Tarihid - instructions for use, doses, side effects, contraindications

Ofloxacin is a broad-spectrum bactericidal antimicrobial agent from the group of fluoroquinolones. The main mechanism of action of quinolones is specific inhibitionbacterial DNA gyrase. DNA-gyrase is necessary for replication, transcription, repair and recombination of bacterial DNA. Its inhibition leads to the unwinding and destabilization of bacterial DNA and, as a result, to the death of the microbial cell.

Ofloxacin is highly active (MIC <0.5 mg / l) against the following 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 enterica, Serratia marcescens, Shigella spp., Staphylococcus spp. (coagulase-negative), including Staphylococcus aureus (methicillin-sensitive), Yersinia enterolytica.

Moderately sensitive to ofloxacin Acinetobacter calcoaceticus, Anaerobic Gram positive cocci (anaerobic Gram-positive cocci), Bacteroides fragilis, Chlamydia psittaci, Gardnerella vaginalis, Mycobacterium tuberculosis, Mycobacterium leprae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Streptococcus spp. Resistant microorganisms (IPC >1 mg / l): Acinetobacter baumannii, Clostridium difficile, Enterococcus spp., Listeria monocytogenes, Staphylococcus aureus (methicillin-resistant), Nocardia asteroides.

Pharmacokinetics:

The maximum serum concentration with a 30-minute intravenous infusion of TARIVID® is achieved at the end of the infusion. Concentrations of ofloxacin in serum after a 30-minute intravenous infusion of Tariw®.

Dose	Whey	Whey	Whey
	concentration	concentration	concentration
	ofloxacin	ofloxacin	ofloxacin
	after infusion	in 4 hours	in 12 hours
		after infusion	after infusion
100 mg	2.9 mg / L	0.5 mg / l	0,2 mg / l
200 mg	5.2 mg / l	1.1 mg / l	0.3 mg / l

In the course of the use of ofloxacin, serum concentration is not significantly increases (the coefficient of accumulation upon administration twice per day is 1.5).

Half-life with intravenous infusion introduction is 5 hours, a decrease in serum concentration of ofloxacin after infusion occurs linearly. The volume of distribution is 120 liters. The drug penetrates into many organs and tissues, including, lung tissue, ear tissue, throat, nose, skin, soft tissue, bone tissue, joints, abdominal organs, bile, small pelvis organs, kidneys, prostate gland, urethra. The connection with plasma proteins is approximately 25%. Less than 5% ofloxacin undergoes biotransformation. In the urine, two major metabolites are detected: demethylfloxacin and N-oxide ofloxacin. Excretion by the kidneys (80-90% of the dose) in unchanged form. In the bile ofloxacin is found in a glucuronated form.

In elderly patients, the half-life increases, but the maximum serum concentration does not change.

With renal failure, the serum half-life increases; total and renal clearance decrease in proportion to the decrease in creatinine clearance.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to ofloxacin:

- kidneys, 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 in acute tonsillitis caused by β-hemolytic streptococcus);respiratory tract, with the exception of cases establishedth pneumococcal (some pneumococcal strains are only partially susceptible to ofloxacin, so it should not be used as the first-choice drug for community-acquired pneumonia caused by pneumococcus);

- septicemia;

- prophylaxis of infections caused by microorganisms sensitive to ofloxacin in patients with a predisposition to the development of infections (e.g., neutropenia).

Contraindications:

- Hypersensitivity to ofloxacin, other quinolones or excipients preparation.

- Epilepsy (including in the anamnesis).

- Lesions of tendons with a history of fluoroquinolones.

- Children and adolescence under 18 years.

- Pregnancy (can not completely exclude the risk of cartilage growth points in the fetus).

- lactation (it is impossible to completely eliminate the risk of cartilaginous bone growth points of the child).

If you have one of the listed diseases or conditions, before taking the drug must be consulted with your doctor.

Carefully:

- Patients predisposed to the development of seizures (in patients with previous lesions of the central nervous system (CNS), such as a pronounced cerebral arteriosclerosis, cerebrovascular disease history, organic CNS, brain trauma history; patients concomitantly receiving drugs reducing the threshold of convulsive readiness of the brain, such as fenbufen, theophylline) (cm."Interaction with other drugs, laboratory and diagnostic tests").

