LEVOFLOXACIN KABI

Levofloxacin solution for infusion is administered by slow intravenous infusion once or twice daily. The dosage depends on the type and severity of the infection and the susceptibility of the presumed causative pathogen. Treatment with Levofloxacin after initial use of the intravenous preparation may be completed with an appropriate oral presentation as considered appropriate for the individual patient.

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) Indication Daily dose regimen (according to severity) Total duration of treatment1 (according to severity) 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 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 1 Treatment duration includes intravenous plus oral treatment.

The time to switch from intravenous to oral treatment depends on the clinical situation but is normally 2 to 4 days. Special populations Impaired renal function (creatinine clearance ≤50 ml/min) Dosage Regimen 250 mg/24h 500 mg/24 h 500 mg/ 12 h Creatinine clearance 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 (including haemodialysis and CAPD) 1 then: 125 mg/48 h then: 125 mg/24 h then: 125 mg/24 h 1No additional doses are required after haemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

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. 4 “Tendinitis and tendon rupture” and “QT interval prolongation”).

3). Method of administration Levofloxacin solution for infusion is only intended for slow intravenous infusion; it is administered once or twice daily. 6.

The information given below is based on data from clinical studies in more than 8300 patients and on extensive post marketing experience. Frequencies in this table are defined using the following convention: very common ( 1/10), common ( 1/100, <1/10), uncommon ( 1/1000 , <1/100), rare ( 1/10000 to <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. g. g. g. g. due to interstitial nephritis) General disorders and administration site conditions* Applies to iv form only: Infusion site reaction (pain, reddening) Asthenia Pyrexia Pain (including pain in back, chest, and extremities) a Anaphylactic and anaphylactoid reactions may sometimes occur even after the first dose.

4). A range of psychiatric symptoms may occur as part of these side effects, which may include, but are not necessarily limited to, sleep disorders, anxiety, panic attacks, confusion, or depression. There are no pharmacological treatments established to be effective treatments of the symptoms of long lasting or disabling side effects associated with fluoroquinolones.

The frequency of these prolonged, disabling and potentially irreversible serious drug reactions cannot be estimated with precision using available data, but the reporting incidence from adverse drug reaction reports indicates the frequency is at minimum between 1/1,000 and 1/10,000 (corresponding to the Rare frequency category).

4). Other undesirable effects which have been associated with fluoroquinolone administration […]

8). 3). Aortic aneurysm and dissection, and heart valve regurgitation/incompetence Epidemiologic studies report an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and of aortic and mitral valve regurgitation after intake of fluoroquinolones.

8). g. g. g. infective endocarditis). The risk of aortic aneurysm and dissection, and their rupture may also be increased in patients treated concurrently with systemic corticosteroids. In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.

Patients should be advised to seek immediate medical attention in case of acute dyspnoea, new onset of heart palpitations, or development of oedema of the abdomen or lower extremities. Acute pancreatitis Acute pancreatitis may be observed in patients taking levofloxacin.

Patients should be informed of the characteristic symptoms of acute pancreatitis. Patients experiencing nausea, malaise, abdominal discomfort, acute abdominal pain or vomiting should have a prompt medical evaluation. If acute pancreatitis is suspected, levofloxacin should be discontinued; if confirmed, levofloxacin should not be restarted.

8). 8). If any of these blood disorders is suspected, blood counts should be monitored. In case of abnormal results, discontinuation of treatment with levofloxacin should be considered. Risks of resistance 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).

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 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.

Infusion Time The recommended infusion time of at least 30 minutes for 250 mg or 60 minutes for 500mg Levofloxacin solution for infusion should be observed. It is known for ofloxacin, that during infusion tachycardia and a temporary decrease in blood pressure may develop.

In rare cases, as a consequence of a profound drop in blood pressure, circulatory collapse may occur. Should a conspicuous drop in blood pressure occur during infusion of levofloxacin, (l-isomer of ofloxacin) the infusion must be halted immediately.

85 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. Prolonged, disabling and potentially irreversible serious adverse drug reactions Cases of prolonged (continuing for months or years), disabling and potentially irreversible serious adverse drug reactions affecting different, sometimes multiple, body systems (including musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk factors.

There are no pharmacological treatments established to be effective treatments of the symptoms of long lasting or disabling side effects associated with fluoroquinolones. 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, so that symptoms can be appropriately investigated and to avoid further exposure which could potentially worsen adverse reactions.

Tendinitis and 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 […]

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.