Instructions for Ofor film-coated tablets, blister pack No. 10
Composition
active ingredients: ofloxacin, ornidazol;
1 tablet contains ofloxacin 200 mg and ornidazole 500 mg;
Excipients: corn starch, povidone (K-30), magnesium stearate, croscarmellose sodium, colloidal anhydrous silicon dioxide, Opadry white*, titanium dioxide (E 171), polyethylene glycols, talc, sunset yellow dye (E 110).
* Composition of the Opadry white film coating: hypromellose, titanium dioxide (E 171), lactose monohydrate, polyethylene glycol, talc.
Dosage form
Film-coated tablets.
Main physicochemical properties: orange tablets, oblong, biconvex, with a score on one side, film-coated.
Pharmacotherapeutic group
Combined antibacterial agents. ATX code J01R A09.
Pharmacological properties
Pharmacodynamics.
The pharmacological action of ofloxacin is antibacterial (bactericidal). It inhibits DNA gyrase (topoisomerase II and IV), disrupts the process of supercoiling and crosslinking of DNA breaks, inhibits cell division, causes structural changes in the cytoplasm and the death of microorganisms.
It has a wide spectrum of action. It affects mainly gram-negative and some gram-positive microorganisms: Citrobacter diversus, Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Citrobacter diversus, Neisseria gonorrhoeae, Chlamydia trachomatis, Staphylococcus aureus, Streptococcus pyogenes. It is effective against microorganisms resistant to most antibiotics and sulfonamide drugs.
The pharmacological action of ornidazole is antibacterial and antiprotozoal. It is active against Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia (Giardia intestinalis), as well as some anaerobic bacteria (Clostridium spp., Bacteroides spp., Fusobacterium) and anaerobic cocci. By the mechanism of action, ornidazole is a DNA-tropic drug with selective activity against microorganisms that have enzyme systems capable of reducing the nitro group and catalyzing the interaction of ferredoxin group proteins with nitro compounds. After the drug penetrates the microbial cell, its mechanism of action is due to the reduction of the nitro group under the influence of nitroreductases of the microorganism and the activity of the already reduced nitroimidazole. The reduction products form complexes with DNA, causing its degradation, disrupting the processes of DNA replication and transcription. In addition, the products of the drug's metabolism have cytotoxic properties and disrupt the processes of cellular respiration.
Pharmacokinetics: Not studied.
Indication
Use for the treatment of mixed infections caused by pathogens (microorganisms and protozoa) sensitive to the components of the medicinal product:
complicated urinary tract diseases: cystitis, acute pyelonephritis, bacterial prostatitis, epididymitis;
sexually transmitted diseases.
Official recommendations on the appropriate use of antibacterial agents should be taken into account.
Contraindication
Hypersensitivity to ofloxacin, ornidazole, other fluoroquinolone derivatives, nitroimidazole derivatives or other components of the drug. The drug should be avoided in patients who have previously had serious adverse reactions to fluoroquinolone or quinolone antibiotics.
Central nervous system lesions with a reduced seizure threshold, including multiple sclerosis (after traumatic brain injury, stroke, inflammatory processes of the brain and meninges); epilepsy, including a history; glucose-6-phosphate dehydrogenase deficiency; a history of tendinitis; pathological blood lesions or other hematological abnormalities; prolongation of the QT interval; uncompensated hypoglycemia, childhood (up to 18 years), pregnancy, breastfeeding.
The drug is contraindicated in patients taking class IA (zinidine, procainamide) or class III (amiodarone, sotalol) antiarrhythmics, tricyclic antidepressants, macrolides; in patients with a history of tendon rupture after the use of fluoroquinolones.
The use of the medicinal product should be avoided in patients with a history of serious adverse reactions to medicinal products containing quinolones or fluoroquinolones. The use of the medicinal product in such patients should only be initiated in the absence of alternative treatment options and after a careful assessment of the benefit-risk ratio (see section 4.4).
