Active ingredients: Levofloxacin
Levofloxacin Accord 250 mg film-coated tablets
Levofloxacin Accord 500 mg film-coated tablets
Why is Levofloxacin used - Generic Drug? What is it for?
Levofloxacin Accord contains a substance called levofloxacin. Levofloxacin is an antibiotic that is used to treat bacterial infections
- sinuses
- lungs, in patients with chronic breathing problems or pneumonia
- urinary tract, including kidneys, bladder
- of the prostate gland, where a persistent infection can develop
- skin and subcutaneous tissue, including muscles. These are sometimes called "soft tissues".
In some special situations, Levofloxacin Accord can be used to decrease the likelihood of getting a lung disease called anthrax or worsening of the disease after being exposed to the bacterium that causes anthrax.
Contraindications When Levofloxacin - Generic Drug should not be used
Do not take Levofloxacin Accord and tell your doctor if:
- you are allergic to levofloxacin, to any other quinolone antiobiotics such as moxifloxacin, ciprofloxacin or ofloxacin or to any of the other ingredients of this medicine (listed in section 6). Signs of an allergic reaction include: skin rash, swallowing or breathing problems, swelling of the lips, face, throat or tongue
- had epilepsy
- have problems with your eyesight or if any effects on your eyes occur, consult an ophthalmologist immediately.
- have had tendon problems (such as tendonitis) related to treatment with a 'quinolone antibiotic'. Tendons are fibrous structures that connect muscles to the skeleton
- is a growing child or adolescent
- are pregnant, planning to become pregnant or breastfeeding.
Do not take this medicine if the above may in any way apply to you. If you have any further questions, ask your doctor or pharmacist before taking Levofloxacin Accord.
Precautions for use What you need to know before taking Levofloxacin - Generic Drug
Talk to your doctor or pharmacist before taking Levofloxacin Accord if:
- are 60 or older
- are taking corticosteroids, sometimes called steroids (see "Other medicines and Levofloxacin Accord")
- have ever had epileptic fits
- suffered brain damage from a stroke or other brain damage
- have kidney problems
- you suffer from a disease known as "glucose-6-phosphate dehydrogrenase deficiency". Giving this medicine makes it more likely that you will develop serious blood problems
- suffered from mental problems
- have had heart problems: caution should be exercised when using this type of medicine if you were born with or have a family history of prolongation of the QT interval (seen in the ECG, the recording of the electrical activity of the heart), have a salt imbalance in the blood (particularly a low level of potassium or magnesium in the blood), have a very slow heart rhythm (called 'bradycardia'), have a weak heart (heart failure), have a history of heart attacks ( myocardial infarction), you are female or elderly or are using other medicines that cause changes in your ECG (see section Other medicines and Levofloxacin Accord)
- have diabetes
- have ever had liver problems
- suffer from myasthenia gravis
Other warnings
- Levofloxacin may rarely cause tendon pain and inflammation, particularly if you are elderly or if you are taking steroid medicines (such as cortisone or hydrocortisone). If you have any tendon problems during levofloxacin therapy or shortly after levofloxacin therapy, contact your doctor immediately and keep the affected limb at rest (leg or arm). Do not take the next dose of levofloxacin unless your doctor tells you. In these cases, if there is swelling or pain in the area of the affected tendon, it will probably be necessary to stop the therapy.
- If you start to have severe, persistent and / or bloody diarrhea during or after levofloxacin therapy, please tell your doctor immediately. This could indicate that you have severe bowel inflammation (pseudomembranous colitis), which can sometimes occur after treatment with antibiotics. You will need to stop taking levofloxacin and your doctor will need to prescribe another medicine.
- During levofloxacin therapy it is recommended not to expose yourself to intense sunlight and not to use sunlamps. This is because, during therapy with this medicine, some patients may become more sensitive to light and have skin reactions similar to sunburn.
- Levofloxacin treatment should be discontinued if the patient experiences symptoms such as burning, tingling, pain or numbness. These could be signs of a condition called 'neuropathy'.
- Levofloxacin therapy is not optimal for most cases of pneumococcal pneumonia.
- Infections caused by P. aeruginosa acquired in hospital during treatment may require combination therapy.
- Levofloxacin is not effective against infections caused by methicillin-resistant staphylococcus aureus (MRSA). In infections where MRSA is suspected, levofloxacin should be combined with a medicine indicated to treat these infections.
Interactions Which drugs or foods can modify the effect of Levofloxacin - Generic Drug
Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines. This is because Levofloxacin Accord can affect the way some other medicines work. Also some medicines can affect the way Levofloxacin Accord works.
In particular, tell your doctor if you are taking any of the following medicines. This is because co-administration with Levofloxacin Accord may increase the chance that you will experience side effects:
- Corticosteroids, sometimes called steroids - used to treat inflammation. The chance that you develop inflammation and / or rupture of the tendons is greater.
- Warfarin - used to thin the blood. The chance of "bleeding" is greater. Your doctor should regularly order blood tests to check how well your blood clots.
- Theophylline - used for breathing problems. The chance of you having a seizure (seizure) is higher if you take theophylline in combination with Levofloxacin Accord.
- Non-steroidal anti-inflammatory drugs (NSAIDs) - used for pain and inflammation such as aspirin, ibuprofen, fenbufen, ketoprofen and indomethacin. The chance of you having a seizure (seizure) when taken in combination with Levofloxacin Accord is greater.
