Instructions for use OFLOXACIN

pharmachologic effect

The bactericidal effect of ofloxacin is associated with inhibition of DNA gyrase and topoisomerase IV, which leads to disruption of bacterial DNA replication and death of microbial cells.

Ofloxacin has a broad spectrum of antimicrobial action, including microorganisms resistant to other antibiotics, including strains that produce beta-lactamases. Sensitive microorganisms: Aeromonas hydrophila, Moraxella catarrhalis, Brucella spp., Chlamydia trachomatis, Citrobacter freundii, Clostridium perfringens, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Helicobacter coli, Helicobacter jejuni, K Lebsiella oxytoca, Legionella pneumophila, Morganella morganii, Mycoplasma hominis, Neisseria gonorrhoeae, Neisseria meningitidis, Plesiomonas spp., Proteus mirabilis, Proteus vulgaris, Salmonella enteric, Serratia marcescens, Shigella spp., Staphylococcus spp. (coagulase-negative strains), including Staphylococcus aureus (methicillin-sensitive), Yersinia enterocolitica.

Moderately sensitive microorganisms: Acinetobacter calcoaceticus, anaerobes (Bacteroides fragilis), Chlamydia psittaci, Gardnerella vaginalis, Mycobacterium tuberculosis, Mycobacterium leprae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Streptococcus spp.

Resistant microorganisms: Acinetobacter baumannii, Clostridium difficile, Enterococcus spp., Listeria monocytogenes, Staphylococcus aureus (methicillin-resistant), Nocardia asteroides.

Ofloxacin solution d/inf 2mg/ml 100ml (Synthesis)

Ofloxacin is bactericidal, antibacterial. It acts on the bacterial enzyme DNA gyrase, which ensures supercoiling and, thus, stability of bacterial DNA (destabilization of DNA chains leads to their death). It has a wide spectrum of action and has a bactericidal effect. Pharmacodynamics Active against microorganisms producing beta-lactamases and fast-growing atypical mycobacteria. Sensitive: Staphylococcus aureus, Staphylococcus epidermidis, Neisseria gonorrhoeae, Neisseria meningitidis, Escherichia coli, Citrobacter, Klebsiella spp., (including Klebsiella pneumoniae), Enterobacter spp. (including Enterobacter cloacae), Hafnia, Proteus spp. (including Proteus mirabilis, Proteus vulgaris - indole-positive and indole-negative), Salmonella spp., Shigella spp. (including Shigella sonnei), Yersinia enterocolitica, Campylobacter jejuni, Aeromonas hydrophila, Plesiomonas aeruginosa, Vibrio cholerae, Vibrio parahaemolyticus, Haemophilus influenzae, Chlamydia spp. (including Chlamydia trachomatis), Legionella spp., Serratia spp., Providencia spp., Haemophilus ducreyi, Bordetella parapertussis, Bordetella pertussis, Moraxella catarrhalis, Propionibacterium acnes, Staphylococcus spp., Brucella spp. Various sensitivities to the drug have: Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Serratia marcescens, Pseudomonas aeruginosa, Acinetobacter, Mycoplasma hominis, Mycoplasma pneumoniae, Mycobacterium tuberculosis, Mycobacterium fortuitum, Ureaplasma urealyticum, Clostridium perfringens, Corynebacterium spp., Helicobacter pylori, Listeria monocy togenes, Gardnerella vaginalis. In most cases insensitive: Nocardia asteroides, anaerobic bacteria (for example, Bacteroides spp., Peptococcus spp., Peptostreptococcus spp., Eubacterium spp., Fusobacterium spp., Clostridium difficile). Does not affect Treponema pallidum. Pharmacokinetics: After oral administration, it is quickly and completely absorbed. Bioavailability - over 96%, binding to plasma proteins - 25%. Tmax is 1–2 hours, Cmax after administration at a dose of 100, 300, 600 mg is 1, 3.4 and 6.9 mg/l. After a single dose of 200 or 400 mg, it is 2.5 mcg/ml and 5 mcg/ml, respectively. The apparent volume of distribution is 100 l. Penetrates into tissues, organs and environments of the body: into cells (leukocytes, alveolar macrophages), skin, soft tissues, bones, abdominal and pelvic organs, respiratory system, urine, saliva, bile, prostate secretions, passes well through the BBB, placental barrier, excreted in breast milk. Penetrates into the cerebrospinal fluid with inflamed and non-inflamed meninges (14–60%). Metabolized in the liver (about 5%) with the formation of N-oxide of ofloxacin and dimethylofloxacin. T1/2 does not depend on the dose and is 4.5–7 hours. 75–90% is excreted by the kidneys (unchanged), about 4% with bile. Extrarenal clearance is less than 20%. After a single dose of 200 mg, it is detected in the urine within 20–24 hours. In case of renal/liver failure, excretion may slow down. Does not accumulate.

