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

Excipients: lactose monohydrate - 95.20 mg; corn starch - 47,60 mg; Povidone-25 - 12.00 mg; crospovidone - 20.00 mg, poloxamer - 0.20 mg; magnesium stearate - 8.00 mg; talcum - 4,00 mg;

film sheath: hypromellose - 9.42 mg; Macrogol-6000 - 0.53 mg; talc - 0.70 mg; titanium dioxide - 2.35 mg.

Description:The film-coated tablets are white to almost white in color, round, biconvex, with a notch on one side and with a "200" on the other side. On the fracture tablets from white to almost white.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone

ATX: & nbsp

S.01.A.E.01 Ofloxacin

J.01.M.A.01 Ofloxacin

Pharmacodynamics:

The broad-spectrum antimicrobial agent from the group of fluoroquinolones acts on bacterial enzymes topoisomerase II (DNA-gyrase) and topoisomerase IV, which ensure super-convoliation and, thus, the stability of bacterial DNA (destabilization of DNA chains leads to their death). Has a bactericidal effect.

Ofloxacin is highly active against: Aeromonas hydrophila, Moraxella catarrhalis, Brucella spp., Chlamydia trachomatis, Citrobacter freundii, Clostridium perfringens, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus ducreyi, Haemophilus influenza, Haemophilus parainfluenzae, Helicobacter coli, Helicobacter jejuni, Klebsiella oxytoca, Legionella pneumophila, Morganella morganii, Mycoplasma hominis, Neisseria gonorrhoeae, Nessseria meningitidis, Plesiomonas spp., Proteus mirabilis, Proteus vulgaris, Salmonella enteric, Serratia marcescens, Shigella spp., Staphylococcus spp. (coagulanegative), including Staphylococcus aureus (methicillin-sensitive), Yersinia enterocolitica.

Moderately sensitive to ofloxacin: Acinetobacter calcoaceticus, anaerobic Gram-positive cocci, Bacteroides fragilis, Chlamydia psittaci, Gardnerella vaginalis, Mycobacterium tuberculosis, Mycobacterium leprae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Streptococcus spp.

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

Pharmacokinetics:

Absorption after oral administration is rapid and complete (95%). Bioavailability is over 96%, the connection with plasma proteins is 25%, the time to reach the maximum concentration (TC_m_Oh) with oral intake - 1-2 hours, the maximum concentration (C_m_Oh) after taking 100 mg, 300 mg and 600 mg are 1 mg / L, 3.4 mg / L and 6.9 mg / L, respectively, and depends on the dose: after a single dose of 200 mg and 400 mg it is 2 , 5 μg / ml and 5 μg / ml, respectively.Food can slow absorption, but does not have a significant effect on bioavailability.

Apparent volume of distribution - 100 liters. Distribution: cells (leukocytes, alveolar macrophages), skin, soft tissues, bones, abdominal and pelvic organs, respiratory system, urine, saliva, bile, the secret of the prostate gland; well penetrates the blood-brain barrier, the placental barrier, is secreted with the mother's milk. It penetrates into the cerebrospinal fluid (14-60%).

Metabolized in the liver (about 5%) to form the N-oxide ofloxacin and dimethylfloxacin. The half-life is 4.5-7 h (irrespective of the dose). It is excreted by the kidneys - 75-90% (unchanged), about 4% - with bile. The extrarenal clearance is less than 20%.

After a single application in a dose of 200 mg in urine is detected within 20-24 hours. In renal / hepatic insufficiency, excretion can be slowed down. Do not cumulate. With hemodialysis, 10-30% of the drug is removed.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to ofloxacin:

- respiratory tract (bronchitis, pneumonia);

- ENT organs (sinusitis, pharyngitis, otitis media, laryngitis, tracheitis);

- skin, soft tissues, bones, joints;

- abdominal cavity and biliary tract;

- kidneys (pyelonephritis), lower urinary tract (cystitis, urethritis);

- genitals and pelvic organs (endometritis, salpingitis, oophoritis, cervicitis, parametritis, prostatitis, colpitis, orchitis, epididymitis), gonorrhea, chlamydia;

- prevention of infections in patients with impaired immune status (including neutropenia).