- Ciclosporin - used for organ transplants. You are more likely to experience the typical side effects of cyclosporine.
- Medicines known for their effect on the heartbeat. These include medicines used to treat abnormal heart rhythms (antiarrhythmics such as quinidine, hydroquinidine, disopyramide, sotalol, dofetilide, ibutilide and amiodarone), for depression (tricyclic antidepressants such as amitriptyline and imipramine), for psychiatric disorders (antipsychotics), for bacterial infections ("macrolide" antibiotics such as erythromycin, azithromycin and clarithromycin).
- Probenecid - used to treat gout and cimetidine - used for ulcers and heartburn. You should be especially careful when using any of these medicines in combination with Levofloxacin Accord. If you have kidney problems, your doctor may prescribe a lower dose for you.
Do not take Levofloxacin Accord concomitantly with the following medicines. This is because the mechanism of action of Levofloxacin Accord can be affected:
- Iron salts in tablets (for anemia), zinc supplements, antacids containing magnesium or aluminum (for acidity or heartburn), didanosine or sucralfate (for stomach ulcers). See section 3 "If you are already taking iron salts in tablets, zinc supplements, antacids, didanosine or sucralfate"
Tests for the determination of opiates in urine
Urine tests may indicate 'false-positive' results for the presence of strong pain relieving drugs called 'opiates' in people taking Levofloxacin Accord. If your doctor has to carry out a urinalysis, please tell him that you are taking Levofloxacin Accord.
Tuberculosis test
This medicine may cause "false negative" results in some tests used in the laboratory to look for the bacterium causing tuberculosis.
Taking Levofloxacin Accord with food and drink
Take the tablets with or without meals. Take them with a large amount of water. Taking this product with orange juice can cause reduced plasma levels of quinolone.
Warnings It is important to know that:
Pregnancy and breastfeeding
You must not take Levofloxacin Accord if you are pregnant, trying to become pregnant or breast-feeding.
Driving and using machines
Side effects may occur after taking this medicine which include dizziness, sleepiness, a subjective sensation of movement (vertigo) or disturbed vision. Some of these side effects may affect your ability to concentrate and the speed of reaction. If this happens, do not drive vehicles and do not engage in activities that require a high level of attention.
Dosage and method of use How to use Levofloxacin - Generic Drug: Posology
Always take Levofloxacin Accord exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist
Taking the medicine
- Take this medicine by mouth
- Swallow the tablets whole with water.
- The tablets can be taken with meals or between meals.
Protect your skin from sunlight
Do not expose yourself to direct sunlight while taking this medicine and for 2 days after stopping treatment. This is because your skin will become much more sensitive to the sun and can burn, itch, or serious injuries can occur if you do not observe the following precautions:
- Make sure you use a high protection factor sunscreen
- Always wear a hat and clothing that covers your arms and legs
- Avoid sun beds
If you are already taking iron tablets, zinc supplements, antacids, didanosine or sucralfate
- Do not take these medicines at the same time as Levofloxacin Accord. Take the prescribed dose of these medicines at least 2 hours before or after taking Levofloxacin Accord.
How much medicine to take
- Your doctor will decide how much Levofloxacin Accord you should take
- The dose will depend on the type of infection you have and on the location of the infection in your body
- The duration of treatment will depend on the severity of the infection
- If you think the effect of the medicine is too weak or too strong, do not change the dosages yourself but contact your doctor.
Adults and the elderly
Sinus infection
- Two Levofloxacin Accord 250 mg tablets once a day
- Or, one tablet of Levofloxacin Accord 500 mg once daily 4
Lung infections, in patients with chronic breathing problems
- Two Levofloxacin Accord 250 mg tablets once a day
- Or, one tablet of Levofloxacin Accord 500 mg once a day
Pneumonia
- Two tablets of Levofloxacin Accord 250 mg once or twice a day
- Or, one tablet of Levofloxacin Accord 500 mg once or twice a day
Urinary tract infections including kidney or bladder
- One or two Levofloxacin Accord 250 mg tablets once a day
- Or, ½ tablet of Levofloxacin Accord 500 mg once daily
Infections of the prostate
- Two Levofloxacin Accord 250 mg tablets once a day
- Or, one tablet of Levofloxacin Accord 500 mg once a day
Infections of the skin and subcutaneous tissue, including muscles
- Two tablets of Levofloxacin Accord 250 mg once or twice a day
- Or, one tablet of Levofloxacin Accord 500 mg once or twice a day
Adults and the elderly with kidney problems
The doctor may find it necessary to reduce the dosage.
Children and adolescents
This medicine should not be given to children or adolescents.
Overdose What to do if you have taken an overdose of Levofloxacin - Generic Drug
If you take more Levofloxacin Accord than you should
If you accidentally take more tablets than you should, talk to your doctor or seek medical advice elsewhere. Take the medicine pack with you. This will let the doctor know what you have taken. The following side effects may occur:
fits (seizures), confusion, dizziness, feeling faint, shaking and heart problems - which can lead to irregular heartbeats and feeling sick (nausea) or heartburn.
If you forget to take Levofloxacin Accord
If you forget to take a dose, take it as soon as you remember, unless it is time for your next dose. Do not take a double dose to make up for a forgotten dose.
