Roflox-Scan, 500 mg 10 pcs

Pharmacotherapeutic group

Antimicrobial agent – fluoroquinolone

ATX code

J01MA

Pharmacodynamics:

Roflox-Scan is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones containing levofloxacin, the left-handed isomer ofloxacin, as the active substance.

Levofloxacin blocks DNA-giase and topoisomerase IV disrupts superspiralization and cross-linking of DNA breaks inhibits DNA synthesis and causes deep morphological changes in cytoplasm of cell wall and microbial cell membranes.

Levofloxacin is active against most strains of microorganisms both in vitro and in vivo.

In vitro

Sensitive microorganisms (MAC ≤ 2 mg/L; zone of inhibition ≥17 mm)

– Aerobic Gram-positive microorganisms: Bacillus anthracis Corynebacterium diphtheriae Corynebacterium jeikeium Enterococcus faecalis Enterococcus spp. Listeriamonocytogenes Staphylococcus coagulase-negative methi-S(I) [coagulase-negative methicillin-sensitive/ moderately sensitive] Staphylococcus aureus methi-S (methicillin-sensitive) Staphylococcus epidermidis methi-S (methicillin-sensitive) Staphylococcus spp. CNS (coagulase-negative) Streptococci spp. C and G Streptococcus agalactiae Streptococcus pneumoniae peni I/S/R (penicillin-moderately sensitive/sensitive/resistant) Streptococcus pyogenes Viridans streptococci peni-S/R (penicillin-sensitive/resistant).

– Aerobic Gram-negative microorganisms: Acinetobacter baumannii Acinetobacter spp. Actinobacillus actinomycetemcomitans Citrobacter freundii Eikenella corrodens Enterobacter aerogenes Enterobacter cloacae Enterobacter spp. Escherichia coli Gardneirella vaginalis Haemophilus ducreyi Haemophilus influenzae ampi-S/R (ampicillin-sensitive/resistant) Haemophilus parainfluenzae Helicobacter pylori Klebsiella oxytoca Klebsiella pneumonia Klebsiella spp. Moraxella catarrhalis ß+/ß- (producing and non-producing beta-Morganella morganii Neisseria gonorrhoeae non PPNG/PPNG (non-producing and producing penicillinase) Neisseria meningitidis Pasteurelia canis Pasteurella dagmatis Pasteurella multocida Pasteurella spp Proteus mirabilis Proteus vulgaris Providencia rettgeri Providencia stuartii Providencia spp. Pseudomonas aeruginosa (hospital infections caused by Pseudomonas aeruginosa may require combined treatment) Pseudomonas spp. Salmonella spp. Serratia marcescens Serratia spp.

– Anaerobic microorganisms: Bacteroides fragilis Bifidobacterium spp. Clostridium perfringens Fusobacterium spp. Peptostreptococcus Propionibacterium spp. Veillonella spp.

– Other microorganisms: Bartonella spp. Chlamydia pneumoniae Chlamydia psittaci Chlamydia trachomatis Legionella pneumophila Legionella spp. Mycobacterium spp. Mycobacterium leprae Mycobacterium tuberculosis Mycoplasma hominis Mycoplasma pneumoniae Rickettsia spp. Ureaplasma urealyticum.

Moderately susceptible microorganisms (MPC = 4 mg/L; inhibition zone 16-14 mm)

– Aerobic Gram-positive microorganisms: Corynebacterium urealyticum Corynebacterium xerosis Enterococcus faecium Staphylococcus epidermidis methi-R (methicillin-resistant) Staphylococcus haemolyticus methi-R (methicillin-resistant).

– Aerobic Gram-negative microorganisms: Campylobacter jejuni/coli

– Anaerobic microorganisms: Prevotella spp. Porphyromonas spp.

Levofoloxacin-resistant microorganisms (MPC ≥8 mg/L; inhibition zone ≤ 13 mm):

– Aerobic gram-positive microorganisms: Staphylococcus aureus methi-R (methicillin-resistant) Staphylococcus coagulase-negative methi-R (coagulase-negative methicillin-resistant).

– Aerobic Gram-negative microorganisms: Alcaligenes xylosoxidans.

– Anaerobic microorganisms: Bacteroides thetaiotaomicron.

– Other microorganisms: Mycobacterium avium.

