Levoflox (Levofloxacin)

Levofloxacin is a widely used fluoroquinolone approved for treating community-acquired pneumonia and several other bacterial infections, such as bronchitis, urinary tract infections, and skin infections. In Australia, it is used in clinical practice for bacterial infections when an appropriate antibiotic is needed, supported by its high oral bioavailability, broad-spectrum activity, tolerability, and once-daily dosing.

Levofloxacin was first launched in Japan in 1993 and has been widely available since 1998. More recently, a new high-dose formulation (750 mg) was approved, giving patients a shortened five-day treatment course for community-acquired pneumonia. The medicine lost patent protection in the United States and Japan in 2010 (the Patent Cliff) and in Europe in 2011. It is available in oral and IV formulations.

Levofloxacin overview: efficacy and studies

Levofloxacin is the levo enantiomer of ofloxacin. Its mechanism of action involves inhibiting bacterial topoisomerase IV and DNA gyrase, enzymes needed for DNA replication, transcription, repair, and recombination. Levofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms.

Observational studies

In 10 patients who took levofloxacin 500 mg/day and rifampicin 600 mg/day for 2-6 months, there were no side effects in 46% of patients, occasional digestive symptoms in 40%, and mild diarrhoea in 13%; these patients also took unspecified anti-inflammatory medicines. Sleeplessness occurred in 6%, but there was no tendinitis and no changes in liver function.

In a prospective, multicentre, open trial, 313 patients with clinical signs and symptoms of bacterial infections of the respiratory tract, skin, or urinary tract were treated with levofloxacin. Of these, 134 patients had a pathogen recovered from the primary infection site and had the pathogen's MIC to levofloxacin determined.

Levofloxacin produced clinical and microbiological response rates of about 95%. These response rates included pathogens such as Streptococcus pneumoniae and Staphylococcus aureus. In a logistic regression analysis, clinical outcome was predicted by the ratio of peak plasma concentration to MIC and by the site of infection. Microbiological eradication was predicted by the peak concentration/MIC ratio. Both clinical and microbiological outcomes were most likely to be favourable if the peak concentration/MIC ratio was at least 12.

Of 17 individuals with suspected latent multidrug-resistant tuberculosis treated with pyrazinamide and levofloxacin, 11 developed musculoskeletal side effects related to treatment, 5 had nervous system effects, and 15 had raised liver enzymes, uric acid, or creatinine kinase.

Comparative studies

Levofloxacin's efficacy in adult inpatients and outpatients with community-acquired pneumonia was evaluated in two pivotal Phase III clinical studies. In the first study, 590 patients were treated with levofloxacin (500 mg) once daily by mouth or intravenously for 7 to 14 days, or with the cephalosporin ceftriaxone (1-2 grams), given intravenously once or twice daily, followed by the cephalosporin cefuroxime axetil (500 mg) taken by mouth twice daily for a total of 7 to 14 days (Ortho-McNeil, 2004).

Patients assigned to treatment with the cephalosporins were allowed to receive erythromycin (or doxycycline if intolerant of erythromycin) if infection due to atypical pathogens was suspected or confirmed. Clinical success, defined as the percentage of patients cured or improved at 5 to 7 days after treatment, was higher with levofloxacin (95%) than in the control group (83%). In a second, non-comparative study, 264 patients were treated with 500 mg levofloxacin by mouth or intravenously once daily for 7 to 14 days; the clinical success rate in evaluable patients in this study was 93%.

In comparative trials involving commonly used regimens, levofloxacin had equivalent, if not greater, activity in the treatment of community-acquired pneumonia, acute bacterial exacerbations of chronic bronchitis, acute bacterial sinusitis, acute pyelonephritis, and complicated urinary tract infection.

Interactions

As with ciprofloxacin, using levofloxacin with medicines that alter blood glucose concentrations increases the risk of blood glucose disturbances.

Chinese medicines

Chinese medicines did not influence the systemic availability or renal excretion of levofloxacin.

Efavirenz

Levofloxacin pharmacokinetics in HIV-positive patients were not altered by steady-state treatment with efavirenz.

HIV protease inhibitors

Levofloxacin pharmacokinetics in HIV-positive patients were not altered by steady-state treatment with nelfinavir.