Pharmacokinetics

At the end of a 30-minute intravenous infusion of 200 mg ofloxacin, serum concentrations are 5.2 mg/l, 4 hours after infusion - 1.1 mg/l, after 12 hours - 0.3 mg/l. Quickly penetrates and is well distributed in many organs, tissues and body fluids, penetrates into cells. Therapeutically significant concentrations exceeding serum concentrations are observed in interstitial tissue, saliva, sputum, lung tissue, myocardium, bones, intestinal mucosa and wall, peritoneal fluid, pancreatic juice and pancreatic tissue, prostate, seminal fluid, organs of the female reproductive system , skin and subcutaneous tissue; penetrates leukocytes and alveolar macrophages. The distribution volume is 120 l. Penetrates well through the blood-brain barrier, reaching therapeutic concentrations; in high concentrations passes through the hematoplacental barrier and is excreted in breast milk. About 25% of the administered dose is bound to blood plasma proteins. The half-life is 4.7 - 7 hours and does not depend on the administered dose. With repeated administrations, the cumulative effect is not pronounced, serum concentrations increase slightly. After administration at a dose of 200 mg, the total clearance is 258 ml/min. Ofloxacin is excreted predominantly by the kidneys unchanged - 80 - 90% of the administered dose, creating high concentrations in the urine. In small quantities it is excreted through the intestines. About 5% of the administered dose undergoes biotransformation in the liver; the main metabolites are ofloxacin N-oxide and N-dimethylofloxacin, which are excreted by the kidneys. In patients with renal impairment, the half-life of ofloxacin is prolonged; total and renal clearance decrease in proportion to the decrease in creatinine clearance. During a hemodialysis session, 10–30% of the drug is removed.

Indications for use

Infectious and inflammatory diseases caused by microorganisms sensitive to ofloxacin: kidney, urinary tract, prostate; gonococcal urethritis; skin and soft tissues; bones and joints; female genital organs; abdominal cavity and biliary tract; ENT organs, with the exception of cases of acute tonsillitis caused by β-hemolytic streptococcus (some strains of β-hemolytic streptococcus are only partially sensitive to ofloxacin, so it should not be used as a first-line drug for acute tonsillitis caused by β-hemolytic streptococcus) ; lower respiratory tract, except in cases of established or suspected pneumococcal infection (some strains of Streptococcus pneumonia are only partially sensitive to ofloxacin, so it should not be used as a first-line drug for community-acquired pneumonia caused by this pathogen); septicemia. Prevention of infections in patients with impaired immune status (including neutropenia).

Contraindications

Hypersensitivity to fluoroquinolones and excipients of the drug, children under 18 years of age, patients with glucose-6-phosphate dehydrogenase deficiency; patients with epilepsy (including a history), decreased seizure threshold (including after traumatic brain injury, stroke or inflammatory processes in the central nervous system); if there are indications of tendon damage due to previous use of fluoroquinolones.

Carefully

Severe atherosclerosis of cerebral vessels, cerebrovascular accidents, including a history of other organic lesions of the central nervous system, renal dysfunction, prolongation of the QT interval, simultaneous use of drugs that reduce the threshold of convulsive readiness of the brain, such as fenbufen, theophylline; drugs that can lower blood pressure, drugs for non-inhalation general anesthesia from the group of barbiturates (increased risk of hypotension); liver failure; known risks of QT prolongation (older age, uncorrected electrolyte disturbances (hypokalemia, hypomagnesemia), congenital long QT syndrome, heart disease (heart failure, myocardial infarction, bradycardia), concomitant use of drugs that can prolong the QT interval (see section " Interaction with other drugs")); myasthenia gravis; hepatic porphyria; history of psychosis and other mental disorders; severe adverse reactions to other quinolones, such as neurological reactions (increased risk of similar reactions when using ofloxacin); in patients with diabetes mellitus taking oral hypoglycemic agents (for example, glibenclamide) or insulin (the risk of hypoglycemia increases).

Use during pregnancy and breastfeeding

The drug is contraindicated during pregnancy. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Ofloxacin

Kidney failure

Since ofloxacin is excreted primarily by the kidneys, dosage adjustments are required in patients with impaired renal function.

