Levofloxacin 500mg & 750mg Film-coated Tablets is indicated in adults for the
treatment of the following infections (see sections 4.4 and 5.1):
• Acute bacterial sinusitis
• Uncomplicated cystitis (see section 4.4)
• Acute exacerbation of chronic obstructive pulmonary disease including bronchitis
• Complicated skin and soft tissue infections/complicated skin and skin structure
infections 

For the above-mentioned infections Levofloxacin 500mg & 750mg Film-coated
Tablets should be used only when it is considered inappropriate to use other
antibacterial agents that are commonly recommended for the treatment of these
infections.
• Acute pyelonephritis and complicated urinary tract infections (see section 4.4)
• Chronic bacterial prostatitis
• Community-acquired pneumonia
• Inhalation Anthrax: post exposure prophylaxis and curative treatment (see section
4.4)
Levofloxacin 500mg & 750mg Film-coated Tablets may also be used to complete a
course of therapy in patients who have shown improvement during initial treatment
with intravenous levofloxacin.
Consideration should be given to official guidance on the appropriate use of
antibacterial agents.

The dosage depends on the type and severity of the infection and the susceptibility
of the presumed causative pathogen.
Levofloxacin 500mg & 750mg Film-coated Tablets may also be used to complete a
course of therapy in patients who have shown improvement during initial treatment
with intravenous levofloxacin; given the bioequivalence of the parenteral and oral
forms, the same dosage can be used.
Posology
The following dose recommendations can be given for Levofloxacin 500mg & 750mg
Film-coated Tablets:
Dosage in patients with normal renal function
(creatinine clearance >50 ml/min)

Impaired liver function
No adjustment of dose is required since levofloxacin is not metabolised to any
relevant extent by the liver and is mainly excreted by the kidneys.
Elderly population
No adjustment of dose is required in the elderly, other than that imposed by
consideration of renal function (see section 4.4 “Tendinitis and tendon rupture” and
“QT interval prolongation”).
Paediatric population
Levofloxacin 500mg & 750mg Film-coated Tablets is contraindicated in children and
growing adolescents (see section 4.3).
Method of administration
Levofloxacin 500mg & 750mg Film-coated Tablets should be swallowed without
crushing and with sufficient amount of liquid. They may be divided at the score line to
adapt the dose. The tablets may be taken during meals or between meals.
Levofloxacin 500mg & 750mg Film-coated Tablets should be taken at least two
hours before or after iron salts, zinc salts, magnesium- or aluminium-containing
antacids, or didanosine (only didanosine formulations with aluminium or magnesium
containing buffering agents), and sucralfate administration, since reduction of
absorption can occur (see section 4.5).

