Levofloxacin, 500 mg 5 pcs

Pharmacotherapeutic group:

An antimicrobial agent, fluoroquinolone.

ATX code:

J01MA12

Pharmacological properties

Pharmacodynamics

Levofloxacin is a synthetic broad-spectrum antibacterial drug from the group of fluoroquinolones, containing levofloxacin, the left-handed isomer of ofloxacin, as an active substance. Levofloxacin blocks DNA-enzyme and topoisomerase IV, breaks supercoiling and cross-linking of DNA breaks, inhibits DNA synthesis and causes deep morphological changes in cytoplasm, cell wall and membranes of microbial cells.

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

Sensitive microorganisms (MPC ≤2 mg/L, zone of inhibition >17 mm)

• aerobic gram-positive microorganisms: Bacillus anthracis, Corynebacterium diphtheriae, Corynebacterium jeikeium, Enterococcus spp. (including. Enterococcus faecalis), Listeria monocytogenes, 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 (coagulazonegative), Streptococci group C and G, Streptococcus agalactiae, Streptococcus pneumoniae peni I/S/R (penicillin-moderately sensitive/sensitive/resistant), Streptococcus pyogenes, Viridans streptococci repi-S/R (penicillin-sensitive/resistant);
• aerobic Gram-negative microorganisms: Acinetobacter spp. (including Acinetobacter baumannii), Actinobacillus actinomycetemcomitans, Citrobacter freundii, Eikenella corrodens, Enterobacter aerogenes, Enterobacter spp. Enterobacler cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae ampi-S/R (ampicillin-sensitive/resistant), Haemophilus parainfluenzae, Helicobacter pylori, Klebsiella oxytoca, Klebsiella spp. (including Klebsiella pneumoniae, Klebsiella oxytoca), Moraxella catarrhalis /β+//β- (producing and non-producing beta-lactamases), Morganella morganii, Neisseria gonorrhoeae nonPPNG/PPNG (non-producing and producing penicillinase), Neisseria meningitidis, Pasteurella spp. Pasteurella multocida, Pasteurella dagmatis, Pasteurella canis), Proteus mirabilis, Proteus vulgaris, Providencia spp. (including Providencia rettgeri, Providencia Stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa [hospital infections caused by Pseudomonas aeruginosa may require combined treatment]), Salmonella spp, Serratia spp. (including Serratia marcescens);
• 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., (including 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 bacteria: Campylobacter jejuni, Campylobacter coli;
• anaerobic microorganisms: Prevotella spp., Porphyromonas spp.

Levofloxacin-resistant microorganisms (MAC ≥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), Corynebacterium jeikeium;
• 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 (a mechanism characteristic of Pseudomonas aeruginosa) and the mechanism of efflux (active elimination of the 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 studies 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 quickly and almost completely absorbed after oral administration; food has little effect on its absorption. Absolute bioavailability when administered orally is 99-100%. After a single use of 500 mg of levofloxacin maximum concentration (Cmax) in plasma is reached within 1-2 hours and is 5.2±1.2 µg/ml. Pharmacokinetics of levofloxacin is linear in dose range from 50 mg to 1000 mg. Equilibrium concentration of levofloxacin in plasma when 500 mg of levofloxacin is taken orally 1 or 2 times per day is reached within 48 hours.

On day 10 of oral levofloxacin 500 mg once daily, the Cmax of levofloxacin was 5.7±1.4 µg/ml, and the minimum plasma concentration of levofloxacin (concentration before the next dose) (Cmin) was 0.5±0.2 µg/ml.

On day 10 of oral levofloxacin 500 mg twice daily, the Cmax in plasma was 7.8±1.1 µg/ml and the Cmin was 3.0±0.9 µg/ml.

