients taking Tiflox should avoid exposure to sunlight and UV radiation (mercury-quartz lamps, tanning beds) due to the possibility of photosensitization. If photosensitivity reactions (e.g., sunburn-like reactions) occur, treatment with Tiflox should be discontinued.

Arterial hypotension. If severe arterial hypotension occurs, administration of Tiflox should be discontinued.

Patients with a history of psychotic or psychiatric disorders. Psychotic reactions may occur, which may progress to suicidal thoughts, self-destructive behavior, including suicide attempts, sometimes even after a single dose. If such reactions develop, the drug should be discontinued and appropriate therapeutic measures taken. The drug should be used with caution in patients with a history of psychotic disorders or psychiatric diseases.

Diabetes mellitus. Hypoglycemia may occur during treatment with quinolones, usually in diabetic patients receiving concomitant therapy with oral hypoglycemic agents (e.g., glyburide) or insulin. Careful monitoring of blood glucose levels is recommended in such diabetic patients.

Development of secondary infection. Prolonged or repeated antibiotic therapy may lead to the development of opportunistic infections and overgrowth of resistant microorganisms. Appropriate measures should be taken if a secondary infection develops.

Exacerbation of candidiasis may occur, which will require appropriate treatment.

Resistance of certain Pseudomonas aeruginosa strains. During treatment with Tiflox, as with other fluoroquinolone agents, resistance in certain strains of Pseudomonas aeruginosa may develop rapidly.

Pneumococcal or mycoplasma pneumonia, tonsillar angina caused by β-hemolytic streptococci. Tiflox is not the drug of choice for treating patients with these conditions.

Medicinal products containing magnesium, aluminum, iron, zinc, and sucralfate. Tiflox should not be taken within 4 hours after administration of medicinal products containing magnesium, aluminum, iron, zinc, or sucralfate.

Alcohol consumption. Incompatible with alcohol. Alcoholic beverages should not be consumed during treatment with Tiflox.

Myasthenia gravis. Tiflox should be used with caution in patients with a history of myasthenia gravis.

Except for very rare isolated cases (e.g., isolated disturbances of smell, taste, and hearing), all adverse effects of the drug resolve after discontinuation.

If adverse effects occur, particularly those affecting the nervous system or allergic reactions, which may arise immediately after the first dose, the drug must be discontinued.

Lithium therapy. Serum lithium, creatinine, and electrolyte concentrations should be monitored during concomitant lithium therapy.

The effect of other medicinal products may be enhanced or diminished during treatment with Tiflox.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy leading to paresthesia, hypesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. If symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness occur, patients should inform their physician to prevent the development of a potentially irreversible condition.

Glucose-6-phosphate dehydrogenase deficiency. Patients with latent or confirmed glucose-6-phosphate dehydrogenase deficiency may be susceptible to hemolytic reactions during treatment with quinolones. Therefore, ofloxacin should be administered with caution in such patients.

Excipients.

The medicinal product contains sodium methylparaben (E 219) and sodium propylparaben (E 217), which may cause allergic reactions (possibly delayed).

Use during pregnancy or breastfeeding.

Tiflox is contraindicated during pregnancy. Breastfeeding should be discontinued during treatment with Tiflox.

Ability to affect reaction speed when driving or operating machinery.

Psychomotor reaction speed may be reduced; therefore, patients should refrain from driving or operating machinery.

Method of Administration and Dosage

The medication should be taken orally, without chewing, with water. The medication may be taken either before or after meals.

The dosage and duration of treatment depend on the microbial sensitivity, severity, and type of infectious process. The adult dosage is 1 tablet twice daily for 5 days, followed by an additional 2–5 days of ofloxacin tablets. Treatment should continue for at least 3 days after the disappearance of clinical symptoms of the disease.

Children.

The medication is contraindicated in children under 18 years of age.

Overdose.