If you stop taking Levofloxacin Accord
Do not stop taking Levofloxacin Accord just because you feel better. It is important that you complete the course of tablets that your doctor has prescribed for you. Do not stop until you have finished all the tablets, even if you start to feel better. If you stop taking the tablets too soon, the infection may come back and your condition may get worse or the bacteria may develop resistance to the medicine.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Levofloxacin - Generic Drug
Like all medicines, this medicine can cause side effects, although not everybody gets them.
These effects are usually mild or moderate in severity and often disappear after a short time.
Stop taking Levofloxacin Accord and see your doctor or hospital straight away if you notice the following side effect:
Very rare (may affect up to 1 in 10,000 patients)
- He has an allergic reaction. The signs may include: skin rash, trouble swallowing or breathing difficulties, swelling of the lips, face, throat or tongue.
Stop taking Levofloxacin Accord and see your doctor immediately if you notice any of the following serious side effects - you may need urgent medical treatment:
Rare (may affect up to 1 in 1000 patients)
- Watery diarrhea with possible blood, possibly accompanied by stomach cramps and high fever. This can indicate a severe bowel problem.
- Pain and inflammation of the tendons or ligaments that can rupture. The Achilles tendon is most often affected.
- Epileptic attack (convulsions).
Very rare (may affect up to 1 in 10,000 patients)
- Burning, tingling, pain or numbness. These symptoms may indicate a disease called "neuropathy"
Other:
- Severe rash which may include lesions or peeling of the skin around the lips, eyes, mouth, nose and genitals.
- Loss of appetite, yellowing of the skin and eyes, dark urine, itchy or sore stomach (abdomen). These may be signs of liver problems which can include fatal liver failure.
If your vision becomes blurred or if you experience any eye discomfort when taking Levofloxacin Accord, consult your ophthalmologist immediately.
Tell your doctor if any of the following side effects get worse or last more than a few days:
Common (may affect up to 1 in 10 patients)
- Problems sleeping
- Headache, feeling dizzy
- Feeling sick (nausea, vomiting) and diarrhea
- Increased levels of liver enzymes in the blood
Uncommon (may affect up to 1 in 100 patients)
- Change in the number of other bacteria or fungi, infection with a fungus called Candida, which may require treatment
- Change in the number of white blood cells shown in the results of some blood tests (leukopenia, eosinophilia)
- Feeling stressed (anxiety), feeling confused, feeling jittery, sleepy, shaking, feeling dizzy (vertigo)
- Shortness of breath (dyspnoea)
- change in the taste of things, loss of appetite, upset stomach or indigestion (dyspepsia), pain in the stomach area, feeling bloated (flatulence) or constipation
- Itching and rash, severe itching or hives, excessive sweating (hyperhidrosis)
- Joint pain or muscle aches
- Blood tests may show abnormal results due to liver (increased bilirubin) or kidney (increased creatinine) problems
- Generalized weakness
Rare (may affect up to 1 in 1000 patients)
- Bruising and bleeding easily due to a reduction in the number of platelets in the blood (thrombocytopenia)
- Low white blood cell count (neutropenia)
- Exaggerated immune response (hypersensitivity)
- Low blood sugar levels (hypoglycaemia). This is important for those with diabetes
- Seeing or hearing things that are not there (hallucinations, paranoia), changes of opinion and second thoughts (psychotic reactions) with the possibility of developing suicidal ideation or suicidal acts
- Feeling depressed, mental problems, feeling restless (agitated), abnormal dreams or nightmares
- Tingling sensation in the hands and feet (paraesthesia)
- Problems with hearing (tinnitus) or vision (blurred vision)
- Unusually fast heartbeat (tachycardia) or low blood pressure (hypotension)
- Muscle weakness. This is important for patients suffering from myasthenia gravis (a rare disease of the nervous system)
- Changes in kidney function and occasional kidney failure which may be caused by an allergic kidney reaction called interstitial nephritis
- Fever
Other side effects include:
- Decrease in red blood cells (anemia): this can lead to pale or yellow skin due to damage to the red blood cells; decrease in the number of all types of blood cells (pancytopenia)
- Fever, sore throat and a general feeling of being unwell that does not go away. This may be due to a decrease in the number of white blood cells in the blood (agranulocytosis)
- Lack of blood supply (anaphylactic-type shock)
- Increased blood sugar levels (hyperglycaemia) or decreased blood sugar levels leading to coma (hypoglycemic coma). This is important for those with diabetes.
- Change in the smell of things, loss of smell or taste (parosmia, anosmia, ageusia)
- Difficulty moving and walking (dyskinesia, extrapyramidal disorders)
- Temporary loss of consciousness or posture (syncope)
- Temporary loss of vision
- Worsening or loss of hearing
- Unusually fast heartbeat, life-threatening irregular heartbeat including cardiac arrest, changes in heart rate (called "QT prolongation" seen on ECG, electrical activity of the heart)
- Difficulty in breathing or wheezing (bronchospasm)
- Allergic reactions affecting the lungs
- Pancreatitis
- Inflammation of the liver (hepatitis)
- Increased sensitivity of the skin to the sun or ultraviolet rays (photosensitivity)
- Inflammation of the vessels that carry blood throughout the body due to an allergic reaction (vasculitis)
- Inflammation of the internal tissues of the mouth (stomatitis)
- Breakdown of muscles and destruction of muscles (rhabdiomyolysis)
- Joint redness and swelling (arthritis)
- Pain, including pain in the back, chest, extremities
- Attacks of porphyria in patients who already suffer from porphyria (a very rare metabolic disorder)
- Persistent headache with or without blurred vision (benign intracranial hypertension)
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.