Methicillin-resistant S. aureus are very likely to possess co-resistance to
fluoroquinolones, including levofloxacin. Therefore levofloxacin is not recommended
for the treatment of known or suspected MRSA infections unless laboratory results have confirmed susceptibility of the organism to levofloxacin (and commonly
recommended antibacterial agents for the treatment of MRSA-infections are
considered inappropriate).
Levofloxacin may be used in the treatment of Acute Bacterial Sinusitis and Acute
Exacerbation of Chronic Bronchitis when these infections have been adequately
diagnosed.
Resistance to fluoroquinolones of E. coli – the most common pathogen involved in
urinary tract infections – varies across the European Union. Prescribers are advised
to take into account the local prevalence of resistance in E. coli to fluoroquinolones.
Inhalation Anthrax: Use in humans is based on in vitro Bacillus
anthracis susceptibility data and on animal experimental data together with limited
human data. Treating physicians should refer to national and/or international
consensus documents regarding the treatment of anthrax.
The use of levofloxacin should be avoided in patients who have experienced serious
adverse reactions in the past when using quinolone or fluoroquinolone containing
products (see section 4.8). Treatment of these patients with levofloxacin should only
be initiated in the absence of alternative treatment options and after careful
benefit/risk assessment (see also section 4.3).
Tendinitis and tendon rupture
Tendinitis may rarely occur. It most frequently involves the Achilles tendon and may
lead to tendon rupture. Tendinitis and tendon rupture (especially but not limited to
Achilles tendon), sometimes bilateral, may occur as early as within 48 hours of
starting treatment with quinolones and fluoroquinolones and have been reported to
occur even up to several months after discontinuation of treatment in patients
receiving daily doses of 1000 mg levofloxacin. The risk of tendinitis and tendon
rupture is increased in older patients, patients with renal impairment, patients with
solid organ transplants and those treated concurrently with corticosteroids.
Therefore, concomitant use of corticosteroids should be avoided.
At the first sign of tendinitis (e.g. painful swelling, inflammation) the treatment with
levofloxacin should be discontinued and alternative treatment should be considered.
The affected limb(s) should be appropriately treated (e.g. immobilisation).
Corticosteroids should not be used if signs of tendinopathy occur.
The daily dose should be adjusted in elderly patients based on creatinine clearance
(see section 4.2). Close monitoring of these patients is therefore necessary if they
are prescribed levofloxacin.
Clostridium difficile -associated disease
Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment
with levofloxacin (including several weeks after treatment), may be symptomatic
of Clostridium difficile-associated disease (CDAD). CDAD may range in severity from mild to life threatening, the most severe form of which is pseudomembranous
colitis(see section 4.8). It is therefore important to consider this diagnosis in patients
who develop serious diarrhoea during or after treatment with levofloxacin. If CDAD is
suspected or confirmed, levofloxacin should be stopped immediately and appropriate
treatment initiated without delay. Anti-peristaltic medicinal products are
contraindicated in this clinical situation.
Patients predisposed to seizures
Quinolones may lower the seizure threshold and may trigger seizures. Levofloxacin
is contraindicated in patients with a history of epilepsy (see section 4.3) and, as with
other quinolones, should be used with extreme caution in patients predisposed to
seizures or concomitant treatment with active substances that lower the cerebral
seizure threshold, such as theophylline (see section 4.5). In case of convulsive
seizures (see section 4.8), treatment with levofloxacin should be discontinued.
Patients with G-6- phosphate dehydrogenase deficiency
Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity
may be prone to haemolytic reactions when treated with quinolone antibacterial
agents. Therefore, if levofloxacin has to be used in these patients, potential
occurrence of haemolysis should be monitored.
Patients with renal impairment
Since levofloxacin is excreted mainly by the kidneys, the dose of levofloxacin should
be adjusted in patients with renal impairment (see section 4.2).
Hypersensitivity reactions
Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g.
angioedema up to anaphylactic shock), occasionally following the initial dose (see
section 4.8). Patients should discontinue treatment immediately and contact their
physician or an emergency physician, who will initiate appropriate emergency
measures.
Severe cutaneous adverse reactions
Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis
(TEN: also known as Lyell's syndrome), Stevens Johnson syndrome (SJS) and drug
reaction with eosinophilia and systemic symptoms (DRESS), which could be lifethreatening
or fatal, have been reported with levofloxacin (see section 4.8). At the
time of prescription, patients should be advised of the signs and symptoms of severe
skin reactions, and be closely monitored. If signs and symptoms suggestive of these
reactions appear, levofloxacin should be discontinued immediately and an alternative
treatment should be considered. If the patient has developed a serious reaction such
as SJS, TEN or DRESS with the use of levofloxacin, treatment with levofloxacin
must not be restarted in this patient at any time. Dysglycaemia
As with all quinolones, disturbances in blood glucose, including both hypoglycaemia
and hyperglycaemia have been reported (see section 4.8), usually in diabetic
patients receiving concomitant treatment with an oral hypoglycaemic agent (e.g.
glibenclamide) or with insulin. Cases of hypoglycaemic coma have been reported. In
diabetic patients, careful monitoring of blood glucose is recommended.
Prevention of photosensitisation
Photosensitisation has been reported with levofloxacin (see section 4.8). It is
recommended that patients should not expose themselves unnecessarily to strong
sunlight or to artificial UV rays (e.g. sunray lamp, solarium), during treatment and for
48 hours following treatment discontinuation in order to prevent photosensitisation.
Patients treated with Vitamin K antagonists
Due to possible increase in coagulation tests (PT/INR) and/or bleeding in patients
treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin),
coagulation tests should be monitored when these drugs are given concomitantly
(see section 4.5).
Psychotic reactions
Psychotic reactions have been reported in patients receiving quinolones, including
levofloxacin. In very rare cases these have progressed to suicidal thoughts and selfendangering
behaviour- sometimes after only a single dose of levofloxacin (see
section 4.8). In the event that the patient develops these reactions, levofloxacin
should be discontinued and appropriate measures instituted. Caution is
recommended if levofloxacin is to be used in psychotic patients or in patients with
history of psychiatric disease.
QT interval prolongation:
Caution should be taken when using fluoroquinolones, including levofloxacin in
patients with known risk factors for prolongation of the QT interval such as, for
example:
- congenital long QT syndrome
- concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA
and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics).
- uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
- cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
- Elderly patients and women may be more sensitive to QTc-prolonging medications.
Therefore, caution should be taken when using fluoroquinolones, including
levofloxacin, in these populations. (See sections 4.2 Elderly, 4.5, 4.8 and 4.9).
Peripheral neuropathy
Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesia,
hypaesthesia, dysesthesia, or weakness have been reported in patients receiving
quinolones and fluoroquinolones. Patients under treatment with levofloxacin should
be advised to inform their doctor prior to continuing treatment if symptoms of
neuropathy such as pain, burning, tingling, numbness, or weakness develop in order
to prevent the development of potentially irreversible condition (see section 4.8).
Hepatobiliary disorders
Cases of hepatic necrosis up to fatal hepatic failure have been reported with
levofloxacin, primarily in patients with severe underlying diseases, e.g. sepsis (see
section 4.8). Patients should be advised to stop treatment and contact their doctor if
signs and symptoms of hepatic disease develop such as anorexia, jaundice, dark
urine, pruritus or tender abdomen.
Exacerbation of myasthenia gravis
Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and
may exacerbate muscle weakness in patients with myasthenia gravis. Postmarketing
serious adverse reactions, including deaths and the requirement for respiratory
support, have been associated with fluoroquinolone use in patients with myasthenia
gravis. Levofloxacin is not recommended in patients with a known history of
myasthenia gravis.
Vision disorders
If vision becomes impaired or any effects on the eyes are experienced, an eye
specialist should be consulted immediately (see sections 4.7 and 4.8).
Superinfection
The use of levofloxacin, especially if prolonged, may result in overgrowth of nonsusceptible
organisms. If superinfection occurs during therapy, appropriate
measures should be taken.
Aortic aneurysm and dissection
Epidemiologic studies report an increased risk of aortic aneurysm and dissection
after intake of fluoroquinolones, particularly in the older population.
Therefore, fluoroquinolones should only be used after careful benefit-risk
assessment and after consideration of other therapeutic options in patients with
positive family history of aneurysm disease, or in patients diagnosed with preexisting
aortic aneurysm and/or aortic dissection, or in presence of other risk factors
or conditions predisposing for aortic aneurysm and dissection (e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis,
Behcet's disease, hypertension, known atherosclerosis).
In case of sudden abdominal, chest or back pain, patients should be advised to
immediately consult a physician in an emergency department.
Prolonged, disabling and potentially irreversible serious adverse drug reactions
Very rare cases of prolonged (continuing months or years), disabling and potentially
irreversible serious adverse drug reactions affecting different, sometimes multiple,
body systems (musculoskeletal, nervous, psychiatric and senses) have been
reported in patients receiving quinolones and fluoroquinolones irrespective of their
age and pre-existing risk factors. Levofloxacin should be discontinued immediately at
the first signs or symptoms of any serious adverse reaction and patients should be
advised to contact their prescriber for advice.
Interference with laboratory tests
In patients treated with levofloxacin, determination of opiates in urine may give falsepositive
results. It may be necessary to confirm positive opiate screens by more
specific method.
Levofloxacin may inhibit the growth of Mycobacterium tuberculosis and, therefore,
may give false-negative results in the bacteriological diagnosis of tuberculosis.
Sodium
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say
essentially 'sodium-free'.

