LEVOBAT 500 is indicated in adults for the treatment of the following infections:
• Acute bacterial sinusitis.
• Acute exacerbations of chronic bronchitis.
• Community-acquired pneumonia.
• Complicated skin and soft tissue infections.
For the above-mentioned infections LEVOBAT 500 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.
• Chronic bacterial prostatitis .

• Uncomplicated cystitis.
• Inhalation Anthrax: post exposure prophylaxis and curative treatment.
LEVOBAT 500 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.

LEVOBAT 500 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.
Posology
The following dose recommendations can be given for LEVOBAT 500 Tablets:
Dosage in patients with normal renal function (creatinine clearance > 50 ml/min)

Acute bacterial sinusitis
500 mg once daily
10 - 14 days

Acute bacterial exacerbations of chronic
bronchitis
500 mg once daily
7 - 10 days

Community
acquired pneumonia 500 mg once or twice daily
7 - 14 days

Pyelonephritis
500 mg once daily
7-10 days

Complicated urinary tract infections
500 mg once daily
7 - 14 days

Uncomplicated cystitis
250 mg once daily
3 days

Chronic bacterial prostatitis. 500 mg once daily
28 days

Complicated skin and soft tissue infections
500 mg once
or twice
daily
7 - 14 days

Inhalation Anthrax
500 mg once daily
8 weeks

 

Special populations
Impaired renal function (creatinine clearance ≤ 50ml/min)

Creatinine clearance
Dose regimen
                                            250 mg / 24 h                                         500 mg / 24 hrs.                                       500 mg / 12 hrs.

                                     first dose: 250 mg                                      first dose: 500 mg                                     first dose: 500 mg

50-20 ml/min            then: 125 mg / 24 h                                     then: 250 mg/24 h                                     then: 250 mg/12 h

19-10 ml/min             then: 125 mg / 48 h                                     then: 125 mg/24 h                                      then: 125 mg/12 h

< 10 ml/min (includinghaemodialysis and CAPD)

                                  1 then: 125 mg / 48 h                                     then: 125 mg/24 h                                     then: 125 mg/24 h

 

1 No additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
Impaired liver function
No adjustment of dose is required since levofloxacin is not metabolized 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”).
Pediatric population
LEVOBAT 500 Tablets is contraindicated in children and growing adolescents.
Method of administration:

LEVOBAT 500 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.
LEVOBAT 500 Tablets should be taken at least two hours before or after iron salts, zinc salts, magnesium- or aluminum-containing antacids, or didanosine (only didanosine formulations with aluminum or magnesium containing buffering agents), and sucralfate administration, since reduction of absorption can occur.

Levofloxacin tablets must not be used:  I n patients hypersensitive to levofloxacin or other quinolones or any of the excipients listed in section 6.1 6.1.  I n patients with epilepsy epilepsy.  I n p atients with history of tendon disorders related to fluoroquinolone administration administration.  I n children or growing adolescents  D uring pregnancy and breast feeding.

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.
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, sometimes bilateral, may occur within 48 hours of starting treatment with levofloxacin and have been reported up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in patients aged over 60 years, 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 section 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 substance 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 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, disturbances 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 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
Peripheral sensory neuropathy and peripheral sensory motor neuropathy have been reported in patients receiving fluoroquinolones, including levofloxacin, which can be rapid in its onset (see section 4.8). Levofloxacin should be discontinued if the patient experiences symptoms of neuropathy in order to prevent the development of an irreversible condition.
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 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.
Levofloxacin 500mg Film-coated Tablets contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Effect of other medicinal products on LEVOBAT 500 Tablets
-Iron salts, zinc salts, magnesium- or aluminium-containing antacids, didanosine:
-Levofloxacin absorption is significantly reduced when iron salts, or magnesium- or aluminum-containing antacids, or didanosine (only didanosine formulations with aluminum or magnesium containing buffering agents) are administered concomitantly with LEVOBAT 500 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 aluminum-containing antacids, or didanosine (only didanosine formulations with aluminum or magnesium containing buffering agents) should not be taken 2 hours before or after LEVOBAT 500 tablets administration. Calcium salts have a minimal effect on the oral absorption of levofloxacin.
-Sucralfate:
The bioavailability of LEVOBAT 500 tablets is significantly reduced when administered together with sucralfate. If the patient is to receive both sucralfate and LEVOBAT 500 tablets, it is best to administer sucralfate 2 hours after the LEVOBAT 500 tablets administration.
-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 co-administered with drugs that affect the tubular renal secretion such as probenecid and cimetidine, especially in renal impaired patients.
-Other relevant information
Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin was not affected to any clinically relevant extent when levofloxacin was administered together with the following drugs: calcium carbonate, digoxin, glibenclamide, ranitidine.

Effect of LEVOBAT 500 tablets on other medicinal products
-Cyclosporine
The half-life of cyclosporine was increased by 33% when co-administered 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.
-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 anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics.