Reporting of side effects
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
- This medicine does not require any special storage conditions.
- Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the carton and blister strip after EXP. The expiry date refers to the last day of the month.
- Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What Levofloxacin Accord contains:
Each tablet contains 250 mg or 500 mg of levofloxacin, equivalent to 256.23 mg or 512.46 mg of levofloxacin hemihydrate.
The excipients are:
Tablet core: povidone, crospovidone (Type-B), microcrystalline cellulose, magnesium stearate, anhydrous colloidal silica.
Tablet coating: hypromellose E5, talc, titanium dioxide (E171), macrogol 400, red iron oxide (E172) and yellow iron oxide (E172).
What Levofloxacin Accord looks like and contents of the pack
For 250 mg tablets: Pink, capsule-shaped, biconvex, film-coated tablet with score line on both sides. The letters' L "and" F "are embossed on both sides of the score line on one side.
The tablets can be divided into equal halves.
For 500 mg tablets: Pink, capsule-shaped, biconvex, film-coated tablet, scored on both sides. The letters' L "and" V "are embossed on both sides of the score line on one side.
The tablets can be divided into equal halves.
The tablets are packed in PVC / aluminum blisters.
For 250 mg, the tablets are supplied in packs of 1, 2, 3, 5, 7, 10, 30, 50 and 200 tablets.
For 500 mg, the tablets are supplied in packs of 1, 2, 5, 7, 10, 30, 50, 200 and 500 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
LEVOFLOXACINA ACCORD 250 - 500 MG TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
For 250 mg:
Each film-coated tablet contains 250 mg of levofloxacin as the active ingredient, equivalent to 256.23 mg of levofloxacin hemihydrate.
For the full list of excipients, see section 6.1.
For 500mg:
Each film-coated tablet contains 500 mg of levofloxacin as the active substance, equivalent to 512.46 mg of levofloxacin hemihydrate.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet
For 250 mg tablets: Pink, capsule-shaped, biconvex, film-coated tablet with score line on both sides. On one side the letters "L" and "F" are embossed on both sides of the incision line.
The tablet can be divided into equal halves.
For 500 mg tablets: Pink, capsule-shaped, biconvex, film-coated tablet with score line on both sides. On one side the letters "L" and "V" are embossed on both sides of the incision line.
The tablet can be divided into equal halves.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Levofloxacin Accord is indicated in adults for the treatment of the infections listed below (see sections 4.4 and 5.1)
- Acute bacterial sinusitis.
- Acute exacerbation of chronic bronchitis.
- Community-acquired pneumonia.
- Complicated skin and soft tissue infections.
For the infections mentioned above Levofloxacin Accord should only be used when the use of commonly recommended antibacterial agents for the initial treatment of these infections is considered inappropriate.
- Pyelonephritis and uncomplicated urinary tract infections (see section 4.4).
- Chronic bacterial prostatitis.
- Uncomplicated cystitis (see section 4.4).
- Anthrax inhalations: post-exposure prophylaxis and curative treatment (see section 4.4).
Levofloxacin Accord can also be used to complete a course of therapy in patients who have shown improvement during initial intravenous levofloxacin treatment.
Official guidelines on the appropriate use of antibacterial agents should be considered.
04.2 Posology and method of administration
Levofloxacin Accord tablets are administered once or twice a day. The dosage depends on the type, severity of the infection and the sensitivity of the pathogen believed to be causing the infection.
Duration of treatment
The duration of therapy varies according to the course of the disease (see table below). As with any antibiotic therapy in general, administration of Levofloxacin Accord tablets should be continued for a minimum of 48-72 hours after the patient has become afebrile or after bacterial eradication has been achieved.
The following dosage recommendations can be provided for
Levofloxacin Accord tablets:
Dosage in patients with normal renal function (clearance of creatinine> 50 ml / min)
Special populations
Compromise of the functionality renal (clearance d And lla creatinine ≤ 5 0 m l / min)
1 No additional doses are required after hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
Impaired liver function
No dosage adjustment is required as levofloxacin is not significantly metabolised by the liver and is mainly excreted by the kidney.
Elderly population
No dosage adjustment is required in elderly patients other than that imposed by considerations on renal function (see section 4.4 "Tendonitis and tendon rupture" And "Prolongation of the QT interval').
Pediatric population
Levofloxacin is contraindicated in growing children and adolescents (see section 4.3).
Method of administration
Levofloxacin Accord tablets should be swallowed without chewing and with a sufficient amount of liquid. They can be split at the score to adjust the dose. The tablets can be taken with meals or between meals. Levofloxacin Accord tablets should be taken at least two hours before or after taking iron salts, zinc salts, antacids containing magnesium or aluminum, or didanosine (didanosine formulations containing aluminum or magnesium buffers only), and sucralfate, as absorption may be reduced (see section 4.5).
04.3 Contraindications
Levofloxacin Accord Tablets should not be used:
- in patients hypersensitive to levofloxacin or other quinolones or to any of the excipients listed in section 6.1,
- in epileptic patients,
- in patients with a history of tendon disorders related to fluoroquinolone administration,
- in children or adolescents in the period of growth,
- during pregnancy,
- in women who are breastfeeding.