Lithium

Co-administration with levofloxacin can cause severe lithium toxicity; the authors did not discuss the mechanism.

Theophylline

Theophylline clearance was reduced by levofloxacin plus clarithromycin in a 59-year-old Japanese man, who developed stimulation, insomnia, and tachycardia due to theophylline toxicity.

The mechanism was probably inhibition of theophylline metabolism by CYP1A2 and CYP3A4.

Warfarin

Enhanced hypoprothrombinaemia has been reported when levofloxacin was given with warfarin.

Medicines to tell your doctor about

Tell your doctor if you're taking any of the following:

• Iron salts (used to treat anaemia), magnesium- or aluminium-containing antacids (medicines for heartburn and stomach pain), or medicines containing these salts. These can reduce the absorption and effectiveness of levofloxacin, so they should be taken at least 2 hours before or after Evoxil tablets (US: Levaquin tablets);
• Sucralfate (used to protect the stomach lining). It may affect absorption and reduce the effectiveness of levofloxacin. It is best to take sucralfate 2 hours after Evoxil tablets (or another levofloxacin-containing medicine);
• Probenecid (used to prevent gout) or cimetidine (used to treat ulcers), as they reduce your kidneys' ability to excrete levofloxacin;
• Ciclosporin (for example, used to treat psoriasis, dermatitis, or rheumatism). The effect of this medicine may be prolonged if it is used in combination with levofloxacin;
• Corticosteroids, sometimes called steroids, used for inflammation. You may be more likely to develop inflammation and/or rupture of your tendons;
• Non-steroidal anti-inflammatory drugs used for pain and inflammation, such as aspirin, ibuprofen, fenbufen, ketoprofen, and indomethacin. You are more likely to have a fit (seizure) if these are taken with Evoxil tablets;
• Medicines that can affect your heart rhythm: medicines from the antiarrhythmic group (for example, quinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide), tricyclic antidepressants, some antimicrobials (macrolides), and some antipsychotics.

Taking levofloxacin with food and drink

Evoxil tablets can be taken with meals or at any time between meals. Swallow the tablets with a glass of water.

Antimicrobial action

As with ciprofloxacin, levofloxacin is generally considered to be about twice as active as ofloxacin, the racemic substance. Levofloxacin has a broad spectrum of activity, including gram-positive bacteria.

Pharmacokinetics

Levofloxacin is absorbed rapidly and almost completely after oral doses, with peak plasma concentrations occurring within 1 to 2 hours. It is widely distributed into body tissues, including the bronchial mucosa and lungs, but penetration into CSF is relatively poor. Levofloxacin is about 30 to 40% bound to plasma proteins. Only small amounts are metabolised to inactive metabolites. The elimination half-life of levofloxacin is 6 to 8 hours, although this may be prolonged in patients with renal impairment. Levofloxacin is excreted largely unchanged, mainly in the urine, with less than 5% as metabolites. It is not removed by haemodialysis or peritoneal dialysis.

Uses and administration

Levofloxacin is the S-(-)-isomer of the fluoroquinolone antibacterial ofloxacin. It is given by mouth or by intravenous infusion as a 5 mg/mL solution over 30 to 90 minutes to treat susceptible infections, including tuberculosis.

Uses

Evoxil and other levofloxacin tablets are used to treat infections caused by bacteria that are sensitive to levofloxacin. Your Australian doctor will decide whether your infection can be treated with this medicine. Levofloxacin can be used to treat infections of the:

• Sinuses;
• Lungs, in people with long-term breathing problems or pneumonia;
• Urinary tract, including the kidneys or bladder;
• Prostate gland, where there is a long-lasting infection;
• Skin and underneath the skin, including muscles. This is sometimes called 'soft tissue'.

Oral administration

Oral levofloxacin may be taken with or without food. Food does not significantly affect how quickly or how much of the medicine is absorbed.

Antacids containing magnesium or aluminium, sucralfate, metal cations such as iron or zinc, and didanosine (Videx®) chewable/dispersible tablets or unbuffered paediatric powder for an oral solution prepared for administration as an admixture with antacids may interfere with oral absorption of levofloxacin, resulting in subtherapeutic systemic concentrations of the quinolone. To minimise the possibility of an interaction, patients should be advised not to take antacids containing magnesium or aluminium, sucralfate, metal cations such as iron or zinc (including multivitamin preparations containing zinc), or didanosine (Videx®) chewable/dispersible tablets or unbuffered paediatric powder for an oral solution prepared for administration as an admixture with antacids at the same time as, or within 2 hours of, an oral dose of levofloxacin.