Interaction with other medicinal products and other types of interactions
Interactions related to ofloxacin
Antihypertensive drugs
When ofloxacin is used simultaneously with antihypertensive agents or during barbiturate anesthesia, a sudden decrease in blood pressure is possible. In such cases, cardiovascular function should be monitored.
QT-prolonging drugs
It is contraindicated to use ofloxacin simultaneously with drugs that prolong the QT interval (class IA antiarrhythmics - quinine, procainamide, and class III - amiodarone, sotalol, tricyclic antidepressants, macrolides).
Ofloxacin, like other fluoroquinolones, should be used with caution in patients receiving antipsychotics.
The simultaneous use of ofloxacin with NSAIDs (including phenylpropionic acid derivatives), nitroimidazole derivatives and methylxanthines increases the risk of nephrotoxic effects and enhances the stimulating effect on the central nervous system, which leads to a decrease in the seizure threshold. In the event of seizures, the drug should be discontinued.
Drugs that lower the seizure threshold
If quinolones are used concomitantly with other drugs that lower the seizure threshold, such as theophylline, an additional decrease in the seizure threshold of the brain may be observed.
Drugs secreted by tubular secretion
Concomitant administration of high doses of ofloxacin with drugs excreted by tubular secretion may lead to increased plasma concentrations due to decreased excretion.
Medicinal products metabolized by cytochrome P450
Since the simultaneous use of most quinolones, including ofloxacin, inhibits the enzymatic activity of cytochrome P450, the simultaneous use of ofloxacin with drugs metabolized by this system (cyclosporine, theophylline, methylxanthine, caffeine, warfarin, etc.) prolongs the half-life of these drugs.
Anticoagulants, including vitamin K antagonists
Prolonged bleeding time has been reported with the concomitant use of ofloxacin and anticoagulants.
When ofloxacin is used concomitantly with vitamin K antagonists (e.g. warfarin), an increase in coagulation tests (prothrombin time (PT)/international normalized ratio (INR)) and/or bleeding, which may be severe, has been reported. Therefore, coagulation parameters should be monitored in patients receiving concomitant vitamin K antagonists due to a possible increase in the activity of coumarin derivatives.
Drugs that reduce the absorption of ofloxacin
Simultaneous use of the drug with antacids containing calcium, magnesium or aluminum, with sucralfate, with bivalent or trivalent iron, with multivitamins containing zinc, reduces the absorption of ofloxacin. Therefore, the interval between taking these drugs should be at least 4 hours.
Hypoglycemic drugs
When ofloxacin is used simultaneously with oral hypoglycemic agents and insulin, hypoglycemia or hyperglycemia is possible, therefore, it is necessary to monitor parameters for their compensation. When used simultaneously with glibenclamide, an increase in serum glibenclamide levels is possible; patients receiving this combination should be carefully monitored.
Drugs that increase urine pH
When used with drugs that alkalinize urine (carbonic anhydrase inhibitors, citrates, sodium bicarbonate), the risk of crystalluria and nephrotic effects increases.
Probenecid, cimetidine, furosemide, and methotrexate
Simultaneous use of ofloxacin with probenecid, cimetidine, furosemide, methotrexate leads to an increase in the concentration of ofloxacin in the blood plasma and an increase in the risk of its toxic effects.
Ofloxacin may inhibit the growth of Mycobacterium tuberculosis and give false-negative results in bacteriological tests for the diagnosis of tuberculosis.
Unlike other nitroimidazoles, ornidazole does not inhibit alcohol dehydrogenase, however, Ofor® should also not be taken simultaneously with alcohol.
Theophylline
No pharmacokinetic interaction of ofloxacin with theophylline was found.
Theophylline steady-state serum concentrations, half-life, and risk of theophylline-related adverse reactions may be increased with concomitant use. Serum theophylline levels should be monitored closely and theophylline dosage adjusted as necessary. Adverse reactions (including seizures) may occur with or without increased serum theophylline levels.
