Levofloxacin Fresenius

/ Neopharm (Israel) 1996 Ltd.

Levofloxacin Fresenius 5mg/ml 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 Fresenius 5mg/ml 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.
See prescribing information for full details.

For adults treatment of the following infections:
* Acute pyelonephritis and complicated urinary tract infections
* Chronic bacterial prostatitis
Levofloxacin 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

* Hypersensitive to levofloxacin or any other quinolone and any
of the excipients
* Epilepsy
* History of tendon disorders related to fluoroquinolone administration
* Children or adolescents
* Pregnancy
* Breast-feeding

The use of this medical product should be avoided in patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone containing products. Treatment should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment.
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. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones. 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 congenital heart valve disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissection or heart valve disease, or in presence of other risk factors or conditions predisposing
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. Caution should be exercised in patients with a history of pancreatitis.
Infusion time
The recommended infusion time of at least 30 minutes for 250 mg or 60 minutes for 500 mg Levofloxacin. 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, the infusion must be halted immediately.
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 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 patients receiving daily doses of 1,000 mg levofloxacin in older patients, patients with renal impairment, patients with solid organ transplants, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.
At the first sign of tendinitis (e.g. painful swelling, inflammation), the treatment should be discontinued and alternative treatment should be considered.
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.
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.
Severe cutaneous adverse reactions
Severe cutaneous adverse reactions (SCARs) including toxic epidermal necrolysis (TEN : also known as Lyell’s Syndrome), Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which could be life threatening or fatal , have been reported with levofloxacin. At the time of prescription, patients should be advised of the signs and symptoms of severe skin reactions, and be closely monitored. If signs and symptoms suggestive of these reactions appear, levofloxacin should be discontinued immediately and an alternative treatment should be considered. If the patient has developed a serious reaction such as SJS, TEN or DRESS with the use of levofloxacin, treatment with levofloxacin must not be restarted in this patient at any time.
Dysglycaemia
As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have been reported, occurring more frequently in the elderly, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glibenclamide) or with insulin. Cases of hypoglycaemic coma have been reported. In diabetic patients, careful monitoring of blood glucose is recommended. Levofloxacin treatment should be stopped immediately if a patient reports blood glucose disturbance and alternative nonfluoroquinolone antibacterial therapy should be considered.
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.
Treatment 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 immediately at the first signs or symptoms of these reactions. Alternative nonfluoroquinolone antibacterial therapy should be considered, 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:
* Congenital long QT syndrome.
* Concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmic, tricyclic antidepressants, macrolides, antipsychotics).
* Uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesemia).
* 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.
Peripheral neuropathy
Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesia, hypaesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. Advise patients to discontinue treatment immediately if they develop any signs or symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness develop in order to prevent the development of potentially 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.
Advise patients to discontinue treatment immediately if they develop any signs or 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.
Interference with laboratory test
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.
See prescribing information for full details.

Common: Insomnia, Headache, Dizziness, Diarrhoea, Vomiting, Nausea, Hepatic enzyme increased (ALT/AST, alkaline phosphatase, GGT), Phlebitis, Infusion site reaction (pain, reddening).

Effect of other medicinal products on Levofloxacin
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 effect the tubular renal secretion such as probenecid and cimetidine, especially in renally impaired patients.
Effect of Levofloxacin Fresenius 5mg/ml 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.
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 antiarrhythmic, tricyclic antidepressants, macrolides, antipsychotics).

Pregnancy: There is a limited amount of data from the use of levofloxacin in pregnant women. However, 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 pregnant women.
Lactation: this medical product 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 that experimental data suggest a risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism, this medical product must not be used in breast-feeding women

See prescribing information for full details.