- In patients with latent or manifested deficiency of glucose-6- phosphate dehydrogenase (an increased risk of hemolytic reactions in the treatment of quinolones).

- In patients with impaired renal function (mandatory monitoring of kidney function, as well as correction of the dosing regimen, see "Method of administration and dose").

- In patients with hepatic insufficiency (monitoring the indicators of liver function).

- In patients with known risk factors for lengthening the interval QT: in elderly patients, in patients with uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); with the syndrome of congenital extension of the interval QT; with diseases of the heart (heart failure, myocardial infarction, bradycardia); while concomitantly taking medications that can lengthen the interval QT (see "Interaction with Other Drugs, Laboratory and Diagnostic Tests").

- In patients with diabetes mellitus, receiving oral hypoglycemic agents (for example, glibenclamide) or insulin (the risk of developing hypoglycemia increases).

- In patients with severe adverse reactions to other quinolones, such as severe neurologic reactions (increased risk of similar undesirable reactions with ofloxacin).

- In patients with myasthenia gravis.

- Patients with hepatic porphyria.

- In patients with psychoses and other psychiatric disorders in the anamnesis.

- With the simultaneous administration of drugs that can reduce arterial

pressure, drugs for non-inhaling general anesthesia from the barbiturate group (increased risk of hypotension).

If you have one of the listed diseases or conditions, before taking the drug must be consulted with your doctor.

Pregnancy and lactation:

Pregnancy

Ofloxacin can not be used in pregnancy (see Contraindications).

Lactation period

As ofloxacin is excreted into breast milk, then due to the risk to the child, breastfeeding women should not use ofloxacin, and in case of urgent need for its use, breastfeeding for this time should be discontinued.

Dosing and Administration:

The dosage regimen depends on the type and severity of the infection and the function of the kidneys.

Dosing regimen in adults with normal kidney function (creatinine clearance more than 50 ml / min)

In the treatment of infections caused by microorganisms that are sensitive to ofloxacin, the recommended dose is 200 mg twice a day or 400 mg once a day. Usually the daily dose is 400 mg. In case of treatment of severe infections or in patients with overweight, the daily dose can be increased to 600 mg.

Dosage regimen for renal dysfunction When creatinine clearance is 50-20 ml / min, a single dose in (mg) *

Creatinine clearance	Single dose (mg) *	Multiplicity of the introduction
50-20 ml / min	100-200	1 time per day (every 24 hours)
<20 ml / min[1]	100	Once a day (every 24 hours)
or hemodialysis	or	hours)
and peritoneal	200	Once every 2 days (every 48 hours)
dialysis		hours)

[1] In accordance with the testimony.

In cases where there is no way to determine the clearance of creatinine (C1_FROM_r), it can be calculated from the serum creatinine concentration using the Cockcroft formula for adults:

for men:

Body weight (kg) х (140 - age in years)

FROMl_FROM_r (ml / min) = --------------------------------------------

72 x creatinine (mg / dL)

Body weight (kg) х (140 - age in years)

FROMl_FROM_r (ml / min) = --------------------------------------------

0.814 × creatinine (μmol / L)

for women:

FROMl_FROM_r (ml / min) = 0.85 x for men Dosage regimen for violations of liver function

In case of severe impairment of liver function (eg, with cirrhosis of the liver with ascites), it is not recommended to exceed the dose of ofloxacin 400 mg / day.

Dosage regimen in elderly patients

The age of the patient, as such, does not require dose adjustment of ofloxacin. However, when the drug is used in elderly patients, special attention should be paid to the function of the patient's kidneys, since in the event of a decrease, a corresponding correction of the dosing regimen may be required (see above).

Administration of the drug

The ofloxacin solution is intended only for slow infusion administration. Intravenous infusion is performed once or twice a day. The duration of the infusion should be at least 30 minutes for each dose of ofloxacin 200 mg. This is especially important if ofloxacin is administered concomitantly with other drugs that can reduce blood pressure or means for non-general general anesthesia from the barbiturate group. The daily dose to 400 mg ofloxacin can be administered once a day.In this case, it is preferable to administer the drug in the morning.

A daily dose of more than 400 mg should be divided into two parts and administered at 12-hour intervals.

The compatibility of ofloxacin solution with infusion solutions (see "Interaction with other drugs, laboratory and diagnostic tests").