IV infusion

Before IV infusion, commercially available levofloxacin concentrate for injection in single-use vials containing 25 mg/mL must be diluted with a compatible IV solution to provide a solution containing 5 mg/mL. Alternatively, commercially available levofloxacin injection for IV infusion containing 5 mg/mL in 5% dextrose injection may be used without further dilution. Because commercially available levofloxacin concentrate for injection and levofloxacin injection for IV infusion contain no preservative, any unused portions of the solutions should be discarded.

Solutions compatible with levofloxacin IV include:

• 0.9% Sodium Chloride Injection;
• 5% Dextrose Injection;
• 5% Dextrose/0.9% Sodium Chloride Injection;
• 5% Dextrose in Lactated Ringer's;
• Plasma-Lyte 56/5% Dextrose Injection;
• 5% Dextrose/0.45% Sodium Chloride;
• 1.5% Potassium Chloride Injection;
• Sodium Lactate Injection (M/6).

IV infusions of levofloxacin should be given slowly. Levofloxacin doses of 250 or 500 mg should be administered over 60 minutes. Levofloxacin doses of 750 mg should be administered over 90 minutes. Because of the risk of hypotension, faster or bolus IV infusion should be avoided. Levofloxacin solutions should be checked visually for particulate matter before administration whenever the solution and container allow.

Because only limited information is available on the physical and/or chemical compatibility of levofloxacin and other drugs, levofloxacin should not be mixed with other drugs or infused at the same time through the same tubing as other drugs. Fluoroquinolones, including levofloxacin, should not be infused through the same tubing as any solution containing multivalent cations (for example, magnesium). If a Y-type administration set is used, the other IV solution flowing through the tubing should be stopped while levofloxacin is being infused. If the same administration set is used for sequential infusion of several different drugs, the tubing should be flushed before and after administration of levofloxacin with an IV solution that is compatible with both levofloxacin and the other drug(s).

Dosage

The dosage of oral and IV levofloxacin is identical.

When levofloxacin treatment is started using IV levofloxacin, it may be changed, when appropriate, to oral levofloxacin at the same dosage to complete the course of treatment. The timing of the change from IV to oral therapy should be individualised, taking into account the patient's clinical condition.

The dosage of levofloxacin does not need to be modified in geriatric patients based on age alone.

Respiratory tract infections

For the treatment of acute maxillary sinusitis, acute bacterial exacerbations of chronic bronchitis, or community-acquired pneumonia in adults, the usual dosage of levofloxacin is 500 mg once every 24 hours. The usual duration of treatment is 10-14 days for acute maxillary sinusitis, 7 days for acute bacterial exacerbations of chronic bronchitis, and 7-14 days for community-acquired pneumonia.

For the treatment of hospital-acquired pneumonia in adults, the usual dosage of levofloxacin is 750 mg once daily for 7-14 days.

Skin and skin structure infections

For the treatment of uncomplicated skin and skin structure infections in adults, the usual dosage of levofloxacin is 500 mg once every 24 hours for 7-10 days. The usual dosage for complicated skin and skin structure infections in adults is 750 mg once every 24 hours for 7-14 days.

Urinary tract infections and prostatitis

The usual dosage of levofloxacin for the treatment of uncomplicated urinary tract infections, complicated urinary tract infections, or acute pyelonephritis in adults is 250 mg once every 24 hours. The usual duration of treatment is 3 days for uncomplicated urinary tract infections and 10 days for complicated urinary tract infections and acute pyelonephritis.

The usual dosage of levofloxacin for the treatment of chronic prostatitis in adults is 500 mg once daily for 28 days.

GI infections

For the treatment of travellers' diarrhoea that is severe or associated with fever or bloody stools, some clinicians recommend that 500 mg of levofloxacin be given once daily for up to 3 days. Although the use of anti-infectives for prophylaxis of travellers' diarrhoea is generally discouraged, if levofloxacin is used, the recommended oral dosage is 500 mg once daily during the period of risk (for up to 3 weeks).

