LEVOFLOXACIN - levofloxacin tablet, film coated
Macleods Pharmaceuticals Limited
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HIGHLIGHTS OF PRESCRIBING INFORMATIONHIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use levofloxacin tablets safely and effectively. See full prescribing information for levofloxacin tablets Levofloxacin Tablet, Film Coated for Oral use Initial U.S. Approval: 1996 WARNING: Fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart and or lung transplants [See Warnings and Precautions (5.1)].Fluoroquinolones, including levofloxacin tablets, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid levofloxacin tablets in patients with a known history of myasthenia gravis [See Warnings and Precautions (5.2)]. RECENT MAJOR CHANGESINDICATIONS AND USAGELevofloxacin is a fluoroquinolone antibacterial indicated in adults (≥18 years of age) with infections caused by designated, susceptible bacteria (1, 12.4).
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHS
WARNINGS AND PRECAUTIONS
ADVERSE REACTIONSThe most common reactions (≥3%) were nausea, headache, diarrhea, insomnia, constipation and dizziness (6.2). To report SUSPECTED ADVERSE REACTIONS, contact AB Pharmaceuticals at (1) 314 814-2833 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch DRUG INTERACTIONS
USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. Revised: 05/2012 |
Fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants [See Warnings and Precautions (5.1)].
Fluoroquinolones, including levofloxacin, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid levofloxacin in patients with a known history of myasthenia gravis [See Warnings and Precautions (5.2)].
To reduce the development of drug-resistant bacteria and maintain the effectiveness of levofloxacin and other antibacterial drugs, levofloxacin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Levofloxacin Tablets are indicated for the treatment of adults (≥18 years of age) with mild, moderate, and severe infections caused by susceptible strains of the designated microorganisms in the conditions listed in this section.
Culture and susceptibility testing
Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin [see Clinical Pharmacology (12.4)]. Therapy with levofloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be selected.
As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin tablets. Culture and susceptibility testing performed periodically during therapy will provide information about the continued susceptibility of the pathogens to the antimicrobial agent and also the possible emergence of bacterial resistance.
Levofloxacin is indicated for the treatment of nosocomial pneumonia due to methicillinsusceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an antipseudomonal β-lactam is recommended [see Clinical Studies (14.1)].
Levofloxacin is indicated for the treatment of community-acquired pneumonia due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multidrug-resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.2)].
Levofloxacin is indicated for the treatment of acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see Clinical Studies (14.4)].
Levofloxacin is indicated for the treatment of acute bacterial exacerbation of chronic bronchitis due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis.
Levofloxacin is indicated for the treatment of uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to methicillin-susceptible Staphylococcus aureus, or Streptococcus pyogenes.
Levofloxacin is indicated for the treatment of chronic bacterial prostatitis due to Escherichia coli, Enterococcus faecalis, or methicillin-susceptible Staphylococcus epidermidis [see Clinical Studies (14.6)].
Levofloxacin is indicated for the treatment of complicated urinary tract infections (mild to moderate) due to Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa [see Clinical Studies (14.8)].
Levofloxacin is indicated for the treatment of acute pyelonephritis caused by Escherichia coli, including cases with concurrent bacteremia [see Clinical Studies(14.7, 14.8)].].
Levofloxacin is indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.
The usual dose of Levofloxacin Tablets is 250 mg, 500 mg, or 750 mg administered orally every 24 hours, as indicated by infection and described in Table 1.
These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance <50 mL/min, adjustments to the dosing regimen are required [see Dosage and Administration (2.3)].
Table 1: Dosage in Adult Patients with Normal Renal Function (creatinine clearance ≥ 50 mL/min)>
|
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Type of Infection*
| Dosed Every 24 hours
| Duration (days)†
|
Nosocomial Pneumonia | 750 mg | 7–14 |
Community Acquired Pneumonia‡
| 500 mg | 7–14 |
Community Acquired Pneumonia§
| 750 mg | 5 |
Acute Bacterial Sinusitis | 750 mg | 5 |
500 mg | 10–14 |
|
Acute Bacterial Exacerbation of Chronic Bronchitis | 500 mg | 7 |
Complicated Skin and Skin Structure Infections (SSSI) | 750 mg | 7–14 |
Uncomplicated SSSI | 500 mg | 7–10 |
Chronic Bacterial Prostatitis | 500 mg | 28 |
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)¶ | 750 mg | 5 |
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)#
| 250 mg | 10 |
Uncomplicated Urinary Tract Infection | 250 mg | 3 |
Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kg and ≥ 6 months of ageÞ,ß Pediatric patients < 50 kg and ≥ 6 months of ageÞ,ß | 500 mg see Table 2 below (2.2) | 60ß
60ß |
Type of infection* | Dose | Freq. Once every | Duration† |
---|---|---|---|
|
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Inhalational Anthrax (post exposure)‡,§
| | | |
Pediatric patients > 50 kg and ≥ 6 months of age | 500 mg | 24 hr | 60 days§
|
Pediatric patients < 50 kg and ≥ 6 months of age | 8 mg/kg (not to exceed 250 mg per dose) | 12 hr | 60 days§
|
Administer levofloxacin with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.
No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.
Dosage in Normal Renal Function Every 24 hours | Creatinine Clearance 20 to 49 mL/min | Creatinine Clearance 10 to 19 mL/min | Hemodialysis or Chronic Ambulatory Peritoneal Dialysis (CAPD) |
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750 mg | 750 mg every 48 hours |
750 mg initial dose, then 500 mg every 48 hours |
750 mg initial dose, then 500 mg every 48 hours |
500 mg |
500 mg initial dose, then 250 mg every 24 hours |
500 mg initial dose, then 250 mg every 48 hours |
500 mg initial dose, then 250 mg every 48 hours |
250 mg | No dosage adjustment required |
250 mg every 48 hours. If treating uncomplicated UTI, then no dosage adjustment is required | No information on dosing adjustment is available |
Levofloxacin Tablets
Levofloxacin Tablets should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine chewable/buffered tablets or the pediatric powder for oral solution [see Drug Interactions (7.1) and Patient Counseling Information (17.2)] .
Food and Levofloxacin Tablets
Levofloxacin Tablets can be administered without regard to food.
Hydration for Patients Receiving Levofloxacin Tablets
Adequate hydration of patients receiving oral levofloxacin should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones [see Adverse Reactions (6.1) and Patient Counseling Information (17.2)].
TABLETS, Film-coated, capsule-shaped
Levofloxacin is contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see Warnings and Precautions (5.3)].
The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is further increased in older patients usually over 60 years of age, in those taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Factors, in addition to age and corticosteroid use, that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have been reported in patients taking fluoroquinolones who do not have the above risk factors. Tendon rupture can occur during or after completion of therapy; cases occurring up to several months after completion of therapy have been reported. Levofloxacin should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon. Patients should be advised to rest at the first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing to a non-quinolone antimicrobial drug. [see Adverse Reactions ( 6.3 ); Patient Counseling Information ( 17.3 )]
Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid levofloxacin in patients with a known history of myasthenia gravis [see Adverse Reactions (6.3); Patient Counseling Information (17.3)].
Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with fluoroquinolones, including levofloxacin. These reactions often occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat, or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), dyspnea, urticaria, itching, and other serious skin reactions. Levofloxacin should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity. Serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated [see Adverse Reactions (6); Patient Counseling Information (17.3)].
The drug should be discontinued immediately at the first appearance of skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted [see Adverse Reactions (6); Patient Counseling Information (17.3)].
Post-marketing reports of severe hepatotoxicity (including acute hepatitis and fatal events) have been received for patients treated with levofloxacin. No evidence of serious drug-associated hepatotoxicity was detected in clinical trials of over 7,000 patients. Severe hepatotoxicity generally occurred within 14 days of initiation of therapy and most cases occurred within 6 days. Most cases of severe hepatotoxicity were not associated with hypersensitivity [see Warnings and Precautions (5.4)]. The majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. Levofloxacin should be discontinued immediately if the patient develops signs and symptoms of hepatitis [see Adverse Reactions (6); Patient Counseling Information (17.3)].
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including levofloxacin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
Some fluoroquinolones, including levofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. Rare cases of torsade de pointes have been spontaneously reported during postmarketing surveillance in patients receiving fluoroquinolones, including levofloxacin. Levofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving ClassIA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval [see Adverse Reactions (6.3), Use in Specific Populations (8.5), and Patient Counseling Information (17.3)].
