PRODUCT LEVOFLOX 5 mg/ml solution for infusion 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each 100 ml vial contains: Levofloxacin hemihydrate 512.42 mg (Equivalent to Levofloxacin 500mg). Excipients with known effect: 100ml of solution for infusion contains 354 mg of sodium. For the full list of excipients, see section 6.1 3 PHARMACEUTICAL FORM Solution for I.V. infusion. Clear yellow solution free from particulate matter. 4 CLINICAL PARTICULARS 4.1 Therapeutic indications LEVOFLOX solution for infusion is indicated in adults for the treatment of the following infections (see sections 4.4 and 5.1): - Acute pyelonephritis and complicated urinary tract infections (see section 4.4) - Chronic bacterial prostatitis - Inhalation Anthrax: postexposure prophylaxis and curative treatment (see section 4.4). In the below-mentioned infections LEVOFLOX should be used only when it is considered inappropriate to use other antibacterial agents that are commonly recommended for the treatment of these infections. - Community-acquired pneumonia - Complicated skin and soft tissue infections - LEVOFLOX solution for infusion should not be used in the following indications: • To treat infections that might get better without treatment or are not severe (such as throat infections); • To treat non-bacterial infections, e.g. non-bacterial (chronic) prostatitis; • For preventing traveller’s diarrhoea or recurring lower urinary tract infections (urine infections that do not extend beyond the bladder); To treat mild or moderate bacterial infections unless other antibacterial medicines commonly recommended for these infections cannot be used. Consideration should be given to official guidance on the appropriate use of antibacterial agents. 4.2 Posology and method of administration LEVOFLOX 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 LEVOFLOX after initial use of the intravenous preparation may be completed with an appropriate oral presentation according to the SPC for the film-coated tablets and 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 LEVOFLOX: 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 Acute 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 ≤50ml/min) Dose regimen 250 mg/24 h 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. Elderly population No adjustment of dosage is required in the elderly, other than that imposed by consideration of renal function (See section 4.4 "tendonitis and tendon rupture" and "QT interval prolongation"). Paediatric population LEVOFLOX is contraindicated in children and growing adolescents (see section 4.3). Method of administration LEVOFLOX solution for infusion is only intended for slow intravenous infusion; it is administered once or twice daily. The infusion time must be at least 30 minutes for 250 mg or 60 minutes for 500 mg LEVOFLOX solution for infusion (see section 4.4). LEVOFLOX solution for infusion should be used immediately after perforation of the rubber stopper in order to prevent any bacterial contamination. No protection from light is necessary during infusion. This medicinal product is for single use only . For incompatibilities see section 6.2 and compatibility with other infusion solutions see section 6.6. 4.3 Contraindications Levofloxacin solution for infusion must not be used: - in patients hypersensitive to levofloxacin or any other quinolone 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 breastfeeding women. 4.4 Special warnings and precautions for use The use of Levofloxacin should be avoided in patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone containing products (see section 4.8). Treatment of these patients with Levofloxacin should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment (see also section 4.3). Risks of resistance Methicilin-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 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. Prolonged, disabling and potentially irreversible serious adverse drug reactions Very rare cases of prolonged (continuing months or years), disabling and potentially irreversible serious adverse drug reactions affecting different, sometimes multiple, body systems (musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk factors. Levofloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should be advised to contact their prescriber for advice. Infusion Time The recommended infusion time of at least 30 minutes for 250 mg or 60 minutes for 500 mg LEVOFLOX 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. Tendonitis 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 treatment with quinolones and fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in older patients aged over 60 years, patients with renal impairment, patients with solid organ transplants, patients receiving daily doses of 1000 mg, and those treated concurrently with corticosteroids. Tendinitis was reported in patients with CF receiving Levoflox as an uncommon adverse reaction during clinical trials. Therefore, concomitant use of corticosteroids should be avoided. At the first sign of tendinitis (e.g. painful swelling, inflammation) the treatment with levofloxacin should be discontinued, and alternative treatment should be considered. The affected limb(s) should be appropriately treated (e.g. immobilisation). Corticosteroids should not be used if signs of tendinopathy occur. Myoclonus Cases of myoclonus have been reported in patients receiving levofloxacin (see section 4.8). The risk of myoclonus is increased in older patients, and in p