Contraindications:

- Hypersensitivity to the components of the drug or other fluoroquinolones;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- deficiency of glucose-6-phosphate dehydrogenase;

- epilepsy (including in the anamnesis);

- reduction of convulsive threshold (including after traumatic brain injury, stroke or inflammatory processes in the central nervous system);

- lesions of tendons during previous treatment with fluoroquinolones;

- age to 18 years (until the skeleton has been completed);

- pregnancy, the period of breastfeeding.

Carefully:

Atherosclerosis of cerebral vessels, cerebral circulatory disorders (in the anamnesis), organic diseases of the central nervous system, predisposition to convulsive reactions, myasthenia gravis, hepatic porphyria, known risks of lengthening the interval QT (old age, uncorrected electrolyte disorders (hypokalemia, hypomagnesemia), congenital interval syndrome QT, heart disease (heart failure, myocardial infarction, bradycardia), simultaneous use of drugs that can lengthen the interval QT (antiarrhythmic drugs IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including antihistamines. astemizole, terfenadine, ebastine)); simultaneous use of drugs that can reduce blood pressure, drugs for non-general general anesthesia from the barbiturate group; simultaneous use of drugs that reduce the threshold of convulsive brain readiness, such as fenbufen, theophylline; simultaneous use of drugs that affect glomerular secretion; impaired renal / hepatic function; 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 sugardiabetes, taking oral hypoglycemic agents (for example, glibenclamide) or insulin.

Pregnancy and lactation:

The use of the drug during pregnancy is contraindicated. Controlled studies on the use of ofloxacin in pregnant and lactating women were not conducted. Studies in animals have shown a disruption in the formation of the fetal skeleton when using ofloxacin. Do not use ofloxacin in pregnant women and women, who can not reliably exclude pregnancy.

Ofloxacin penetrates into breast milk. Due to possible arthropathy and other serious toxic effects in infants who are breastfed, breastfeeding should be discontinued for the duration of ofloxacin treatment.

Dosing and Administration:

Inside. Doses of the drug are selected individually depending on the location, the severity of the infection, the sensitivity of microorganisms, as well as the general condition of the patient and the function of the liver and kidneys.

Apply 200-800 mg / day, the frequency of application - 2 times a day.

In patients with impaired renal function the dose should be reduced depending on the creatinine clearance (CC)

CK, ml / min	Single dose, mg	Interval between doses
50-20	100-200	24 h
<20 or hemodialysis	100	24 h
peritoneal dialysis	200	48 h

The maximum daily dose for liver failure - 400 mg / day. With gonorrhea, the drug is prescribed at a dose of 400 mg once.

A dose of up to 400 mg per day can be prescribed in a single dose.

Tablets should be taken whole, washed down with water, both before and during meals.

The duration of treatment is determined by the sensitivity of the pathogen and the clinical picture; treatment should be continued for at least 3 more days after disappearance of symptoms of the disease and complete normalization of body temperature.

In the treatment of uncomplicated and complicated infections of the lower urinary tract treatment course - 7 and 10 days respectively, with prostatitis - up to 6 weeks, with infections of the pelvic organs - 10-14 days, with infections of the respiratory system and skin - 10 days.

Have elderly patients no dose adjustment is required.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very often (≥1 / 10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥1 / 10000 to <1/1000),very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

From the gastrointestinal tract (GIT)

infrequently: abdominal pain, diarrhea, nausea, vomiting;

rarely: enterocolitis, sometimes hemorrhagic enterocolitis;

rarely: pseudomembranous colitis;

frequency is unknown: constipation, flatulence, dyspepsia, pancreatitis.

From the nervous system

infrequently: headache, dizziness;

rarely: drowsiness, paresthesia, dysgeusia, parosmia, impaired sense of smell, confusion;

rarely: peripheral sensory neuropathy, peripheral sensory-motor neuropathy, convulsions, extrapyramidal disorders and other disorders of muscle coordination;

frequency is unknown: rise intracranial pressure, tremor, dyskinesia, agvesia, syncope.