As with other fluoroquinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported with levofloxacin, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glyburide) or with insulin. In these patients, careful monitoring of blood glucose is recommended. If a hypoglycemic reaction occurs in a patient being treated with levofloxacin, levofloxacin should be discontinued and appropriate therapy should be initiated immediately [see Adverse Reactions (6.2); Drug Interactions (7.3); Patient Counseling Information (17.4)]
Prescribing levofloxacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria [see Patient Counseling Information (17.1)].
The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:
Crystalluria and cylindruria have been reported with quinolones, including levofloxacin. Therefore, adequate hydration of patients receiving levofloxacin should be maintained to prevent the formation of a highly concentrated urine [see Dosage and Administration (2.5)].
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
System/Organ Class | Adverse Reaction | % (N=7537) |
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---|---|---|---|---|---|
Infections and Infestations |
moniliasis |
1 |
|||
Psychiatric Disorders |
insomnia* [see Warnings and Precautions (5.6)] |
4 |
|||
Nervous System Disorders |
headache dizziness [see Warnings and Precautions (5.6)] |
6 3 |
|||
Respiratory, Thoracic and Mediastinal Disorders |
dyspnea [see Warnings and Precautions (5.3)] |
1 |
|||
Gastrointestinal Disorders |
nausea diarrhea constipation abdominal pain vomiting dyspepsia |
7 5 3 2 2 2 |
|||
Skin and Subcutaneous Tissue Disorders |
rash [see Warnings and Precautions (5.3)] pruritus |
2 1 |
|||
Reproductive System and Breast Disorders |
vaginitis |
1† |
|||
General Disorders and Administration Site Conditions |
edema injection site reaction chest pain |
1 1 1 |
System/Organ Class | Adverse Reaction |
---|---|
Infections and Infestations
| genital moniliasis |
Blood and Lymphatic System Disorders
| anemia thrombocytopenia granulocytopenia [see Warnings and Precautions (5.4)] |
Immune System Disorders
| allergic reaction [See Warnings and Precautions ( 5.3,5.4)]
|
Metabolism and Nutrition Disorders
| hyperglycemia hypoglycemia [see Warnings and Precautions (5.11)] hyperkalemia |
Psychiatric Disorders
| anxiety agitation confusion depression hallucination nightmare* [see Warnings and Precautions (5.6)] sleep disorder* anorexia abnormal dreaming* |
Nervous System Disorders
| tremor convulsions [see Warnings and Precautions (5.6)] paresthesia [see Warnings and Precautions (5.8)] vertigo hypertonia hyperkinesias abnormal gait somnolence* syncope |
Respiratory, Thoracic and Mediastinal Disorders
| epistaxis |
Cardiac Disorders
| cardiac arrest palpitation ventricular tachycardia ventricular arrhythmia |
Vascular Disorders
| phlebitis |
Gastrointestinal Disorders
| gastritis stomatitis pancreatitis esophagitis gastroenteritis glossitis pseudomembraneous/ C. difficile colitis [see Warnings and Precautions (5.7)] |
Hepatobiliary Disorders
| abnormal hepatic function increased hepatic enzymes increased alkaline phosphatase |
Skin and Subcutaneous Tissue Disorders
| urticaria [see Warnings and Precautions (5.3)] |
Musculoskeletal and Connective Tissue Disorders
| arthralgia tendinitis [see Warnings and Precautions (5.1)] myalgia skeletal pain |
Renal and Urinary Disorders
| abnormal renal function acute renal failure [see Warnings and Precautions (5.4)] |
System/Organ Class | Adverse Reaction |
---|---|
Blood and Lymphatic System Disorders
| pancytopenia aplastic anemia leukopenia hemolytic anemia [see Warnings and Precautions (5.4)] eosinophilia |
Immune System Disorders
| hypersensitivity reactions, sometimes fatal including: anaphylactic/anaphylactoid reactions anaphylactic shock angioneurotic edema serum sickness [see Warnings and Precautions (5.3, 5.4)] |
Psychiatric Disorders
| psychosis paranoia isolated reports of suicide attempt and suicidal ideation [see Warnings and Precautions (5.6)] |
Nervous System Disorders
| Exacerbation of myasthenia gravis [see Warnings and Precautions (5.2)]
anosmia ageusia parosmia dysgeusia peripheral neuropathy [see Warnings and Precautions (5.8)] isolated reports of encephalopathy abnormal electroencephalogram (EEG) dysphonia pseudotumor cerebri [see Warning and Precautions (5.6)] |
Eye Disorders
| vision disturbance, including diplopia visual acuity reduced vision blurred scotoma |
Ear and Labyrinth Disorders
| hypoacusis tinnitus |
Cardiac Disorders
| isolated reports of torsade de pointes electrocardiogram QT prolonged [see Warnings and Precautions (5.9)] tachycardia |
Vascular Disorders
| vasodilatation |
Respiratory, Thoracic and Mediastinal Disorders
| isolated reports of allergic pneumonitis [see Warnings and Precautions (5.4)]
|
Hepatobiliary Disorders
| hepatic failure (including fatal cases) hepatitis jaundice [see Warnings and Precautions 5.4, 5.5)] |
Skin and Subcutaneous Tissue Disorders | bullous eruptions to include: Stevens-Johnson Syndrome toxic epidermal necrolysis erythema multiforme [see Warnings and Precautions (5.4)] photosensitivity/photoxicity reaction [see Warnings and Precautions (5.12)] leukocytoclastic vasculitis |
Musculoskeletal and Connective Tissue Disorders
| tendon rupture [see Warnings and Precautions (5.1)]
muscle injury, including rupture rhabdomyolysis |
Renal and Urinary Disorders
| interstitial nephritis [see Warnings and Precautions (5.4)]
|
General Disorders and Administration Site Conditions
| multi-organ failure pyrexia |
Investigations
| prothrombin time prolonged international normalized ratio prolonged muscle enzymes increased |
No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for R- and S- warfarin was detected in a clinical study involving healthy volunteers. Similarly, no apparent effect of warfarin on levofloxacin absorption and disposition was observed. However, there have been reports during the postmarketing experience in patients that levofloxacin enhances the effects of warfarin. Elevations of the prothrombin time in the setting of concurrent warfarin and levofloxacin use have been associated with episodes of bleeding. Prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if levofloxacin is administered concomitantly with warfarin. Patients should also be monitored for evidence of bleeding [see Adverse Reactions (6.3); Patient Counseling Information (17.4)].
Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered [see Warnings and Precautions (5.11); Adverse Reactions (6.2), Patient Counseling Information (17.4)].
No significant effect of levofloxacin on the plasma concentrations, AUC, and other disposition parameters for theophylline was detected in a clinical study involving healthy volunteers. Similarly, no apparent effect of theophylline on levofloxacin absorption and disposition was observed. However, concomitant administration of other fluoroquinolones with theophylline has resulted in prolonged elimination half-life, elevated serum theophylline levels, and a subsequent increase in the risk of theophylline-related adverse reactions in the patient population. Therefore, theophylline levels should be closely monitored and appropriate dosage adjustments made when levofloxacin is co-administered. Adverse reactions, including seizures, may occur with or without an elevation in serum theophylline levels [see Warnings and Precautions (5.6)].
No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for digoxin was detected in a clinical study involving healthy volunteers. Levofloxacin absorption and disposition kinetics were similar in the presence or absence of digoxin. Therefore, no dosage adjustment for levofloxacin or digoxin is required when administered concomitantly.
There are, however, no adequate and well-controlled studies in pregnant women. Levofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Based on data on other fluoroquinolones and very limited data on levofloxacin, it can be presumed that levofloxacin will be excreted in human milk. Because of the potential for serious adverse reactions from levofloxacin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species. [see Warnings and Precautions [5.10] and Animal Toxicology and/or Pharmacology (13.2)]
Inhalational Anthrax (Post-Exposure)
Levofloxacin is indicated in pediatric patients for inhalational anthrax (post-exposure). The risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate. The safety of levofloxacin in pediatric patients treated for more than 14 days has not been studied. The pharmacokinetics of levofloxacin following a single intravenous dose were investigated in pediatric patients ranging in age from six months to 16 years. Pediatric patients cleared levofloxacin faster than adult patients resulting in lower plasma exposures than adults for a given mg/kg dose [see Indications and Usage (1.13), Dosage and Administration (2.2), Clinical Pharmacology (12.3) and Clinical Studies (14.9)].
