L-Stafloxin

Levofloxacin.

Each L-Stafloxin 250 film-coated tablet contains: Levofloxacin (as levofloxacin hemihydrate) 250 mg.
Each L-Stafloxin 500 film-coated tablet contains: Levofloxacin (as levofloxacin hemihydrate) 500 mg.
Excipients q.s. to 1 tablet.
Excipients/Inactive Ingredients: Microcrystalline cellulose, hypromellose, crospovidone, sodium stearyl fumarate, macrogol 6000, titanium dioxide, talc, red ferric oxide.

L-Stafloxin 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 L-Stafloxin 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.
L-Stafloxin 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.

L-Stafloxin is administered once or twice daily. The dosage depends on the type and severity of the infection and the susceptibility of the presumed causative pathogen.
L-Stafloxin 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: Dosage in patients with normal renal function (creatinine clearance > 50 ml/min): See Table 1.

Click on icon to see table/diagram/image

Special populations: Renal impairment (creatinine clearance ≤ 50 ml/min): See Table 2.

Click on icon to see table/diagram/image

Hepatic impairment: No adjustment of dosage is required since levofloxacin is not metabolised to any relevant extent by the liver and is mainly excreted by the kidneys.
Elderly: No adjustment of dose is required in the elderly, other than that imposed by consideration of renal function.
Paediatric population: Levofloxacin is contraindicated in children and growing adolescents.
Method of administration: For oral use.
L-Stafloxin 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. L-Stafloxin 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.

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 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.

Levofloxacin must not be used: in patients hypersensitive to the active substance or other quinolones or to any of the excipients in the formula; 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. 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. 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. 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.
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. 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 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. In case of convulsive seizures, 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.
Hypersensitivity reactions: Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g. angioedema up to anaphylactic shock), occasionally following the initial dose. 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. 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.
Prevention of photosensitisation: Photosensitisation has been reported with levofloxacin. 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.
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. 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 anti-arrhythmics, 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.
Exacerbation of myasthenia gravis: Fluoroquinolones have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Post-marketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid fluoroquinolones in patients with known history of myasthenia gravis.
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. 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.
Peripheral neuropathy: Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones, including levofloxacin. Symptoms may occur soon after initiation of levofloxacin and may be irreversible. Levofloxacin should be discontinued immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness, or other alterations in sensations including light touch, pain, temperature, position sense and vibratory sensation.
Vision disorders: If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.
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.
Disabling and potentially irreversible serious adverse reactions including tendinitis and tendon rupture, peripheral neuropathy, and central nervous system effects: Fluoroquinolones, including levofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting levofloxacin. Patients of any age or without pre-existing risk factors have experienced these adverse reactions.
Discontinue levofloxacin immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including levofloxacin, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.
Because fluoroquinolones, including levofloxacin, have been associated with serious adverse reactions, reserve levofloxacin for use in patients who have no alternative treatment options for the following indications: Uncomplicated urinary tract infection; Acute bacterial exacerbation of chronic bronchitis; Acute bacterial sinusitis.
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 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.
Effects on ability to drive and use machines: 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).

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. However, in the absence of human data and due to the experimental data that suggest a risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism, levofloxacin must not be used in pregnant women.
Breast-feeding: Levofloxacin is contraindicated in breast-feeding 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 the experimental data that 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.

The information given below is based on data from clinical studies 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.
Infections and infestations: Uncommon: Fungal infection including Candida infection, pathogen resistance.
Blood and lymphatic system disorders: Uncommon: Eosinophilia, leukopenia.
Rare: Neutropenia, thrombocytopenia.
Not known: Haemolytic anaemia, pancytopenia, agranulocytosis.
Immune system disorders: Rare: Angioedema, hypersensitivity.
Not known: Anaphylactic shock, anaphylactoid shock (Anaphylactic and anaphylactoid reactions may sometimes occur even after the first dose).
Metabolism and nutrition disorders: Uncommon: Anorexia.
Rare: Hypoglycaemia, particularly in diabetic patients.
Not known: Hyperglycaemia, hypoglycaemic coma.
Psychiatric disorders: Common: Insomnia.
Uncommon: Confusional state, anxiety, nervousness.
Rare: Psychotic reactions (with e.g. hallucination, paranoia), depression, agitation, abnormal dreams, nightmares.
Not known: Psychotic disorders with self-endangering behaviour including suicidal 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: Visual disturbances such as blurred vision.
Not known: Transient vision loss, uveitis.
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 torsades de pointes (reported predominantly in patients with risk factors for QT prolongation), electrocardiogram QT prolonged.
Vascular disorders: Rare: Hypotension.
Respiratory, thoracic and mediastinal disorders: Uncommon: Dyspnoea.
Not known: Bronchospasm, pneumonitis, allergic.
Gastrointestinal disorders: Common: Diarrhoea, vomiting, nausea.
Uncommon: Abdominal pain, dyspepsia, flatulence, constipation.
Not known: Diarrhoea-haemorrhagic which in very rare cases may be indicative of enterocolitis, including pseudomembranous colitis, pancreatitis.
Hepatobiliary disorders: Common: Hepatic enzyme increased (ALT/AST, alkaline phosphatase, GGT).
Uncommon: Blood bilirubin increased.
Not known: Jaundice and severe liver injury, including cases with fatal acute liver failure, primarily in patients with severe underlying diseases, hepatitis.
Skin and subcutaneous tissue disorders (Mucocutaneous reactions may sometimes occur even after the first dose): Uncommon: Rash, pruritus, urticarial, hyperhidrosis.
Not known: Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, 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 special 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 increased.
Rare: Renal failure acute (e.g. due to interstitial nephritis).
General disorders and administration site conditions: Uncommon: Asthenia.
Rare: Pyrexia.
Not known: Pain (including pain in back, chest, and extremities).
Other undesirable effects which have been associated with fluoroquinolone administration include attacks of porphyria in patients with porphyria.

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. 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 levofloxacin administration. Calcium salts have a minimal effect on the oral absorption of levofloxacin.
Sucralfate: The bioavailability of levofloxacin 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 administration.
Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs: 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 and probenecid.
Caution should be exercised when levofloxacin is co-administered with drugs that affect the tubular renal secretion such as probenecid and cimetidine, especially in renally impaired patients.
Effect of levofloxacin on other medicinal products: Ciclosporin: The half-life of ciclosporin 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 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).
Food: There is no clinically relevant interaction with food. Levofloxacin may therefore be administered regardless of food intake.

Store in a well-closed container, in a dry place. Protect from light. Do not store above 30°C.

Quinolones

J01MA12 - levofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.

P₁S₁S₃