Distribution

The binding to serum proteins is 30-40%. After single and repeated oral 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 bronchial mucosa, epithelial lining fluid, alveolar macrophages

. After a single oral dose of 500 mg of levofloxacin, Cmax in bronchial mucosa and epithelial lining fluid were reached within 1 h or 4 h and were 8.3 µg/g and 10.8 µg/mL, respectively, with penetration rates in bronchial mucosa and epithelial lining fluid compared with plasma concentrations of 1.1-1.8 and 0.8-3.0, 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 9.94 µg/mL and in alveolar macrophages were 97.9 µg/mL.

Pulmonary tissue penetration

Cmax in pulmonary tissue after oral administration of 500 mg of levofloxacin was approximately 11.3 µg/g and was reached 4-6 h after drug administration with penetration ratios of 2.0-5.0 compared to plasma concentrations.

The penetration into alveolar fluid

. After 3 days of administration of 500 mg of levofloxacin 1 or 2 times daily, the Cmax of levofloxacin in alveolar fluid was reached 2-4 hours after drug administration and was 4.0 µg/ml and 6.7 µg/ml, respectively, with a penetration ratio of 1.0 compared to plasma concentrations.

Bone penetration

Levofloxacin penetrates well into cortical and cancellous bone tissue in both the proximal and distal femur, with a penetration ratio (bone tissue/plasma) of 0.1-3.0. Cmaxes of levofloxacin in the cancellous bone tissue of the proximal femur after oral administration of 500 mg of the drug were approximately 15.1 mcg/g (2 hours after drug administration).

Cerebrospinal fluid penetration

Levofloxacin poorly penetrates into the cerebrospinal fluid.

Permeasurement in prostate tissue

After oral administration of 500 mg of levofloxacin once daily for 3 days, the average concentration of levofloxacin in prostate tissue was 8.7 µg/g and the average prostate/plasma concentration ratio was 1.84.

Urinary concentrations

The mean urinary concentrations 8-12 h after oral doses of 150 mg, 300 mg, 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 desmethyllevofloxacin and levofloxacin N-oxide, which are excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral transformations.

Levofloxacin is relatively slowly excreted from the blood plasma after oral administration (elimination half-life [T1/2] is 6-8 hours). Excretion is mainly by the kidneys (more than 85% of the administered dose). Total clearance of levofloxacin after a single dose of 500 mg was 175±29.2 ml/minute.

There are no significant differences in the pharmacokinetics of levofloxacin when administered intravenously and when administered orally, 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 failure, the pharmacokinetics of levofloxacin are altered. As renal function deteriorates, renal excretion and renal clearance (CIR) decreases and T1/2 is prolonged.

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

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Indications

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

Active ingredient

Composition

1 capsule 500 mg contains:

The active ingredient: Levofloxacin hemihydrate 512.46 mg, in terms of anhydrous levofloxacin 500 mg.

Excipients: microcrystalline cellulose, type 101 71.07 mg, hypromellose 2.4 mg, povidone K30 8.07 mg, calcium stearate 6.0 mg.

Capsule shell composition:
body: titanium dioxide (E171) – 2.0%, gelatin – up to 100%.
cap: titanium dioxide (E171) – 1.00%, indigo carmine (E132) – 0.13330%, gelatin – up to 100%.

How to take, the dosage

“Levofloxacin, capsules, 250 mg or 500 mg” is taken orally 1 or 2 times a day. The capsules should be swallowed without chewing and with plenty of fluid (0.5 to 1 cup).

The drug can be taken before meals or at any time between meals because food does not affect absorption of the drug (see section “Pharmacological properties”, subsection “Pharmacokinetics”).

The drug “Levofloxacin, Capsules, 250 mg and 500 mg” should be taken at least 2 hours before or 2 hours after taking drugs containing magnesium and/or aluminum, iron, zinc, or sucralfate (see section “Interaction with other medicinal products”). Taking into account the fact that the bioavailability of levofloxacin while taking the drug “Levofloxacin capsules, 250 mg and 500 mg” is 99-100%, in case a patient is transferred from intravenous infusion of levofloxacin to capsule administration it should be continued in the same dose that was used for intravenous infusion (see section “Pharmacological properties”, subsection “Pharmacokinetics”).