Effect of other medicinal products on levofloxacin
Iron salts, zinc-salts, magnesium- or aluminium-containing antacids, didanosine
Levofloxacin absorption is significantly reduced when iron salts, or magnesium- or
aluminium-containing antacids, or didanosine (only didanosine formulations with
aluminium or magnesium containing buffering agents) are administered
concomitantly with levofloxacin tablets.. Concurrent administration of
fluoroquinolones with multi-vitamins containing zinc appears to reduce their oral
absorption. It is recommended that preparations containing divalent or trivalent
cautions such as iron salts, zinc-salts or magnesium- or aluminium-containing
antacids, or didanosine (only didanosine formulations with aluminium or magnesium
containing buffering agents should not be taken 2 hours before or after Levofloxacin
500mg & 750mg Film-coated Tablets administration (see section 4.2). Calcium salts
have a minimal effect on the oral absorption of levofloxacin. Sucralfate
The bioavailability of Levofloxacin 500mg & 750mg Film-coated Tablets is
significantly reduced when administered together with sucralfate. If the patient is to
receive both sucralfate and levofloxacin, it is best to administer sucralfate 2 hours
after the Levofloxacin 500mg & 750mg Film-coated Tablets administration (see
section 4.2).
Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs
No pharmacokinetic interactions of levofloxacin were found with theophylline in a
clinical study. However a pronounced lowering of the cerebral seizure threshold may
occur when quinolones are given concurrently with theophylline, non-steroidal antiinflammatory
drugs, or other agents which lower the seizure threshold.
Levofloxacin concentrations were about 13% higher in the presence of fenbufen than
when administered alone.
Probenecid and cimetidine
Probenecid and cimetidine had a statistically significant effect on the elimination of
levofloxacin. The renal clearance of levofloxacin was reduced by cimetidine (24%)
and probenecid (34%). This is because both drugs are capable of blocking the renal
tubular secretion of levofloxacin. However, at the tested doses in the study, the
statistically significant kinetic differences are unlikely to be of clinical relevance.
Caution should be exercised when levofloxacin is coadministered with drugs that
affect the tubular renal secretion such as probenecid and cimetidine, especially in
renally impaired patients.
Other relevant information
Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin
were not affected to any clinically relevant extent when levofloxacin was
administered together with the following drugs: calcium carbonate, digoxin,
glibenclamide, ranitidine.
Effect of levofloxacin on other medicinal products
Ciclosporin
The half-life of ciclosporin was increased by 33% when coadministered with
levofloxacin.
Vitamin K antagonists
Increased coagulation tests (PT/INR) and/or bleeding, which may be severe, have
been reported in patients treated with levofloxacin in combination with a vitamin K
antagonist (e.g. warfarin). Coagulation tests, therefore, should be monitored in
patients treated with vitamin K antagonists (see section 4.4). Drugs known to prolong QT interval
Levofloxacin, like other fluoroquinolones, should be used with caution in patients
receiving drugs known to prolong the QT interval (e.g Class IA and III
antiarrhythmics, tricyclic antidepressants, macrolides and, antipsychotics) (see
section 4.4. QT interval prolongation)
Other relevant information
In a pharmacokinetic interaction study, levofloxacin did not affect the
pharmacokinetics of theophylline (which is a probe substrate for CYP1A2), indicating
that levofloxacin is not a CYP1A2 inhibitor.
Other forms of interactions
Food
There is no clinically relevant interaction with food. Levofloxacin 500mg & 750mg
Film-coated Tablets may therefore be administered regardless of food intake.

