Levofloxacin, 500 mg 10 pcs

Pharmacotherapeutic group

Antimicrobial agent – fluoroquinolone

ATX code: J01MA

Pharmacodynamics:

Levofloxacin 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- 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 in both in-vitro and in-vivo conditions.

Invitro

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

– Aerobic Gram-positive microorganisms: BacillusanthracisCorynebacteriumdiphtheriaeCorynebacteriumjeikeiumEnterococcusfaecalisEnterococcusspp. ListeriamonocytogenesStaphylococcuscoagulase-negativemethi-S( I) [coagulase-negative methicillin-sensitive/ moderately sensitive] Staphylococcusaureusmethi-S(methicillin-sensitive) Staphylococcusepidermidismethi-S(methicillin-sensitive) Staphylococcusspp. CNS (coagulazonegative) Streptococcispp. C and GStreptococcoccusagalactiaeStreptococcuspneumoniapeniI/S/R (penicillin-moderately sensitive/sensitive/resistant) StreptococcuspyogenesViridansstreptococcipeni-S/R (penicillin-sensitive/resistant).

– Aerobic Gram-negative microorganisms: AcinetobacterbaumanniiAcinetobacterspp.

ActinobacillusactinomycetemcomitansCitrobacterfreundiiEikenellacorrodensEnterobactereraerogenesEnterobactercloacaeEnterobacterspp. EscherichiacoliGardnerellavaginalisHaemophilusducreyiHaemophilusinfluenzaeampi-S/R (ampicillin-sensitive/resistant) Haemophilusparainfluenzae Helicobacterpylori Klebsiellaoxytoca Klebsiellapneumoniae. Klebsiellaspp. Moraxellacatarrhalis /?+//?- (producing and non-producing beta-lactamases) Morganellamorganii Neisseriagonorrhoeaenon PPNG/PPNG (non-producing and producing penicillinase) Neisseriameningitidis Pasteurellacanis Pasteurelladagmatis Pasteurellamultocida Pasteurellaspp Proteusmirabilis Proteusvulgaris Providenciarettgeri Providenciastuartii Providenciaspp. Pseudomonasaeruginosa (hospital infections caused by Pseudomonasaeruginosa may require combined treatment) Pseudomonasspp. Salmonellaspp. Serratiamarcescens Serratiaspp.

– Anaerobic microorganisms: BacteroidesfragilisBifidobacteriumspp. ClostridiumperfringensFusobacteriumspp. PeptostreptococcusPropionibacteriumspp. Veillonellaspp.

– Other microorganisms: Bartonellaspp. ChlamydiapneumoniaeChlamydiapsittaciChlamydiatrachomatisLegionellapneumophilaLegionellaspp. Mycobacteriumspp. MycobacteriumlepraeMycobacteriumtuberculosisMycoplasmahominisMycoplasmapneumoniaeRickettsiaspp. Ureaplasmaurealyticum.

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

– Aerobic Gram-positive microorganisms: Corynebacteriumurealyticum CorynebacteriumxerosisEnterococcusfaeciumStaphylococcusepidermidismethi-R(methicillin-resistant) Staphylococcoccushaemolyticusmethi-R(methicillin-resistant).

– Aerobic Gram-negative microorganisms: Campylobacterjejuni/coli

– Anaerobic microorganisms: Prevotellaspp. Porphyromonasspp.

Levofloxacin-resistant microorganisms (MAC ≥ 8 mg/L: inhibition zone ≤ 13 mm):

– Aerobic Gram-positive microorganisms: Staphylococcusaureusmethi-R

(methicillin-resistant) Staphylococcuscoagulase-negativemethi-R (coagulazonegative methicillin-resistant).

– Aerobic Gram-negative microorganisms: Alcaligenesxylosoxidans.

– 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.

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: EnterococcusfaecalisStaphylococcusaureusStreptococcuspneumoniaeStreptococcuspyogenes.

– Aerobic Gram-negative microorganisms: CitrobacterfreundiiEnterobactercloacaeEscherichiacoliHaemophilusinfluenzaeHaemophilusparainfluenzaeKlebsiellapneumoniaeMoraxella (Branhamella) catarrhalisMorganellamorganiiProteusmirabilisPseudomonasaeruginosaSerratiamarcescens.

– 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 mcg/ml. Pharmacokinetics of levofloxacin is linear in the dose range from 50 to 1000 mg. The equilibrium state of plasma concentrations of levofloxacin when receiving 500 mg of levofloxacin 1 or 2 times a day is reached within 48 hours.

On day 10 of oral levofloxacin 500 mg once daily the Cmax of levofloxacin was 57 ± 14 mcg/ml and the minimum plasma concentration of levofloxacin (concentration before the next dose) 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 intake 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 administration 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 into 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, maximum concentrations of levofloxacin in alveolar fluid were reached 2-4 h after drug administration and were 40 and 67 µg/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 proximal femur after oral administration of 500 mg of the drug 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 hours 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 are excreted by the kidneys. Levofloxacin is stereochemically stable and does not undergo chiral conversions.