Adverse Events
In clinical trials, 1534 children (6 months to 16 years of age) were treated with oral and intravenous levofloxacin. Children 6 months to 5 years of age received levofloxacin 10 mg/kg twice a day and children greater than 5 years of age received 10 mg/kg once a day (maximum 500 mg per day) for approximately 10 days.
A subset of children in the clinical trials (1340 levofloxacin -treated and 893 non-fluoroquinolone-treated) enrolled in a prospective, long-term surveillance study to assess the incidence of protocol-defined musculoskeletal disorders (arthralgia, arthritis, tendinopathy, gait abnormality) during 60 days and 1 year following the first dose of study drug. Children treated with lebvofloxacin had a significantly higher incidence of musculoskeletal disorders when compared to the non-fluoroquinolone-treated children as illustrated in Table 9.
Follow-up Period | Levofloxacin N = 1340 | Non-Fluoroquinolone*
N = 893 | p-value† | ||||
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|
|||||||
60 days | 28 (2.1%) | 8 (0.9%) | p = 0.038 |
||||
1 year‡
| 46 (3.4%) | 16 (1.8%) | p = 0.025 |
Vomiting and diarrhea were the most frequently reported adverse events, occurring in similar frequency in the levofloxacin -treated and non-fluoroquinolone-treated children.
In addition to the events reported in pediatric patients in clinical trials, events reported in adults during clinical trials or post-marketing experience [see Adverse Reactions (6)] may also be expected to occur in pediatric patients.
Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as levofloxacin. This risk is further increased in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. Caution should be used when prescribing levofloxacin to elderly patients especially those on corticosteroids. Patients should be informed of this potential side effect and advised to discontinue levofloxacin and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [see Boxed Warning; Warnings and Precautions (5.1); and Adverse Reactions (6.3)].
Severe, and sometimes fatal, cases of hepatotoxicity have been reported post-marketing in association with levofloxacin. The majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. Levofloxacin should be discontinued immediately if the patient develops signs and symptoms of hepatitis [see Warnings and Precautions (5.5)].
Elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, precaution should be taken when using levofloxacin with concomitant drugs that can result in prolongation of the QT interval (e.g., Class IA or Class III antiarrhythmics) or in patients with risk factors for torsade de pointes (e.g., known QT prolongation, uncorrected hypokalemia) [see Warnings and Precautions (5.9)].
Clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in patients with impaired renal function (creatinine clearance < 50 mL/min), requiring dosage adjustment in such patients to avoid accumulation. Neither hemodialysis nor continuous ambulatory peritoneal dialysis (CAPD) is effective in removal of levofloxacin from the body, indicating that supplemental doses of levofloxacin are not required following hemodialysis or CAPD [see Dosage and Administration (2.3)].
In the event of an acute overdosage, the stomach should be emptied. The patient should be observed and appropriate hydration maintained. Levofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis.
Levofloxacin exhibits a low potential for acute toxicity. Mice, rats, dogs and monkeys exhibited the following clinical signs after receiving a single high dose oflevofloxacin: ataxia, ptosis, decreased locomotor activity, dyspnea, prostration, tremors, and convulsions. Doses in excess of 1500 mg/kg orally and 250 mg/kg IV produced significant mortality in rodents.
The empirical formula is C18H20FN3O4 •½ H2O and the molecular weight is 370.38. Levofloxacin is a light yellowish-white to yellow-white crystal or crystalline powder. The molecule exists as a zwitterion at the pH conditions in the small intestine.
The data demonstrate that from pH 0.6 to 5.8, the solubility of levofloxacin is essentially constant (approximately 100 mg/mL). Levofloxacin is considered soluble to freely soluble in this pH range, as defined by USP nomenclature. Above pH 5.8, the solubility increases rapidly to its maximum at pH 6.7 (272 mg/mL) and is considered freely soluble in this range. Above pH 6.7, the solubility decreases and reaches a minimum value (about 50 mg/mL) at a pH of approximately 6.9.
Levofloxacin Tablets are available as film-coated tablets and contain the following inactive ingredients:
Levofloxacin is a member of the fluoroquinolone class of antibacterial agents [see Clinical Pharmacology (12.4)].
Regimen | Cmax | Tmax | AUC | CL/F* | Vd/F† | t1/2 | CLR | |
---|---|---|---|---|---|---|---|---|
(mcg/mL) | (h) | (mcg∙h/mL) | (mL/min) | (L) | (h) | (mL/min) | ||
Single dose | ||||||||
|
||||||||
250 mg oral tablet‡
| 2.8 ± 0.4 | 1.6± 1.0 | 27.2 ± 3.9 | 156 ± 20 | ND | 7.3 ± 0.9 | 142±21 |
|
500 mg oral tablet‡,§
| 5.1 ± 0.8 | 1.3 ± 0.6 | 47.9±6.8 | 178 ± 28 | ND | 6.3 ± 0.6 | 103±30 |
|
500 mg oral solution¶
| 5.8 ± 1.8 | 0.8 ± 0.7 | 47.8±10.8 | 183 ± 40 | 112 ± 37.2 | 7.0 ± 1.4 | ND |
|
500 mg IV‡
| 6.2 ± 1.0 | 1.0 ± 0.1 | 48.3±5.4 | 175 ± 20 | 90 ± 11 | 6.4 ± 0.7 | 112±25 |
|
750 mg oral tablet#,§
| 9.3 ± 1.6 | 1.6 ± 0.8 | 101±20 | 129 ± 24 | 83 ± 17 | 7.5 ± 0.9 | ND |
|
750 mg IV#
| 11.5 ± 4.0Þ
| ND | 110±40 | 126 ±39 | 75±13 | 7.5 ± 1.6 | ND |
|
Multiple dose | ||||||||
500 mg every 24h oral tablet‡
| 5.7 ± 1.4 | 1.1 ± 0.4 | 47.5±6.7 | 175 ± 25 | 102 ± 22 | 7.6 ± 1.6 | 116±31 |
|
500 mg every 24h IV‡
| 6.4 ± 0.8 | ND | 54.6±11.1 | 158 ± 29 | 91 ± 12 | 7.0 ± 0.8 | 99±28 |
|
500 mg or 250 mg every 24h IV, patients with bacterial infectionß
| 8.7± 4.07à
| ND | 72.5±51.27 | 154 ± 72 | 111 ± 58 | ND | ND |
|
750 mg every 24h oral tablet#
| 8.6 ± 1.9 | 1.4 ± 0.5 | 90.7±17.6 | 143 ± 29 | 100 ± 16 | 8.8 ± 1.5 | 116±28 |
|
750 mg every 24h IV#
| 12.1±4.14Þ
| ND | 108±34 | 126 ± 37 | 80 ± 27 | 7.9 ± 1.9 | ND |
|
500 mg oral tablet single dose, effects of gender and age:
|
||||||||
Maleè
| 5.5 ± 1.1 | 1.2± 0.4 | 54.4 ± 18.9 | 166 ± 44 | 89 ± 13 | 7.5 ± 2.1 | 126 ± 38 |
|
Femaleð
| 7.0 ± 1.6 | 1.7± 0.5 | 67.7 ± 24.2 | 136 ± 44 | 62 ± 16 | 6.1 ± 0.8 | 106 ± 40 |
|
Youngø
| 5.5 ± 1.0 | 1.5± 0.6 | 47.5 ± 9.8 | 182 ± 35 | 83 ± 18 | 6.0 ± 0.9 | 140 ± 33 |
|
Elderlyý
| 7.0 ± 1.6 | 1.4± 0.5 | 74.7 ± 23.3 | 121 ± 33 | 67 ± 19 | 7.6 ± 2.0 | 91 ± 29 |
|
500 mg oral single dose tablet, patients with renal insufficiency:
|
||||||||
CLCR 50–80 mL/min | 7.5 ± 1.8 | 1.5 ± 0.5 | 95.6 ± 11.8 | 88 ± 10 | ND | 9.1 ± 0.9 | 57 ± 8 |
|
CLCR 20–49 mL/min | 7.1 ± 3.1 | 2.1 ± 1.3 | 182.1 ± 62.6 | 51 ± 19 | ND | 27 ± 10 | 26 ± 13 |
|
CLCR <20 mL/min | 8.2 ± 2.6 | 1.1 ± 1.0 | 263.5 ± 72.5 | 33 ± 8 | ND | 35 ± 5 | 13 ± 3 |
|
Hemodialysis | 5.7 ± 1.0 | 2.8 ± 2.2 | ND | ND | ND | 76 ± 42 | ND |
|
CAPD | 6.9 ± 2.3 | 1.4 ± 1.1 | ND | ND | ND | 51 ± 24 | ND |
Levofloxacin is rapidly and essentially completely absorbed after oral administration. Peak plasma concentrations are usually attained one to two hours after oral dosing. The absolute bioavailability of levofloxacin from a 500 mg tablet and a 750 mg tablet of levofloxacin are both approximately 99%, demonstrating complete oral absorption of levofloxacin. Following a single intravenous dose of levofloxacin to healthy volunteers, the mean ±SD peak plasma concentration attained was 6.2 ±1.0 mcg/mL after a 500 mg dose infused over 60 minutes and 11.5 ±4.0 mcg/mL after a 750 mg dose infused over 90 minutes. Levofloxacin Oral Solution and Tablet formulations are bioequivalent.