Resistance

Resistance to levofloxacin develops as a result of a stepwise process of mutations in the genes encoding both type II topoisomerases: DNA-Gyrase and topoisomerase IV. Other mechanisms of resistance such as the mechanism of influence on the penetration barriers of the microbial cell (mechanism typical for Pseudomonas aeruginosa) and mechanism of efflux (active excretion of antimicrobial agent from the microbial cell) can also decrease the sensitivity of microorganisms to levofloxacin.

In view of the specific mechanism of action of levofloxacin there is usually no cross-resistance between levofloxacin and other antimicrobial agents.

Clinical efficacy (effectiveness in clinical trials in the treatment of infections caused by the following microorganisms)

Aerobic gram-positive microorganisms: Enterococcus faecalis Staphylococcus aureus Streptococcus pneumoniae Streptococcus pyogenes.

– Aerobic Gram-negative microorganisms: Citrobacter freundii Enterobacter cloacae Escherichia coli Haemophilus influenzae Haemophilus parainfluenzae Klebsiella pneumoniae Moraxella (Branhamella) catarrhalis Morganella morganii Proteus mirabilis Pseudomonas aeruginosa Serratia marcescens.

– Others: Chlamydia pneumoniae Legionella pneumophila Mycoplasma pneumoniae.

Pharmacokinetics:

Absorption

Levofloxacin is rapidly and almost completely absorbed after ingestion food has little effect on its absorption. Absolute bioavailability when taken orally is 99-100%. After a single use of 500 mg of levofloxacin maximum concentration in blood plasma (Cmax) is reached within 1-2 hours and is 52±12 µg/ml. Pharmacokinetics of levofloxacin is linear in dose range from 50 to 1000 mg. Equilibrium state of plasma concentration of levofloxacin is reached within 48 hours when receiving 500 mg of levofloxacin 1 or 2 times per day.

On day 10 of oral administration of 500 mg of levofloxacin once daily, the Cmax of levofloxacin was 57±14 mcg/mL and the minimum plasma concentration of levofloxacin (pre-dose concentration) (Cmin) was 05±02 mcg/mL.

On day 10 of oral administration of 500 mg of levofloxacin 2 times daily, the Cmax of levofloxacin was 78±11 mcg/mL and the Cmin was 30±09 mcg/mL.

Distribution

The binding to serum proteins is 30-40%. After single and repeated administration of 500 mg of levofloxacin the volume of distribution of levofloxacin averaged 100 L which indicates good penetration of levofloxacin into human organs and tissues.

Infiltration into the mucous membrane of the bronchial mucosa by the epithelial lining of alveolar macrophages

Infiltration into the mucous membrane of the bronchi by alveolar macrophages

. After a single oral dose of 500 mg of levofloxacin, maximum concentrations of levofloxacin in bronchial mucosa and epithelial lining fluid were reached within 1 h or 4 h and were 83 µg/g and 108 µg/ml, respectively, with penetration rates in bronchial mucosa and epithelial lining fluid compared to plasma concentrations of 11-18 and 08-3, respectively.

After 5 days of oral administration of 500 mg of levofloxacin, mean concentrations of levofloxacin 4 hours after the last drug administration in the epithelial lining fluid were 994 µg/mL and in alveolar macrophages were 979 µg/mL.

Pulmonary tissue penetration

The maximum pulmonary tissue concentrations after oral administration of 500 mg of levofloxacin were approximately 113 µg/g and were reached 4-6 h after drug administration with penetration ratios of 2-5 compared to plasma concentrations.

Alveolar fluid penetration

After 3 days of administration of 500 mg of levofloxacin once or twice daily, the maximum alveolar fluid concentrations of levofloxacin were reached 2-4 h after drug administration and were 40 and 67 mg/ml, respectively, with a penetration factor of 1 compared to plasma concentrations.

Bone penetration

Levofloxacin penetrates well into cortical and cancellous bone tissue in both proximal and distal femur with a penetration coefficient (bone tissue/plasma) of 01-3. Maximum concentrations of levofloxacin in cancellous bone tissue of the proximal femur after 500 g of oral administration were approximately 151 µg/g (2 hours after drug administration.)

Perfusion into cerebrospinal fluid

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Permeability to prostate tissue

After oral administration of 500 mg of levofloxacin once daily for 3 days, the mean concentration of levofloxacin in prostate tissue was 87 mcg/g and the mean prostate/plasma concentration ratio was 184.