During laboratory tests
During treatment with ofloxacin, false-positive results may occur in urine tests for opiates or porphyrins. Therefore, more specific methods should be used.
Ofloxacin may inhibit the growth of Mycobacterium tuberculosis and give false-negative results in bacteriological tests for the diagnosis of tuberculosis.
Interactions related to ornidazole
Anticoagulants
Ornidazole enhances the effect of oral coumarin anticoagulants. During concomitant use, prothrombin time should be carefully monitored or an appropriate coagulation test should be performed to adjust the anticoagulant dosage accordingly.
Vecuronium bromide
Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.
Liver enzyme inducers
Concomitant use of phenobarbital and other inducers of microsomal enzymes reduces the circulation period of ornidazole in the blood serum, while enzyme inhibitors (e.g. cimetidine) increase it.
Liver enzyme inhibitors
Concomitant use of enzyme inhibitors (e.g. cimetidine) with ornidazole increases its circulation period in the blood serum.
Alcohol
Although ornidazole (unlike other nitroimidazole derivatives) does not inhibit aldehyde dehydrogenase, alcohol should not be consumed during the course of drug therapy and for at least 3 days after its discontinuation.
The concomitant use of ornidazole with drugs containing lithium salts should be accompanied by monitoring of lithium and electrolyte concentrations, as well as serum creatinine levels.
Application features
Before starting treatment, it is necessary to perform tests: culture for microflora and determination of sensitivity to ofloxacin and ornidazole.
The drug should be avoided in patients who have had serious adverse reactions to quinolones or fluoroquinolones in the past. Treatment of these patients should only be initiated when there are no alternative treatment options and after a careful benefit/risk assessment.
When using high doses of the drug and in the case of treatment for more than 10 days, clinical and laboratory monitoring is recommended.
In case of side effects, especially from the nervous system, allergic reactions, severe arterial hypotension, which may occur immediately after the first dose, the drug must be discontinued.
The effect of other medicines may be enhanced or weakened when using this medicine.
Features of use associated with ofloxacin
Prolonged, disabling and potentially irreversible serious adverse reactions
In very rare cases, patients treated with quinolones and fluoroquinolones, regardless of age and the presence of risk factors, have experienced prolonged (several months or years), disabling and potentially irreversible serious adverse reactions affecting various, and sometimes several, body systems (including musculoskeletal, nervous, mental and sensory). The drug should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and a doctor should be consulted.
Kidney dysfunction
When using the drug Ofor®, it is necessary to maintain adequate hydration (patients should consume sufficient water) to prevent crystalluria.
Patients with impaired renal function should be prescribed the drug with caution (do not exceed the average daily dose) and monitor laboratory parameters of renal function. For patients with reduced renal function, the prescribed dose of ofloxacin should be adjusted, taking into account that ofloxacin is excreted mainly by the kidneys.
Liver dysfunction
Patients with impaired liver function should be prescribed the drug with caution (due to the possibility of worsening liver function) and monitor laboratory indicators of liver function. Against the background of treatment with fluoroquinolones, the development of fulminant hepatitis is possible, which can lead to the development of liver failure and death. Patients should stop treatment and urgently consult a doctor if signs of liver disease such as anorexia, jaundice, dark urine, itching or abdominal tenderness occur (see section "Adverse reactions").
Patients with severe liver damage (cirrhosis) should not exceed the average daily dose.
Diseases caused by Clostridium difficile
Diarrhoea, particularly severe, persistent and/or occurring after treatment with ofloxacin (including several days after treatment), may be a symptom of pseudomembranous colitis (a disease caused by Clostridium difficile (CDAD)). CDAD can range in severity from mild to life-threatening; the most severe form is pseudomembranous colitis (see section 4.8). It is therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with the drug. If pseudomembranous colitis is suspected, the drug should be discontinued immediately and appropriate symptomatic antibiotic therapy (e.g. oral vancomycin, oral teicoplanin or metronidazole) should be initiated without delay. In such situations, drugs that inhibit intestinal motility are contraindicated.
