Ofloxacin - instructions for use, dose, side effects, contraindications

The bactericidal effect of ofloxacin is associated with inhibition of DNA gyrase and topoisomerase IV, which leads to a disruption in the replication of bacterial DNA and the 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, Klebsiella 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 (Bacte- roides 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.

Pharmacokinetics:

At the end A 30 minute intravenous infusion of 200 mg ofloxacin serum concentrations of 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 fluids of the body, penetrates into cells. Therapeutically significant concentrations exceeding serum levels are observed in the interstitial tissue, saliva, sputum, lung tissue, myocardium, bones, mucosa and intestinal wall, peritoneal fluid, pancreatic juice and pancreatic tissue, prostate, semen, organs of the female reproductive system , skin and subcutaneous tissue; penetrates into leukocytes and alveolar macrophages.The volume of distribution is 120 liters. It penetrates well through the blood-brain barrier, reaching therapeutic concentrations; in high concentrations passes through the hematoplacental barrier, excreted in breast milk. About 25% of the administered dose binds to blood plasma proteins. The half-life is 4.7 - 7 hours and does not depend on the dose administered. With multiple administrations, the cumulative effect is not expressed, serum concentrations increase slightly. After administration in a dose of 200 mg, the total clearance is 258 ml / min. Ofloxacin is excreted mainly by the kidneys in an unchanged form - 80-90% of the administered dose, creating high concentrations in the urine. In small quantities is excreted through the intestine. Biotransformation in the liver undergoes about 5% of the administered dose; major metabolites - ofloxacin Noxide and N-dimethylofloxacin, which are excreted by the kidneys. In patients with renal failure, the half-life of ofloxacin increases; total and renal clearance decrease in proportion to the decrease in creatinine clearance. At the time of hemodialysis, 10-30% of the drug is removed.

Indications:Infectious-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; LOP-organ, except for cases of acute tonsillitis caused by β-hemolytic streptococcus (some strains of β-hemolytic streptococcus are only partially sensitive to ofloxacin, therefore it should not be used as a first-choice drug for acute tonsillitis caused by β-hemolytic streptococcus), lower respiratory tract, with the exception of cases of established pneumococcal infection or suspected of it (some strains Streptococcus pneumonia are only partially sensitive to ofloxacin, therefore it should not be used as the first-choice 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 deficiency of glucose-6-phosphate dehydrogenase; patients with epilepsy (including history), lowering convulsive threshold (including after traumatic brain injury, stroke, or inflammatory processes in the central nervous system); if there are indications of a lesion of the tendons against the background of the previous administration of fluoroquinolones.

Carefully:

Severe atherosclerosis of cerebral vessels, cerebral circulation, including history, other organic lesions of the central nervous system, impaired renal function, lengthening of the interval QT, simultaneous use of drugs that reduce the threshold of convulsive brain readiness, such as fenbufen, theophylline; drugs that can reduce blood pressure, medicines for non-inhaling general anesthesia from the barbiturate group (increased risk of hypotension); liver failure; known risks of lengthening the interval QT (old age, uncorrected electrolyte disorders (hypokalemia, hypomagnesemia), congenital lengthening syndrome QT, heart disease (heart failure, myocardial infarction, bradycardia), simultaneous use of drugs that can lengthen the interval QT (see the section "Interaction with other medicinal products")); myasthenia gravis; hepatic porphyria; psychoses and other psychiatric disorders in the anamnesis; severe adverse reactions to other quinolones, for example, neurological reactions (increased risk of similar reactions with ofloxacin); in patients with diabetes mellitus, taking oral hypoglycemic agents (for example, glibenclamide) or insulin (the risk of developing hypoglycemia increases).

Pregnancy and lactation:

The drug during pregnancy is contraindicated. If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Intravenously 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, which is administered twice a day at intervals of 12 hours. When the patient's condition is improved, they are transferred to oral intake of the drug at the same daily dose.