Urinary concentrations

The mean urinary concentrations 8-12 h after oral doses of 150,300 and 600 mg of levofloxacin were 44 µg/mL 91 µg/mL and 162 µg/mL, respectively.

Metabolism

Levofloxacin is metabolized to a small extent (5% of the dose taken). Its metabolites are demethyllevofloxacin and levofloxacin N-oxide which is excreted by the kidneys. Levofloxacin is stereochemically stable and undergoes chiral transformations.

Levofloxacin is relatively slowly eliminated from the blood plasma after oral administration (elimination half-life (T1/2) is 6-8 hours). Excretion is mainly through the kidneys (more than 85% of the dose taken). Total clearance of levofloxacin after a single dose of 500 mg was 175±292 ml/min.

There are no significant differences in the pharmacokinetics of levofloxacin with intravenous versus oral administration, confirming that oral and intravenous administration are interchangeable.

Pharmacokinetics in selected patient groups

The pharmacokinetics of levofloxacin do not differ in men and women.

Pharmacokinetics in elderly patients does not differ from that in younger patients except for differences in pharmacokinetics associated with differences in creatinine clearance (CK).

In renal insufficiency, the pharmacokinetics of levofloxacin are altered. decreased renal function decreases renal excretion and renal clearance (ClR) and T1/2 is increased.

Pharmacokinetics in renal failure after a single oral administration of 500 mg of levofloxacin/

Indications

Treatment of infectious and inflammatory diseases caused by microorganisms sensitive to levofloxacin:

– community-acquired pneumonia;

– hospital-acquired pneumonia (for 750 mg dosage);

– Complicated urinary tract infections and pyelonephritis;

– Chronic bacterial prostatitis;

– skin and soft tissue infections;

– for the complex treatment of drug-resistant forms of tuberculosis;

– prevention and treatment of anthrax in the airborne route of infection.

For the treatment of the following infectious and inflammatory diseases levofloxacin can only be used as an alternative to other antimicrobial agents:

– acute sinusitis;

– exacerbation of chronic bronchitis;

– uncomplicated cystitis.

When using Roflox-Scan, the official national guidelines for the appropriate use of antibacterial agents as well as the sensitivity of pathogens in a particular country should be taken into account.

Active ingredient

Composition

1 tablet contains:

The active ingredient:

levofloxacin hemihydrate 512.45 mg (in terms of levofloxacin 500.00 mg.

Excipients:

Corn starch 59.25 mg;

Microcrystalline cellulose 40.00 mg;

Sodium carboxymethyl starch 15.00 mg;

crospovidone 15.00 mg;

colloidal silicon dioxide 15.00 mg;

talc 10.00 mg;

hypromellose 6.80 mg;

magnesium stearate 6.50 mg.

The composition of the shell: WT-19022P pink film coating 6.14 mg (polyvinyl alcohol 49.00 %; titanium dioxide (E 171) 21.79 %; polyethylene glycol 6000 13.20 %; talc 12.60 %; soy lecithin 3.40 %; iron oxide red dye (E 172) 0.01 %); sunset yellow dye (E 110) 0.86 mg.

How to take, the dosage

Tablets Roflox-Scan 250 mg 500 mg or 750 mg are taken orally once or twice a day. Tablets should be swallowed without chewing and with plenty of liquid (05 to 1 cup). If necessary, the tablets may be crushed at the risk.

The drug can be taken before meals or at any time between meals because eating has no effect on absorption of the drug (see section “Pharmacokinetics”).

The drug should be taken at least 2 hours before or 2 hours after taking preparations containing magnesium and/or aluminum iron zinc or sucralfate (see section “Interaction with other medicinal products”).

With regard to the fact that the bioavailability of levofloxacin in tablet formulation of Roflox-Scan is 99% to 100% if the patient is switched from intravenous infusion of Roflox-Scan to tablet formulation, treatment should continue at the same dose as used for intravenous infusion (see section “Pharmacokinetics”).

If one or more doses of the drug are missed by accident, the next dose should be taken as soon as possible and Roflox-Scan should be continued according to the recommended dosing regimen.

Doses and duration of treatment

The dosing regimen is determined by the nature and severity of the infection and the sensitivity of the suspected pathogen. The duration of treatment varies depending on the course of the disease.