04.4 Special warnings and appropriate precautions for use
Methicillin-resistant Staphylococcus aureus (MRSA)
Methicillin-resistant S. aureus is most likely to demonstrate cross-resistance to fluoroquinolones, including levofloxacin. Therefore levofloxacin is not recommended for the treatment of known or suspected MRSA infections unless laboratory results have confirmed the organism's susceptibility to levofloxacin (and commonly recommended antibacterial agents for the treatment of MRSA infections are considered inappropriate).
Levofloxacin can be used in the treatment of acute bacterial sinusitis and acute flare-up of chronic bronchitis if these infections have been adequately diagnosed.
Resistance to fluoroquinolones of E. coli - the pathogen most commonly involved in urinary tract infections - varies in different areas of the European Union. Prescribers should take into account the local prevalence of resistance of E. coli to fluoroquinolones.
Inhalation of anthrax: Use in humans is based on in vitro susceptibility data for Bacillus anthrax and animal experiments together with limited human data. Prescribers should refer to national and / or international consensus documents on anthrax treatment.
Tendonitis and tendon rupture
Tendonitis can rarely occur. It most frequently involves the Achilles tendon and can cause it to rupture. Tendonitis and tendon rupture, sometimes bilateral, can occur within 48 hours of starting treatment with levofloxacin and have been reported for up to several months after stopping treatment. The risk of tendonitis and tendon ruptures is increased in patients with more than 60 years, in patients receiving daily doses of 1000 mg and in patients using corticosteroids. In elderly patients the daily dose should be adjusted according to creatinine clearance (see section 4.2). Close monitoring of these patients is therefore necessary if Levofloxacin is prescribed for them. All patients should consult their treating physician if they experience symptoms of tendonitis. If tendonitis is suspected, treatment with levofloxacin should be stopped immediately and appropriate treatment (e.g. immobilization) initiated of the involved tendon (see sections 4.3 and 4.8).
Clostridium difficile disease
If diarrhea occurs, particularly if severe, persistent and / or bleeding, during or after treatment with levofloxacin (even several weeks after treatment), this may be symptomatic of the disease. Clostridium difficile (CDAD). The severity of CDAD can range from mild to life-threatening; the most severe form is pseudomembranous colitis (see section 4.8). It is therefore important to consider this diagnosis in patients who develop severe diarrhea during or after treatment with levofloxacin. In case of suspected or confirmed CDAD, levofloxacin should be discontinued immediately and therapeutic measures taken without delay (e.g. with metronidazole or oral vancomycin). In this clinical situation, drugs that inhibit peristalsis are contraindicated.
Patients predisposed to seizures
Quinolones can lower the seizure threshold and consequently can trigger seizures.
Levofloxacin is contraindicated in patients with a history of epilepsy (see section 4.3), and as with other quinolones, it should be used with extreme caution in patients predisposed to seizures, or in concomitant treatment with active substances that lower the cerebral seizure threshold, such as theophylline (see section 4.5). In the event of seizures (see section 4.8), levofloxacin treatment should be discontinued.
Patients with G-6-phosphate-dehydrogenase deficiency
Patients with latent or known defects in glucose-6-phosphate dehydrogenase activity may be predisposed to haemolytic reactions when treated with quinolone antibacterial agents. For this reason, if levofloxacin is to be used in this type of patient, it should be monitored. the potential for hemodialysis.
Patients with renal impairment
Since levofloxacin is mainly excreted by the kidneys, the dosage of Levofloxacin tablets should be adjusted in patients with renal impairment. (see section 4.2).
Hypersensitivity reactions
Levofloxacin may occasionally cause serious and life-threatening hypersensitivity reactions (eg from angioedema to anaphylactic shock) after the initial dose (see section 4.8). Patients should discontinue treatment immediately and contact their doctor or a professional. emergency room doctor, who will take appropriate emergency measures.
Severe bullous reactions
Cases of severe bullous skin reactions such as Steven-Johnson syndrome or toxic epidermal necrolysis have been reported with levofloxacin (see section 4.8). Patients should be advised to contact their physician immediately if skin and / or mucosal reactions occur before continuing treatment.
Dysglycemia
As with all quinolones, blood glucose disturbances, including both hypoglycemia and hyperglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with oral hypoglycemic agents (e.g. glibenclamide) or with insulin. Cases of hypoglycemic coma have been reported. Careful blood glucose monitoring is recommended in these diabetic patients (see section 4.8).
Prevention of photosensitization
Photosensitivity has been reported with levofloxacin (see section 4.8). It is recommended that patients do not expose themselves unnecessarily to intense sunlight or artificial ultraviolet rays (e.g. sun lamp, solarium) during treatment and 24 hours after treatment, in order to avoid photosensitization.
Patients treated with vitamin K antagonists
Due to a possible increase in coagulation test values (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 administered concurrently (see section 4.5).
Psychotic reactions
Psychotic reactions have been reported in patients taking quinolones, including levofloxacin. In very rare cases these have progressed to suicidal thoughts and self-endangering behaviors, sometimes after only a single dose of levofloxacin (see section 4.8). If the patient develops these reactions, levofloxacin should be discontinued and appropriate measures instituted. Caution is advised if levofloxacin is to be used in psychotic patients or in patients with a history of psychiatric illness.