Distribution
The mean volume of distribution of levofloxacin generally ranges from 74 to 112 L after single and multiple 500 mg or 750 mg doses, indicating widespread distribution into body tissues. Levofloxacin reaches its peak levels in skin tissues and in blister fluid of healthy subjects at approximately 3 hours after dosing. The skin tissue biopsy to plasma AUC ratio is approximately 2 and the blister fluid to plasma AUC ratio is approximately 1 following multiple once-daily oral administration of 750 mg and 500 mg doses of levofloxacin, respectively, to healthy subjects. Levofloxacin also penetrates well into lung tissues. Lung tissue concentrations were generally 2- to 5- fold higher than plasma concentrations and ranged from approximately 2.4 to 11.3 mcg/g over a 24-hour period after a single 500 mg oral dose.
In vitro, over a clinically relevant range (1 to 10 mcg/mL) of serum/plasma levofloxacin concentrations, levofloxacin is approximately 24 to 38% bound to serum proteins across all species studied, as determined by the equilibrium dialysis method. Levofloxacin is mainly bound to serum albumin in humans. Levofloxacin binding to serum proteins is independent of the drug concentration.
Metabolism
Levofloxacin is stereochemically stable in plasma and urine and does not invert metabolically to its enantiomer, D-ofloxacin. Levofloxacin undergoes limited metabolism in humans and is primarily excreted as unchanged drug in the urine. Following oral administration, approximately 87% of an administered dose was recovered as unchanged drug in urine within 48 hours, whereas less than 4% of the dose was recovered in feces in 72 hours. Less than 5% of an administered dose was recovered in the urine as the desmethyl and N-oxide metabolites, the only metabolites identified in humans. These metabolites have little relevant pharmacological activity.
ExcretionLevofloxacin is excreted largely as unchanged drug in the urine. The mean terminal plasma elimination half-life of levofloxacin ranges from approximately 6 to 8 hours following single or multiple doses of levofloxacin given orally or intravenously. The mean apparent total body clearance and renal clearance range from approximately 144 to 226 mL/min and 96 to 142 mL/min, respectively. Renal clearance in excess of the glomerular filtration rate suggests that tubular secretion of levofloxacin occurs in addition to its glomerular filtration. Concomitant administration of either cimetidine or probenecid results in approximately 24% and 35% reduction in the levofloxacin renal clearance, respectively, indicating that secretion of levofloxacin occurs in the renal proximal tubule. No levofloxacin crystals were found in any of the urine samples freshly collected from subjects receiving levofloxacin.
GeriatricThere are no significant differences in levofloxacin pharmacokinetics between young and elderly subjects when the subjects' differences in creatinine clearance are taken into consideration. Following a 500 mg oral dose of levofloxacin to healthy elderly subjects (66 – 80 years of age), the mean terminal plasma elimination half-life of levofloxacin was about 7.6 hours, as compared to approximately 6 hours in younger adults. The difference was attributable to the variation in renal function status of the subjects and was not believed to be clinically significant. Drug absorption appears to be unaffected by age. Levofloxacin dose adjustment based on age alone is not necessary [See Use in Specific Populations (8.5)].
Pediatrics
The pharmacokinetics of levofloxacin following a single 7 mg/kg intravenous dose were investigated in pediatric patients ranging in age from 6 months to 16 years. Pediatric patients cleared levofloxacin faster than adult patients, resulting in lower plasma exposures than adults for a given mg/kg dose. Subsequent pharmacokinetic analyses predicted that a dosage regimen of 8 mg/kg every 12 hours (not to exceed 250 mg per dose) for pediatric patients 6 months to 17 years of age would achieve comparable steady state plasma exposures (AUC0-24 and Cmax) to those observed in adult patients administered 500 mg of levofloxacin once every 24 hours.
Gender
There are no significant differences in levofloxacin pharmacokinetics between male and female subjects when subjects' differences in creatinine clearance are taken into consideration.
Following a 500 mg oral dose of levofloxacin to healthy male subjects, the mean terminal plasma elimination half-life of levofloxacin was about 7.5 hours, as compared to approximately 6.1 hours in female subjects. This difference was attributable to the variation in renal function status of the male and female subjects and was not believed to be clinically significant. Drug absorption appears to be unaffected by the gender of the subjects. Dose adjustment based on gender alone is not necessary.
Race
The effect of race on levofloxacin pharmacokinetics was examined through a covariate analysis performed on data from 72 subjects: 48 white and 24 non-white. The apparent total body clearance and apparent volume of distribution were not affected by the race of the subjects.
Renal Impairment
Clearance of levofloxacin is substantially reduced and plasma elimination half-life is substantially prolonged in adult patients with impaired renal function (creatinine clearance< 50 mL/min), requiring dosage adjustment in such patients to avoid accumulation. Neither hemodialysis nor continuous ambulatory peritoneal dialysis (CAPD) is effective in removal of levofloxacin from the body, indicating that supplemental doses of levofloxacin are not required following hemodialysis or CAPD [see Dosage and Administration (2.3), Use in Specific Populations (8.6)].
Hepatic Impairment
Pharmacokinetic studies in hepatically impaired patients have not been conducted. Due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment [See Use in Specific Populations (8.7)]
Bacterial Infection
The pharmacokinetics of levofloxacin in patients with serious community-acquired bacterial infections are comparable to those observed in healthy subjects.
Drug-Drug Interactions
The potential for pharmacokinetic drug interactions between levofloxacin and antacids warfarin, theophylline, cyclosporine, digoxin, probenecid, and cimetidine has been evaluated [see Drug Interactions (7)].
Mechanism of Action
Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination.
Drug Resistance
Fluoroquinolone resistance can arise through mutations in defined regions of DNA gyrase or topoisomerase IV, termed the Quinolone-Resistance Determining Regions (QRDRs), or through altered efflux.
Fluoroquinolones, including levofloxacin, differ in chemical structure and mode of action from aminoglycosides, macrolides and β-lactam antibiotics, including penicillins. Fluoroquinolones may, therefore, be active against bacteria resistant to these antimicrobials.
Levofloxacin has in vitro activity against a wide range of Gram-negative and Gram-positive microorganisms.
Levofloxacin is often bactericidal at concentrations equal to or slightly greater than inhibitory concentrations.
Levofloxacin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in Indications and Usage (1):
Aerobic Gram-Positive Microorganisms
Enterococcus faecalis (many strains are only moderately susceptible)
Staphylococcus aureus (methicillin-susceptible strains)
Staphylococcus epidermidis (methicillin-susceptible strains)
Staphylococcus saprophyticus
Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP]1)
Streptococcus pyogenes
1MDRSP (Multi-drug resistant Streptococcus pneumoniae) isolates are strains resistant to two or more of the following antibiotics: penicillin (MIC ≥2 mcg/mL), 2nd generation cephalosporins, e.g., cefuroxime; macrolides, tetracyclines and trimethoprim/sulfamethoxazole.
Aerobic Gram-Negative Microorganisms
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella pneumoniae
Legionella pneumophila
Moraxella catarrhalis
Proteus mirabilis
Pseudomonas aeruginosa
Serratia marcescens
2As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin.
Other Microorganisms
Chlamydophila pneumoniae
Mycoplasma pneumoniae
Levofloxacin has been shown to be active against Bacillus anthracis both in vitro and by use of plasma levels as a surrogate marker in a rhesus monkey model for anthrax (post-exposure) [see Indications and Usage (1.13), Clinical Studies (14.9)].