-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. LEVOBAT 500 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 re spect to reproductive toxicity . However in the
absence of human data and due to that experimenta l data suggest a risk of damage by fluoroquinolones
to the weight bearing cartilage of the growing organism, LEVOBAT 500 tablets mus t not be used in
pregnant women
Nursing Mothers
LEVOBAT 500 tablets are contraindicated in breast feeding women. There is i nsufficient 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 be aring cartilage of the growing organism, levofloxacin must not be
used in breast feeding women
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, <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).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness

Infections and infestations
Uncommon: Fungal infection
Including Candida
Pathogen, resistance

Blood and lymphatic system disorders

Uncommon: Leukopenia,
Eosinophilia
Rare: Thrombocytopenia Neutropenia
Not known: Pancytopenia, Agranulocytosis, Hemolytic anemia

Immune system disorders
Rare:Angioedema Hypersensitivity
Not known: Anaphylactic shock

Metabolism and nutrition disorders
Rare:Anorexia
Hypoglycemia
Not known:particularly in diabetic patients
Hyperglycemia
Hypoglycemic coma

Psychiatric disorders
Common: Insomnia
Uncommon: Anxiety
Confusional state
Nervousness
Rare: Psychotic reactions (with e.g. hallucination, paranoia) Depression Agitation Abnormal dreams Nightmares
Not known: Psychotic disorders with self endangering
behaviour includingsuicidal ideation or suicide attempt

Nervous system disorders
common: Headache
Dizziness
uncommon: Somnolence
Tremor
Dysgeusia
Rare: Convulsion, Paraesthesia
Not known: Peripheral sensory neuropathy, Peripheral sensory motor, neuropathy, Parosmia including anosmia, Dyskinesia, Extrapyramidal disorder
Ageusia , Syncope Benign intracranial hypertension

Eye disorders
Rare: Blurred vision
not known: Transient vision loss

Ear and Labyrinth disorders
uncommon:Vertigo
rare:Tinnitus
not known: Hearing loss
Hearing impaired

Cardiac disorders
rare: Tachycardia,
Palpitation
not known: Ventricular tachycardia,
which may result in
cardiac arrest Ventricular
arrhythmia and torsade
de pointes (reported
predominantly in patients
with risk factors of QT
prolongation),
Electrocardiogram QT
prolonged

Vascular disorders
rare: Hypotension

Respiratory, thoracic and mediastinal
disorders
uncommon: Dyspnea
not known: Bronchospasm,
Pneumonitis allergic

astrointestinal disorders
common: Diarrhea
Vomiting
Nausea
uncommon:Abdominal pain
Dyspepsia
Flatulence
Constipation
not known: Diarrhea –hemorrhagic which in very rare cases may be indicative of enterocolitis, including pseudomembranous colitis and Pancreatitis

Hepato-biliary disorders
common:Hepatic enzyme increased (ALT/AST, alkaline, phosphatase, GGT)
uncommon:Blood bilirubin increased
rare:Jaundice and severe liver injury, including cases with fatal acute liver failure, primarily in patients with severe underlying diseases Hepatitis

Skin and subcutaneous tissue disordersb
uncommon:Rash
Pruritus
Urticaria
Hyperhidrosis

rare:Toxic epidermal necrolysis
Stevens-Johnson syndrome
Erythema multiform
Photosensitivity reaction
Leukocytoclastic vasculitis , Stomatitis

Musculoskeletal and connective tissue disorders
uncommon:Arthralgia
Myalgia
rare:Tendon disorder including tendinitis (e.g. Achilles tendon)
Muscular weakness which may be of importance in patients with myasthenia gravis
not known:Rhabdomyolysis
Tendon rupture (e.g. Achilles tendon), Ligament rupture
Muscle rupture
Arthritis

Renal and urinary disorders
uncommon:Blood creatinine
rare: increased Renal failure acute (e.g. due to intersti tial nephritis)

General disorders and administration site conditions
uncommon: Asthenia
rare: Pyrexia
not known: Pain (including pain in
back, chest, and
extremities)

 

b Mucocutaneous reactions may sometimes occur even after the first dose
Other undesirable effects which have been associated with fluoroquinolone administration include:
 Attacks of porphyria in patients with porphyria.
-
To report any side effect(s) in Saudi Arabia;
-
National Pharmacovigilance Center (NPC)
 Fax: +966 11 205 7662
 Toll free number: 8002490000 / 19999
 E mail: npc.drug@sfda.gov.sa
 Website: https://ade.sfda.gov.sa

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 LEVOBAT 500 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 confusion, 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. Hemodialysis, 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 th
e 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.

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 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 metabolized 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 stereo chemically 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
Cl                                                  cr [ml/ < 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 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 photo mutagenicity assay, and it reduced tumor development in a photo carcinogenetic 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.

Tablet core:
 Pregelatinised Starch.
 Crospovidone.
 Microcrystalline cellulose.
 Lactose anhydrous DC.
 Magnesium stearate.
Tablet coat:
 Hydoxypropyl methylcellulose.(HPMC 15 cp)
 Opadry red OY-S-35002.

Not applicable.

24 months

Do not store above 30°C.

Carton box containing one PVC /PVDC Aluminium blister (of 5 coated tablets ) and a

No special requirements.