Prolongation of the QT interval
Caution is advised when using fluoroquinolones, including levofloxacin, in patients with known risk factors for QT interval prolongation, such as, for example:
- congenital long QT syndrome
- concomitant use of medicinal products known to prolong the QT interval (eg class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics)
- incorrect electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
- heart disease (eg, heart failure, myocardial infarction, bradycardia).
Elderly patients and women may be more sensitive to medicinal products that prolong the QTc interval. Therefore, caution should be exercised when using fluoroquinolones, including levofloxacin, in these populations (see sections 4.2. Elderly population, 4.5, 4.8, 4.9).
Peripheral neuropathy
Peripheral sensory or sensorimotor neuropathy which can occur rapidly has been reported in patients treated with fluoroquinolones, including levofloxacin (see section 4.8). If the patient presents with symptoms of neuropathy, levofloxacin treatment should be discontinued to prevent the development of irreversible conditions.
Hepatobiliary disorders
Cases of hepatic necrosis which can escalate to fatal hepatic failure have been reported with levofloxacin, especially in patients with severe concomitant diseases, eg. sepsis (see section 4.8). Patients should be advised to discontinue treatment and contact their physician if signs and symptoms of liver disease develop, such as anorexia, jaundice, dark urine, itchy, or pressure-sore abdomen.
Exacerbation of myasthenia gravis
Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Post-marketing serious adverse reactions, including death and the need for respiratory support, have been associated with the use of fluoroquinolones in patients with myasthenia gravis. Levofloxacin is not recommended in patients with a history of myasthenia gravis.
Visual disturbances
If vision becomes blurred or any effect on the eyes occurs, an ophthalmologist should be consulted immediately (see sections 4.7 and 4.8).
Superinfection
The use of levofloxacin, especially if prolonged, may result in the growth of non-sensitive organisms. If superinfection occurs during therapy, appropriate measures should be taken.
Interference with laboratory analyzes
In patients treated with levofloxacin, the determination of opioids in urine may give false-positive results. To confirm positivity it may be necessary to perform the analysis by a more specific method.
Levofloxacin can inhibit the growth of Mycobacterium tuberculosis and, therefore, can give false negative results in the bacteriological diagnosis of tuberculosis.
04.5 Interactions with other medicinal products and other forms of interaction
Effect of other medicinal products on levofloxacin
Iron salts, zinc salts, antacids containing magnesium or aluminum, didanosine
The absorption of levofloxacin is significantly reduced when iron salts, antacids containing magnesium or aluminum or didanosine (only formulations of didanosine containing aluminum or magnesium buffers) are co-administered with Levofloxacin Accord. Concomitant administration of fluoroquinolones with zinc-containing multivitamins , appears to reduce oral absorption. It is recommended that preparations containing divalent or trivalent cations, such as iron salts, zinc salts or antacids containing magnesium or aluminum, or didanosine (didanosine formulations containing aluminum or magnesium buffers only) are not administered 2 hours before or after taking Levofloxacin Accord tablets (see section 4.2). Calcium salts have a minimal effect on the oral absorption of levofloxacin.
Sucralfate
The bioavailability of Levofloxacin Accord tablets significantly decreases when administered concomitantly with consucralfate. If the patient is to receive both sucralfate and Levofloxacin Accord tablets, it is best to administer sucralfate 2 hours after administration of Levofloxacin Accord tablets (see section 4.2).
Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs
No pharmacokinetic interactions between vofloxacin and theophylline were shown in a clinical study. However, a marked reduction in the seizure threshold may occur when quinolones are administered concomitantly with theophylline, non-steroidal anti-inflammatory drugs, or other agents that lower the seizure threshold.
Levofloxacin concentrations were approximately 13% higher in the presence of phenbufen than when given alone.
Probenecid and cimetidine
Probenecid and ecimetidine 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 due to the fact that both drugs are able to block the renal tubular secretion of levofloxacin. However, at the dosages tested in the study course, statistically significant kinetic differences are unlikely to be of clinical relevance. Caution is advised when levofloxacin is administered concomitantly with drugs that induce renal tubular secretion, such as probenecid and ecimetidine, especially in patients with renal impairment.
Other relevant information
Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin are not changed in a clinically relevant way when levofloxacin is co-administered with the following drugs:
- calcium carbonate
- digoxin
- glibenclamide
- ranitidine
Effect of levofloxacin on other drugs
Cyclosporine
The half-life of ciclosporin was increased by 33% when administered concomitantly with levofloxacin.
Vitamin K antagonists
Increases in coagulation test values (PT / INR) and / or bleeding, which can be serious, have been reported in patients treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin). Therefore, coagulation tests should be monitored in patients treated with vitamin K antagonists (see section 4.4).
Drugs known to prolong the QT interval
Levofloxacin, like other fluoroquinolones, should be used with caution in patients being treated with drugs known to prolong the QT interval (eg class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics). (See section 4.4 Prolongation of the QT interval).
Other important information
In a pharmacokinetic interaction study, levofloxacin did not change the pharmacokinetics of theophylline (which is a CYP1A2 substrate), indicating that levofloxacin is not a CYP1A2 inhibitor.
Other forms of interaction
Food
There are no clinically relevant interactions with food. Levofloxacin Accord tablets can therefore be administered without regard to food.