Disorders of the psyche

infrequently: agitation, insomnia, sleep disorders;

rarely: psychotic disorders (eg, hallucinations), anxiety, nightmares, intense dreams, depression;

frequency is unknown: psychotic reactions and depression with self-harm, in rare cases, up to suicidal thoughts or attempts, increased excitability.

From the side of the musculoskeletal system

rarely: tendonitis;

rarely: arthralgia, myalgia, tendon rupture (as with the use of other fluoroquinolones, this unwanted reaction can develop within 48 hours after the initiation of treatment and can be bilateral);

frequency unknown: rhabdomyolysis or myopathy, muscle weakness, muscle rupture, muscle tear, ligament rupture, arthritis, pain in the extremities.

From the sense organs

infrequently: mucosal irritation the shell of the eye, conjunctivitis;

rarely: impaired vision, hearing impairment, violation of color perception, diplopia;

rarely: noise in the ears, hearing loss.

From the side of the cardiovascular system

rarely: tachycardia, lowering of blood pressure:

frequency is unknown: ventricular arrhythmia "torsades de pointes"(in patients with an elongated QT interval), interval elongation QT.

From the skin and subcutaneous tissues

infrequently: itching, rash;

rarely: urticaria, "hot flashes" of blood to the skin of the face, hyperhidrosis, pustular rash;

rarely: erythema multiforme, toxic epidermal necrolysis, reactions photosensitivity, vasculitis (which can lead in some cases to necrosis of the skin), persistent drug-induced rash;

frequency unknown: Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, stomatitis.

From the immune system

rarely: anaphylactic reactions, anaphylactoid reactions, angioedema;

rarely: anaphylactic shock, anaphylactoid shock.

On the part of the organs of hematopoiesis

rarely: anemia, hemolytic anemia, leukopenia, eosinophilia, thrombocytopenia, pancytopenia;

frequency is unknown: agranulocytosis, impaired bone marrow function.

From the urinary system

rarely: increasing the concentration of creatinine in the blood;

rarely: acute renal insufficiency;

frequency is unknown: acute interstitial nephritis.

From the respiratory system

infrequently: dry cough, nasopharyngitis, rhinitis;

rarely: dyspnoea, bronchospasm;

frequency is unknown: allergic pneumonitis, severe shortness of breath, chest pain.

Co hand liver and biliary tract

rarely: increased activity "hepatic" enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (ACT), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT) and / or alkaline phosphatase (FA)), an increase in the concentration bilirubin in the blood;

rarely: cholestatic jaundice;

frequency is unknown: hepatitis (can be severe).

Other

infrequently: fungal infection, superinfection;

rarely: anorexia;

frequency is unknown: hypoglycemia in patients taking hypoglycemic drugs, hypoglycemic coma, exacerbation of porphyria, vaginitis, intestinal dysbacteriosis, asthenia, fever, hyperglycemia.

Overdose:

Symptoms from the central nervous system: dizziness, confusion, retardation, disorientation, drowsiness, convulsions.

Symptoms from the digestive tract: nausea, vomiting, erosion on the mucous membranes.

Treatment: gastric lavage no later than 1-2 hours after taking ofloxacin, administration of activated charcoal and other adsorbents for the first 30 minutes, symptomatic therapy, forced diuresis and adequate hydration. With hemodialysis, 10-30% of the drug is removed. It is necessary to conduct ECG monitoring due to possible lengthening of the interval QT.

There is no specific antidote.

Interaction:

Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs

In clinical studies, there was no evidence of pharmacokinetic interactions of ofloxacin with theophylline.Nevertheless, a marked decrease in the convulsive threshold of the brain can be observed with the simultaneous use of quinolones, with theophylline, non-steroidal anti-inflammatory drugs or other means, reducing the convulsive threshold.

Ofloxacin can cause a slight increase in concentration glibenclamide in blood plasma when combined, so for patients receiving simultaneously ofloxacin and glibenclamide, it is recommended that the blood glucose concentration be closely monitored.

Increases serum concentration cyclosporine.

Cimetidine, furosemide, methotrexate and drugs, blocking tubular secretion, increase the concentration of ofloxacin in blood plasma.