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 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 changes. As renal function decreases, renal excretion and renal clearance (C1R) decreases and T1/2 increases.

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

Indications

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

– acute sinusitis;

– exacerbation of chronic bronchitis;

– community-acquired pneumonia;

– uncomplicated cystitis;

– complicated urinary tract infections including 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.

Active ingredient

Composition

One film-coated tablet contains:

The active ingredient:

levofloxacin hemihydrate 512.46 mg converted to 500.0 mg levofloxacin.

Auxiliary substances (core):

Microcrystalline cellulose (type 101) 38.54 mg,

low-substituted hyprolose 10.0 mg,

sodium carboxymethyl starch 16.0 mg,

povidone K-30 12.0 mg,

croscarmellose sodium 6.0 mg,

colloidal silica 8.0 mg,

talc 4.0 mg/ 8.0 mg/ 20.0 mg,

magnesium stearate 4.0 mg.

The excipients of the finished water-soluble tablet shell/capsule: hypromellose-E6 4.028 m, talc 1.040 mg, titanium dioxide 2.900 mg, iron oxide yellow dye 0.016 mg, iron oxide red dye 0.016 mg.

How to take, the dosage

Tablets Levofloxacin are taken orally once or twice a day.

The tablets should be swallowed without chewing and with plenty of fluid (05 to 1 cup). If necessary, the tablets may be crushed at the risk. The drug may 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 when receiving Levofloxacin tablets is 99-100% if the patient is switched from intravenous infusion of Levofloxacin to administration of tablets the treatment should be continued at the same dose that was used for intravenous infusion (see section “Pharmacokinetics”).

Missing one or more doses of the drug

If you accidentally miss a dose, take the next dose as soon as possible and continue taking Levofloxacin according to the recommended dosing regimen.

Dosages 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):

– Acute sinusitis: 2 tablets of Levofloxacin 250 mg or 1 tablet of Levofloxacin 500 mg once daily (respectively daily dose of 500 mg levofloxacin) – 10-14 days; 1 tablet of Levofloxacin 750 mg once daily (daily dose of 750 mg levofloxacin) – 5 days;

– Exacerbation of chronic bronchitis: 2 tablets of the drug Levofloxacin 250 mg or 1 tablet of the drug Levofloxacin 500 mg 1 time per day (respectively, daily dose of 500 mg of levofloxacin) – 7-10 days;

– Community-acquired pneumonia: 2 tablets of the drug Levofloxacin 250 mg or 1 tablet of the drug Levofloxacin 500 mg 1-2 times a day (respectively, the daily dose of 500-1000 mg of levofloxacin) for 7-14 days; 1 tablet of Levofloxacin 750 mg once daily (daily dose of 750 mg of levofloxacin) – 5 days (Community-acquired pneumonia caused by Streptococcuspneumoniae (penicillin-moderately sensitive/insensitive/resistant) Haemophilusinfluenzae Mycoplasmapneumoniae Chlamydiapneumoniae);

Hospital pneumonia: 1 tablet of Levofloxacin 750 mg once daily (daily dose of 750 mg levofloxacin) – 7-14 days;

– Uncomplicated cystitis: 1 tablet of Levofloxacin 250 mg once daily (daily dose of 250 mg levofloxacin) – 3 days;

– Complicated urinary tract infections: 2 tablets of the drugLevofloxacin 250 mg once daily or 1 tablet of the drug Levofloxacin 500 mg once daily (respectively, daily dose of 500 mg of levofloxacin) – 7-14 days; 1 tablet of Levofloxacin 750 mg once daily (daily dose of 750 mg of levofloxacin) – 5 days (complicated urinary tract infections caused by EscherichiacoliKlebsiellapneumoniaeProteusmirabilis);

– pyelonephritis: 2 tablets of the drug Levofloxacin 250 mg once a day or 2 tablets of the drug Levofloxacin 500 mg once a day (respectively, the daily dose of 500 mg of levofloxacin) – 7-10 days; 1 tablet of Levofloxacin 750 mg once daily (daily dose of Levofloxacin 750 mg) – 5 days (acute pyelonephritis caused by Escherichiacoli, including cases of concomitant bacteremia);

– Chronic bacterial prostatitis: 2 tablets of Levofloxacin 250 mg or 1 tablet of Levofloxacin 500 mg once daily (respectively, daily dose of 500 mg of Levofloxacin) – 28 days;

– Skin and soft tissue infections: 2 tablets of Levofloxacin 250 mg or 1 tablet of Levofloxacin 500 mg 1-2 times daily (respectively, daily dose of 500 to 1000 mg of levofloxacin) – 7-14 days;

– Complicated skin and soft tissue infections: 1 tablet of Levofloxacin 750 mg once daily (daily dose of 750 mg of levofloxacin) – 10-14 days;

– Complex treatment of drug-resistant forms of tuberculosis: 1 tablet of the drug Levofloxacin 500 mg 1-2 times a day (respectively, the daily dose of 500 – 1000 mg of levofloxacin) for up to 3 months;

– Prevention and treatment of anthrax in the airborne route of infection: 2 tablets of Levofloxacin 250 mg or 1 tablet of Levofloxacin 500 mg (respectively, a daily dose of 500 mg of levofloxacin) once a day for up to 8 weeks.