Prevention of photosensitivity

When using ofloxacin, due to the risk of photosensitization, exposure to strong solar or artificial ultraviolet radiation should be avoided.

Superinfection

As with the use of other antimicrobial drugs, the use of ofloxacin, especially for a long time, can lead to increased proliferation of microorganisms that are insensitive to it (bacteria and fungi). Therefore, during treatment, it is imperative to re-evaluate the patient’s condition, and if superinfection develops during treatment, appropriate measures should be taken to treat it.

Peripheral neuropathy

Sensory and sensorimotor peripheral neuropathy, which may have a rapid onset, has been reported in patients receiving fluoroquinolones, including ofloxacin. If the patient develops symptoms of neuropathy, ofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes.

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients diagnosed with glucose-6-phosphate dehydrogenase deficiency are predisposed to hemolytic reactions when treated with quinolones. Therefore, caution should be exercised when using ofloxacin in such patients.

Pseudomembranous colitis caused by
Clostridium difficile
The occurrence of diarrhea, especially severe, persistent and/or bloody diarrhea, during or after treatment, may be a manifestation of pseudomembranous colitis. If the development of pseudomembranous colitis is suspected, treatment with ofloxacin should be stopped immediately, and appropriate specific therapy (Vancomycin orally, teicoplanin orally or metronidazole orally) should be immediately prescribed. If this clinical situation occurs, drugs that inhibit intestinal motility are contraindicated.

Patients predisposed to developing seizures

Like other fluoroquinolones, ofloxacin should be used with caution in patients with a predisposition to the development of seizures: in patients with previous lesions of the central nervous system, in patients simultaneously receiving drugs that lower the seizure threshold of the brain (theophylline, fenbufen and other similar non-steroidal anti-inflammatory drugs). If seizures develop, treatment with ofloxacin should be discontinued.

Tendinitis

Tendinitis, which occurs rarely with quinolones, can sometimes lead to rupture of tendons, including the Achilles tendon, especially in elderly patients and in patients concomitantly taking corticosteroids. This side effect may develop within 48 hours of starting treatment and may be bilateral. If signs of tendinitis (inflammation of the tendon) appear, it is recommended to immediately stop treatment with the drug. The affected tendon may need to be treated appropriately, for example by providing sufficient immobilization.

QT
interval Some caution is required when using fluoroquinolones, including ofloxacin, in patients with known risk factors for prolongation of the QT interval, such as: advanced age; uncorrected electrolyte disturbances (hypokalemia, hypomagnesemia); congenital prolongation of the QT interval; diseases of the cardiovascular system (heart failure, myocardial infarction, bradycardia); simultaneous use with other drugs that prolong the QT interval (class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics).

Exacerbation of pseudoparalytic myasthenia gravis (myasthenia
gravis )
Fluoroquinolones, including ofloxacin, can block neuromuscular activity and increase muscle weakness in patients with pseudoparalytic myasthenia. In the post-marketing period, serious adverse reactions, including pulmonary failure requiring mechanical ventilation and death, have been observed with the use of fluoroquinolones in patients with myasthenia gravis. The use of ofloxacin in patients with an established diagnosis of pseudoparalytic myasthenia gravis is not recommended.

Severe skin reactions

When using ofloxacin, cases of severe bullous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been observed. Patients should be informed that if any reactions from the skin or mucous membranes develop, the patient should immediately consult a doctor and not continue treatment until his consultation.

Hypersensitivity reactions and allergic reactions

With the use of fluoroquinolones, the development of hypersensitivity reactions and allergic reactions (anaphylactic shock and anaphylactoid reactions, which can progress to a life-threatening condition) has been reported. In these cases, treatment with ofloxacin should be stopped and the necessary therapeutic measures should be initiated.

Psychotic reactions

Psychotic reactions, including suicidal thoughts/attempts, have been reported in patients taking fluoroquinolones, including ofloxacin. If patients develop such reactions, ofloxacin should be discontinued and appropriate treatment should be prescribed. Ofloxacin should be used with caution in patients with psychotic disorders, including a history of psychotic disorders.

Liver dysfunction

Ofloxacin should be used with caution in patients with impaired liver function as liver damage may occur. Cases of fulminant hepatitis leading to liver failure (including fatal cases) have been reported with the use of fluoroquinolones. Patients should be advised to stop treatment and consult a doctor if symptoms and signs of liver disease are observed, such as anorexia, jaundice, dark urine, itching, abdominal pain.