Pregnancy
There are limited amount of data from the use of levofloxacin in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to
reproductive toxicity (see section 5.3). However in the absence of human data and
due to that experimental data suggest a risk of damage by fluoroquinolones to the
weight-bearing cartilage of the growing organism, levofloxacin must not be used in
pregnant women (see sections 4.3 and 5.3).
Breastfeeding
Levofloxacin 500mg & 750mg Film-coated Tablets is contraindicated in breastfeeding
women. There is insufficient information on the excretion of levofloxacin in
human milk; however other fluoroquinolones are excreted in breast milk. In the
absence of human data and due to that experimental data suggest a risk of damage
by fluoroquinolones to the weight-bearing cartilage of the growing organism,
levofloxacin must not be used in breast-feeding women (see sections 4.3 and 5.3).
Fertility
Levofloxacin caused no impairment of fertility or reproductive performance in rats.

Some undesirable effects (e.g. dizziness/vertigo, drowsiness, visual disturbances)
may impair the patient's ability to concentrate and react, and therefore may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery).

The information given below is based on data from clinical studies in more than 8300
patients and on extensive post marketing experience.
Frequencies are defined using the following convention:
Very common (≥1/10)
Common (≥1/100 to <1/10)
Uncommon (≥1/1,000 to <1/100)
Rare (≥1/10,000 to <1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from the available data)
Within each frequency grouping, undesirable effects are presented in order of
decreasing seriousness. 

Other undesirable effects which have been associated with fluoroquinolone
administration include:
- attacks of porphyria in patients with porphyria
To Report Any Side Effects
• Saudi Arabia
The National Pharmacovigilance Centre (NPC):
• Fax: +966-11-205-7662
• Call NPC at +966-11-2038222, Ext 2317-2356-2340
• SFDA Call Center: 19999
• E-mail: npc.drug@sfda.gov.sa
• Website: www.sfda.gov.sa/npc
• Other GCC States:
• Please contact the relevant competent authority.

