Levaquin is indicated in adults for the treatment of the following infections (see sections 4.4 and
5.1):
• Acute bacterial sinusitis
• Acute exacerbations of chronic bronchitis
• Community-acquired pneumonia
• Complicated skin and soft tissue infections
For the above-mentioned infections Levaquin should be used only when it is considered
inappropriate to use antibacterial agents that are commonly recommended for the initial treatment
of these infections.
• Pyelonephritis and complicated urinary tract infections (see section 4.4)
• Chronic bacterial prostatitis
• Uncomplicated cystitis (see section 4.4)
• Inhalation Anthrax: postexposure prophylaxis and curative treatment (see section 4.4)
Levaquin 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.
 

Levaquin tablets are administered once or twice daily. The dosage depends on the type and
severity of the infection and the susceptibility of the presumed causative pathogen.
Levaquin 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 Levaquin :
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
Levaquin is contraindicated in children and growing adolescents (see section 4.3).
Method of administration
Levaquin 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. Levaquin 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).
 

Levofloxacin tablets must not be used: • in patients hypersensitive to levofloxacin or other quinolones or any of the excipients listed in section 6.1, • in patients with epilepsy, • in patients with history of tendon disorders related to fluoroquinolone administration, • in children or growing adolescents, • during pregnancy, • in breast-feeding women.

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.
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 pre-existing 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.
Tendinitis and tendon rupture
Tendinitis may rarely occur. It most frequently involves the Achilles tendon and may lead to
tendon rupture. Tendonitis and tendon rupture, sometimes bilateral, may occur within 48 hours
of starting treatment with levofloxacin and have been reported up t o several months after
discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in patients aged
over 60 y ears, in patients receiving daily doses of 1000 mg and in patients using corticosteroids.
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.
All patients should consult their physician if they experience symptoms of tendinitis. If tendinitis
is suspected, treatment with levofloxacin must be halted immediately, and appropriate treatment
(e.g. immobilisation) must be initiated for the affected tendon (see sections 4.3 and 4.8).
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 Levaquin 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 bullous reactions
Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal
necrolysis have been reported with levofloxacin (see section 4.8). Patients should be advised to
contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions
occur.
Dysglycaemia
As with all quinolones, disturbences in blood glucose, including both hypoglycaemia and
hyperglycaemia have been reported, 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 (see section 4.8).
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 self-endangering behavioursometimes 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. hypokalemia, hypomagnesemia)
- cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
Elderly patinets and women may be more sensitive to QTc-prolonging medications. Therefore,
caution should be taken when using fluoroquinolones, including levofloxacin, in these
populations.
(See section 4.2 Elderly, 4.5, 4.8, and 4.9).
Peripheral neuropathy
_ Peripheral neuropathy (serious nerve damage) is an identified risk of fluoroquinolone drugs
taken by mouth or by injection.
_ (Peripheral neuropathy symptoms in the arms or legs such as pain, burning, tingling,
numbness, weakness or a change in sensation to light touch, pain, or temperature).
_ Peripheral neuropathy can occur at any time during treatment with fluoroquinolones (may occur
soon after these drugs are taken) and can last for months to years after the drug is stopped
or be permanent.
_ If a patient develops symptoms of peripheral neuropathy, the fluoroquinolone should be stopped
and the patient should be switched to another non- fluoroquinolone antibacterial drug, unless the
benefit of continued treatment with a fluoroquinolone outweighs the risk.
Cases of hepatic necrosis up t o 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 eye 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 non-susceptible
organisms. If superinfection occurs during therapy, appropriate measures should be taken.
Interference with laboratory tests
In patients treated with levofloxacin, determination of opiates in urine may give false-positive
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.
 

Effect of other medicinal products on Levaquin
Iron salts, zinc salts, magnesium- or aluminium-containing antacids, didanosine
Levofloxacin absorption is significantly reduced when iron salts, or magnesium- or aluminiumcontaining antacids, or didanosine (only didanosine formulations with aluminium or magnesium
containing buffering agents) are administered concomitantly with Levaquin 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 cations 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 Levaquin tablet administration (see section 4.2). Calcium salts
have a minimal effect on the oral absorption of levofloxacin.
Sucralfate
The bioavailability of Levaquin tablets is significantly reduced when administered together with
sucralfate. If the patient is to receive both sucralfate and Levaquin , it is best to administer
sucralfate 2 hours after the Levaquin tablet 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 anti-inflammatory 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 Levaquin 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 the 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, 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. Levaquin tablets may therefore be
administered regardless of food intake.
 