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 it is necessary to reduce the dose of the drug.

Dosing regimen in patients with hepatic impairment:

In patients with hepatic impairment no dosing regimen adjustment is required 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

Interactions With 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 pharmaceutical forms containing aluminum or magnesium as a buffer) are recommended to be taken at least 2 hours before or 2 hours after taking Levofloxacin tablets.

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

With sucralfate

The effect of Levofloxacin is significantly impaired when sucralfate (a gastric mucosal protection agent) is used at the same time.

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 decreasing cerebral seizure threshold

Pharmacokinetic interaction of levofloxacin with theophylline has not been identified. However, with concomitant use of quinolones and theophylline, 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 fenbufen is increased only by 13%.

With indirect anticoagulants (vitamin K antagonists)

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

With probenecid and cimetidine

When concomitant use of drugs that interfere with renal tubular secretion such as probenecid and cimetidine and levofloxacin care should be taken 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.

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 medications that prolong the QT interval.

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

Other

Clinical and pharmacological 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 prevalence of acquired resistance of bacterial strains can vary by geographic region and over time. This requires information about resistance to the drug in a particular country. For therapy of severe infections or in case of ineffective treatment it is necessary to establish microbiological diagnosis with pathogen isolation and determination of its sensitivity to levofloxacin.

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 if the laboratory tests have not confirmed the sensitivity of this microorganism to levofloxacin.

Patients susceptible to seizures

Levofloxacin, like other quinolones, 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 taking concomitant medications which lower the seizure threshold such as phenbufen or other similar non-steroidal anti-inflammatory drugs or other drugs which lower the seizure threshold such as theophylline (see section “Interaction with other medicinal products”).

Pseudomembranous colitis

Diarrhea during or after treatment with levofloxacin which is particularly severe and 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. Drugs which inhibit intestinal peristalsis are contraindicated.

Tendinitis

Tendinitis is rarely seen with quinolones including levofloxacin and can sometimes lead to tendon rupture including Achilles tendon. This side effect can occur within 48 hours of starting treatment and may be bilateral. Elderly patients are more prone to the development of 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. If tendinitis is suspected, treatment with Levofloxacin should be stopped immediately and appropriate treatment of the affected tendon should be initiated, e.g. sufficient immobilization should be provided (see sections “Contraindications” and “Side effects”).

Hypersensitivity reactions

Levofloxacin can 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

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 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 taken into account that in this group of patients renal dysfunction is often observed (see section “Dosage and administration”).

Preventing photosensitization reactions

While photosensitization by levofloxacin is very rare to prevent its development patients are not recommended during the treatment and within 48 hours after 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 use of drugs that can prolong the QT interval such as antiarrhythmic drugs class IA and III 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 them (see sections “Caution”, “Dosage and administration”, “Side effects” “Overdose” and “Interaction with other medicines”).

Patients with glucose-6-phosphate dehydrogenase deficiency

Patients with latent or manifest glucose-6-phosphate dehydrogenase deficiency have a predisposition to develop 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 a patient develops symptoms of neuropathy the use of levofloxacin should be discontinued. This minimizes the possible risk of developing irreversible changes.

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 pulmonary failure requiring artificial ventilation and lethal outcome have been observed 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 sensitivity of Vacillus Anthrax is 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 represent 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

In patients taking levofloxacin, urinalysis for opiates may give false-positive results and should be confirmed by more specific methods.

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

Such side effects of Levofloxacin as dizziness or vertigo drowsiness and visual disturbances (see side effects section) may impair psychomotor reactions 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 Levofloxacin;

– Epilepsy;

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

– Tendon lesions with a history of fluoroquinolones;

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

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

He breastfeeding period (we cannot completely rule out the risk of cartilage growth points in the baby).

-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 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 uncorrelated electrolyte disorders (with hypokalemia hypomagnesemia); with congenital QT interval prolongation syndrome; with heart disease (heart failure myocardial infarction bradycardia); in concurrent administration of drugs that can prolong the QT interval (class IA and III tricyclic antidepressants macrolides neuroleptics) (see (see sections “Overdose” “Interaction with other medicinal products” “Cautions”).