Probenecid Ofloksacin reduced the total clearance by 24% and increased the area under the concentration-time curve by 16%. The proposed mechanism for this interaction is competitive binding or inhibition of active transport during excretion in the renal glomeruli. Care should be taken when applying simultaneously ofloxacin with preparations that affect glomerular secretion, such as probenecid, cimetidine, furosemide and methotrexate.

With simultaneous reception with indirect anticoagulants (coumarin derivatives, including warfarin) it is necessary to monitor the parameters of the blood coagulation system (prothrombin time (PV) and the international normalized ratio (INR)) in connection with the possible enhancement of the effect of these drugs.

When appointed with nonsteroidal anti-inflammatory drugs, nitroimidazole derivatives and methylxanthines increased risk of neurotoxic effects, including convulsions.

With the simultaneous appointment of glucocorticosteroids the risk of rupture of tendons increases, especially in the elderly.

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

With the simultaneous appointment of hypoglycemic agents it is possible to develop both hypo- and hyperglycemia, in connection with which it is necessary to monitor the concentration of glucose in the blood plasma.

Food products, antacids, metal cations, containing salts aluminum, calcium, magnesium or iron salts, reduce the absorption of ofloxacin,forming insoluble complexes (the time interval between the appointment of these drugs should be at least 2 hours).

Ofloxacin, like other quinolones, should be used with caution in patients receiving drugs, extension intervals QT (antiarrhythmic drugs IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some antihistamines, including antihistamines. astemizole, terfenadine, ebastine), it is possible to extend the interval QT.

Special instructions:

Methicillin-resistant S. aureus is also likely to have resistance to fluoroquinolones, including ofloxacin. Consequently, ofloxacin is not recommended for the treatment of known or suspected infections caused by MRSA, except when the sensitivity of the microorganism to ofloxacin has been proven in a laboratory (and antibacterial drugs usually recommended for the treatment of MRSA infections are not applicable).

It is not a drug of choice for pneumonia caused by pneumococci or mycoplasmas. Not indicated for the treatment of acute tonsillitis caused by beta-hemolytic streptococcus.

Allergic reactions

With the use of ofloxacin, cases of severe bullous skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis. With the development of reactions from the skin and mucous membranes, patients should immediately contact the attending physician before resuming treatment.

During the use of ofloxacin, like other fluoroquinols, it is possible development of allergic reactions, including after taking the first dose: anaphylactic and anaphylactoid reactions, up to a life-threatening shock. In such cases, it is necessary to stop the treatment with ofloxacin and take appropriate measures (for example, shock therapy, the introduction of sympathomimetics, antihistamines and glucocorticosteroids, if necessary, ventilation).

Clostridium difficile-Associated diseases

Diarrhea, especially severe, persistent and / or blood-mixed, occurring during or after treatment with ofloxacin, may be a symptom of pseudomembranous colitis. If there is a suspicion of pseudomembranous colitis, the use of ofloxacin should be discontinued immediately.

With pseudomembranous colitis, confirmed by colonoscopy and / or histology, shows the oral administration of vancomycin, teicoplanin, or metronidazole. Preparations that inhibit intestinal motility are contraindicated in this clinical condition.

Secondary infection

As with other antibiotics, the use of ofloxacin, especially prolonged, may lead to the development of resistance to ofloxacin. It is important to re-determine sensitivity to antibiotics.

QT interval extension

Very rare cases of prolongation of the QT interval have been reported in patients taking fluoroquinolones. Caution should be exercised when using ofloxacin in patients with known risk factors for prolonging the QT interval:

- elderly age;

- uncorrected electrolyte balance (eg, hypokalemia, hypomagnesemia);

- syndrome of congenital elongated QT interval;

- heart disease (eg, heart failure, myocardial infarction, bradycardia);

- simultaneous use of drugs that cause prolongation of the QT interval (antiarrhythmic drugs IA and III classes, tricyclic and tetracyclic antidepressants, neuroleptics, macrolides, antifungal, imidazole derivatives, some aitigistamic, including. astemizole, terfenadine, ebastine).