The recommended dosing regimen and duration of treatment in patients with normal renal function (CK> 50 ml/min)

Indication

Daily dose of mg

Frequency of administration per day

Treatment duration days

Acute sinusitis

500

1

10-14

5

An exacerbation of chronic bronchitis

500

1

Hospital pneumonia

750

1

7-14

Out-of-hospital pneumonia

500-1000

7-14

750 *

1

5

Uncomplicated cystitis

250

1

3

Complicated urinary tract infections

/td>

500

1

7-14

750 **

1

5

Pyelonephritis

500

1

7-10

750 **

1

Chronic bacterial prostatitis

500

1

/td>

28

Infections of the skin and soft tissues

500

1

8 weeks

19- 10 mL/min

first dose: 250 mg

then 125 mg/48 h

first dose: 500 mg

then 125 mg/24 h

first dose: 500 mg

then 125 mg/12 h

first dose: 750 mg/48 h

then 250

mg/24 h

the first dose: 250 mg

followed by 125

mg/48 h

first dose: 500 mg

then 125

mg/24 h

first dose: 500 mg

then 125 mg/24 h

first dose: 750 mg/48 h

then 250

mg/24 h

1= No additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

The dosing regimen in patients with hepatic impairment

The dosing regimen does not need to be adjusted if hepatic function is impaired because levofloxacin is only slightly metabolized in the liver.

The dosing regimen in elderly patients

The dosing regimen does not need to be changed in elderly patients unless the CK falls to 50 ml/min or lower.

Interaction

Cautious Interactions

With drugs containing magnesium aluminum iron and zinc didanosine

Drugs containing bivalent or trivalent cations such as zinc or iron salts (drugs to treat anemia) magnesium- and/or aluminum-containing drugs (such as antacids) didanosine (only pharmaceutical forms containing aluminum or magnesium as a buffer) should be taken at least 2 hours before or 2 hours after taking Roflox-Scan.

Calcium salts have minimal effect on the absorption of levofloxacin when taken orally.

With sucralfate

The effect of levofloxacin is significantly impaired when sucralfate (gastric mucosal protection agent) is used simultaneously.

Patients receiving levofloxacin and sucralfate are recommended to take sucralfate 2 hours after taking levofloxacin.

With phenbufen theophylline or similar drugs from the group of non-steroidal anti-inflammatory drugs which decrease cerebral seizure threshold

Pharmacokinetic interaction of levofloxacin with theophylline has not been identified.

With the concomitant use of quinolones and theophylline, however, nonsteroidal anti-inflammatory drugs and other drugs which decrease cerebral seizure threshold may significantly decrease cerebral seizure threshold.

The concentration of levofloxacin with concomitant administration of phenbufen increases only by 13%.

With indirect anticoagulants (vitamin K antagonists)

In patients treated with levofloxacin in combination with indirect anticoagulants (e.g. warfarin) increased prothrombin time/international normalized ratio and/or development of bleeding, including severe. Therefore, when concomitant use of indirect anticoagulants and levofloxacin is necessary, regular monitoring of blood clotting parameters.

With probenicid and cimetidine

When concomitant use of drugs that disrupt renal tubular secretion such as probenicid and cimetidine and levofloxacin care should be taken especially in patients with renal insufficiency. Excretion (renal clearance) of levofloxacin is slowed down by 24% by cimetidine and by 34% by probenicid. This is unlikely to be clinically relevant in normal renal function.

With cyclosporine

Levofloxacin increased the T1/2 of cyclosporine by 33%. Since this increase is clinically insignificant, no dose adjustment of cyclosporine is required when used concomitantly with levofloxacin.

With glucocorticosteroids

The concomitant use of glucocorticosteroids increases the risk of tendon rupture.

With drugs prolonging the QT interval

Levofloxacin as well as other fluoroquinolones should be used with caution in patients treated with drugs prolonging the QT interval (e.g. antiarrhythmic drugs of class IA and III tricyclic antidepressants macrolides neuroleptics).

Other

Clinical and pharmacologic studies to explore possible pharmacokinetic interactions of levofloxacin with digoxin glibenclamide ranitidine and warfarin have shown that the pharmacokinetics of levofloxacin with these drugs does not change enough to be of clinical significance.

Special Instructions

Hospital infections caused by Pseudomonas aeruginosa may require combined treatment.

The risk of developing resistance

The prevalence of acquired resistance of bacterial strains being bred may vary by geographic region and over time. This requires information about drug resistance in a particular country. For therapy of severe infections or in case of treatment failure a microbiological diagnosis with pathogen isolation and determination of its sensitivity to levofloxacin should be established.