According to toxicity studies in animals or clinical pharmacology studies performed
with supra-therapeutic doses, the most important signs to be expected following
acute overdose of levofloxacin tablets are central nervous system symptoms such as
confusion, dizziness, impairment of consciousness and convulsive seizures,
increases in QT interval as well as gastro-intestinal reactions such as nausea and
mucosal erosions.
CNS effects including confusional state, convulsion, hallucination, and tremor have
been observed in post marketing experience.
In the event of overdose, symptomatic treatment should be implemented. ECG
monitoring should be undertaken, because of the possibility of QT interval
prolongation. Antacids may be used for protection of gastric mucosa. Haemodialysis,
including peritoneal dialysis and CAPD, are not effective in removing levofloxacin
from the body. No specific antidote exists

Pharmacotherapeutic group: quinolone antibacterials, fluoroquinolones, ATC code:
J01MA12
Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone class and is the
S (-) enantiomer of the racemic active substance ofloxacin.
Mechanism of action
As a fluoroquinolone antibacterial agent, levofloxacin acts on the DNA-DNA-gyrase
complex and topoisomerase IV.
PK/PD relationship
The degree of the bactericidal activity of levofloxacin depends on the ratio of the
maximum concentration in serum (Cmax) or the area under the curve (AUC) and the
minimal inhibitory concentration (MIC).
Mechanism of resistance
Resistance to levofloxacin is acquired through a stepwise process by target site
mutations in both type II topoisomerases, DNA gyrase and topoisomerase IV. Other
resistance mechanisms such as permeation barriers (common in Pseudomonas
aeruginosa) and efflux mechanisms may also affect susceptibility to levofloxacin.
Cross-resistance between levofloxacin and other fluoroquinolones is observed.
Due to the mechanism of action, there is generally no cross-resistance between
levofloxacin and other classes of antibacterial agents.
Breakpoints
The EUCAST recommended MIC breakpoints for levofloxacin, separating
susceptible from intermediately susceptible organisms and intermediately
susceptible from resistant organisms are presented in the below table for MIC testing
(mg/l).
EUCAST clinical MIC breakpoints for levofloxacin (version 2.0 2012-01-01): 

1. The breakpoints for levofloxacin relate to high dose therapy.
2. Low-level fluoroquinolone resistance (ciprofloxacin MICs of 0.12-0.5 mg/l) may
occur but there is no evidence that this resistance is of clinical importance in
respiratory tract infections with H. influenzae.
3. Strains with MIC values above the susceptible breakpoint are very rare or not yet
reported. The identification and antimicrobial susceptibility tests on any such isolate
must be repeated and if the result is confirmed the isolate must be sent to a
reference laboratory. Until there is evidence regarding clinical response for
confirmed isolates with MIC above the current resistant breakpoint they should be
reported resistant.
4. Breakpoints apply to an oral dose of 500 mg x 1 to 500 mg x 2 and an intravenous
dose of 500 mg x 1 to 500 mg x 2.
The prevalence of resistance may vary geographically and with time for selected
species and local information on resistance is desirable, particularly when treating
severe infections. As necessary, expert advice should be sought when the local
prevalence of resistance is such that the utility of the agent in at least some types of
infections is questionable.
Commonly susceptible species
Aerobic Gram-positive bacteria
Bacillus anthracis
Staphylococcus aureus methicillin-susceptible
Staphylococcus saprophyticus
Streptococci, group C and G
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes
Aerobic Gram- negative bacteria
Eikenella corrodens
Haemophilus influenzae
Haemophilus para-influenzae 

Klebsiella oxytoca
Moraxella catarrhalis
Pasteurella multocida
Proteus vulgaris
Providencia rettgeri
Anaerobic bacteria
Peptostreptococcus
Other
Chlamydophila pneumoniae
Chlamydophila psittaci
Chlamydia trachomatis
Legionella pneumophila
Mycoplasma pneumoniae
Mycoplasma hominis
Ureaplasma urealyticum
Species for which acquired resistance may be a problem
Aerobic Gram-positive bacteria
Enterococcus faecalis
Staphylococcus aureus methicillin-resistant#
Coagulase negative Staphylococcus spp
Aerobic Gram- negative bacteria
Acinetobacter baumannii
Citrobacter freundii
Enterobacter erogenes
Enterobacter cloacae
Escherichia coli
Klebsiella pneumoniae
Morganella morganii
Proteus mirabilis 

Providencia stuartii
Pseudomonas aeruginosa
Serratia marcescens
Anaerobic bacteria
Bacteroides fragilis
Inherently Resistant Strains
Aerobic Gram-positive bacteria
Enterococcus faecium
# Methicillin-resistant S. aureus are very likely to possess co-resistance to
fluoroquinolones, including levofloxacin.