Treatment of active tuberculosis

If oral levofloxacin is used as an alternative agent in multiple-drug regimens for the treatment of active tuberculosis, the US Centers for Disease Control and Prevention (CDC), American Thoracic Society (ATS), and Infectious Diseases Society of America (IDSA) recommend that adults and children 15 years of age or older receive 0.5-1 g daily. These experts state that data are not available to support intermittent regimens of levofloxacin for the treatment of tuberculosis.

Anthrax

If oral levofloxacin is used as an alternative agent for post-exposure prophylaxis following suspected or confirmed exposure to aerosolised anthrax spores (inhalational anthrax), or if oral levofloxacin is used for the treatment of anthrax when a parenteral regimen is not available (for example, when there are supply or logistical problems because large numbers of individuals require treatment in a mass casualty setting), the US Working Group on Civilian Biodefense suggests that adults can receive a dosage of 500 mg once daily.

Because of the possible persistence of anthrax spores in lung tissue following aerosol exposure, the US Centers for Disease Control and Prevention (CDC) and the Working Group on Civilian Biodefense state that anti-infective therapy for treatment of inhalational anthrax or for post-exposure prophylaxis should be continued for 60 days.

Gonorrhoea and associated infections

If oral levofloxacin is used for the treatment of uncomplicated cervical, urethral, or rectal gonorrhoea in adults and adolescents, the CDC recommends a single 250-mg dose. If levofloxacin is used for the treatment of disseminated gonococcal infection in adults and adolescents, the CDC recommends an initial IV dosage of 250 mg once daily, continued for 24-48 hours after improvement begins; treatment may be switched to an oral levofloxacin regimen of 500 mg once daily to complete at least 1 week of therapy.

Unless the presence of coexisting chlamydial infection has been excluded by appropriate testing, patients receiving levofloxacin for uncomplicated or disseminated gonococcal infections should also receive an anti-infective regimen effective for presumptive treatment of chlamydia (for example, a single dose of oral azithromycin or a 7-day regimen of oral doxycycline).

Nongonococcal urethritis

If oral levofloxacin is used for the treatment of nongonococcal urethritis, the CDC recommends 500 mg once daily for 7 days.

Chlamydial infections

For the treatment of urogenital chlamydial infections in adults and adolescents, the CDC recommends oral levofloxacin in a dosage of 500 mg once daily for 7 days.

Pelvic inflammatory disease

For the treatment of acute pelvic inflammatory disease (PID) in adults and adolescents, when a parenteral regimen is indicated, IV levofloxacin may be given in a dosage of 500 mg once daily with or without IV metronidazole (500 mg every 8 hours). The parenteral regimen may be stopped 24 hours after clinical improvement; however, oral doxycycline (100 mg twice daily) should be continued to complete 14 days of treatment. If an oral levofloxacin regimen is used for the treatment of PID, the drug should be given in a dosage of 500 mg once daily for 14 days with or without oral metronidazole (500 mg twice daily for 14 days).

Levofloxacin is also used topically as the hemihydrate in eye drops. A solution containing the equivalent of 0.5% levofloxacin is used for the treatment of bacterial conjunctivitis, and 1.5% is used for corneal ulcers caused by susceptible strains of bacteria.

Overdose

If you accidentally take an extra tablet, there should be no serious long-term consequences. Contact your doctor as soon as possible for exact instructions. If possible, take your tablets or the box with you to show the doctor. Signs of an overdose include:

• Confusion;
• Dizziness;
• Impaired consciousness;
• Convulsions and heart problems;
• Abnormal heart rhythm.

Missing a dose

If you forget to take a dose, take it as soon as you remember unless it is nearly time for your next dose. Then continue as prescribed. Do not take a double dose to make up for a missed dose.

Stopping the course early

It is important to finish your course of tablets as prescribed by your doctor. Do not stop taking them, even if you begin to feel better before you have finished them all. Stopping the medicine early may cause your condition to worsen.

If you notice signs of a side effect, tell a doctor straight away before taking the next dose. If you have any further questions about using this product, ask your doctor or pharmacist.

Administration in children

Because fluoroquinolones can cause degenerative changes in weight-bearing joints in young animals, they should only be used in children and adolescents when the expected benefits outweigh the risks. In Australia, levofloxacin is not generally approved for routine use in this age group, but a pharmacokinetic study has suggested that the following doses would be needed:

• Children 5 years of age and older: 10 mg/kg/day;
• Infants and children from 6 months to less than 5 years of age: 10 mg/kg every 12 hours.