Symptoms: dizziness, excitement, headache, confusion, drowsiness, lethargy, abdominal pain, disorientation, diarrhea, nausea, vomiting, seizures, erosive mucosal damage; interstitial nephritis may develop or symptoms of other adverse reactions may intensify.

Treatment: gastric lavage, forced hydration, detoxification, desensitizing, and symptomatic therapy aimed at correcting impairments in internal organs. Administer enterosorbents, magnesium sulfate, and antacids to protect the gastric mucosa. There is no specific antidote. ECG monitoring is necessary due to the potential for QT interval prolongation. Hemodialysis and peritoneal dialysis slightly reduce the drug concentration in the blood. Diazepam is indicated in case of seizures.

Adverse Reactions

Skin and subcutaneous tissue disorders: pruritus, skin rashes including urticaria, vesicular eruptions, pustular eruptions, erythema multiforme, vasculitic purpura, acute generalized exanthematous pustulosis; hyperhidrosis; photosensitization, hypersensitivity reactions manifesting as sunburn-like erythema; skin discoloration; nail separation.

Immune system disorders: hypersensitivity reactions, including skin allergic reactions and anaphylactic/anaphylactoid reactions; shock, including anaphylactic/anaphylactoid shock, e.g., tachycardia, fever, dyspnea, shock, angioneurotic edema, eosinophilia. In such cases, treatment must be discontinued immediately and replacement therapy initiated if necessary. Quincke's edema (including edema of the tongue, larynx, pharynx with possible asphyxia, facial swelling/edema); Stevens-Johnson syndrome; Lyell's syndrome; drug-induced dermatitis; vasculitis, which in rare cases may lead to necrosis, and may also involve internal organs; pneumonitis.

Cardiovascular system disorders: flushing; arterial hypotension, tachycardia, collapse (due to decreased blood pressure); ventricular arrhythmia, torsades de pointes arrhythmia, ventricular flutter/fibrillation (mainly observed in patients with risk factors for QT interval prolongation), QT interval prolongation on electrocardiogram; cerebral vessel thrombosis; pulmonary edema.

In patients receiving fluoroquinolones, cases of aortic aneurysm and dissection have been reported, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any heart valve (see section "Special Warnings and Precautions for Use").

Blood and lymphatic system disorders: neutropenia, leukopenia, anemia, hemolytic anemia, eosinophilia, thrombocytopenia, pancytopenia, bone marrow suppression, blood dyscrasia of medullary aplasia type, petechiae, ecchymosis/bruising, prolonged prothrombin time, thrombocytopenic purpura, signs of impaired bone marrow hematopoiesis.

Respiratory system disorders: cough, dyspnea, shortness of breath, bronchospasm, severe wheezing, stridor, nasopharyngitis, pharyngitis.

Central nervous system disorders: headache; dizziness (vertigo, lightheadedness); confusion, transient loss of consciousness; sleep disturbances (insomnia or somnolence), nightmares; restlessness, psychomotor agitation, anxiety; slowed reaction time; increased intracranial pressure, nuchal rigidity, seizures; paresthesia, sensory or sensorimotor neuropathy, peripheral sensory disturbances (paresthesia, impaired coordination, taste disturbances), hearing disturbances such as tinnitus or hearing loss; extrapyramidal disorders including tremor, impaired muscle coordination (disturbance in balance sensation, unsteady gait); exacerbation of myasthenia gravis; dysphasia.

Psychiatric disorders: psychotic disorders, anxiety states, depression with self-destructive behavior, including suicidal thoughts or suicide attempts, epileptic seizures, hallucinations; delirium (rare).

Eye disorders: visual disturbances (e.g., blurred vision), transient vision loss, uveitis.

Ear and labyrinth disorders: vertigo, tinnitus, hearing loss, hearing disturbances.