Hypersensitivity to fluoroquinolones
Hypersensitivity and allergic reactions to fluoroquinolones have been reported after initial administration. Anaphylactic and anaphylactoid reactions may progress to life-threatening shock, even after initial administration. In such cases, the drug should be discontinued and appropriate treatment (e.g., treatment of shock) initiated.
Severe bullous reactions
Cases of severe bullous reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, have been reported with ofloxacin (see section 4.8). Patients should be advised to seek immediate medical attention before continuing treatment with the drug if skin and/or mucous membrane reactions occur.
Tendinitis and tendon rupture
At the first sign of tendinitis (e.g. painful swelling, inflammation), treatment with the drug should be discontinued and alternative treatment should be considered. Affected limbs should be treated appropriately (e.g. immobilization). Corticosteroids should not be used if signs of tendinopathy occur.
QT prolongation
Very rare cases of QT prolongation have been reported with fluoroquinolones. The drug is contraindicated in patients with QT prolongation (see section 4.3). Caution should be exercised when administering fluoroquinolones, including ofloxacin, to patients with known risk factors for QT prolongation, the elderly, electrolyte imbalance (hypokalemia, hypomagnesemia), congenital or acquired long QT syndrome, and cardiac disease (heart failure, myocardial infarction, bradycardia).
Patients taking vitamin K antagonists
Due to the possible increase in coagulation test values (PT/INR) and/or bleeding in patients receiving fluoroquinolones in combination with vitamin K antagonists (e.g. warfarin), coagulation test results should be monitored when these two groups of drugs are used concomitantly (see section 4.5).
Prevention of photosensitivity
Patients taking Ofor® should avoid exposure to sunlight and UV rays due to possible photosensitization. To prevent photosensitization, patients are advised to avoid exposure to strong sunlight or artificial UV sources (e.g., artificial ultraviolet lamps, solariums) during treatment with the drug and for 48 hours after its discontinuation. If photosensitivity reactions (e.g., sunburn-like) occur, treatment with the drug should be discontinued.
Superinfections
As with other antibiotics, the use of ofloxacin, especially long-term use, may lead to the growth of resistant microorganisms, therefore, during treatment, it is necessary to periodically check the condition of patients. If a secondary infection develops during drug therapy, appropriate measures should be taken.
Arterial hypotension
In case of severe arterial hypotension, the use of the drug Ofor® should be discontinued.
Patients with a history of psychotic disorders or psychiatric illness Psychotic reactions have been reported in patients receiving fluoroquinolones. In isolated cases, these have progressed to suicidal ideation and self-harming behavior, including suicide attempts, sometimes after only a single dose of the drug. If a patient develops these reactions, the drug should be discontinued and appropriate medical measures should be taken. The drug should be used with caution in patients with a history of psychotic disorders or in patients with psychiatric illness.
Peripheral neuropathy
Cases of sensory or sensorimotor polyneuropathy resulting in paresthesia, hypoesthesia, dysesthesia or weakness have been reported in patients treated with quinolones and fluoroquinolones. If symptoms of neuropathy such as pain, burning, tingling, numbness or weakness occur, patients taking this medicine should inform their doctor to prevent the development of a potentially irreversible condition. If peripheral neuropathy occurs, treatment should be discontinued.
Patients with a tendency to seizures
Quinolones may lower the seizure threshold and cause seizures. The drug is contraindicated in patients with epilepsy, including a history of epilepsy, or a lowered seizure threshold.
The simultaneous use of ofloxacin with NSAIDs (including phenylpropionic acid derivatives), nitroimidazole derivatives and methylxanthines enhances the stimulating effect on the central nervous system, which leads to a decrease in the seizure threshold (see section "Interaction with other medicinal products and other types of interactions").
If seizures occur, the drug should be discontinued.
Diabetes mellitus
Ofloxacin may potentiate the hypoglycemic effect of insulin and oral hypoglycemic drugs (including glibenclamide). Cases of hypoglycemic coma have been reported. In these patients, blood sugar levels should be monitored.