If you accidentally miss one or more doses of the drug, you should take the next dose as soon as possible and continue taking Levofloxacin Capsules, 250 mg or 500 mg 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)

Dosing regimen in patients with impaired renal function (CK ≤50 ml/min)

Levofloxacin is mainly excreted by the kidneys; therefore, when treating patients with impaired renal function the drug dose must be reduced (see table below).

Dosing regimen in patients with impaired hepatic function

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

Interaction

Cautious interactions

Drugs containing magnesium, aluminum, iron and zinc, didanosine

. Drugs containing bivalent or trivalent cations, such as zinc or iron salts (drugs for treatment of anemia), magnesium- and/or aluminum-containing drugs (such as antacids), didanosine (only dosage forms containing aluminum or magnesium as a buffer) are recommended to be taken at least 2 hours before or 2 hours after taking the drug “Levofloxacin, 250 mg and 500 mg capsules”. Calcium salts have minimal effect on the absorption of levofloxacin when taken orally.

Sucralfate

The effect of the drug “Levofloxacin, 250 mg and 500 mg capsules” is significantly impaired when sucralfate (gastric mucosal protection agent) is used concomitantly. Patients receiving levofloxacin and sucralfate are recommended to take sucralfate 2 hours after taking levofloxacin.

Theophylline, phenbufen or similar drugs from the group of non-steroidal anti-inflammatory drugs (NSAIDs) decreasing cerebral seizure threshold

Pharmacokinetic interaction of levofloxacin with theophylline was not identified. However, with the simultaneous use of quinolones and theophylline. NSAIDs and other drugs that reduce cerebral seizure threshold, there may be a marked decrease in cerebral seizure threshold.

The concentration of levofloxacin is increased by only 13% when concomitant administration of fenbufen.

Indirect anticoagulants (vitamin K antagonists)

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

Probenecid and cimetidine

Caution should be exercised when concomitant use of drugs that impair renal tubular secretion (e.g., probenecid and cimetidine) and levofloxacin, especially in patients with renal insufficiency. The excretion (renal clearance) of levofloxacin is slowed by 24% by cimetidine and 34% by probenecid. This is unlikely to be clinically relevant in normal renal function.

Cyclosporine

The concomitant use of levofloxacin prolonged the T1/2 of cyclosporine by 33%. Since this prolongation is clinically insignificant, no dose adjustment of cyclosporine is required when used concomitantly with levofloxacin.

Glucocorticosteroids

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

Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving medications that prolong the QT interval (e.g., antiarrhythmic drugs of classes IA and III, tricyclic antidepressants, macrolides, neuroleptics).

Other

. Clinical and pharmacological studies conducted to investigate possible pharmacokinetic interactions of levofloxacin with digoxin, glibenclamide, ranitidine and warfarin have shown that the pharmacokinetics of levofloxacin with these drugs does not change sufficiently 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 levofloxacin 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 (MRSA)

There is a high probability that MRSA will be resistant to fluoroquinolones, including levofloxacin. Therefore, levofloxacin is not recommended for the treatment of established or suspected MRSA infections. unless laboratory tests have confirmed sensitivity of the organism to levofloxacin.

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

The use of fluoroquinolones, including levofloxacin, has been associated with disability and development of irreversible serious adverse reactions from various body systems that can develop simultaneously in the same patient. Fluoroquinolone-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 and without the presence of 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. These patients include those with previous CNS lesions such as stroke, severe craniocerebral trauma, patients simultaneously taking drugs that lower the cerebral seizure threshold such as phenbufen and other similar NSAIDs or other drugs that lower the seizure threshold such as theophylline (see section “Interaction with other medicinal products”).

The treatment with levofloxacin should be discontinued if seizures develop.