Dysglycemia (hypo- and hyperglycemia)

Both hypoglycemia and hyperglycemia have been reported with fluoroquinolones, including ofloxacin. Hypoglycemic coma has been reported in patients with diabetes mellitus receiving concomitant treatment with oral hypoglycemic drugs (eg, glibenclamide) or insulin drugs. In patients with diabetes mellitus, careful monitoring of blood glucose concentrations is required.

Patients

Taking
vitamin K antagonists
Due to the possible increase in prothrombin time/international normalized ratio and/or bleeding in patients taking both ofloxacin and vitamin K antagonists (for example, warfarin), regular monitoring of blood clotting parameters is necessary.

Risk of developing resistance

The prevalence of acquired resistance may vary geographically and over time for individual microorganism species. Therefore, local information on resistance is required; Microbiological diagnostics should be carried out with isolation of the pathogen and determination of its sensitivity, especially in severe infections or lack of response to treatment.

Escherichia coli
infections Resistance to fluoroquinolones in Escherichia coli, the most common causative agent of urinary tract infections, varies among geographic regions. Physicians are advised to take into account the local resistance of Escherichia coli to fluoroquinolones.

Infections due to
Neisseria gonorrhoeae
Due to increasing resistance in Neisseria gonorrhoeae, ofloxacin should not be used as empirical treatment for suspected gonococcal urinary tract infection. Susceptibility testing of the pathogen to ofloxacin should be performed to guide targeted therapy.

Methicillin-resistant Staphylococcus aureus

There is a high likelihood that Staphylococcus aureus (methicillin-resistant strains) will be resistant to fluoroquinolones, including ofloxacin. Therefore, ofloxacin is not recommended for the treatment of established or suspected infections caused by Staphylococcus aureus (methicillin-resistant strains) unless laboratory tests have confirmed the sensitivity of this microorganism to ofloxacin.

Bone and joint infections

For infections of bones and joints, the need for combined use of ofloxacin with other antibacterial drugs should be considered.

Effect on laboratory parameters and diagnostic tests

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

special instructions

Ofloxacin is not the drug of choice for diseases of the upper and lower respiratory tract caused by pneumococci.

As with other fluoroquinolones, due to possible photosensitization, it is recommended to avoid prolonged exposure to direct sunlight or ultraviolet radiation.

Rarely, tendinitis can lead to tendon rupture (mostly the Achilles tendon), especially in older patients. If signs of tendinitis occur, you should immediately stop treatment, immobilize the Achilles tendon and consult an orthopedist.

In the presence of severe liver disease, individual selection of the dose of the drug is required depending on the degree of liver dysfunction.

If severe and prolonged diarrhea occurs during or after treatment with ofloxacin, it is necessary to exclude the development of pseudomembranous colitis (immediate discontinuation of the drug and oral administration of vancomycin and metronidazole are required). Drugs that suppress intestinal motility are contraindicated.

Ofloxacin inhibits the growth of Mycobacterium tuberculosis, which may lead to false negative results of bacteriological tests in patients with tuberculosis.

During treatment, the course of myasthenia gravis may worsen and attacks of porphyria may increase in predisposed patients.

When determining porphyrin in urine, a false positive result may be obtained.

For the treatment of mixed aerobic-anaerobic infections (peritonitis, endometritis and others), it is recommended to combine ofloxacin with one of the antianaerobic antibiotics that have antianaerobic activity.

The drug should be used with caution in patients predisposed to the development of seizures (patients with a history of lesions of the central nervous system, patients taking fenbufen or other non-steroidal anti-inflammatory drugs that reduce the threshold of convulsive readiness of the brain, as well as other drugs that reduce the threshold of convulsive readiness of the brain , such as theophylline) (see section "Interaction with other drugs").

In very rare cases, prolongation of the QT interval has been observed in patients taking fluoroquinolones. In the following patient groups with known risk factors for QT prolongation, the use of fluoroquinolones, including ofloxacin, should be used with caution (monitoring the QT interval):

— elderly patients;

- patients with uncorrected disorders of the electrolyte composition of the blood, such as hypokalemia, hypomagnesemia;

— congenital long QT syndrome;

- heart diseases (such as heart failure, myocardial infarction, bradycardia);

- simultaneous use of drugs that can prolong the QT interval (classes IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, terfenadine) (see section “Interaction with other drugs”).