Development of secondary infection
With prolonged or repeated treatment with antibiotics, the development of opportunistic infections and the growth of resistant microorganisms is possible. In the event of the development of a secondary infection, appropriate measures must be taken. Exacerbation of candidomycosis may occur, which will require appropriate treatment.
Resistance of some strains of Pseudomonas aeruginosa
During treatment with the drug, as with other drugs from the fluoroquinolone group, resistance of some strains of Pseudomonas aeruginosa may develop quite quickly.
Methicillin-resistant Staphylococcus aureus (MRSA) is very likely to be resistant to fluoroquinolones, including ofloxacin. Therefore, the drug is not recommended for the treatment of infections caused by MRSA, unless laboratory tests have confirmed the susceptibility of the pathogen to ofloxacin (and the use of antibacterial agents usually recommended for the treatment of infections caused by MRSA is considered inappropriate).
Infections caused by Escherichia coli (E.coli)
Fluoroquinolone resistance in E. coli (the most common cause of urinary tract infections) varies across the European Union. When prescribing fluoroquinolones, the local prevalence of fluoroquinolone resistance in E. coli should be taken into account.
Pneumonia caused by pneumococci or mycoplasmas, tonsillitis caused by β-hemolytic streptococci
Ofor® is not the drug of choice for the treatment of patients with these diseases.
Infections caused by Neisseria gonorrhoeae
Due to the increasing resistance of Neisseria gonorrhoeae, the drug should not be used as empirical antibacterial therapy for suspected gonococcal infection (gonococcal urethritis, pelvic inflammatory disease and epididymo-orchitis), unless the pathogen has been identified and its sensitivity to ofloxacin has been confirmed. If clinical improvement has not been achieved after 3 days of treatment, therapy should be reviewed.
Drugs containing magnesium, aluminum, iron, zinc, and sucralfate
It is not recommended to take Ofor® within 4 hours of taking medications containing magnesium, aluminum, iron, zinc, and sucralfate.
Myasthenia gravis
Fluoroquinolones, including ofloxacin, block neuromuscular transmission and may cause muscle weakness in patients with myasthenia gravis. Serious adverse reactions, including fatalities and the need for respiratory support, have been associated with the use of fluoroquinolones in patients with myasthenia gravis during post-marketing experience. Ofor® should be used with caution in patients with a history of myasthenia gravis.
Glucose-6-phosphate dehydrogenase deficiency
Patients with latent or confirmed glucose-6-phosphate dehydrogenase deficiency may be prone to hemolytic reactions when treated with quinolones. Ofor® should be prescribed with caution to such patients.
Aortic aneurysm/dissection, regurgitation/valve insufficiency
Epidemiological studies have documented an increased risk of aortic aneurysm and dissection, especially in elderly patients, and aortic and mitral valve regurgitation after the use of fluoroquinolones.
Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal cases), and regurgitation/insufficiency of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.8).
Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other possible treatment options in patients with a positive family history of aneurysm or congenital heart valve disease, or in patients with an existing diagnosis of aneurysm and/or aortic dissection, or heart valve disease, or in the presence of other risk factors, such as:
risk factors for both aortic aneurysm/dissection and heart valve regurgitation/insufficiency (e.g., connective tissue diseases such as Marfan syndrome or vascular Ehlers-Danlos syndrome, Turner syndrome, Behçet's disease, hypertension, rheumatoid arthritis);
risk factors for aortic aneurysm/dissection (e.g., vascular disease such as Takayasu arteritis or giant cell arteritis, atherosclerosis, or Sjögren's syndrome);
risk factor for regurgitation/heart valve insufficiency (e.g., infective endocarditis).
The risk of aortic aneurysm/dissection and rupture is increased in patients receiving concomitant corticosteroids.
Patients should seek emergency medical attention immediately if they experience sudden abdominal, chest, or back pain.