Administration in patients with renal impairment

Although initial doses (see above) remain unchanged in patients with renal impairment, subsequent doses of levofloxacin should be adjusted according to creatinine clearance (CC). In Australian practice, the following dose adjustments are commonly used:

• CC 20 to 50 mL/minute: subsequent doses are halved;
• CC 10 to 19 mL/minute: subsequent doses are reduced to one-quarter of the usual dose; a regimen of 250 mg daily should be reduced to 125 mg every 48 hours;
• CC less than 10 mL/minute (including haemodialysis and continuous peritoneal dialysis patients): usual doses of 250 mg or 500 mg daily are reduced to 125 mg every 48 or 24 hours, respectively.

After an initial dose of 750 mg daily:

• CC 20 to 49 mL/minute: subsequent doses are 750 mg every 48 hours;
• CC up to 19 mL/minute (including haemodialysis and continuous peritoneal dialysis patients): subsequent doses are 500 mg every 48 hours.

After an initial dose of 500 mg daily:

• CC 20 to 49 mL/minute: subsequent doses are 250 mg every 24 hours;
• CC up to 19 mL/minute (including haemodialysis and continuous peritoneal dialysis patients): subsequent doses are 250 mg every 48 hours.

After an initial dose of 250 mg daily:

• CC 10 to 19 mL/minute: subsequent doses are 250 mg every 48 hours.

A pharmacokinetic study in 10 critically ill patients receiving continuous renal replacement therapy with either venovenous haemofiltration or haemodiafiltration suggested that levofloxacin 250 mg every 24 hours or 500 mg every 48 hours would be suitable in these situations.

Peptic Ulcer Disease

Go here to read about the effects of levofloxacin in eradication regimens for Helicobacter pylori.

Levofloxacin Effects on Different Body Systems

Cardiovascular

Preclinical data, clinical trial data, and phase IV study data suggest that levofloxacin can prolong the QT interval. Cardiovascular problems were reported in 1 in 15 million prescriptions, compared with 1-3% of patients taking sparfloxacin, in whom QTc prolongation to more than 500 ms occurred. Polymorphic ventricular tachycardia with a normal QT interval has been associated with oral levofloxacin when no other cause was identified.

Among 23 patients who took levofloxacin 500 mg/day, the QTc interval was prolonged by more than 30 ms in four patients and by 60 ms in two patients.

The absolute QT interval was prolonged to more than 500 ms in four patients, one of whom developed torsade de pointes.

Phlebitis can occur during parenteral administration of levofloxacin. High concentrations of levofloxacin (5 mg/mL) significantly reduced intracellular adenosine and adenosine triphosphate content in cultured endothelial cells and also reduced ADP, GTP, and GDP concentrations. These in vitro findings suggest that high doses of levofloxacin are not compatible with maintaining endothelial cell function and may help explain cases of phlebitis. Commercial formulations should be diluted and given into large veins.

Respiratory

Eosinophilic pneumonia complicated by bronchial asthma has been attributed to levofloxacin.

A 76-year-old woman took levofloxacin for a productive cough with non-segmental infiltration in both lung fields. She developed eosinophilia in both the peripheral blood (24%) and sputum (10%), airflow limitation, hypoxaemia, and increased airway responsiveness to methacholine.

Bronchoalveolar lavage fluid showed an increased total cell count and a 55% increase in eosinophils, and the CD4/CD8 ratio was reduced to 0.8. Histological features included increased infiltration of eosinophils in the alveolar and interstitial compartments and goblet cell metaplasia. Levofloxacin was stopped, and her symptoms improved without steroid treatment. A leukocyte migration test for levofloxacin was weakly positive.

Nervous System

Levofloxacin can cause seizures. In one study, convulsions occurred in two per million prescriptions.

• A 75-year-old white woman was given oral levofloxacin (500 mg on day 1 followed by 250 mg/day) for ischaemic toes. After three doses, she had a seizure. One month later, she was challenged with ciprofloxacin 400 mg intravenously every 12 hours and again had a seizure;
• A 74-year-old white woman was given oral levofloxacin 500 mg/day for bacterial pneumonia and had a seizure after five doses.