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

If the liver is severely disabled, it is not recommended to exceed the dose of the drug 400 mg / day.

In elderly patients, correction of the dosing regimen is not required, however, attention should be paid to the function of the patient's kidneys, as in the event of a decrease, the dosage regimen may need to be adjusted accordingly. Duration of ledepends on the severity of the disease. Treatment with the drug should continue for at least 48 - 72 hours after the normalization of body temperature or if there is evidence 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 localization and severity of the infection.

Further doses and dosage regimens are set taking into account the value of creatinine clearance (see table).

Creatinine clearance, ml / min	>80	80-50	50-20	<20
Dosing regimen	200-400 mg every 12 hours	200-400 mg every 12 hours	100-200 mg every 24 hours	100 mg every 24 hours or 200 mg every 48 hours
Dosing regimen	With hemodialysis and peritoneal dialysis: 100 mg every 24 hours or 200 mg every 48 hours.

Attention! The solution of ofloxacin can not be mixed and dissolve in it other medications.

For the infusion of ofloxacin, it is necessary to use a separate system for intravenous infusions.

If there is an unused solution of ofloxacin in the bottle, it should be disposed of and not used for other patients.

Ofloksatsin solution for infusions of 2 mg / ml is compatible with 0.9% solution of sodium chloride, 5% solution of dextrose.

Side effects:

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 sense organs: headache, dizziness, lack of confidence in movements, imbalance,drowsiness, tremor, convulsions, numbness and paresthesia of the limbs, "nightmarish" dreams, insomnia, psychotic reactions and depression with self-harm, down to suicidal thoughts or attempts, anxiety, arousal, phobias, confusion, hallucinations, peripheral sensory neuropathy, peripheral sensory-motor neuropathy, vertigo, increased intracranial pressure, violation of color perception, diplopia, impaired taste, smell, hearing loss.

From the side of the musculoskeletal system: tendonitis, myalgia, arthralgia, rupture of tendons, rhabdomyolysis and / or myopathy, muscle weakness.

From the side of the cardiovascular system: "tides" 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 medications that promote the lengthening of the interval QT).

Allergic reactions: skin rash, pustular rash, itching, hives, purpura, allergic pneumonitis, allergic nephritis, eosinophilia, fever, angioedema, bronchospasm,multiforme exudative erythema (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 hematopoiesis: leukopenia, agranulocytosis, anemia, including hemolytic and aplastic, thrombocytopenia, pancytopenia, petechiae.

From the urinary system: acute interstitial nephritis, impaired renal function, acute renal failure, hyperhidrosis, hypercreatininaemia, increased urea concentration.

Local Reactions: pain, hyperemia at the site of intravenous injection, thrombophlebitis. Other: intestinal dysbacteriosis, superinfection, hyper- or hypoglycemia (in patients with diabetes mellitus against the background of taking antidiabetic drugs), exacerbation of porphyria, vaginitis, irritation of the mucous membrane of the eye, fungal infections.

Overdose:

Symptoms: dizziness, confusion, inhibition, disorientation, convulsions, drowsiness, vomiting, symptoms of irritation of the mucous membranes.

Treatment: forced diuresis, symptomatic therapy; for the reduction of neurological disorders (convulsive syndrome) use diazepam.

Interaction:

The simultaneous use of ofloxacin and barbiturates can lead to a sharp decrease in blood pressure, therefore, while using barbiturates, for example, as an anesthetic and ofloxacin, the function of the cardiovascular system should be monitored.

Reduces the clearance of theophylline by 25% (with simultaneous use should reduce the dose of theophylline).

Simultaneous use with theophylline, fenbufen, other non-steroidal anti-inflammatory drugs may reduce the threshold of convulsive activity. Ofloxacin practically does not affect the concentration of theophylline in the blood serum. Probenecid, cimetidine, furosemide, methotrexate of tubular secretion of ofloxacin, which, when used simultaneously, leads to an increase in the concentration of antibiotic in serum, increasing the likelihood of developing unwanted drug reactions.