-In patients with diabetes mellitus receiving oral hypoglycemic agents such as glibenclamide or insulin preparations (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, post-transplant patients and concomitant use of glucocorticosteroids (increased risk of tendonitis and tendon rupture) (see section “Special Precautions”).

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 (no data available to determine frequency of occurrence).

Data from clinical studies and post-marketing use of the drug

Cardiac disorders

Rarely: sinus tachycardia palpitations.

Prevalence unknown (postmarketing data): prolongation of the QT interval ventricular arrhythmia ventricular tachycardia ventricular pirouette tachycardia which may lead to cardiac arrest (see sections “Overdose” “Special Precautions”).

Disorders of the blood and lymphatic system

Infrequent: leukopenia (decreased number of leukocytes in peripheral blood) eosinophilia (increased number of eosinophils in peripheral blood).

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

Frequency is unknown (post-marketing data): pancytopenia (decrease in the number of all the forms in peripheral blood) agranulocytosis (absence or a sharp decrease in the number of granulocytes in peripheral blood) hemolytic anemia.

Vascular disorders

Rarely: decrease of blood pressure.

Nervous system disorders

Often: headache dizziness.

Infrequent: drowsiness tremor dysgeusia (perversion of taste).

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

Frequency unknown (post-marketing data): peripheral sensory neuropathy peripheral sensory-motor neuropathy (see Special Indications) dyskinesia extrapyramidal disorders agueusia (loss of taste sensation) parosmia (disorder of sense of smell especially subjective sense of smell objectively absent) including loss of smell fainting benign intracranial hypertension.

Visual disturbances

Rarely: visual disturbances such as blurred vision.

Prevalence unknown (post-marketing data): transient loss of vision uveitis.

Hearing and labyrinth disorders

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

Rarely: ringing in the ears.

Prevalence unknown (post-marketing data): hearing loss hearing loss.

Respiratory system disorders of the thorax and mediastinum

Infrequent: dyspnea.

Infrequent unknown (post-marketing data): bronchospasm allergic pneumonitis.

Gastrointestinal disorders

Often: diarrhea vomiting nausea.

Infrequent: abdominal pain dyspepsia flatulence constipation.

Frequency unknown (post-marketing data): hemorrhagic diarrhea which in very rare cases may 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 interstitial nephritis).

Skin and subcutaneous tissue disorders

Infrequent: rash itching urticaria hyperhidrosis.

Prevalence unknown (post-marketing data): toxic epidermal necrolysis Stevens-Johnson syndrome exudative erythema multiforme reactions of photosensitization (hypersensitivity to sun 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: tendon involvement including tendonitis (e.g., Achilles tendon) muscle weakness which can be especially dangerous in patients with pseudoparalytic myasthenia gravis (see See section “Special Precautions”).

Prevalence unknown (post-marketing data): rhabdomyolysis tendon rupture (e.g. Achilles tendon. This side effect may occur within 48 hours of treatment initiation and may be bilateral (see also “Special Indications”)) ligament tear muscle tear arthritis.

Metabolic and nutritional disorders

Infrequent: anorexia.

Rare: 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 taking oral hypoglycemic drugs or insulin (see section “Cautions”).

Infectious and parasitic diseases

Infrequent: fungal infections development of resistance of pathogenic microorganisms.

General disorders

Infrequent: asthenia.

Rarely: pyrexia (increase in body temperature).

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

Immune system disorders

Rarely: angioedema.

Frequency unknown (postmarketing data): anaphylactic shock anaphylactoid shock.

Anaphylactic and anaphylactoid reactions can 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.

Prevalence unknown (post-marketing data): severe liver failure including cases of acute liver failure sometimes with fatal outcome especially in patients with severe underlying disease (e.g. patients with sepsis) (see section “Indications”); hepatitis jaundice.

Mental disorders

Often: insomnia.

Infrequent: anxiety anxiety confusion.

Rarely: psychiatric disorders (e.g. hallucinations paranoia) depression agitation (agitation) sleep disturbance nightmares.

Frequency unknown (post-marketing 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 the data obtained in toxicological studies conducted in animals the most important expected symptoms of acute overdose of levofloxacin are symptoms of the central nervous system (disorders of consciousness including confusion, dizziness and seizures).

In postmarketing use of levofloxacin in overdose, central nervous system effects including confusion, seizures, hallucinations and tremors have been observed.

The development of nausea and gastrointestinal mucosal erosions may occur.

In clinical and pharmacological studies conducted with doses of levofloxacin greater than 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 Levofloxacin it is indicated gastric lavage and administration of antacids for protection of gastric mucosa. Levofloxacin is not excreted by dialysis (hemodialysis peritoneal dialysis and continuous ambulatory peritoneal dialysis). There is no specific antidote.

Pregnancy use

Similarities