Sensory and sensorimotor neuropathy, which may have a rapid onset, has been reported in patients receiving fluoroquinolones, including ofloxacin. If patients develop symptoms of neuropathy, treatment with ofloxacin should be discontinued to help minimize the possible risk of developing irreversible conditions.

Instructions for use OFLOXACIN

It is not the drug of choice for pneumonia caused by pneumococci. Not indicated for the treatment of acute tonsillitis.

It is not recommended to use the drug for more than 2 months. Avoid exposure to sunlight and ultraviolet rays (mercury-quartz lamps, solarium).

In case of side effects from the central nervous system, allergic reactions, pseudomembranous colitis, discontinuation of the drug is necessary. For pseudomembranous colitis confirmed by colonoscopy and/or histology, oral administration of vancomycin and metronidazole is indicated.

It should be borne in mind that when using Ofloxacin-Borimed, rare tendinitis can lead to tendon rupture (mainly the Achilles tendon), especially in elderly patients. If symptoms of tendinitis occur, you should immediately stop treatment, immobilize the Achilles tendon and consult an orthopedist.

When using the drug, women are not recommended to use Tampax-type tampons, due to the increased risk of developing vaginal candidiasis.

During treatment, the course of myasthenia gravis may worsen and attacks of porphyria may increase in predisposed patients.

When using the drug, false negative results are possible in the bacteriological diagnosis of tuberculosis (prevents the isolation of Mycobacterium tuberculosis).

In patients with impaired liver or kidney function, monitoring of plasma concentrations of ofloxacin is necessary. In case of severe renal and hepatic insufficiency, the risk of developing toxic effects increases (dose adjustment is required).

During treatment with the drug, you should avoid drinking alcohol.

Use in pediatrics

In children, Ofloxacin-Borimed is prescribed only when there is a threat to life, taking into account the expected benefits and the potential risk of side effects, when it is impossible to use other, less toxic drugs.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, it is necessary to refrain from driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

The drug should be prescribed with caution in case of atherosclerosis of cerebral vessels, cerebrovascular accidents (history), chronic renal failure, QT prolongation, organic lesions of the central nervous system.

Directions for use and doses

Intravenous drip.

The duration of administration of 200 mg ofloxacin is 30 minutes. Doses are selected individually depending on the location and severity of the infection, as well as the sensitivity of microorganisms and the general condition of the patient.

In patients with normal renal function, the average therapeutic single dose of ofloxacin is 200 mg, administered twice daily with an interval of 12 hours. If the patient's condition improves, the patient is transferred to oral administration of the drug in the same daily dose.

For the treatment of severe infections, including in patients with impaired immune status, the single dose can be increased to 400 mg, which is administered intravenously 2 times a day.

In case of severe liver dysfunction, it is not recommended to exceed the dose of the drug 400 mg/day.

In elderly patients, no adjustment of the dosage regimen is required; however, attention should be paid to the patient's renal function, since if it decreases, a corresponding adjustment of the dosage regimen may be required. The duration of treatment depends on the severity of the disease. Treatment with the drug should continue for at least 48–72 hours after body temperature has normalized or if there is confirmation of eradication of the pathogen.

In patients with impaired renal function, the first loading dose is the same as in patients with normal renal function and depends on the location and severity of the infection.

Subsequently, doses and dosage regimens are established taking into account the value of creatinine clearance (see table).

Attention!
Ofloxacin solution should not be mixed or dissolved in it with other medications. For infusion of ofloxacin, a separate intravenous system must be used. If there is any unused ofloxacin solution left in the bottle, it should be discarded and not used on other patients.
Ofloxacin solution for infusion 2 mg/ml is compatible with 0.9% sodium chloride solution, 5% dextrose solution.

Side effect

From the digestive system

: nausea, vomiting, diarrhea, flatulence, abdominal pain, increased activity of liver transaminases, hyperbilirubinemia, cholestatic jaundice, hepatitis, decreased appetite, pseudomembranous colitis, enterocolitis (in some cases hemorrhagic), constipation, anorexia.

From the nervous system and sensory organs

: headache, dizziness, uncertainty of movements, imbalance, drowsiness, tremors, convulsions, numbness and paresthesia of the limbs, nightmares, insomnia, psychotic reactions and depression with self-harm, up to suicidal thoughts or attempts, anxiety, state of agitation , phobias, confusion, hallucinations, peripheral sensory neuropathy, peripheral sensory-motor neuropathy, vertigo, increased intracranial pressure, impaired color vision, diplopia, impaired taste, smell, hearing loss.