Pseudomembranous colitis

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

Tendinitis and tendon rupture

Tendinitis, which rarely occurs with fluoroquinolones, can sometimes lead to tendon rupture, including of the Achilles tendon, and can be bilateral. This side effect may develop within 48 h after treatment initiation or several months after completion of fluoroquinolone therapy. Elderly patients are more prone to develop tendonitis; in patients taking fluoroquinolones, the risk of tendon rupture may increase with concomitant 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 CK. Patients should be advised to remain at rest at the first signs of tendinitis or tendon rupture and consult their physician. If tendinitis or tendon rupture is suspected, treatment with Levofloxacin should be stopped immediately and appropriate treatment of the affected tendon should be initiated, e.g. sufficient immobilization (see “Contraindications” and “Adverse effects”).

Aortic aneurysm and dissection

Epidemiologic studies have reported an increased risk of aortic aneurysm and aortic dissection after fluoroquinolones, particularly in elderly patients.

. Therefore, fluoroquinolones should be used only after careful assessment of benefit-risk ratio and consideration of other therapy options in patients with a family history of aortic aneurysm, or in patients with diagnosed aortic aneurysm and/or aortic dissection or in the presence of other risk factors or conditions, predisposing to the development of an aortic aneurysm or aortic dissection (e.g., Marfan syndrome, Ehlers-Danlos vascular syndrome, Takayasu arteritis, gigantocellular arteritis, Behcet’s disease, arterial hypertension, atherosclerosis) (see See section “Caution”). In case of sudden pain in the abdomen, chest or back, patients should immediately consult a physician in the emergency department.

Hypersensitivity reactions

Levofloxacin may cause serious, potentially fatal hypersensitivity reactions (angioedema, anaphylactic shock) even when using initial doses (see section “Side effects”). In case of their development the drug should be stopped immediately and a physician should be consulted.

Serious bullous reactions

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

Patients with impaired hepatic and biliary tract function

Cases of hepatic necrosis, including development of 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 warned to discontinue treatment and seek urgent medical attention if signs and symptoms of liver damage, such as anorexia, jaundice, darkened urine, itching of the skin and abdominal pain appear.

Patients with impaired renal function

Because levofloxacin is excreted primarily by the kidneys, patients with impaired renal function require mandatory renal function monitoring as well as dosing regimen adjustment (see sections “Contraindications” and “Dosage and administration”). When treating elderly patients it should be taken into account that patients of this group often have impaired renal function (see section “Dosage and administration”).

Preventing photosensitization reactions

While photosensitization by levofloxacin is very rare, to prevent its development the patients are not recommended to be exposed to intense sunlight or artificial ultraviolet radiation during the treatment and within 48 hours after treatment with levofloxacin (for example, using a solarium).

Superinfection

As with other antibiotics, the use of levofloxacin, especially for a long time, may lead to increased reproduction of microorganisms that are not sensitive to it (bacteria and fungi), which may cause changes in the microflora that are normally present in humans. This can result in superinfection. Therefore, it is imperative that the patient is reassessed during treatment, and if superinfection develops during treatment, appropriate measures should be taken.

Long QT interval

Very rare cases of prolongation of the QT interval have been reported in patients receiving therapy with fluoroquinolones, including levofloxacin.

When using 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 use of drugs that can prolong the QT interval, such as class IA and III antiarrhythmic agents, tricyclic antidepressants, macrolides, neuroleptics.

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

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency are prone to develop hemolytic reactions when treated with quinolones and this must be taken into account when treating with levofloxacin.

Hypo- and hyperglycemia (dysglycemia)

As with other fluoroquinolones, cases of hyperglycemia and hypoglycemia have been observed with levofloxacin. 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 increases, up to hypoglycemic coma. Patients should be informed about the symptoms of hypoglycemia (confusion, dizziness, “wolfish” appetite, headache, nervousness, palpitations or increased pulse rate, pale skin, sweating, trembling, weakness). If the patient develops hypoglycemia, treatment with levofloxacin should be stopped immediately and appropriate therapy should be started. In these cases it is recommended to switch to therapy with another antibiotic other than fluoroquinolones, if 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, cases of sensory and sensory-motor peripheral neuropathy have been reported, 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 to inform their physician of any symptoms of neuropathy. Fluoroquinolones should not be prescribed in patients with a history of peripheral neuropathy.