(Pregnancy Category C)
Levofloxacin was not teratogenic in rats at oral doses as high as 810 m g/kg/day which correspond
to 9.4 times the highest recommended human dose based upon relative body surface area, or at
intravenous doses as high as 160 mg/kg/day corresponding to 1.9 times the highest
recommended human dose based upon r elative body surface area. The oral dose of 810 mg/kg/day
to rats caused decreased fetal body weight and increased fetal mortality. No teratogenicity was
observed when rabbits were dosed orally as high as 50 m g/kg/day which corresponds to 1.1
times the highest recommended human dose based upon relative body surface area, or when
dosed intravenously as high as 25 m g/kg/day, corresponding to 0.5 t imes the highest
recommended human dose based upon relative body surface area.
There are, however, no a dequate and well-controlled studies in pregnant women. Levaquin should
be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Breast-feeding
Levaquin is contraindicated in breast-feeding women. There is insufficient information on t he
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.
a. Summary of the safety profile
Serious and Otherwise Important Adverse Reactions
The following serious and otherwise important adverse drug reactions are discussed in greater
detail in other sections of labeling:
• Tendon Effects [see WARNINGS AND PRECAUTIONS]
• Exacerbation of Myasthenia Gravis [see WARNINGS AND PRECAUTIONS]
• Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
• Other Serious and Sometimes Fatal Reactions [see WARNINGS AND PRECAUTIONS]
• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Central Nervous System Effects [see WARNINGS AND PRECAUTIONS]
• Clostridium difficile-Associated Diarrhea [see WARNINGS AND PRECAUTIONS]
• Peripheral Neuropathy that may be irreversible [see WARNINGS AND
PRECAUTIONS]
• Prolongation of the QT Interval [see WARNINGS AND PRECAUTIONS]
• Musculoskeletal Disorders in Pediatric Patients [see WARNINGS AND
PRECAUTIONS]
• Blood Glucose Disturbances [see WARNINGS AND PRECAUTIONS]
• Photosensitivity/Phototoxicity [see WARNINGS AND PRECAUTIONS]
• Development of Drug Resistant Bacteria [see WARNINGS AND PRECAUTIONS]
Hypotension has been associated with rapid or bolus intravenous infusion of LEVAQUIN .
LEVAQUIN should be infused slowly over 60 to 90 minutes, depending on dosage [see
DOSAGE AND ADMINISTRATION].
Crystalluria and cylindruria have been reported with quinolones, including LEVAQUIN .
Therefore, adequate hydration of patients receiving LEVAQUIN should be maintained to prevent
the formation of a highly concentrated urine [see DOSAGE ANDADMINISTRATION].
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials
of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to LEVAQUIN in 7537 patients in 29 pooled Phase 3
clinical trials. The population studied had a mean age of 50 years (approximately 74% of the
population was < 65 years of age), 50% were male, 71% were Caucasian, 19% were Black.
Patients were treated with Levaquin for a w ide variety of infectious diseases [see INDICATIONS
AND USAGE]. Patients received Levaquin doses of 750 mg once daily, 250 mg once daily, or
500 mg once or twice daily. Treatment duration was usually 3–14 days, and the mean number
of days on therapy was 10 days.
The overall incidence, type and distribution of adverse reactions was similar in patients receiving
Levaquin doses of 750 m g once daily, 250 m g once daily, and 500 m g once or twice daily.
Discontinuation of Levaquin due to adverse drug reactions occurred in 4.3% of patients overall,
3.8% of patients treated with the 250 mg and 500 mg doses and 5.4% of patients treated with the
750 mg dose. The most common adverse drug reactions leading to discontinuation with the 250
and 500 m g doses were gastrointestinal (1.4%), primarily nausea (0.6%); vomiting (0.4%);
dizziness (0.3%); and headache (0.2%). The most common adverse drug reactions leading to
discontinuation with the 750 m g dose were gastrointestinal (1.2%), primarily nausea (0.6%),
vomiting (0.5%); dizziness (0.3%); and headache (0.3%).
Adverse reactions occurring in ≥ 1% of Levaquin-treated patients and less common adverse
reactions, occurring in 0.1 to < 1% of Levaquin-treated patients, are shown in below tables. The
most common adverse drug reactions (≥ 3%) are nausea, headache, diarrhea, insomnia,
constipation, and dizziness.
b. Tabulated list of adverse reactions
Frequencies are defined using the following convention: very common (≥1/10), common (≥1/100,
<1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), not known
(cannot be estimated from the available data).
Common ( ≥ 1%) Adverse Reactions Reported in Clinical Trials with Levaquin

 

According to toxicity studies in animals or clinical pharmacology studies performed with supratherapeutic doses, the most important signs to be expected following acute overdose of Levaquin
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 t he 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):
Pathogen                                                          Susceptible                                        Resistant
 Enterobacteriacae                                          ≤1 mg/l                                                 >2 mg/l
Pseudomonas spp.                                          ≤1 mg/l                                                 >2 mg/l
Acinetobacter spp.                                         ≤1 mg/l                                                  >2 mg/l
Staphylococcus spp.                                       ≤1 mg/l                                                  >2 mg/l
S.pneumoniae1                                                ≤2 mg/l                                                  >2 mg/l
Streptococcus A,B,C,G                                    ≤1 mg/l                                                   >2 mg/l
H. influenzae2, 3                                              ≤1 mg/l                                                   >1 mg/l
M. catarrhalis 3                                                ≤1 mg/l                                                   >1 mg/l
Non-species related breakpoints4               ≤1 mg/l                                                   >2 mg/l

1. The breakpoints for levofloxacin relate to high dose therapy.
2. Low-level fluoroquinolones resitance (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 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 aerogenes
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 hour s following a 500 m g 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 100 l after single and repeated
500 mg 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 into cerebro-spinal fluid.
Biotransformation
Levofloxacin is metabolised to a very small extent, the metabolites being desmethyl-levofloxacin
and levofloxacin N-oxide. These metabolites account for < 5 % of the dose 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 h). 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

Clcr [ml/min]	< 20	20 - 49	50 - 80
ClR [ml/min]	13	26	57
t1/2 [h]	35	27	9

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 foetuses 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.
 

6.1 List of excipient(s)
Levaquin 500 mg film-coated tablets contain the following excipients for a weight of 700 mg:
Tablet core:
Crospovidone, Hypromellose, Microcrystalline cellulose (Avicel PH 101), Sodium Stearyl
Fumarate.
Tablet coating:
Opadry Pink 03F14895
 

Not applicable.
 

4 years

Store below 30 °C.
 

PVC-PVDC/Aluminum blisters containing film-coated tablets.
Pack size for 500 mg tablets: 5 tablets/box as commercially available.
 

A score line allows adaptation of the dose in patients with impaired renal function.
As for all medicines, any unused medicinal product should be disposed of accordingly and in
compliance with local environmental regulations.