The following in vitro data are available, but their clinical significance is unknown: Levofloxacin exhibits in vitro minimum inhibitory concentrations (MIC values) of 2 mcg/mL or less against most (≥90%) strains of the following microorganisms; however, the safety and effectiveness of levofloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials
Aerobic Gram-Positive Microorganisms
Staphylococcus haemolyticus
β-hemolytic Streptococcus (Group C/F)
β-hemolytic Streptococcus (Group G)
Streptococcus agalactiae
Streptococcus milleri
Viridans group streptococci
Aerobic Gram-Negative Microorganisms
Acinetobacter baumannii
Acinetobacter lwoffii
Bordetella pertussis
Citrobacter koseri
Citrobacter freundii
Enterobacter aerogenes
Enterobacter sakazakii
Klebsiella oxytoca
Morganella morganii
Pantoea agglomerans
Proteus vulgaris
Providencia rettgeri
Providencia stuartii
Pseudomonas fluorescens
Anaerobic Gram-Positive Microorganisms
Clostridium perfringens
Susceptibility Tests
Minimum Inhibitory Concentrations (mcg/mL) | Disk Diffusion (zone diameter in mm) |
||||||||
---|---|---|---|---|---|---|---|---|---|
Pathogen | S | I | R | S | I | R | |||
|
|||||||||
Enterobacteriaceae
| ≤2 | 4 | ≥8 | ≥17 | 14–16 | ≤13 |
|||
Enterococcus faecalis
| ≤2 | 4 | ≥8 | ≥17 | 14–16 | ≤13 |
|||
Methicillin-susceptible Staphylococcus species | ≤2 | 4 | ≥8 | ≥17 | 14–16 | ≤13 |
|||
Pseudomonas aeruginosa
| ≤2 | 4 | ≥8 | ≥17 | 14–16 | ≤13 |
|||
Haemophilus influenzae
| ≤2*
| --†
| --†
| ≥17‡
| --†
| --†
|
|||
Haemophilus parainfluenzae
| ≤2*
| --†
| --†
| ≥17‡
| --†
| --†
|
|||
Streptococcus pneumoniae
| ≤2§
| 4§
| ≥8§
| ≥17¶
| 14–16¶
| ≤13¶
|
|||
Streptococcus pyogenes
| ≤2 | 4 | ≥8 | ≥17 | 14–16 | ≤13 |
· Quality Control:
Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. For dilution technique, standard levofloxacin powder should give the MIC values provided in Table 12. For diffusion technique, the 5 mcg levofloxacin disk should provide zone diameters provided in Table 12
Microorganism QC Number | MIC (mcg/mL) | Disk Diffusion (zone diameter in mm) |
|||||
---|---|---|---|---|---|---|---|
|
|||||||
Enterococcus faecalis | ATCC 29212 | 0.25 – 2 | -- |
||||
Escherichia coli | ATCC 25922 | 0.008 – 0.06 | 29 – 37 |
||||
Escherichia coli*
| ATCC 35218 | 0.015 – 0.06 | -- |
||||
Haemophilus influenzae | ATCC 49247 | 0.008 – 0.03†
| 32 – 40‡
|
||||
Pseudomonas aeruginosa | ATCC 27853 | 0.5 – 4 | 19 – 26 |
||||
Staphylococcus aureus | ATCC 29213 | 0.06 – 0.5 | -- |
||||
Staphylococcus aureus | ATCC 25923 | -- | 25 – 30 |
||||
Streptococcus pneumoniae | ATCC 49619 | 0.5 – 2§
| 20 – 25¶
|
Levofloxacin was not mutagenic in the following assays: Ames bacterial mutation assay (S. typhimurium and E. coli), CHO/HGPRT forward mutation assay, mouse micronucleus test, mouse dominant lethal test, rat unscheduled DNA synthesis assay, and the mouse sister chromatid exchange assay. It was positive in the in vitro chromosomal aberration (CHL cell line) and sister chromatid exchange (CHL/IU cell line) assays.
Levofloxacin caused no impairment of fertility or reproductive performance in rats at oral doses as high as 360 mg/kg/day, corresponding to 4.2 times the highest recommended human dose based upon relative body surface area and intravenous doses as high as 100 mg/kg/day, corresponding to 1.2 times the highest recommended human dose based upon relative body surface area.
Pathogen | N | Levofloxacin No. (%) of Patients Microbiologic/Clinical Outcomes | N | Imipenem/Cilastatin No. (%) of Patients Microbiologic/Clinical Outcomes |
---|---|---|---|---|
MSSA* | 21 | 14 (66.7)/13 (61.9) | 19 | 13 (68.4)/15(78.9) |
P. aeruginosa† | 17 | 10 (58.8)/11 (64.7) | 17 | 5 (29.4)/7 (41.2) |
S. marcescens | 11 | 9 (81.8)/7 (63.6) | 7 | 2 (28.6)/3 (42.9) |
E. coli | 12 | 10 (83.3)/7 (58.3) | 11 | 7 (63.6 )/8 (72.7) |
K. pneumoniae‡ | 11 | 9 (81.8)/5 (45.5) | 7 | 6 (85.7)/3 (42.9) |
H. influenzae | 16 | 13 (81.3)/10 (62.5) | 15 | 14 (93.3)/11(73.3) |
S. pneumoniae | 4 | 3 (75.0)/3 (75.0) | 7 | 5 (71.4)/4 (57.1) |
Table 14: Microbiologic Eradication Rates Across 2 Community Acquired Pneumonia Clinical Studies | ||
---|---|---|
Pathogen | No. Pathogens | Microbiologic Eradication Rate (%) |
H. influenzae
| 55 | 98 |
S. pneumoniae
| 83 | 95 |
S. aureus
| 17 | 88 |
M. catarrhalis
| 18 | 94 |
H. parainfluenzae
| 19 | 95 |
K. pneumoniae
| 10 | 100.0 |
Community-Acquired Pneumonia Due to Multi-Drug Resistant Streptococcus pneumoniae
Table 15: Clinical and Bacterial Success Rates for Levofloxacin-Treated MDRSP in Community Acquired Pneumonia Patients (Population Valid for Efficacy) | ||||
---|---|---|---|---|
Screening Susceptibility | Clinical Success | Bacteriological Success* | ||
n/N† | % | n/N‡ | % | |
|
||||
|
||||
Penicillin-resistant | 16/17 | 94.1 | 16/17 | 94.1 |
2nd generation Cephalosporin resistant | 31/32 | 96.9 | 31/32 | 96.9 |
Macrolide-resistant | 28/29 | 96.6 | 28/29 | 96.6 |
Trimethoprim/ Sulfamethoxazole resistant | 17/19 | 89.5 | 17/19 | 89.5 |
Tetracycline-resistant | 12/12 | 100 | 12/12 | 100 |
Not all isolates were resistant to all antimicrobial classes tested. Success and eradication rates are summarized in Table 16.
Table 16: Clinical Success and Bacteriologic Eradication Rates for Resistant Streptococcus pneumoniae (Community Acquired Pneumonia) | ||
---|---|---|
Type of Resistance | Clinical Success | Bacteriologic Eradication |
Resistant to 2 antibacterials | 17/18 (94.4%) | 17/18 (94.4%) |
Resistant to 3 antibacterials | 14/15 (93.3%) | 14/15 (93.3%) |
Resistant to 4 antibacterials | 7/7 (100%) | 7/7 (100%) |
Resistant to 5 antibacterials | 0 | 0 |
Bacteremia with MDRSP | 8/9 (89%) | 8/9 (89%) |
To evaluate the safety and efficacy of higher dose and shorter course oflevofloxacin, 528 outpatient and hospitalized adults with clinically and radiologically determined mild to severe community-acquired pneumonia were evaluated in a double-blind, randomized, prospective, multicenter study comparing levofloxacin 750 mg, IV or orally, every day for five days or levofloxacin 500 mg IV or orally, every day for 10 days.
Table 17: Microbiological Eradication Rates (Community-Acquired Pneumonia)
|
|
Penicillin susceptible S. pneumoniae
| 19/20 |
Haemophilus influenzae
| 12/12 |
Haemophilus parainfluenzae
| 10/10 |
Mycoplasma pneumoniae
| 26/27 |
Chlamydophila pneumoniae
| 13/15 |
Rates of clinical success by pathogen in the microbiologically evaluable population who had specimens obtained by antral tap at study entry showed comparable results for the five- and ten-day regimens at the test-of-cure visit 22 days post treatment.