Simultaneous application with vitamin K antagonists leads to an increase in the activity of coumarin derivatives, which requires monitoring of the parameters of the blood coagulation system.

Ofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs that can lengthen the interval QT (antiarrhythmic drugs IA and III classes, tricyclic antidepressants, macrolides, terfenadine) (see sections "With caution", "Special instructions").

With simultaneous use with glibenclamide, a slight increase in the concentration of glibenclamide and, as a consequence, hypoglycemia may be observed, which requires monitoring of blood glucose concentration.

When used simultaneously with other hypoglycemic agents for ingestion and insulin, the risk of developing hypoglycemia increases, and more careful monitoring of the glucose concentration in the blood is required.

When used simultaneously with glucocorticosteroids, the risk of rupture of tendons increases, especially in elderly patients.

When used with drugs that alkalinize urine (inhibitors of carbonic anhydrase, citrates, sodium hydrogen carbonate), the risk of crystalluria increases and nephrotoxic effects.

A solution of ofloxacin should not be mixed with heparin because of the risk of precipitation in solution.

Special instructions:

Ofloxacin is not a 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 developing tendonitis can lead to rupture of tendons (mainly Achilles tendon), especially in elderly patients. In case of signs of tendonitis, it is necessary immediately to stop treatment, to immobilize the Achilles tendon and consult an orthopedist.

In the presence of severe liver disease requires an individual selection of the dose depending on the degree of impaired liver function.

If you experience during or after treatment with ofloxacin severe and prolonged diarrhea is necessary to exclude the development of pseudomembranous colitis (requires immediate withdrawal of the drug and oral vancomycin and metronidazole). Drugs that suppress the intestinal peristalsis are contraindicated.

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

Against the backdrop of treatment, myasthenia flow may worsen, and porphyria attacks may be more frequent in predisposed patients.

When determining in the urine of porphyrin, a false positive result can result. For the treatment of mixed aerobic-anaerobic infections (peritonitis, endometritis and others) it is recommended to combine ofloxacin with one of the antianaerobic antibiotics, which have antianaerobic activity.

The drug should be used with caution in patients predisposed to developing seizures (patients with lesions of the central nervous system in the anamnesis, 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, lowering the threshold of convulsive readiness of the brain, such as theophylline) (see the section "Interaction with other medicinal products").

In patients taking fluoroquinolones, in very rare cases, an increase in the duration of the interval QT. The following groups of patients with known risk factors increase the duration of the interval QT, the use of fluoroquinolones, including ofloxacin, should be conducted with caution (under the control of the duration of the interval QT):

- patients of advanced age;

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

- congenital lengthening syndrome QT;

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

- simultaneous reception of drugs that can lengthen the interval QT (antiarrhythmic drugs IA and III classes, tricyclic antidepressants, macrolides, terfenadine) (see section "Interaction with other drugs").

In patients who received fluoroquinolones, including ofloxacin, reported on the development Sensory and sensory-motor neuropathy, which can have fast start. If patients develop neuropathy symptoms, ofloxacin should be discontinued, thereby minimizing the possible risk of developing irreversible conditions.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions. In case of occurrence of the undesirable phenomena from nervous system it is necessary to refrain from the specified kinds of activity.

Form release / dosage:

Solution for infusions 2 mg / ml.

Packaging:

100 ml in bottles glass for blood, transfusion and infusion preparations, corked with rubber stoppers and crimped with aluminum caps.

1. Each bottle, together with instructions for use, is placed in a pack of cardboard.

2. For hospitals. For 56 bottles with an equal number of instructions for use are placed in a group box - boxes of cardboard corrugated.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C. Freezing is not allowed.

Keep out of the reach of children.

Shelf life:

2 of the year. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002734

Date of registration:28.11.2014

Expiration Date:28.11.2019

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Information update date: & nbsp18.06.2017

Illustrated instructions

Instructions

Ofloxacin (Ofloxacin)