Methicillin-resistant Staphylococcus aureus

There is a high probability that methicillin-resistant Staphylococcus aureus will be resistant to fluoroquinolones including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of established or suspected infections caused by methicillin-resistant Staphylococcus aureus unless laboratory testing has confirmed the sensitivity of this organism to levofloxacin.

Disability (disability) and sweating irreversible serious adverse reactions due to fluoroquinolones

The use of fluoroquinolones including levofloxacin has been associated with disability and irreversible serious adverse reactions in various body systems that can occur simultaneously in the same patient. Fluoroquinolones-induced adverse reactions include tendonitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and nervous system side effects (hallucinations, anxiety, depression, insomnia, headaches, and confusion). These reactions may occur within a few hours to a few weeks after the start of therapy with levofloxacin. The development of these adverse reactions has been noted in patients of any age or without previous risk factors. If the first signs or symptoms of any serious adverse reactions occur, the use of levofloxacin should be stopped immediately. The use of fluoroquinolones, including levofloxacin, should be avoided in patients who have had any of these serious adverse reactions.

Patients susceptible to seizures

Like other quinolones, levofloxacin should be used with great caution in patients with a predisposition to seizures. This includes patients with previous central nervous system injuries such as stroke or severe traumatic brain injury; patients receiving concomitant medications which lower the cerebral seizure threshold such as phenbufen or other similar non-steroidal anti-inflammatory drugs or other medications which lower the seizure threshold such as theophylline (see section “Interaction with other medicinal products”).

If convulsions occur, treatment with levofloxacin should be discontinued.

Pseudomembranous colitis

Diarrhea developing during or after treatment with levofloxacin especially severe persistent and/or with blood may be a symptom of pseudomembranous colitis caused by Clostridiumdifficile. If pseudomembranous colitis is suspected, treatment with levofloxacin should be stopped immediately and specific antibiotic therapy (oral vancomycin teicoplanin or metronidazole) started immediately. Agents which inhibit intestinal peristalsis are contraindicated.

Tendinitis and tendon rupture

Tendinitis is rarely seen with quinolones including levofloxacin and can sometimes lead to tendon rupture including Achilles tendon and can be bilateral. This side effect may develop within 48 hours of starting treatment or several months after completion of fluoroquinolone therapy. Elderly patients are more prone to the development of tendonitis; in patients taking fluoroquinolones the risk of tendon rupture may increase with the simultaneous use of glucocorticosteroids. In addition, patients after transplantation have an increased risk of tendinitis, so caution is recommended when prescribing fluoroquinolones for this category of patients. In patients with impaired renal function the daily dose should be adjusted based on creatinine clearance.

Patients should be advised to remain at rest at the first signs of tendinitis or tendon rupture and see their physician. If tendonitis or tendon rupture is suspected, treatment with the drug should be stopped immediately and appropriate treatment of the affected tendon should be initiated, such as adequate immobilization (see contraindications and side effects).

Hypersensitivity reactions

Levofloxacin may cause serious potentially fatal hypersensitivity reactions (angioedema anaphylactic shock) even when initial doses are used (see section “Side effects”). Patients should immediately stop taking the drug and consult a physician.

Serious bullous reactions

There have been cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis when taking levofloxacin (see section “Adverse effects”). In case of any reactions of the skin or mucous membranes, the patient should immediately consult a physician and do not continue treatment until he or she has been consulted.

Hepatic and biliary tract disorders

Cases of hepatic necrosis including hepatic failure with fatal outcome have been reported when using levofloxacin mainly in patients with severe underlying diseases such as sepsis (see section “Adverse effects”). Patients should be advised to discontinue treatment and seek prompt medical attention if signs and symptoms of liver damage occur, such as anorexia, jaundice, darkened urine, itching and abdominal pain.

Patients with impaired renal function

Because levofloxacin is mainly excreted through the kidneys in patients with impaired renal function it is necessary to monitor renal function and adjust the dosing regimen (see section “Dosage and administration”). When treating elderly patients it should be borne in mind that renal dysfunction is often noted in this group of patients (see section “Dosage and administration”).

While photosensitization by levofloxacin is very rare to prevent its development patients are not recommended during the treatment and within 48 hours after the treatment with levofloxacin to be exposed to strong sunlight or artificial ultraviolet radiation without any special need (for example, to visit a solarium).