Table 18: Clinical Success Rate by Pathogen at the TOC in Microbiologically Evaluable Subjects Who Underwent Antral Puncture (Acute Bacterial Sinusitis) | |||
---|---|---|---|
Pathogen | Levofloxacin 750 mg×5 days | Levofloxacin 500 mg × 10 days |
|
|
|||
Streptococcus pneumoniae*
| 25/27 (92.6%) | 26/27 (96.3%) |
|
Haemophilus influenzae*
| 19/21 (90.5%) | 25/27 (92.6%) |
|
Moraxella catarrhalis*
| 10/11 (90.9%) | 13/13 (100%) |
Among those who could be evaluated clinically 2–5 days after completion of study drug, overall success rates (improved or cured) were 116/138 (84.1%) for patients treated with levofloxacin and 106/132 (80.3%) for patients treated with the comparator.
Success rates varied with the type of diagnosis ranging from 68% in patients with infected ulcers to 90% in patients with infected wounds and abscesses. These rates were equivalent to those seen with comparator drugs.
|
||||
Levofloxacin (N=136)
| Ciprofloxacin (N=125)
|
|||
Pathogen
| N
| Eradication
| N
| Eradication
|
E. coli
| 15 | 14 (93.3%) | 11 | 9 (81.8%) |
E. faecalis
| 54 | 39 (72.2%) | 44 | 33 (75.0%) |
S. epidermidis*
| 11 | 9 (81.8%) | 14 | 11 (78.6%) |
Clinical success (cure + improvement with no need for further antibiotic therapy) rates in microbiologically evaluable population 5–18 days after completion of therapy were 75.0% for levofloxacin-treated patients and 72.8% for ciprofloxacin-treated patients (95% CI [-8.87, 13.27] for levofloxacin minus ciprofloxacin). Clinical long-term success (24–45 days after completion of therapy) rates were 66.7% for thelevofloxacin-treated patients and 76.9% for the ciprofloxacin-treated patients (95% CI [-23.40, 2.89] for levofloxacin minus ciprofloxacin).
To evaluate the safety and efficacy of the higher dose and shorter course of levofloxacin, 1109 patients with cUTI and AP were enrolled in a randomized, double-blind, multicenter clinical trial conducted in the US from November 2004 to April 2006 comparing levofloxacin 750 mg IV or orally once daily for 5 days (546 patients) with ciprofloxacin 400 mg IV or 500 mg orally twice daily for 10 days (563 patients). Patients with AP complicated by underlying renal diseases or conditions such as complete obstruction, surgery, transplantation, concurrent infection or congenital malformation were excluded. Efficacy was measured by bacteriologic eradication of the baseline organism(s) at the post-therapy visit in patients with a pathogen identified at baseline. The post-therapy (test-of-cure) visit occurred 10 to 14 days after the last active dose of levofloxacin and 5 to 9 days after the last dose of active ciprofloxacin.
Levofloxacin 750 mg orally or IV once daily for 5 days | Ciprofloxacin 400 mg IV/500 mg orally twice daily for 10 days | Overall Difference [95% CI] | |||
---|---|---|---|---|---|
n/N | % | n/N | % | Levofloxacin Ciprofloxacin | |
|
|||||
mITT Population*
|
|||||
Overall (cUTI or AP) | 252/333 | 75.7 | 239/318 | 75.2 | 0.5 (-6.1, 7.1) |
cUTI | 168/230 | 73.0 | 157/213 | 73.7 | |
AP | 84/103 | 81.6 | 82/105 | 78.1 | |
Microbiologically Evaluable Population†
|
|||||
Overall (cUTI or AP) | 228/265 | 86.0 | 215/241 | 89.2 | -3.2 [-8.9, 2.5] |
cUTI | 154/185 | 83.2 | 144/165 | 87.3 | |
AP | 74/80 | 92.5 | 71/76 | 93.4 | |
Pathogen | Microbiologic Eradication Rate (n/N) | % | |||
---|---|---|---|---|---|
|
|||||
Escherichia coli* |
155/172 |
90 |
|||
Klebsiella pneumoniae |
20/23 |
87 |
|||
Proteus mirabilis |
12/12 |
100 |
To evaluate the safety and efficacy of the 250 mg dose, 10 day regimen oflevofloxacin, 567 patients with uncomplicated UTI, mild-to-moderate cUTI, and mild-to-moderate AP were enrolled in a randomized, double-blind, multicenter clinical trial conducted in the US from June 1993 to January 1995 comparing levofloxacin 250 orally once daily for 10 days (285 patients) with ciprofloxacin 500 mg orally twice daily for 10 days (282 patients). Patients with a resistant pathogen, recurrent UTI, women over age 55 years, and with an indwelling catheter were initially excluded, prior to protocol amendment which took place after 30% of enrollment. Microbiological efficacy was measured by bacteriologic eradication of the baseline organism(s) at 1–12 days post-therapy in patients with a pathogen identified at baseline.
The bacteriologic cure rates overall for levofloxacin and control at the test-of-cure (TOC) visit for the group of all patients with a documented pathogen at baseline (modified intent to treat or mITT) and the group of patients in the mITT population who closely followed the protocol (Microbiologically Evaluable) are summarized in Table 22.
Table 22. Bacteriologic Eradication Overall (cUTI or AP) at Test-Of-Cure* | |||||
---|---|---|---|---|---|
Levofloxacin 250 mg once daily for 10 days | Ciprofloxacin 500 mg twice daily for 10 days |
||||
n/N | % | n/N | % | ||
|
|||||
mITT Population†
| 174/209 | 83.3 | 184/219 | 84.0 |
|
Microbiologically Evaluable Population‡
| 164/177 | 92.7 | 159/171 | 93.0 |
The effectiveness of levofloxacin for this indication is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. Levofloxacin has not been tested in humans for the post-exposure prevention of inhalation anthrax. The mean plasma concentrations of levofloxacin associated with a statistically significant improvement in survival over placebo in the rhesus monkey model of inhalational anthrax are reached or exceeded in adult and pediatric patients receiving the recommended oral and intravenous dosage regimens [see Indications and Usage (1.13); Dosage and Administration (2.1, 2.2)].
Levofloxacin pharmacokinetics have been evaluated in adult and pediatric patients. The mean (± SD) steady state peak plasma concentration in human adults receiving 500 mg orally or intravenously once daily is 5.7 ± 1.4 and 6.4 ± 0.8 mcg/mL, respectively; and the corresponding total plasma exposure (AUC0-24) is 47.5 ± 6.7 and 54.6 ± 11.1 mcg.h/mL, respectively. The predicted steady-state pharmacokinetic parameters in pediatric patients ranging in age from 6 months to 17 years receiving 8 mg/kg orally every 12 hours (not to exceed 250 mg per dose) were calculated to be comparable to those observed in adults receiving 500 mg orally once daily [see Clinical Pharmacology (12.3)].
In adults, the safety of levofloxacin for treatment durations of up to 28 days is well characterized. However, information pertaining to extended use at 500 mg daily up to 60 days is limited. Prolonged levofloxacin therapy in adults should only be used when the benefit outweighs the risk.
In pediatric patients, the safety of levofloxacin for treatment durations of more than 14 days has not been studied. An increased incidence of musculoskeletal adverse events (arthralgia, arthritis, tendonopathy, gait abnormality) compared to controls has been observed in clinical studies with treatment duration of up to 14 days. Long-term safety data, including effects on cartilage, following the administration of levofloxacin to pediatric patients is limited [see Warnings and Precautions (5.10), Use in Specific Populations (8.4)].
A placebo-controlled animal study in rhesus monkeys exposed to an inhaled mean dose of 49 LD50 (~2.7 X 106) spores (range 17 - 118 LD50) of B. anthracis (Ames strain) was conducted. The minimal inhibitory concentration (MIC) of levofloxacin for the anthrax strain used in this study was 0.125 mcg/mL. In the animals studied, mean plasma concentrations of levofloxacin achieved at expected Tmax (1 hour post dose) following oral dosing to steady state ranged from 2.79 to 4.87 mcg/mL. Steady state trough concentrations at 24 hours post-dose ranged from 0.107 to 0.164 mcg/mL. Mean (SD) steady state AUC0-24 was 33.4 ± 3.2 mcg.h/mL (range 30.4 to 36.0 mcg.h/mL). Mortality due to anthrax for animals that received a 30 day regimen of oral levofloxacin beginning 24 hrs post exposure was significantly lower (1/10), compared to the placebo group (9/10) [P=0.0011, 2-sided Fisher’s Exact Test]. The one levofloxacin treated animal that died of anthrax did so following the 30-day drug administration period.