The introduction of the drug Tarivid® after opening the vial should be performed immediately.

Duration of treatment

The duration of treatment depends on the severity of the disease. Like any treatment with antimicrobial drugs, ofloxacin should be continued for at least 48-72 hours after the normalization of body temperature or if there is evidence of eradication of the bacterial agent.

A few days after the improvement of the patient's condition, the onloxacin started in the form of intravenous infusions can be continued by taking the drug inside at the same doses.

[1]It is recommended to monitor serum concentrations of ofloxacin in patients with severe renal dysfunction or in patients on dialysis.

Side effects:

The information presented below is based on data obtained from clinical trials and data from a broad post-marketing experience with the drug.

The following side effects are given according to the following gradations of their frequency: very frequent (> 1/10), frequent (> 1/100, <1/10); infrequent (> 1/1000, <1/100); rare (> 1/10000, <1/1000); very rare (<1/10000) (including individual messages), unknown frequency (according to available data, it is not possible to establish frequency of occurrence).

Violations from the heart and blood vessels Frequent: phlebitis.

Infrequent: arterial hypotension.

During the infusion of ofloxacin, a decrease in arterial pressure is possible, accompanied by the development of sinus tachycardia, which in very rare cases is strongly pronounced up to the development of collapse. When a significant reduction in blood pressure should immediately stop the infusion of the drug.

Rare: sinus tachycardia, "hot flashes" of blood to the skin of the face.

Violations of the blood and lymphatic system

Very rare: anemia, hemolytic anemia, leukopenia, thrombocytopenia,

individual cases: agranulocytosis, pancytopenia, oppression of bone marrow hematopoiesis.

Disturbances from the nervous system Infrequent: dizziness, headache.

Rare: drowsiness, paresthesia, dysgeusia (a disorder of perception of taste),

parosmia (odor perception disorder). Very rare: peripheral sensory neuropathy, peripheral

sensory-motor neuropathy, seizures, extrapyramidal symptoms, including tremor, and other disorders of muscle coordination.

Unknown frequency: increased intracranial pressure.

Disturbances on the part of the organ of sight Infrequent: irritation of the mucous membrane of the eye.

Rare: visual impairment.

Hearing disorders and labyrinthine disorders Infrequent: vertigo. Very rare: hearing impairment (ringing in the ears), hearing loss.

Disturbances from the respiratory system, chest and mediastinal organs

Infrequent: cough, nasopharyngitis.

Rare: shortness of breath, bronchospasm.

Very rare (isolated cases): allergic pneumonitis, pronounced dyspnea. Disorders from the gastrointestinal tract Infrequent: abdominal pain, diarrhea, nausea, vomiting.

Rare: enterocolitis (in some cases, hemorrhagic).

Unknown frequency: constipation, flatulence.

Very rare: pseudomembranous colitis.

Disorders from the kidneys and urinary tract

Rare: increased serum creatinine concentration.

Very rare: acute renal failure; individual cases: acute

interstitial nephritis.

Unknown frequency: increased urea concentration in the blood.

Disturbances from the skin and subcutaneous tissues Infrequent: itching, rash.

Rare: urticaria, hyperhidrosis, pustular rash.

Very rare: multiform exudative erythema, toxic

epidermal necrolysis, photosensitization reactions, drug rash, purpura, vasculitis, which in exceptional cases can lead to cutaneous necrosis.

Individual cases: Stevens-Johnson syndrome.

Unknown frequency: spot hemorrhages (petechiae), bullous

hemorrhagic dermatitis.

Disturbances from the musculoskeletal and connective tissue.

Rare: tendonitis.

Very rare: arthralgia; myalgia; rupture of the tendon (Achilles tendon) (as

when using other fluoroquinolones, this side effect can develop within 48 hours after the start of treatment and can be bilateral.) individual cases: rhabdomyolysis and / or myopathy, muscle weakness, which is especially important for patients with pseudo-paralytic myasthenia.

Disorders from the metabolism and nutrition Rare: anorexia

Very rare (isolated cases): hypoglycemia, in patients with sugar

diabetes treated with hypoglycemic agents; Attacks of porphyria in patients with porphyria.

Infectious and parasitic diseases

Infrequent: fungal infections, resistance of pathogenic microorganisms.