Absorption
Orally administered levofloxacin is rapidly and almost completely absorbed with peak
plasma concentrations being obtained within 1-2 h. The absolute bioavailability is 99-
100%.
Food has little effect on the absorption of levofloxacin.
Steady state conditions are reached within 48 hours following a 500 mg once or
twice daily dosage regimen.
Distribution
Approximately 30-40% of levofloxacin is bound to serum protein. The mean volume
of distribution of levofloxacin is approximately 100l after single and repeated 500mg
doses, indicating widespread distribution into body tissues.
Penetration into tissues and body fluids:
Levofloxacin has been shown to penetrate into bronchial mucosa, epithelial lining
fluid, alveolar macrophages, lung tissue, skin (blister fluid), prostatic tissue and urine.
However, levofloxacin has poor penetration intro cerebro-spinal fluid.
Biotransformation
Levofloxacin is metabolised to a very small extent, the metabolites being desmethyllevofloxacin
and levofloxacin N-oxide. These metabolites account for <5% of the
dose and are excreted in urine. Levofloxacin is stereochemically stable and does not
undergo chiral inversion.
Elimination 

Following oral and intravenous administration of levofloxacin, it is eliminated
relatively slowly from the plasma (t½: 6 - 8 hours). Excretion is primarily by the renal
route (>85% of the administered dose).
The mean apparent total body clearance of levofloxacin following a 500 mg single
dose was 175 +/-29.2 ml/min.
There are no major differences in the pharmacokinetics of levofloxacin following
intravenous and oral administration, suggesting that the oral and intravenous routes
are interchangeable.
Linearity
Levofloxacin obeys linear pharmacokinetics over a range of 50 to 1000 mg.
Special populations
Subjects with renal insufficiency
The pharmacokinetics of levofloxacin are affected by renal impairment. With
decreasing renal function, renal elimination and clearance are decreased, and
elimination half-lives increased as shown in the table below:
Pharmacokinetics in renal insufficiency following single oral 500 mg dose  

Elderly subjects
There are no significant differences in levofloxacin pharmacokinetics between young
and elderly subjects, except those associated with differences in creatinine
clearance.
Gender differences
Separate analysis for male and female subjects showed small to marginal gender
differences in levofloxacin pharmacokinetics. There is no evidence that these gender
differences are of clinical relevance.

Non-clinical data reveal no special hazard for humans based on conventional studies
of single dose toxicity, repeated dose toxicity, carcinogenic potential and toxicity to
reproduction and development.
Levofloxacin caused no impairment of fertility or reproductive performance in rats
and its only effect on fetuses was delayed maturation as a result of maternal toxicity.Levofloxacin did not induce gene mutations in bacterial or mammalian cells but did
induce chromosome aberrations in Chinese hamster lung cells in vitro. These effects
can be attributed to inhibition of topoisomerase II. In vivo tests (micronucleus, sister
chromatid exchange, unscheduled DNA synthesis, dominant lethal tests) did not
show any genotoxic potential.
Studies in the mouse showed levofloxacin to have phototoxic activity only at very
high doses. Levofloxacin did not show any genotoxic potential in a
photomutagenicity assay, and it reduced tumour development in a
photocarcinogenity study.
In common with other fluoroquinolones, levofloxacin showed effects on cartilage
(blistering and cavities) in rats and dogs. These findings were more marked in young
animals.

Composition of Levofloxacin 500mg & 750mg Film-coated Tablets
Tablet Core
COLLOIDAL SILICONE DIOXIDE
CROSPOVIDONE
HYPROMELLOSE
MICROCRYSTALLINE CELLULOSE
SODIUM STEARYL FUMARATE
PURIFIED WATER
Tablet coating
INSTACOAT PEACH for Levofloxacin 500 mg film-coated tablets
INSTACOAT Yellow for Levofloxacin 750 mg film-coated tablets

Not applicable.

Store below 30°C, Store in the original package.

Levofloxacin 750 mg film-coated tablets: 5 Tablets per blister. 1 blister per Pack.

Any unused medicinal product or waste material should be disposed of in
accordance with local requirements, Keep out of the reach & sight of children