04.6 Pregnancy and lactation
Pregnancy
There are limited data on the use of levofloxacin in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). However, in the absence of human data and due to experimental risks of damage by fluoroquinolones to the weight-bearing cartilages of the growing organism, levofloxacin should not be used in pregnant women (see sections 4.3 and 5.3).
Feeding time
Levofloxacin Accord is contraindicated in women who are breastfeeding. There is insufficient information on the excretion of levofloxacin in human breast milk; however other fluoroquinolones are excreted in human milk. In the absence of human data and due to potential risk of damage by fluoroquinolones to the weight-bearing cartilages of the growing organism , levofloxacin should not be used in breastfeeding women (see sections 4.3 and 5.3).
Fertility
Levofloxacin did not cause impairment of fertility or reproductive outcomes in rats.
04.7 Effects on ability to drive and use machines
Some undesirable effects (e.g. dizziness / vertigo, somnolence, visual disturbances) could impair the patient's ability to concentrate and react and therefore constitute a risk factor in situations where these abilities are of particular importance (e.g. while driving motor vehicles or use of machinery).
04.8 Undesirable effects
The information below is based on data from clinical studies involving more than 8300 patients and extensive post-marketing experience.
Frequencies are defined using the following convention: very common (1/10), common (1/100,
Within the different frequency groups, undesirable effects are presented in order of decreasing severity.
a Anaphylactic and anaphylactoid reactions can sometimes appear even after the first dose
b Mucocutaneous reactions may sometimes occur even after the first administration
Other side effects associated with fluoroquinolone administration include:
- attacks of porphyria in patients with porphyria.
Reporting of side effects
If you get any side effects, including any possible side effects not listed in this leaflet, contact your doctor or pharmacist. Undesirable effects can also be reported directly through the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects you can help provide more information on the safety of this medicine.
04.9 Overdose
According to animal toxicity studies or clinical pharmacology studies conducted at doses above therapeutic doses, the most important signs that can be expected after acute overdose with levofloxacin are those in the central nervous system, such as confusion. , dizziness, impaired consciousness, seizures, prolongation of the QT interval, and gastrointestinal reactions such as nausea and mucosal erosions.
CNS effects including confusion, convulsions, hallucinations and tremor have been observed in post-marketing experience.
In the event of an overdose, symptomatic treatment should be practiced. Electrocardiographic monitoring (ECG) should be performed, due to a possible prolongation of the QT interval. Antacids may be used to protect the gastric mucosa. Hemodialysis, including peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD) , are not effective in removing levofloxacin from the body. There is no specific antidote.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: anti-infectives for systemic use - antibacterials for systemic use - quinolone antibacterials - fluoroquinolones.
ATC code: J01MA12.
Levofloxacin is a synthetic antibacterial agent belonging to the class of fluoroquinolones and is the S (-) enantiomer of the racemic of ofloxacin.
Mechanism of action
As a fluoroquinolone antibacterial agent, levofloxacin acts on the DNA-DNA-gyrase complex and topoisomerase IV.
PK / PD relationship
The degree of bactericidal activity of levofloxacin depends on the ratio of the maximum serum concentration (Cmax) or area under the curve (AUC) and the minimal inhibitory concentration (MIC).
Resistance mechanism (s)
Resistance to levofloxacin is acquired through a step-by-step process with target site mutations in both type II topoisomerases, DNA gyrase topisomerase IV. Other resistance mechanisms such as permeability barriers (common in Pseudomonas aeruginosa) and efflux mechanisms may also modify susceptibility to levofloxacin.
C "is cross-resistance between levofloxacin and other fluoroquinolones.
Due to the particular mechanism of action, there is generally no cross-resistance between levofloxacin and other classes of antibacterial agents.
Breakpoint
The MIC breakpoints recommended by EUCAST for levofloxacin, which separate susceptible organisms from those with intermediate susceptibility, and the latter from resistant organisms, are presented in the table below according to the tested MICs (mg / L).
EUCAST clinical MIC breakpoints for levofloxacin (version 2.0, 01-01- 2012):
1 The breakpoints for levofloxacin are related to high dose therapy.
2 Low levels of resistance to fluoroquinolones (ciprofloxacin MICs of 0.12-0.5 mg / l) may occur but there is no evidence that this resistance is of clinical importance in respiratory tract infections with H. influenzae.
3 Strains with MIC values above the sensitive breakpoint are very rare or not yet reported. Identification and antimicrobial susceptibility tests on these isolates should be repeated and, if the result is confirmed, the isolate should be sent to a reference laboratory. As long as there is no evidence of a clinical response for confirmed isolates with MICs above current resistance breakpoint levels, these isolates should be reported resistant.
4 Breakpoint values apply to an oral dose of 500 mg x 1 to 500 mg x 2 and an intravenous dose of 500 mg x 1 to 500 mg x 2.
For selected species, the prevalence of resistance may vary geographically and with time and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the medicinal product in at least some types of infections is questionable.
at least some types of infections, it is questionable.
# S. aureus resistant methicillin most likely possesses cross-resistance to fluoroquinolones, including levofloxacin.
05.2 "Pharmacokinetic properties
Absorption
Administered orally, levofloxacin is rapidly and almost completely absorbed with peak plasma concentrations achieved within 1-2 hours. The absolute bioavailability is 99-100%.
Food has little effect on the absorption of levofloxacin.
Steady state is achieved within 48 hours with a 500 mg once or twice daily dosing regimen.