Unknown frequency: dysbacteriosis of the intestine, vaginitis, discharge from the vagina.

General disorders and disorders at the site of administration

Frequent: pain and redness at the site of infusion, phlebitis.

Immune system disorders

Rare: anaphylactic reactions, anaphylactoid reactions,

angioedema.

Very rare: anaphylactic shock, anaphylactoid shock Individual cases: allergic pneumonitis.

Unknown frequency: allergic nephritis, eosinophilia.

Disturbances from the liver and bile ducts

Rare: increased activity of "liver" enzymes, such as

alanine aminotransferase (ALT), aspartate aminotransferase (ACAT), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT) and / or alkaline phosphatase (ACF) and / or bilirubin concentrations in the blood.

Very rare: cholestatic jaundice; individual cases: hepatitis, which

can be heavy.

Disorders of the psyche

Infrequent: agitation, sleep disturbances, insomnia.

Rare: psychotic reactions (eg, hallucinations), anxiety,

anxiety, nervousness, confusion, nightmares, depression. Individual cases: psychotic reactions and depression with self-infliction

harm, in rare cases, up to suicidal thoughts or attempts.

Overdose:

Overdose Symptoms

Symptoms expected in acute overdose are central nervous system symptoms such as dizziness, confusion, and other disorders of consciousness, seizures, and gastrointestinal reactions, such as nausea and erosion of the gastrointestinal mucosa.

Treatment for overdose

Symptomatic treatment should be given. The specific antidote is unknown.

Interaction:

- With theophylline, fenbufen or other non-steroidal

anti-inflammatory drugs; The ability to reduce the threshold of convulsive readiness of the brain

In clinical studies, no pharmacokinetic interactions of ofloxacin with theophylline have been established. However, it is possible to significantly reduce the threshold of convulsive readiness of the brain with the simultaneous use of quinolones with theophylline and nonsteroidal anti-inflammatory drugs that reduce the threshold of convulsive readiness of the brain (with fenbufen).

- With drugs that can lengthen the interval QT

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

- With indirect anticoagulants (warfarin)

It is recommended that blood clotting parameters be carefully monitored in patients undergoing simultaneous treatment with indirect anticoagulants, in connection with the possible increase in the effect of indirect anticoagulants, coumarin derivatives (eg, warfarin).

- With glibenclamide

Ofloxacin can cause a slight increase in serum concentrations of glibenclamide when they are used simultaneously,which increases the risk of developing hypoglycemia, in which case it is recommended to carefully monitor the concentration of glucose in the blood.

With other hypoglycemic agents for oral administration and insulin Oksafloksatsin increases the risk of developing hypoglycemia, requires a more careful monitoring of the concentration of glucose in the blood.

- With probenecid, cimetidine, furosemide, methotrexate

Especially in the case of high doses, the relative delay in excretion and the increase in serum concentrations with the use of quinolones together with drugs that are excreted by the kidney

tubular secretion (such as probenecid, cimetidine, furosemide, methotrexate).

- With drugs that can reduce blood pressure, drugs for non-general anesthesia from the barbiturate group

With simultaneous use with the drug TariV®, a sharp and significant reduction in blood pressure is possible, so in this case, particularly careful monitoring of the functional status of the cardiovascular system is required.

- With glucocorticosteroids

The risk of rupture of tendons increases, especially in the elderly.

- With drugs that alkalinize urine (carbonic anhydrase inhibitors, citrates, sodium hydrogen carbonate)

Increased risk of crystalluria and nephrotoxic effects

- Impact on laboratory performance and diagnostic tests

To ofloxacin is moderately sensitive Mycobacterium tuberculosis, which can lead to false-negative results in the bacteriological diagnosis of tuberculosis (see "Pharmacodynamics").

When determining opiates and porphyrins in urine during ofloxacin treatment, a false positive result is possible. It may be necessary to confirm positive results using more specific methods.

- Compatibility with other drugs and infusion solutions

A solution of heparin should not be mixed with ofloxacin solution (precipitates may form).

The drug Tarium® is compatible with 0.9% sodium chloride solution, Ringer's solution, 5% dextrose solution.