Patients should be advised to seek immediate medical attention in case of acute shortness of breath, new onset of palpitations, or swelling of the abdomen or lower extremities.
Vision impairment
If any visual disturbances occur, you should immediately consult an ophthalmologist.
During laboratory tests
During treatment with the drug, false-positive results may be observed in the determination of opiates or porphyrins in urine. Therefore, more specific methods should be used.
Other application features
With the exception of very rare cases (for example, individual disturbances of smell, taste and hearing), all side effects of the drug disappear immediately after its withdrawal.
Features of use associated with ornidazole
Blood disorders
If there is a history of blood disorders, monitoring of leukocytes is recommended, especially when conducting repeated courses of treatment.
Central and peripheral nervous system dysfunction
In the event of peripheral neuropathy, impaired coordination of movements (ataxia), dizziness or clouding of consciousness, treatment should be discontinued.
Candidiasis
Exacerbation of candidiasis is possible, which will require appropriate treatment.
Hemodialysis
In the case of hemodialysis, it is necessary to take into account the reduction in the half-life of ornidazole and prescribe additional doses of the drug before or after hemodialysis.
Lithium therapy
Lithium salt concentrations, creatinine and electrolyte concentrations should be monitored during lithium therapy.
Alcohol consumption
During treatment with Ofor®, you should not drink alcoholic beverages.
Excipients
The medicine contains the azo dye "sunset yellow" (E 110), which may cause allergic reactions.
Use during pregnancy or breastfeeding
The drug is contraindicated during pregnancy or breastfeeding.
If it is necessary to use the drug, breastfeeding should be discontinued for the period of therapy.
Ability to influence reaction speed when driving vehicles or other mechanisms
When using the drug, undesirable manifestations from the nervous system are possible. The possibility of such manifestations should be taken into account by patients who drive vehicles or work with other mechanisms.
Method of administration and doses
Ofor® should be taken orally, without chewing, with water. The medicine can be taken both before and after meals.
The dose of the drug and the duration of treatment depend on the sensitivity of microorganisms, the severity and type of the infectious process. The dose for adults is 1 tablet 2 times a day for 5 days, then continue therapy for another 2-5 days with ofloxacin tablets. Treatment should be continued for at least 3 days after the disappearance of clinical symptoms of the disease.
Children
The drug is contraindicated in children (under 18 years of age) because skeletal growth in children has not completed.
Overdose
Symptoms
Related to ofloxacin
The most important expected signs of acute ofloxacin overdose are central nervous system symptoms, including confusion, dizziness, impaired consciousness, seizures, QT prolongation, and gastrointestinal reactions such as nausea and erosive mucosal lesions.
During post-marketing studies, central nervous system adverse reactions such as confusion, seizures, hallucinations, and tremor were observed.
Related to ornidazole
Overdose may cause loss of consciousness, headache, dizziness, tremors, convulsions, peripheral neuritis, dyspeptic disorders, and increased symptoms of other adverse reactions.
Treatment. In case of overdose, appropriate measures are recommended, such as gastric lavage, administration of adsorbents and sodium sulfate, if possible, within the first 30 minutes after overdose. Antacids are recommended to protect the gastric mucosa. Ofloxacin fractions can be removed from the body by hemodialysis.
Peritoneal dialysis and continuous ambulatory peritoneal dialysis are not effective in removing ofloxacin from the body. There is no specific antidote to the drug. The elimination of ofloxacin can be enhanced by forced diuresis.
In case of overdose, symptomatic treatment should be applied. ECG monitoring is necessary due to the possibility of QT prolongation. Diazepam is indicated in case of convulsions.
Side effects
Skin: itching, skin rashes, including urticaria, blistering, hyperhidrosis, pustular rashes; erythema multiforme, vascular purpura, acute generalized exanthematous pustulosis, photosensitivity reactions, photosensitization, hypersensitivity (in the form of solar erythema), skin discoloration, nail delamination, skin hyperemia, exfoliative dermatitis.