The aggravation of pseudoparalytic myasthenia gravis

Fluoroquinolones, including levofloxacin, are characterized by blocking neuromuscular conduction activity and may increase muscle weakness in patients with pseudoparalytic myasthenia gravis. In the post-registration period, adverse reactions, including respiratory 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 an established diagnosis of pseudoparalytic myasthenia gravis is contraindicated (see sections “Contraindications” and “Side effects”).

The use of levofloxacin in humans for this indication is based on the sensitivity data of Bacillus anthracis obtained in in vitro studies and in experimental studies conducted 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 a consensus view on the treatment of anthrax.

Psychotic reactions

Psychotic adverse reactions, including suicidal thoughts/attempts, have been reported in patients taking fluoroquinolones, including levofloxacin, sometimes after a single dose.

In case of development of any central nervous system side effects, 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 (see section “Caution”).

With visual impairment

If any visual impairment develops, immediate consultation with an ophthalmologist is necessary (see section on side effects).

Impact on laboratory tests

In patients taking levofloxacin, urinary opioid determination may lead to false-positive results that must be confirmed by more specific methods.

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

Special information about excipients

The drug “Levofloxacin 250 mg and 500 mg capsules” contains the dye indigo carmine E132 which may cause allergic reactions.

Side effects of Levofloxacin, 250 mg and 500 mg capsules such as dizziness or vertigo, drowsiness and visual disturbances (see section “Side effects”) may decrease the speed of psychomotor reactions and the ability to concentrate. This may pose some risk in situations where these abilities are particularly important (e.g., driving, operating machinery, working in unsteady positions).

Synopsis

Contraindications

Because of the impossibility of dosing regimen of 125 mg the use of Levofloxacin, 250 mg and 500 mg capsules, is contraindicated in patients with impaired renal function:

Side effects

The side effects listed below are presented according to the following frequency gradations: very frequently (≥1/10), frequently (≥1/100, < 1/10); infrequently (≥1/1000, < 1/100); rarely (≥1/10000, < 1/1000); very rarely < 1/10000) (including individual reports), frequency is unknown (based on available data the incidence cannot be determined).

Data from clinical trials and post-registration use of levofloxacin

Infectious and parasitic diseases:

Disorders of blood and lymphatic system:

Immune system disorders:

Metabolic and nutritional disorders:

Mental disorders:

Nervous system disorders:

Visual disturbances:

Hearing and labyrinth disorders:

Cardiac disorders:

Vascular disorders:

Respiratory system, thoracic and mediastinal disorders:

Digestive system disorders:

Disorders of the liver and biliary tract:

Skin and subcutaneous tissue disorders:

Musculoskeletal and connective tissue disorders:

Renal and urinary tract disorders:

General disorders:

Other possible adverse effects relevant to all fluoroquinolones: very rare: episodes of porphyria (a very rare metabolic disease) in patients with porphyria.

Overdose

Symptoms

Based on data obtained in toxicological studies conducted in animals, the most important expected symptoms of acute overdose of levofloxacin are CNS symptoms (disturbances of consciousness, including confusion, dizziness and seizures).

In post-registration use of levofloxacin in case of overdose CNS effects including confusion, seizures, hallucinations and tremors were observed.

The development of nausea and gastrointestinal mucosal erosions may occur.

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

Treatment

In case of overdose, close patient monitoring is required, including electrocardiogram monitoring. Treatment is symptomatic. In case of acute overdose with the drug “Levofloxacin, capsules 250 mg and 500 mg” gastric lavage and administration of antacids for protection of gastric mucosa are indicated. Levofloxacin is not excreted by dialysis (hemodialysis, peritoneal dialysis and PAPD). There is no specific antidote.

Pregnancy use

Similarities