From the musculoskeletal system

: tendinitis, myalgia, arthralgia, tendon rupture, rhabdomyolysis and/or myopathy, muscle weakness.

From
the cardiovascular system:
“flushes” of blood to the skin of the face, arterial hypotension, collapse (with a sharp decrease in blood pressure, the administration is stopped), tachycardia, arrhythmia (risk factor - hypokalemia, diseases and taking drugs that prolong the QT interval).

Allergic reactions

: skin rash, pustular rash, pruritus, urticaria, purpura, allergic pneumonitis, allergic nephritis, eosinophilia, fever, angioedema, bronchospasm, erythema multiforme exudative (including Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyell's syndrome), photosensitivity , vasculitis, bullous hemorrhagic dermatitis, anaphylactic shock, cough, nasopharyngitis, shortness of breath.

From the blood system and hematopoietic organs

: leukopenia, agranulocytosis, anemia, including hemolytic and aplastic, thrombocytopenia, pancytopenia, petechiae.

From the urinary system

: acute interstitial nephritis, impaired renal function, acute renal failure, hyperhidrosis, hypercreatininemia, increased urea concentration.

Local reactions

: pain, hyperemia at the intravenous injection site, thrombophlebitis.

Others

: intestinal dysbiosis, superinfection, hyper- or hypoglycemia (in patients with diabetes while taking antidiabetic drugs), exacerbation of porphyria, vaginitis, irritation of the mucous membrane of the eye, fungal infections.

OFLOXACIN solution for infusion 100ml 2mg/ml

From the digestive system:

nausea, vomiting, diarrhea, abdominal pain and cramps, loss of appetite, dry mouth, flatulence, gastrointestinal dysfunction, constipation; rarely - liver dysfunction, liver necrosis, jaundice, hepatitis, intestinal perforation, pseudomembranous colitis, bleeding from the gastrointestinal tract, disorders of the oral mucosa, heartburn, increased activity of liver enzymes, including GGT and LDH, increased bilirubin levels in the blood serum.

From the nervous system:

insomnia, dizziness, fatigue, drowsiness, nervousness; rarely - convulsions, anxiety, cognitive changes, depression, pathological dreams, euphoria, hallucinations, paresthesia, syncope, tremor, confusion, nystagmus, suicidal thoughts or attempts, disorientation, psychotic reactions, paranoia, phobia, agitation, aggressiveness, emotional lability, peripheral neuropathy, ataxia, coordination disorders, exacerbation of extrapyramidal disorders, speech impairment.

Allergic reactions:

skin rash, itching; rarely - angioedema, urticaria, vasculitis, allergic pneumonitis, anaphylactic shock, erythema multiforme, Stevens-Johnson syndrome, erythema nodosum, exfoliative dermatitis, toxic epidermal necrolysis, conjunctivitis.

From the reproductive system:

itching in the area of ​​the external genitalia in women, vaginitis, vaginal discharge; rarely - burning, irritation, pain and rash in the genital area in women, dysmenorrhea, menorrhagia, metrorrhagia, vaginal candidiasis.

From the cardiovascular system:

rarely - cardiac arrest, edema, arterial hypertension, arterial hypotension, palpitation, vasodilation, cerebral thrombosis, pulmonary edema, tachycardia.

From the urinary system:

rarely - dysuria, increased urination, urinary retention, anuria, polyuria, kidney stone formation, renal failure, nephritis, hematuria, albuminuria, candiduria.

From the musculoskeletal system:

rarely - arthralgia, myalgia, tendinitis, muscle weakness, exacerbation of myasthenia gravis.

From the side of metabolism:

rarely - thirst, weight loss, hyper- or hypoglycemia (especially in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents), acidosis, increase in serum TG, cholesterol, potassium.

From the respiratory system:

rarely - cough, nasal discharge, respiratory arrest, dyspnea, bronchospasm, stridor.

From the senses:

rarely - hearing impairment, tinnitus, diplopia, nystagmus, impaired clarity of visual perception, impaired taste, smell, photophobia.

Dermatological reactions:

rarely - photosensitivity, hyperpigmentation, vesiculobullous rashes.

From the hematopoietic system:

rarely - anemia, bleeding, pancytopenia, agranulocytosis, leukopenia, reversible inhibition of bone marrow hematopoiesis, thrombocytopenia, thrombocytopenic purpura, petechiae, ecchymosis, increased prothrombin time.

Other:

chest pain, pharyngitis, fever, body pain; rarely - asthenia, chills, general malaise, nosebleeds, increased sweating.