Superinfection

As with other antibiotics levofloxacin administration especially over a long period of time may lead to increased reproduction of microorganisms (bacteria and fungi) which are not sensitive to it and which may cause changes in the microflora which is normally present in humans. As a result, superinfection may develop. Therefore, it is mandatory to reassess the patient’s condition during treatment and take appropriate measures if superinfection develops during treatment.

Translongation of the QT interval

Very rare cases of prolongation of the QT interval have been reported in patients taking fluoroquinolones including levofloxacin.

With fluoroquinolones including levofloxacin, caution should be exercised in patients with known risk factors for QT interval prolongation: In patients with uncorrected electrolyte abnormalities (with hypokalemia hypomagnesemia); with congenital QT interval prolongation syndrome; with heart disease (heart failure myocardial infarction bradycardia); with concurrent administration of drugs that can prolong the QT interval such as antiarrhythmic drugs class IA and III tricyclic antidepressants macrolides neuroleptics.

The elderly and female patients may be more sensitive to agents that prolong the QT interval. Therefore, fluoroquinolones including levofloxacin should be used with caution in these patients (see sections Caution, Dosage and administration, Side effects and Overdose, Interaction with other medicinal products).

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency have a predisposition to hemolytic reactions when treated with quinolones which must be considered when treating with levofloxacin.

Hypo- and hyperglycemia (dysglycemia)

As with the use of other quinolones with levofloxacin cases of hyperglycemia and hypoglycemia have been observed. During therapy with levofloxacin dysglycemia occurred more frequently in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic agents (e.g. glibenclamide) or insulin. When using levofloxacin in such patients the risk of hypoglycemia up to hypoglycemic coma increases. Patients should be informed about the symptoms of hypoglycemia (confusion of consciousness, dizziness, “wolfish” appetite, headache, nervousness, palpitations or increased heart rate, pale skin, sweating, shivering, weakness). If the patient develops hypoglycemia, it is necessary to immediately stop treatment with levofloxacin and start an appropriate therapy. In these cases it is recommended to switch to therapy with other antibiotic not fluoroquinolones, if it is possible. During treatment with levofloxacin in elderly patients with diabetes mellitus close monitoring of blood glucose concentration is recommended.

Peripheral neuropathy

In patients taking fluoroquinolones including levofloxacin there have been reported cases of sensory and sensory-motor peripheral neuropathy which may have a rapid onset. If the patient develops symptoms of neuropathy the use of levofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes. Patients should be informed of the need to report any symptoms of neuropathy to their physician. Fluoroquinolones should not be administered to patients with a history of peripheral neuropathy.

Pseudoparalytic myasthenia gravis exacerbation

Fluoroquinolones including levofloxacin are characterized by nerve-muscle blocking activity and may exacerbate muscle weakness in patients with pseudoparalytic myasthenia gravis. In the post-registration period, adverse reactions including pulmonary failure requiring artificial ventilation and death have been observed that have been associated with fluoroquinolone use in patients with pseudoparalytic myasthenia gravis. The use of levofloxacin in a patient with a confirmed diagnosis of pseudoparalytic myasthenia gravis is not recommended (see section “Side effects”).

The use of levofloxacin in humans for this indication is based on the data on the sensitivity of Bacillus anthracis in in-vitro studies and in experimental studies performed on animals, as well as on limited data on the use of levofloxacin in humans. Treating physicians should refer to national and/or international documents that reflect the consensus view of anthrax treatment.

Psychotic reactions

Psychotic reactions including suicidal thoughts/attempts have been reported in patients taking fluoroquinolones including levofloxacin sometimes after a single dose. In case of any side effects on the central nervous system, including mental disorders, treatment with levofloxacin should be stopped immediately and appropriate therapy should be prescribed. In these cases it is recommended to switch to therapy with another antibiotic other than fluoroquinolones, if possible. Caution should be exercised when prescribing the drug in patients with psychosis or patients with a history of mental illness.

Visual disturbances

In case of any visual disturbances, immediate consultation with an ophthalmologist is necessary (see section on side effects).

Impact on laboratory tests

Patients taking levofloxacin may have false-positive urinary opiates that must be confirmed by more specific methods.

Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and may lead to subsequent false-negative bacteriologic diagnosis of tuberculosis.