Special instructions:

- Pseudomembranous colitis (bowel disease caused by Clostridium

The appearance of diarrhea, especially in severe, persistent and / or mixed with blood, during or after treatment with ofloxacin may be a manifestation of pseudomembranous colitis.If there is a suspected development of pseudomembranous colitis, ofloxacin should be stopped immediately, and appropriate specific antibacterial therapy should be immediately prescribedvancomycin inside, teicoplanin inside or metronidazole inside). In the emergence of this clinical situation, preparations that suppress the intestinal peristalsis are contraindicated.

- Patients who are predisposed to develop seizures

Like other quinolones, ofloxacin should be used with caution in patients who are predisposed to the development of seizures (patients with CNS lesions in history, patients taking fenbufen or other nonsteroidal anti-inflammatory drugs that reduce the seizure threshold of the brain availability, as well as other drugs that lower seizure threshold of the brain availability, such as theophylline) (see "Interaction with Other Drugs, Laboratory and Diagnostic Tests").

- Tendonitis

Tendinitis, rarely caused by the use of quinolones, can sometimes lead to rupture of tendons, including Achilles tendon, especially in elderly patients and patients taking glucocorticosteroids simultaneously.This undesirable effect can develop within 48 hours after the start of treatment and be bilateral. In case of signs of tendonitis (inflammation of the tendon), it is recommended to immediately stop treatment. An appropriate treatment (for example, immobilization) of a damaged tendon may be required.

- Patients with renal insufficiency

Due to ofloxacin is excreted mainly by the kidneys, patients with renal insufficiency need a dose adjustment of ofloxacin (see "Dosage and Administration").

- Prevent photosensitivity

During the treatment with ofloxacin, due to the risk of

photosensitization, direct exposure to sunlight and exposure to ultraviolet rays (mercury quartz lamps, solarium) should be avoided.

- Secondary infection

As with the treatment of other antimicrobials with the use of ofloxacin, especially prolonged, it is possible to develop a secondary infection associated with the growth of resistant to the preparation of microorganisms, to exclude and confirm which it is necessary to re-evaluate the patient's condition.If a secondary infection occurs during therapy, appropriate measures should be taken to treat it.

- Increase the duration of the interval QT

In patients taking fluoroquinolones, in very rare cases there was 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 diseases (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 "Interaction with Other Drugs, Laboratory and Diagnostic Tests").

- Patients with hypoglycaemia

As with any other quinolones, the use of ofloxacin reported the development of hypoglycemia, especially in patients with diabetes mellitus receiving oral hypoglycemic agents (glibenclamide) or insulin. In such patients, it is recommended that blood glucose concentration be carefully monitored (see "Side effect").

- Peripheral Neuropathy

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

- Patients with glucose-6-phosphate dehydrogenase deficiency Patients with diagnosed glucose-6-phosphate dehydrogenase deficiency may be predisposed to hemolytic reactions in the treatment with quinolones. Therefore, such patients should be careful when using ofloxacin.

In case of side effects from the central nervous system and allergic reactions, the drug must be withdrawn.

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

Some adverse reactions, such as dizziness / vertigo, drowsiness and visual impairment, can reduce the psychomotor reaction and the ability to concentrate, and therefore increase the risk in situations in which the availability of these abilities is particularly important (for example, when driving or using other mechanisms). In each specific case, the decision on the possibility of driving should be taken individually, in case of the above-mentioned side effects, driving and working with the mechanisms are contraindicated.

Form release / dosage:

Solution for infusion, 2 mg / ml.

Packaging:To 100 ml of solution in a colorless glass bottle (type I). The bottle is sealed with a rubber stopper, crimped with an aluminum cap and covered with a protective plastic lid. 1 bottle with instructions for use in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children!

Shelf life:

3 years.

After the expiration date, the drug can not be used.

Terms of leave from pharmacies:On prescription

Registration number:П N011321 / 02

Date of registration:09.12.2010

Date of cancellation:2017-07-19

The owner of the registration certificate:Sanofi-Aventis Deutschland GmbHSanofi-Aventis Deutschland GmbH Germany

Manufacturer: & nbsp

SANOFI-AVENTIS Deutschland, GmbH Germany

Representation: & nbspSanofi Aventis GroupSanofi Aventis Group

Information update date: & nbsp19.07.2017

Illustrated instructions

Instructions

Tarivid® (Tarivid®)