Distribution
The binding of levofloxacin to serum proteins is approximately 30-40%. The mean volume of distribution of levofloxacin is approximately 100 l after single and repeated doses of 500 mg, indicating "wide distribution in body tissues".
Penetration into the tissues and liquids of the body
Levofloxacin has been shown to penetrate bronchial mucosa, lining epithelial fluids, alveolar macrophages, lung tissue, skin (blister fluid), prostate tissue, and urine. However, levofloxacin has poor brain fluid penetration. -spinal.
Biotransformation
Levofloxacin is metabolised to a small extent to the metabolites desmethyl levofloxacin and levofloxacin N-oxide. These metabolites are found equal to a value
Elimination
After oral and intravenous administration, levofloxacin is eliminated from plasma relatively slowly (t½: 6-8 hours). Excretion is mainly via the kidney (> 85% of the administered dose).
The mean apparent total body clearance of levofloxacin following a single 500 mg dose is 175 +/- 29.2 mL / min.
Since there are no substantial pharmacokinetic differences after intravenous and oral administration, this suggests that the oral and intravenous routes of administration are interchangeable.
Linearity
Levofloxacin follows linear pharmacokinetics over the range of 50 to 1000 mg.
Special populations
Patients with renal insufficiency
The pharmacokinetics of levofloxacin are affected by renal impairment. As renal function decreases, renal elimination and clearance also decrease, while elimination half-lives increase, as shown in the following table.
Elderly patients
There are no significant differences in dilevofloxacin kinetics between young and elderly subjects, except those associated with differences in cratinin clearance.
Differences between the sexes
Separate analyzes between male and female subjects revealed small and marginal differences in the pharmacokinetics of levofloxacin. It is not clear whether these gender differences are of clinical relevance.
05.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of single dose toxicity, repeated dose toxicity, carcinogenic potential and toxicity to reproduction and development.
Levofloxacin did not cause impairment of fertility or reproduction in the rat and the only effect on fetuses was a delay in maturation as a result of maternal toxicity.
Levofloxacin did not induce genetic mutations in bacterial or mammalian cells, but it did induce in vitro Chromosomal aberrations on Chinese hamster lung cells. These effects can be attributed to the inhibition of topoisomerase II. In vivo tests (micronucleus, cell chromatid exchange, unscheduled DNA synthesis, dominant lethal test) show no genotoxic potential.
Studies in mice showed "phototoxic activity of levofloxacin only at very high doses. Levofloxacin shows no potential genotoxic activity in photomutagenesis tests and reduces tumor development in photocarcinogenesis tests."
As with other fluoroquinolones, levofloxacin showed effects on cartilage (blistering and cavity formation) in rats and dogs. These findings are more pronounced in young animals.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Tablet core:
Povidone
Crospovidone (Type-B)
Microcrystalline cellulose
Magnesium stearate
Anhydrous colloidal silica
Tablet coating :
Hypromellose E5
Talc
Titanium dioxide (E171)
Macrogol 400
Yellow iron oxide (E172)
Red iron oxide (E172)
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
The tablets are packed in PVC / aluminum blisters.
For 250 mg, the tablets are supplied in packs of 1, 2, 3, 5, 7, 10, 30,
50 and 200 tablets.
For 500 mg, the tablets are supplied in packs of 1, 2, 5, 7, 10, 30,
50, 200 and 500 tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Accord Healthcare Limited, Sage House, 319 Pinner Road,
North Harrow HA1 4HF, Middlesex, United Kingdom
08.0 MARKETING AUTHORIZATION NUMBER
"250 mg film-coated tablets", 1 tablet in PVC / AL A.I.C. nr .: 041428018
"250 mg film-coated tablets", 2 tablets in PVC / AL A.I.C. nr .: 041428020
"250 mg film-coated tablets", 3 tablets in PVC / AL A.I.C. nr .: 041428032
"250 mg film-coated tablets", 5 tablets in PVC / AL A.I.C. nr .: 041428044
"250 mg film-coated tablets", 7 tablets in PVC / AL A.I.C. nr .: 041428057
"250 mg film-coated tablets", 10 tablets in PVC / AL A.I.C. nr .: 041428069
"250 mg film-coated tablets", 30 tablets in PVC / AL A.I.C. nr .: 041428071
"250 mg film-coated tablets", 50 tablets in PVC / AL A.I.C. nr .: 041428083
"250 mg film-coated tablets", 200 tablets in PVC / AL A.I.C. nr .: 041428095
"500 mg film-coated tablets", 1 tablet in PVC / AL A.I.C. nr .: 041428107
"500 mg film-coated tablets", 2 tablets in PVC / AL A.I.C. nr .: 041428119
"500 mg film-coated tablets", 5 tablets in PVC / AL A.I.C. nr .: 041428121
"500 mg film-coated tablets", 7 tablets in PVC / AL A.I.C. nr .: 041428133
"500 mg film-coated tablets", 10 tablets in PVC / AL A.I.C. nr .: 041428145
"500 mg film-coated tablets", 30 tablets in PVC / AL A.I.C. nr .: 041428158
"500 mg film-coated tablets", 50 tablets in PVC / AL A.I.C. nr .: 041428160
"500 mg film-coated tablets", 200 tablets in PVC / AL A.I.C. nr .: 041428172
"500 mg film-coated tablets", 500 tablets in PVC / AL A.I.C. nr .: 041428184
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
02 March 2012