Sensory Systems

Taste disturbance occurred in fewer than three per million prescriptions of levofloxacin.

Gastrointestinal

Of 48 patients taking pyrazinamide 30 mg/kg/day plus levofloxacin 500 mg/day for 1 year, 27 stopped treatment within 4 months because of adverse events. Gastrointestinal intolerance was the main adverse event leading to early withdrawal.

Levofloxacin can cause pseudomembranous colitis due to Clostridium difficile.

Liver

In a study based on European and international data from about 130 million prescriptions, the adverse-effect profile of levofloxacin was compared with that of other fluoroquinolones; the rate of hepatic abnormalities was low. However, two cases of severe acute liver toxicity were reported in patients who had received intravenous levofloxacin.

Pancreas

Two case reports suggest that levofloxacin can cause pancreatitis.

Urinary Tract

Two reports suggest that levofloxacin can cause tubulointerstitial nephritis. A case of nephrotoxicity and purpura associated with levofloxacin has also been reported; allergic interstitial nephritis or vasculitis was thought to be the underlying pathological process.

A 73-year-old white man took levofloxacin for a lower urinary tract infection for 3 days and developed palpable purpura and erythematous skin lesions over the lower limbs and trunk, with a markedly reduced urine output. Serum creatinine was 560 µmol/L (6.4 mg/dL). Levofloxacin was stopped, and prednisone, furosemide, and intravenous fluids were given. The patient recovered fully over the next 4 weeks.

Skin

In a double-blind, randomised study in 30 healthy adults, oral levofloxacin (500 mg/day for 5 days) showed low photosensitising potential, as seen in preclinical animal studies and postmarketing surveillance. In preclinical studies, levofloxacin was 20 times less phototoxic than sparfloxacin. Phototoxicity occurs in only 1 in 1.8 million cases.

Levofloxacin can cause a rash similar to an ampicillin rash in patients with infectious mononucleosis.

A 78-year-old woman developed a blistering rash 2 days after completing a course of levofloxacin. The rash progressed to toxic epidermal necrolysis within 7 days. She was treated with intravenous fluids and wound dressings. Her condition improved, and she was discharged after 22 days.

Musculoskeletal

Tendinopathy has been reported with levofloxacin. Four cases of Achilles tendinitis have been reported in patients taking levofloxacin. Two were on chronic dialysis, one was a kidney transplant recipient, and one had chronic vasculitis. In all four cases, tendinitis came on suddenly, affected both sides, and was incapacitating. In three cases, it began early during levofloxacin treatment, and in one case, it started 10 days after treatment ended. All patients recovered completely after 3-8 weeks.

Older age, renal dysfunction, and concomitant corticosteroid therapy are predisposing risk factors. Tendon rupture occurred in fewer than four per million prescriptions.

Immunologic

Anaphylactic and anaphylactoid reactions are rare side effects after administration of fluoroquinolones (about 0.46-1.2 per 100,000 patients).

On two occasions, a 49-year-old woman with asthma who took levofloxacin for a chest infection developed worsening respiratory distress that required intubation. The second reaction was accompanied by a marked skin reaction.

An in vitro study in rat peritoneal mast cells showed that levofloxacin-mediated histamine release may be closely linked to activation of pertussis toxin-sensitive G proteins.

Susceptibility Factors

The pharmacokinetics of intravenous levofloxacin have been studied in intensive care patients during continuous venous haemofiltration or haemodiafiltration. Levofloxacin clearance was substantially increased during both types of continuous renal replacement therapy. Levofloxacin 250 mg/day maintained effective plasma drug concentrations in these patients.

Warnings and Precautions

Do not use Evoxil tablets (US: Levaquin):

• If you are allergic (hypersensitive) to levofloxacin, other active substances in the same group of antibiotics (quinolones), or any of the other ingredients in the medicine;
• If you have epilepsy. Otherwise, your risk of having fits (convulsions) is increased;
• If you have ever had tendon problems (for example, tendinitis) related to treatment with an active substance from the same class of antibiotics (fluoroquinolones);
• If you are pregnant, planning to become pregnant, or breastfeeding;
• If the tablets have been prescribed for children or growing teenagers. They could harm the cartilage in growing bones.