Such side effects of Roflox-Scan as dizziness or vertigo sleepiness and visual disturbances (see side effects section) may impair psychomotor responses and ability to concentrate. This may pose some risk in situations where these abilities are particularly important (e.g., driving a car when operating machinery or machinery while working in an unsteady position).

Contraindications

– Hypersensitivity to levofloxacin or other quinolones as well as to any of the excipients of the drug Roflox-Scan;

– epilepsy;

Pseudoparalytic myasthenia gravis (see sections “Side Effects” and “Special Precautions”).

– tendon damage while taking fluoroquinolones in the history;

– childhood and adolescence before 18 years of age (due to incomplete skeletal growth because the risk of cartilage growth zone damage cannot be completely excluded);

Pregnancy (we cannot completely rule out the risk of cartilage problems in the fetus);

Breast-feeding (we cannot completely rule out the risk of cartilage problems in the baby’s growth areas).

-In patients prone to developing seizures [in patients with previous central nervous system (CNS) lesions in patients simultaneously receiving drugs that lower the seizure threshold such as phenbufen theophylline] (see “Interaction with other medications”).

-In patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency (increased risk of hemolytic reactions when treated with quinolones).

-In patients with impaired renal function (mandatory renal function monitoring is required as well as dosage regimen adjustment see section “Dosage and administration”).

In patients with known risk factors for QT interval prolongation: In elderly patients; in female patients; in patients with uncorrected electrolyte abnormalities (with hypokalemia hypomagnesemia); with congenital QT interval prolongation syndrome; with heart disease (heart failure myocardial infarction bradycardia); with concomitant administration of drugs that may prolong the QT interval (antiarrhythmic agents of class IA and III tricyclic antidepressants macrolides neuroleptics) (see “Overdose (see sections “Overdose” “Interaction with other medicinal products” “Cautions”).

-In patients with diabetes mellitus receiving oral hypoglycemic drugs (e.g., glibenclamide) or insulin drugs (increased risk of hypoglycemia).

-In patients with severe adverse reactions to other fluoroquinolones such as severe neurological reactions (increased risk of similar adverse reactions with levofloxacin).

In patients with psychosis or in patients with a history of mental illness (see section “Special Precautions”)

In elderly patients after transplantation also with concomitant use of glucocorticosteroids (increased risk of tendinitis and tendon rupture).

Side effects

The side effects listed below are presented according to the following frequency gradations: very common (≥1/10) common (≥1/100 < 1/10); infrequent (≥1/1000 < 1/100); rare (≥1/10000 < 1/1000); very rare (< 1/10000) (including individual reports); frequency unknown (the incidence cannot be determined from available data).

Cardiac disorders

seldom: sinus tachycardia sensation of palpitations.

incidence unknown: prolongation of the QT interval ventricular arrhythmia ventricular tachycardia ventricular tachycardia type “pirouette” which may lead to cardiac arrest

Blood and lymphatic system disorders

infrequent: Leukopenia (decreased number of leukocytes in peripheral blood) eosinophilia (increased number of eosinophils in peripheral blood).

seldom: neutropenia (decrease in the number of neutrophils in peripheral blood) thrombocytopenia (decrease in the number of platelets in peripheral blood).

frequency unknown: pancytopenia (decrease of all forms in peripheral blood) agranulocytosis (absence or dramatic decrease of granulocytes in peripheral blood) hemolytic anemia.

Nervous system disorders

often: headache dizziness.

infrequent: drowsiness tremor dysgeusia (perversion of taste).

Rarely: paresthesia seizures (see section “Special Precautions”).

frequency unknown: peripheral sensory neuropathy peripheral sensory-motor neuropathy (see section “Special Precautions. Specific Indications) dyskinesia extrapyramidal disorders aguesia (loss of taste sensation) parosmia (disorder of smell sensation especially subjective sense of smell objectively absent) including loss of smell fainting increased intracranial pressure (benign intracranial hypertension pseudotumor brain)

Visual disturbances

rarely: Visual disturbances such as blurred visible images.

frequency unknown: transient loss of vision uveitis.

Hearing and labyrinth disorders

infrequent: vertigo (feeling of deviation or spinning or of own body or surrounding objects).

in rare: ringing in the ears.

frequent unknown: hearing loss hearing loss.

Respiratory system disorders of the thorax and mediastinum

infrequent: dyspnea.

frequency unknown: bronchospasm allergic pneumonitis.