· 250 mg tablets are pink coloured, capsule shaped, biconvex, debossed “ML 62” on one side and plain on other side.
- bottles of 50s (NDC 33342-021-08)
- blister of 50s (NDC 33342-021-31)
- blister of 100s (NDC 33342-021-12)
· 500 mg tablets are: peach coloured, capsule shaped, biconvex, debossed “ML 63” on one side and plain on other side.
- bottles of 50s (NDC 33342-022-08)
- blister of 50s (NDC 33342-022-31)
- blister of 100s (NDC 33342-022-12)
· 750 mg tablets are white coloured, capsule shaped, biconvex, debossed “ML 64” on one side and plain on other side.
- bottles of 20s (NDC 33342-023-32)
- blister of 50s (NDC 33342-023-31)
- blister of 100s (NDC 33342-023-12)
Levofloxacin Tablets should be stored at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86 °F) in well-closed containers.
Levofloxacin Tablets are manufactured by Macleods Pharmaceutical Limited, Village Theda, Post Office Lodhimajra, Tehsil Nalagarh, District Solan, Himachal Pradesh – 174101, India.
See FDA-Approved Medication Guide (17.5)
Antibacterial drugs including levofloxacin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When levofloxacin is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by levofloxacin or other antibacterial drugs in the future
Patients should be informed that Levofloxacin Tablets may be taken with or without food.
Patients should drink fluids liberally while taking levofloxacin to avoid formation of a highly concentrated urine and crystal formation in the urine.
Antacids containing magnesium, or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine should be taken at least two hours before or two hours after oral levofloxacin administration.
Patients should be informed of the following serious adverse reactions that have been associated with levofloxacin or other fluoroquinolone use:
Patients should be informed that if they are diabetic and are being treated with insulin or an oral hypoglycemic agent and a hypoglycemic reaction occurs, they should discontinue levofloxacin and consult a physician.
Manufactured by:
Macleods Pharmaceutical Limited
Village Theda, Post office Lodhimajra,
Tehsil Nalgarh, District Solan,
Himachal Pradesh–174101, India.
MEDICATION GUIDE
Levofloxacin Tablets
250 mg, 500 mg and 750 mg
Rx Only
Read the Medication Guide that comes with levofloxacin tablets before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment.
What is the most important information I should know about levofloxacin tablets?
Levofloxacin belongs to a class of antibiotics called fluoroquinolones. Levofloxacin tablets can cause side effects that may be serious or even cause death. If you get any of the following serious side effects, get medical help right away. Talk with your healthcare provider about whether you should continue to take levofloxacin tablets.
1.Tendon rupture or swelling of the tendon (tendinitis).
· Tendon problems can happen in people of all ages who take levofloxacin tablets. Tendons are tough cords of tissues that connect muscle to bones.
· Some tendon problems include pain, swelling, tears, and inflammation of tendons including the back of the ankle (Achilles), shoulder, hand, or other tendon sites.
· The risk of getting tendon problems while you take levofloxacin tablet is higher if you:
· are over 60 years of age
· are taking steroids (corticosteroids)
· have had a kidney, heart or lung transplant.
· Tendon problems can happen in people who do not have the above risk factors when they take levfloxacin tablets. Other reasons that can increase your risk of tendon problems can include:
· physical activity or exercise
· kidney failure
· tendon problems in the past, such as in people with rheumatoid arthritis (RA).
· Call your healthcare provider right away at the first sign of tendon pain, swelling or inflammation. Stop taking levofloxacin tablets until tendinitis or tendon rupture has been ruled out by your healthcare provider. Avoid exercise and using the affected area. The most common area of pain and swelling is the Achilles tendon at the back of your ankle. This can also happen with other tendons.
· Talk to your healthcare provider about the risk of tendon rupture with continued use of levofloxacin tablets. You may need a different antibiotic that is not a fluoroquinolone to treat your infection.
· Tendon rupture can happen while you are taking or after you have finished taking levofloxacin tablets. Tendon ruptures have happened up to several months after patients have finished taking their fluoroquinolone.
· Get medical help right away if you get any of the following signs or symptoms of a tendon rupture:
· hear or feel a snap or pop in a tendon area
· bruising right after an injury in a tendon area
· unable to move the affected area or bear weight
2.Worsening of myasthenia gravis (a disease that causes muscle weakness). Fluoroquinolones like levofloxacin tablets may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.
See the section “What are the possible side effects of levofloxacin tablets?” for more information about side effects.
What are levofloxacin tablets?
Levofloxacin tablet is a fluoroquinolone antibiotic medicine used in adults, 18 years or older, to treat certain infections caused by certain germs called bacteria.
Children have a higher chance of getting bone, joint, or tendon (musculoskeletal) problems such as pain or swelling while taking levofloxacin tablets.
In children 6 months and older who have breathed the anthrax bacteria germ:
· Levofloxacin tablet is used to prevent anthrax disease (inhalation anthrax).
· It is not known if it is safe to use levofloxacin tablets in children for more than 14 days.
It is not known if levofloxacin tablet is safe and works in children under the age of 6 months.
Sometimes infections are caused by viruses rather than by bacteria. Examples include viral infections in the sinuses and lungs, such as the common cold or flu. Antibiotics, including levofloxacin, do not kill viruses.
Call your healthcare provider if you think your condition is not getting better while you are taking levofloxacin tablets.
Who should not take levofloxacin tablets?
Do not take levofloxacin tablets if you have ever had a severe allergic reaction to an antibiotic known as a fluoroquinolone, or if you are allergic to any of the
ingredients in levofloxacin tablets. Ask your healthcare provider if you are not sure. See the list of the ingredients in levofloxacin tablets at end of this Medication Guide.
What should I tell my healthcare provider before taking levofloxacin tablets?
See “What is the most important information I should know about levofloxacin tablets?”
Tell your healthcare provider about all your medical conditions, including if you:
· have tendon problems
· have a disease that causes muscle weakness (myasthenia gravis)
· have central nervous system problems (such as epilepsy)
· have nerve problems
· have or anyone in your family has an irregular heartbeat, especially a condition called “QT prolongation.”
· have low blood potassium (hypokalemia)
· have a history of seizures
· have bone and joint problems
· have kidney problems. You may need a lower dose of levofloxacin tablets if your kidneys do not work well.
· have liver problems
· have rheumatoid arthritis (RA) or other history of joint problems
· are pregnant or planning to become pregnant. It is not known if levofloxacin tablets will harm your unborn child.
· are breast-feeding or planning to breast-feed. Levofloxacin is thought to pass into breast milk. You and your healthcare provider should decide whether you will take levofloxacin tablets or breast-feed.
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, herbal and dietary supplements. Levofloxacin tablets and other medicines can affect each other causing side effects. Especially tell your healthcare provider if you take:
· an NSAID (Non-Steroidal Anti-Inflammatory Drug). Many common medicines for pain relief are NSAIDs. Taking an NSAID while you take or other fluoroquinolones may increase your risk of central nervous system effects and seizures. See “What are the possible side effects of levofloxacin tablets?”
· an oral anti-diabetes medicine or insulin
· a blood thinner (warfarin, Coumadin, Jantoven)
· a medicine to control your heart rate or rhythm (antiarrhythmics). See “What are the possible side effects of levofloxacin tablets”.
· an anti-psychotic medicine
· a tricyclic antidepressant
· a water pill (diuretic)
· a steroid medicine. Corticosteroids taken by mouth or by injection may increase the chance of tendon injury. See “What is the most important information I should know about levofloxacin tablets?”
· theophylline (Theo-24®, Elixophyllin®, Theochron®, Uniphyl®, Theolair®)
· Certain medicines may keep levofloxacin tablets from working correctly. Take Levofloxacin Tablets either 2 hours before or 2 hours after taking these products:
· an antacid, multivitamin, or other product that has magnesium, aluminum, iron, or zinc.
· sucralfate (Carafate®)
· didanosine (Videx®,Videx® EC)
Ask your healthcare provider if you are not sure if any of your medicines are listed above.
Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I take levofloxacin tablets?
· Take levofloxacin tablets exactly as prescribed by your healthcare provider.
· Take levofloxacin tablets at about the same time each day.
· Drink plenty of fluids while taking levofloxacin tablets
· Levofloxacin Tablets can be taken with or without food.
· If you miss a dose oflevofloxacin tablets, take it as soon as you remember. Do not take more than one dose in one day.
· Do not skip any doses, or stop taking levofloxacin tablets even if you begin to feel better, until you finish your prescribed treatment, unless:
· you have tendon effects (see “What is the most important information I should know about levofloxacin tablets?”),
· you have a serious allergic reaction (see“What are the possible side effects of levofloxacin tablets”), oryour healthcare provider tells you to stop.
· This will help make sure that all of the bacteria are killed and lower the chance that the bacteria will become resistant to levofloxacin. If this happens, levofloxacin and other antibiotic medicines may not work in the future.
If you take too much, call your healthcare provider or get medical help immediately.
If you have been prescribed levofloxacin tablets after being exposed to anthrax:
· Levofloxacin tablet has been approved to lessen the chance of getting anthrax disease or worsening of the disease after you are exposed to the anthrax bacteria germ.
· Take levofloxacin tablets exactly as prescribed by your healthcare provider. Do not stop taking levofloxacin tablets without talking with your healthcare provider. If you stop taking levofloxacin tablets too soon, it may not prevent you from getting the anthrax disease.
· Side effects may happen while you are takinglevofloxacin tablets. When taking levofloxacin tablets to prevent anthrax infection, you and your healthcare provider should talk about whether the risks of stopping your medicine too soon are more important than the risks of side effects withlevofloxacin tablets. It is not known if it is safe to use levofloxacin tablets for more than 28 days in adults and for more than 14 days in children 6 months of age and older.
· If you are pregnant, or plan to become pregnant while taking levofloxacin tablets, you and your healthcare provider should decide whether the benefits of taking levofloxacin tablets for anthrax are more important than the risks.
What should I avoid while taking levofloxacin tablets?
· Levofloxacin tablets can make you feel dizzy and lightheaded. Do not drive, operate machinery, or do other activities that require mental alertness or coordination until you know how levofloxacin tablets affects you.
· Avoid sunlamps, tanning beds, and try to limit your time in the sun. Levofloxacin tablets can make your skin sensitive to the sun (photosensitivity) and the light from sunlamps and tanning beds. You could get severe sunburn, blisters or swelling of your skin. If you get any of these symptoms while taking levofloxacin tablets call your healthcare provider right away. You should use a sunscreen and wear a hat and clothes that cover your skin if you have to be in sunlight.
What are the possible side effects of levofloxacin tablets?
Levofloxacin tablets can cause side effects that may be serious or even cause death. See “What is the most important information I should know aboutlevofloxacin tablets?”
Other serious side effects of levofloxacin tablets include:
· Liver damage (hepatotoxicity): Liver damage (hepatotoxicity) can happen in people who take levofloxacin tablets. Call your healthcare provider right away if you have unexplained symptoms such as:
· nausea or vomiting,
· stomach pain,
· fever,
· weakness,
· abdominal pain or tenderness,
· itching,
· unusual tiredness,
· loss of appetite,
· light colored bowel movements,
· dark colored urine or yellowing of your skin or the whites of your eyes
· Central Nervous System Effects. Seizures have been reported in people who take fluoroquinolone antibiotics includinglevofloxacin tablets. Tell your healthcare provider if you have a history of seizures. Ask your healthcare provider whether taking levofloxacin tablets will change your risk of having a seizure.
Central Nervous System (CNS) side effects may happen as soon as after taking the first dose oflevofloxacin tablets. Talk to your healthcare provider right away if you get any of these side effects, or other changes in mood or behavior:
· seizures
· hear voices, see things, or sense things that are not there (hallucinations)
· feel restless
· tremors
· feel anxious or nervous
· confusion
· depression
· trouble sleeping
· nightmares
· feel lightheaded
· feel more suspicious (paranoia)
· suicidal thoughts or acts
· persistant headche with or without blurred vision.
· Serious allergic reactions.
Allergic reactions can happen in people taking fluoroquinolones, includinglevofloxacin tablets, even after only one dose. Stop taking levofloxacin tablets and get emergency medical help right away if you get any of the following symptoms of a severe allergic reaction:
· hives
· trouble breathing or swallowing
· swelling of the lips, tongue, face
· throat tightness, hoarseness
· rapid heartbeat
· faint
· Yellowing of the skin or eyes. Stop taking levofloxacin tablets and tell your healthcare provider right away if you get yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to levofloxacin tablets (a liver problem).
· Changes in sensation and possible nerve damage (Peripheral Neuropathy).
Damage to the nerves in arms, hands, legs, or feet can happen in people taking fluoroquinolones, includinglevofloxacin tablets. Talk with your healthcare provider right away if you get any of the following symptoms of peripheral neuropathy in your arms, hands, legs, or feet:
Levofloxacin tablets may need to be stopped to prevent permanent nerve damage.
· Serious heart rhythm changes. (QT prolongation and torsades de pointes). Tell your healthcare provider right away if you have a change in your heart beat (a fast or irregular heartbeat), or if you faint. Levofloxacin tablets may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances of this happening are higher in people:
· who are elderly
· with a family history of prolonged QT interval
· with low blood potassium (hypokalemia)
· who take certain medicines to control heart rhythm (antiarrhythmics)
· Changes in blood sugar [low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia)].
People who take levofloxacin tablets and other fluoroquinolone medicines with oral anti-diabetes medicines or with insulin can get low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia). Follow your healthcare provider’s instructions for how often to check your blood sugar. If you have diabetes and you get low blood sugar while takinglevofloxacin tablets, stop taking levofloxacin tablets and call your healthcare provider right away. Your antibiotic medicine may need to be changed.
· Joint Problems.
Increased chance of problems with joints and tissues around joints in children. Tell your child’s healthcare provider if your child has any joint problems during or after treatment withlevofloxacin tablets.
The most common side effects of levofloxacin tablets include:
· dizziness
· headache
· constipation
· nausea
· diarrhea
In children 6 months and older who take levofloxacin tablets to prevent anthrax disease, vomiting is also common.
Levofloxacin tablets may cause false-positive urine screening results for opiates when testing is done with some commercially available kits. A positive result should be confirmed using a more specific test.
These are not all the possible side effects oflevofloxacin tablets. Tell your healthcare provider about any side effect that bothers you or that does not go away.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1 800-FDA-1088.
How should I store levofloxacin tablets?
Store Levofloxacin Film-Coated Tablets at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F). Keep the container closed tightly.
Keep levofloxacin tablets and all medicines out of the reach of children.
General Information about levofloxacin tablets
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use levofloxacin tablets for a condition for which it is not prescribed. Do not give levofloxacin tablets to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about levofloxacin tablets. If you would like more information about levofloxacin tablets, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about levofloxacin tablets that is written for healthcare professionals.
What are the ingredients in levofloxacin tablets?
· 250 mg Levofloxacin Film-Coated Tablets:
· Active ingredient: levofloxacin.
· Inactive ingredients: hypromellose, crospovidone, microcrystalline cellulose, magnesium stearate, polyethylene glycol, titanium dioxide, polysorbate 80 and synthetic red iron oxide.
· 500 mg Levofloxacin Film-Coated Tablets
·Active ingredient: levofloxacin.
· Inactive ingredients: hypromellose, crospovidone, microcrystalline cellulose, magnesium stearate, polyethylene glycol, titanium dioxide, polysorbate 80 and synthetic red and yellow iron oxides.
· 750 mg Levofloxacin Film-Coated Tablets:
· Active ingredient: levofloxacin.
· Inactive ingredients: hypromellose, crospovidone, microcrystalline cellulose, magnesium stearate, polyethylene glycol, titanium dioxide, polysorbate 80.
Manufactured by:
Macleods Pharmaceutical Limited
Village Theda, Post office Lodhimajra,
Tehsil Nalgarh, District Solan,
Himachal Pradesh–174101, India.
Issued April 2012
LEVOFLOXACIN
levofloxacin tablet, film coated |
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LEVOFLOXACIN
levofloxacin tablet, film coated |
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LEVOFLOXACIN
levofloxacin tablet, film coated |
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Labeler - Macleods Pharmaceuticals Limited (862128535) |