Tell your doctor before taking this medicine:

• If you have had fits or brain damage in the past, such as a stroke or severe brain injury. Make sure your doctor knows your medical history so they can give you the right advice;
• If you are exposed to sunlight or UV light. Do not stay in strong sunlight longer than necessary and do not use a sun lamp or solarium. Your skin may become more sensitive to light while using this medicine and may react like sunburn;
• If you get pain or inflammation in your tendons, especially if you are elderly or taking medicines known as corticosteroids (cortisone or similar anti-inflammatories). If you have any tendon symptoms while taking the tablets or shortly afterwards, get medical advice straight away and rest the affected limb to avoid tendon damage. Do not take the next dose of levofloxacin unless your doctor tells you to;
• If you have severe, persistent and/or bloody diarrhoea during or after treatment with the tablets. This may be a sign of serious bowel inflammation (pseudomembranous colitis), which can happen after antibiotic treatment. Tell your doctor straight away. It may be necessary to stop treatment and start specific therapy;
• If you have a family history of, or an actual defect in, the liver enzyme called glucose-6-phosphate dehydrogenase (G6PD), a rare hereditary disease. Patients with G6PD deficiency may be prone to destruction of red blood cells (haemolysis) when treated with quinolone antibacterial agents;
• If you have kidney disease or reduced kidney function (renal insufficiency);
• If you are taking anticoagulants;
• If you have ever had mental health problems. Tell your doctor immediately if you suspect a psychotic reaction;
• If you have ever had symptoms caused by nerve damage, such as movement or sensory problems in your hands and feet;
• If you have diabetes and are taking oral medicines that lower blood glucose levels;
• If you have ever had liver problems. Stop treatment and contact your doctor immediately if symptoms of liver disease develop, such as reduced appetite, yellowing of the skin or the whites of the eyes (jaundice), dark urine, itching, or gastrointestinal symptoms;
• If you were born with, or have a family history of, prolonged QT interval (seen on ECG), have a salt imbalance in the blood (especially low potassium or magnesium), have a very slow heart rhythm (bradycardia), have a weak heart, or have ever had a heart attack (myocardial infarction).

Levofloxacin: Uses

Levofloxacin is used orally or IV to treat respiratory tract infections (acute bacterial exacerbations of chronic bronchitis, acute maxillary sinusitis, community-acquired pneumonia, hospital-acquired pneumonia), uncomplicated or complicated skin and skin structure infections, uncomplicated or complicated urinary tract infections, acute pyelonephritis, and chronic prostatitis caused by susceptible organisms.

Levofloxacin is also used to treat travellers' diarrhoea and pelvic inflammatory disease. In addition, levofloxacin is recommended as an alternative agent for the treatment of gonorrhoea, nongonococcal urethritis, or urogenital chlamydial infections; for the treatment of active tuberculosis; for post-exposure prophylaxis following suspected or confirmed exposure to aerosolised anthrax spores (inhalational anthrax) or for treatment of inhalational anthrax; and for the treatment or prophylaxis of plague. If there are no factors that may interfere with absorption of an oral medicine (such as vomiting), IV levofloxacin does not provide greater efficacy or more potent antimicrobial activity than an equivalent oral dose of levofloxacin.

Therefore, IV levofloxacin is generally reserved for patients who cannot tolerate or are unable to take an oral dosage form, or when the IV route offers a clinical advantage. Before starting levofloxacin therapy, appropriate specimens should be obtained to identify the causative organism(s) and for in vitro susceptibility testing.

Levofloxacin therapy may be started while waiting for susceptibility test results, but it should be stopped and replaced with other appropriate anti-infective therapy if the organism is found to be resistant to levofloxacin. In vitro susceptibility tests should be repeated periodically during levofloxacin therapy to assess the effectiveness of the medicine and to detect the emergence of levofloxacin-resistant strains, which may develop during treatment.

Because resistant strains of Pseudomonas aeruginosa have developed during fluoroquinolone therapy, in vitro susceptibility testing is particularly important when levofloxacin is used to treat infections caused by this organism.

Storage

Here are some recommendations:

• Keep out of the reach and sight of children;
• Do not use this medicine after the expiry date shown on the packaging. The expiry date refers to the last day of that month;
• Keep the blister in the outer carton to protect it from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer need. These measures will help protect the environment.