On the part of the immune system: hypersensitivity reactions, including manifestations of skin allergic reactions; anaphylactic/anaphylactoid reactions, angioedema (including swelling of the tongue, larynx, pharynx, facial edema/swelling), anaphylactic/anaphylactoid shock, tachycardia, fever, shortness of breath, Stevens-Johnson syndrome; Lyell's syndrome; drug dermatitis; vasculitis (which in exceptional cases can lead to skin necrosis), eosinophilia, pneumonitis. In this case, the use of the drug should be discontinued and alternative therapy should be initiated.
Central nervous system*: headache, dizziness (vertigo), depression, sleep disorders (insomnia or drowsiness), restlessness, psychomotor agitation, convulsions, confusion, temporary loss of consciousness, nightmares, slowed reaction time, increased intracranial pressure, paresthesia; sensory or sensorimotor neuropathy, tremor and other extrapyramidal disorders, muscle coordination disorders (impaired sense of balance, unsteady gait), ataxia, psychotic reactions, suicidal thoughts/actions, hallucinations, salivation, anxiety, rigidity, peripheral sensitivity disorders, peripheral neuropathy, taste disorders; photophobia, exacerbation of myasthenia gravis, olfactory disorders, parosmia, dysphasia, dyskinesia, syncope, fatigue, spatial disorientation.
On the part of the digestive system: anorexia (loss of appetite), nausea, vomiting, heartburn, gastralgia (abdominal pain), pain or cramps in the abdomen, diarrhea, frequent loose stools, enterocolitis, sometimes hemorrhagic enterocolitis, flatulence; dysbacteriosis; pseudomembranous colitis, metallic taste in the mouth, change in taste sensations (dysgeusia), taste disturbance, ageusia, including metallic taste in the mouth, gastrointestinal distress, constipation, dry mouth, soreness of the oral mucosa, increased salivation, coated tongue; stomatitis, pancreatitis. A specific form of enterocolitis that can occur with the use of antibiotics is pseudomembranous colitis (in most cases caused by Clostridium difficile). If Clostridium difficile is suspected, the use of the drug should be stopped immediately and adequate treatment should be provided. Medications that reduce peristalsis should not be used in such cases.
On the part of the liver: manifestations of hepatotoxicity, including changes in liver function tests, increased activity of liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT)), bilirubin, cholestatic jaundice, increased levels of triglycerides, cholesterol, in some cases - hepatitis, even very severe, severe liver damage, including cases of acute liver failure, sometimes fatal, mainly in patients with impaired liver function.
From the genitourinary system: renal dysfunction, including urinary retention, acute interstitial nephritis, darkening of urine color, renal failure, acute renal failure, anuria, polyuria, kidney stones, hematuria.
From the reproductive system: genital itching in women, vaginitis, vaginal candidiasis.
Musculoskeletal system*: tendinitis (especially in elderly patients); muscle cramps, myalgia, muscle tears, arthritis, arthralgia; muscle rupture, tendon rupture (including Achilles tendon, which may be bilateral and occur 48 hours after the start of treatment); rhabdomyolysis and/or myopathy, muscular weakness. If there are signs of tendon inflammation, drug therapy should be discontinued immediately and appropriate treatment of the affected tendon should be prescribed.
From the blood system: neutropenia, leukopenia, anemia, hemolytic anemia, eosinophilia, thrombocytopenia, pancytopenia; agranulocytosis, bone marrow hematopoiesis suppression, blood dyscrasia such as medullary aplasia, petechiae, ecchymoses/bruises, prolonged prothrombin time, thrombocytopenic purpura, manifestations of bone marrow effects.
Psychiatric*: psychomotor agitation, psychotic disorders, delirium, anxiety, anxiety, nervousness, depression with self-destructive behavior, including suicidal thoughts or suicide attempts, epileptic seizures, hallucinations.
On the part of the organs of vision*: visual disturbances (e.g. blurred vision), photophobia, Dalton's blindness