Gastrointestinal disorders: anorexia (loss of appetite); altered taste sensation (dysgeusia), including metallic taste in the mouth, dry mouth, oral mucosal pain, increased salivation; dyspepsia, nausea, vomiting, heartburn, gastralgia (abdominal pain), abdominal pain or cramps; diarrhea, frequent loose stools, gastrointestinal distress, constipation, dysbacteriosis, enterocolitis, sometimes hemorrhagic enterocolitis, flatulence, dysbiosis, pseudomembranous colitis (mostly caused by Clostridium difficile). If Clostridium difficile infection is suspected, treatment with the drug must be discontinued immediately and appropriate therapy initiated. Antiperistaltic agents should not be used in such cases.

Hepatobiliary disorders: signs of hepatotoxicity, including changes in liver function tests; cholestatic jaundice, hepatitis, even of very severe degree.

Renal and urinary system disorders: renal function impairment, including urinary retention, anuria, polyuria, hematuria; renal failure; acute renal failure; acute interstitial nephritis; kidney stone formation; acute interstitial nephritis.

Reproductive system disorders: genital pruritus in women, vaginitis, vaginal candidiasis.

Musculoskeletal and connective tissue disorders: tendinitis, especially in elderly patients; muscle rupture, ligament rupture, muscle cramps, myalgia, arthralgia; rhabdomyolysis and/or myopathy, muscle weakness, muscle rupture, tendon rupture (including Achilles tendon), especially in patients concurrently receiving corticosteroids. If signs of tendon inflammation occur, treatment with the drug should be discontinued immediately and appropriate therapy initiated for the affected tendon. Ligament rupture, muscle rupture.

Metabolism and nutrition disorders: hypoglycemia or hyperglycemia (in patients with diabetes mellitus).

Infections and infestations: fungal infections, pathogen resistance, overgrowth of other resistant microorganisms.

Laboratory test abnormalities: increased liver enzyme activity (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase, gamma-glutamyl transferase), elevated bilirubin, cholesterol, triglycerides, potassium levels; excessive increase or decrease in glucose levels; prolonged prothrombin time; increased urea and creatinine levels.

Other: weakness, chills, malaise, fatigue, chest pain, hot flushes, nasal pain, weakness, acute attacks of porphyria in patients with porphyria, hiccups.

Description of selected adverse reactions

During the post-marketing period, patients receiving fluoroquinolones have experienced neuropsychiatric events, including anxiety, suicidal ideation, panic attacks, neuralgia, and disturbances in attention concentration. These may represent potential manifestations of long-lasting and disabling adverse reactions caused by fluoroquinolones, leading to loss of work capacity.

Adverse effects may resolve after discontinuation of Tiflox therapy (e.g., disturbances in smell, taste, and hearing).

In very rare cases, patients receiving quinolones and fluoroquinolones, regardless of existing risk factors, have reported long-term (lasting months or years), disabling, and potentially irreversible serious adverse reactions affecting various, and sometimes multiple simultaneously, organ systems and sensory organs (including reactions such as tendinitis, tendon rupture, arthralgia, limb pain, gait disturbances, neuropathies associated with paresthesia, depression, fatigue, memory impairment, sleep disturbances, hearing, vision, taste, and smell disturbances).

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister; 1 blister in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

Mepro Pharmaceuticals Private Limited / Mepro Pharmaceuticals Private Limited.

Manufacturer's address and place of business.

Unit II, Q-Road, Phase IV, GIDC, Wadhwan, Surendranagar, Gujarat, 363 035, India /
Unit II, Q-Road, Phase IV, GIDC, Wadhwan, Surendranagar, Gujarat, 363 035, India.

Marketing Authorization Holder.

Mili Healthcare Limited / Mili Healthcare Limited.

Address of Marketing Authorization Holder.

Second Floor Office Suite, 4 Chartfield House, Castle Street, Taunton, Somerset, England TA1 4AS, Great Britain /
Second Floor Office Suite, 4 Chartfield House, Castle Street, Taunton, Somerset, England TA1 4AS, Great Britain.