Gastrointestinal disorders

often: diarrhea vomiting nausea.

infrequent: abdominal pain dyspepsia flatulence constipation.

frequent unknown: hemorrhagic diarrhea which in very rare cases can be a sign of enterocolitis including pseudomembranous colitis (see section “Special Indications”) pancreatitis.

Renal and urinary tract disorders

infrequent: increase of serum creatinine concentration.

Rarely: acute renal failure (e.g., due to development of interstitial nephritis).

Skin and subcutaneous tissue disorders

frequent: rash itching urticaria hyperhidrosis.

frequency unknown: toxic epidermal necrolysis Stevens-Johnson syndrome exudative erythema multiforme reaction of photosensitization (hypersensitivity to sunlight and ultraviolet radiation) (see section “Special Indications”) leukocytoclastic vasculitis stomatitis.

Skin and mucous membrane reactions may sometimes develop even after the first dose of the drug.

Musculoskeletal and connective tissue disorders

infrequent: arthralgia myalgia.

rarely: tendonitis including tendonitis (e.g. Achilles tendon) muscle weakness which can be especially dangerous in patients with pseudoparalytic myasthenia gravis (see section “Special Precautions”).

Prevalence unknown: rhabdomyolysis tendon rupture (e.g. Achilles tendon. This side effect may occur within 48 hours of starting treatment and may be bilateral (see also section “Special Precautions”)) ligament tear muscle tear arthritis.

Metabolic and nutritional disorders

infrequent: anorexia.

Rarely: hypoglycemia especially in patients with diabetes mellitus (possible signs of hypoglycemia: “wolf” appetite nervousness sweating trembling).

Prevalence unknown: hyperglycemia severe hypoglycemia up to hypoglycemic coma especially in elderly patients with diabetes receiving oral hypoglycemic agents or insulin (see section “Special Precautions”).

Infectious and parasitic diseases

infrequent: fungal infections development of resistance of pathogenic microorganisms.

Vascular disorders

seldom: decreased blood pressure.

General disorders

infrequent: asthenia.

rarely: pyrexia (increase in body temperature).

frequent unknown: pain (including back pain in the chest and extremities).

Immune system disorders

rarely: angioedema. incidence unknown: anaphylactic shock anaphylactoid shock. Anaphylactic and anaphylactoid reactions may sometimes develop even after the first dose of the drug.

Hepatic and biliary tract disorders

often: increased activity of “hepatic” enzymes in the blood (e.g. alanine aminotransferase (ALT) aspartate aminotransferase (ACT)) increased activity of alkaline phosphatase (ALP) and gammaglutamyltransferase (GGT).

Infrequent: increase of bilirubin concentration in blood.

frequency unknown: severe hepatic failure including cases of acute hepatic failure sometimes with fatal outcome especially in patients with severe underlying disease (e.g. patients with sepsis) (see section “Cautions”); hepatitis jaundice.

Mental disorders

often: insomnia.

infrequent: anxiety anxiety confusion.

seldom: psychiatric disorders (e.g., hallucinations paranoia) depression agitation (agitation) sleep disturbances nightmares.

frequency unknown (post-registration data): mental disorders with self-harm behaviors including suicidal thoughts and suicide attempts attention disorders disorientation nervousness memory disorders delirium.

Other possible adverse effects related to all fluoroquinolones

very rare: episodes of porphyria (a very rare metabolic disease) in patients with porphyria.

Overdose

Symptoms

Based on data obtained in animal toxicology studies, the most important expected symptoms of acute levofloxacin overdose are central nervous system symptoms (disturbances of consciousness including confusion, dizziness and seizures).

In post-registration use, central nervous system effects including confusion, seizures, hallucinations and tremors were observed with overdose.

Possible nausea and gastrointestinal mucosal erosions.

In clinical and pharmacological studies conducted with doses of levofloxacin greater than therapeutic, prolongation of the QT interval was observed.

Treatment of overdose

In case of overdose close monitoring of the patient is required including electrocardiogram monitoring. Treatment is symptomatic. In case of acute overdose of Roflox-Scan it is indicated gastric lavage and administration of antacids for protection of the gastric mucosa. Levofloxacin is not excreted by dialysis (hemodialysis peritoneal dialysis and continuous ambulatory peritoneal dialysis). There is no specific antidote.

Pregnancy use

Similarities