Elderly patients and women may be more sensitive to drugs that extend the QT interval.

Prevention of photosensitization

Due to the risk of photosensitization, during the reception of the drug should not be exposed to sunlight and artificial ultraviolet radiation (mercury-quartz lamps, solarium).

Peripheral Neuropathy

In patients who received fluoroquinolones, including ofloxacin, reported the development of sensory or sensory-motor neuropathy, which can have a rapid onset. If patients develop neuropathy symptoms, ofloxacin should be discontinued in order to minimize the possible risk of developing irreversible disorders.

In the event of undesirable reactions from the central nervous system, allergic reactions, pseudomembranous colitis it is necessary to cancel the drug.

Tendonitis

Rarely developing tendonitis can lead to rupture of tendons (mainly Achilles tendon), especially in elderly patients.Tendonitis and a rupture of tendons, sometimes bilateral, can occur within 48 hours from the start of ofloxacin treatment, they were also recorded several months after discontinuation of the drug. The risk of developing tendonitis may increase with the simultaneous use of corticosteroids. In case of signs of tendonitis, it is necessary immediately to stop treatment, to immobilize the lower extremity in the ankle and consult an orthopedist.

During the period of treatment can not be consumed ethanol.

When using the drug, women are not recommended to use hygienic tampons in connection with the increased risk of thrush development.

Disglycemia

As with all quinolones, changes in plasma glucose concentrations, including both hypo- and hyperglycemia, have been reported, usually in patients taking hypoglycemic agents for oral administration simultaneously (for example, glibenclamide) or insulin. In such patients, concentration should be carefully monitored glucose in blood plasma

Impact on laboratory performance

Can lead to false-negative results in the bacteriological diagnosis of tuberculosis (prevents the isolation Mycobacterium tuberculosis).

Determination of the content of opiates and porphyrins in urine can lead to false positive results in the treatment with ofloxacin.

It is necessary to confirm the positive results of screening for the presence of opiates or porphyrins using more specific methods.

Patients with psychotic disorders in the history

Psychotic reactions were reported in patients who received fluoroquinolones. In some cases, these reactions progressed to suicidal thoughts or self-destructive behavior, including suicide attempts, sometimes after taking a single dose. If the patient develops these reactions, ofloxacin should be discontinued, and appropriate interventions should be initiated.

Ofloxacin should be used with caution in patients with a history of psychotic disorders or in patients with mental illness.

Patients with impaired renal function

Because the ofloxacin is mainly excreted through the kidneys, the dose of ofloxacin should be adjusted in patients with kidney damage.

Patients with impaired hepatic function

Ofloxacin should be used with caution in patients with impaired hepatic function. When fluoroquinolones were used, cases of fulminant hepatitis, leading to acute hepatic insufficiency (including fatal cases) were noted. Patients should be advised to stop treatment and contact their doctor when developing symptoms of liver damage such as anorexia, jaundice, dark urine, pruritus or tenderness of the abdomen.

Patients receiving indirect anticoagulant therapy

At simultaneous reception with indirect anticoagulants it is necessary to carry out the control of coagulating system of blood.

Myasthenia gravis

Fluoroquinolones, including ofloxacin, have a blocking effect on neuromuscular activity and can exacerbate muscle weakness in patients with myasthenia gravis. Expressed unwanted reactions in postmarketing studies (including death and the need for respiratory support) were associated with the use of fluoroquinolones in patients with myasthenia gravis.

Visual disturbances

If vision deteriorates or other eye symptoms appear, consult an ophthalmologist immediately.

Special precautions when destroying an unused preparation

There is no need for special precautions when destroying an unused preparation.

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

Because of the likelihood of side effects such as drowsiness, headache and visual impairment, care should be taken when practicing potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 200 mg.

Packaging:

For 6 or 10 tablets in a blister of PVC / aluminum foil.

For 1, 2, 3, 4 or 5 blisters together with instructions for medical use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002383

Date of registration:27.02.2014

Expiration Date:27.02.2019

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp18.06.2017

Illustrated instructions

Instructions

Ofloxacin Sandoz® (Ofloxacin Sandoz)