LEVOFLOXACIN - levofloxacin injection, solution, concentrate
AuroMedics Pharma LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use levofloxacin injection safely and effectively. See full prescribing information for levofloxacin injection.
LEVOFLOXACIN INJECTION, Solution, Concentrate for Intravenous use Initial U.S. Approval: 1996 WARNING See full prescribing information for complete boxed 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 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 bacteria. RECENT MAJOR CHANGESINDICATIONS AND USAGELevofloxacin injection 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 AuroMedics Pharma LLC at 1-866-850-2876 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: 02/2013 |
Levofloxacin injection is indicated for the treatment of community-acquired pneumonia due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.3)].
Levofloxacin injection is indicated for the treatment of acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see Clinical Studies (14.4)].
Levofloxacin injection 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 injection is indicated for the treatment of complicated skin and skin structure infections due to methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, or Proteus mirabilis [see Clinical Studies (14.5)].
Levofloxacin injection is indicated for the treatment of complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis [see Clinical Studies (14.7)].
Levofloxacin injection 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 injection is indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.
Levofloxacin injection is indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis. The effectiveness of levofloxacin injection is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. Levofloxacin injection has not been tested in humans for the post-exposure prevention of inhalation anthrax. The safety of levofloxacin in adults for durations of therapy beyond 28 days or in pediatric patients for durations of therapy beyond 14 days has not been studied. Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk [see Dosage and Administration (2.1, 2.2) and Clinical Studies (14.9)].
Levofloxacin injection is indicated for treatment of plague, including pneumonic and septicemic plague, due to Yersinia pestis (Y. pestis) and prophylaxis for plague in adults and pediatric patients, 6 months of age and older. Efficacy studies of levofloxacin could not be conducted in humans with plague for ethical and feasibility reasons. Therefore, approval of this indication was based on an efficacy study conducted in animals [see Dosage and Administration (2.1, 2.2) and Clinical Studies (14.10)].
The usual dose of levofloxacin injection is 250 mg or 500 mg administered by slow infusion over 60 minutes every 24 hours or 750 mg administered by slow infusion over 90 minutes 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)
* Due to the designated pathogens [see Indications and Usage (1)].
† Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.
‡Due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Indications and Usage (1.2)].
§ Due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Indications and Usage (1.3)].
¶ This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia.
# This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; and for AP due to E. coli.
Þ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)].
ß The safety of levofloxacin in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk.
á Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Higher doses of levofloxacin typically used for treatment of pneumonia can be used for treatment of plague, if clinically indicated.
The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.
Table 2: Dosage in Pediatric Patients ≥ 6 months of age
Type of Infection*
| Dose
| Freq. Once every
| Duration†
|
Inhalational Anthrax (post-exposure) ‡,§
| | | |
Pediatric patients > 50 kg | 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§ |
Plague¶
| | | |
Pediatric patients > 50 kg | 500 mg | 24 hr | 10 to 14 days |
Pediatric patients < 50 kg and ≥ 6 months of age | 8 mg/kg (not to exceed 250 mg per dose) | 12 hr | 10 to 14 days |
* Due to Bacillus anthracis [see Indications and Usage (1.13)] and Yersinia pestis [see Indications and Usage (1.14)].
† Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.
‡ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)]
§ The safety of levofloxacin in pediatric patients for durations of therapy beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk.
¶ Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis.
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 |
Intravenous Fluids | Final pH of Levofloxacin Solution |
---|---|
0.9% Sodium Chloride Injection, USP | 4.71 |
5% Dextrose Injection, USP | 4.58 |
5% Dextrose/0.9% NaCl Injection | 4.62 |
5% Dextrose in Lactated Ringers | 4.92 |
Plasma-Lyte® 56/5% Dextrose Injection | 5.03 |
5% Dextrose, 0.45% Sodium Chloride, and 0.15% Potassium Chloride Injection | 4.61 |
Sodium Lactate Injection (M/6) | 5.54 |
Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparation of the final intravenous solution. Since the vials are for single-use only, any unused portion remaining in the vial should be discarded. When used to prepare two 250 mg doses from the 20 mL vial containing 500 mg of levofloxacin, the full content of the vial should be withdrawn at once using a single-entry procedure, and a second dose should be prepared and stored for subsequent use [see Stability of Levofloxacin Injection Following Dilution].
Prepare the desired dosage of levofloxacin according to Table 5:
Table 5: Preparation of Levofloxacin Intravenous Solution
Desired Dosage Strength
| From Appropriate Vial, Withdraw Volume
| Volume of Diluent
| Infusion Time
|
250 mg | 10 mL (20 mL Vial) | 40 mL | 60 min |
500 mg | 20 mL (20 mL Vial) | 80 mL | 60 min |
750 mg | 30 mL (30 mL Vial) | 120 mL | 90 min |
For example, to prepare a 500 mg dose using the 20 mL vial (25 mg/mL), withdraw 20 mL and dilute with a compatible intravenous solution to a total volume of 100 mL.
This intravenous drug product should be inspected visually for particulate matter prior to administration. Samples containing visible particles should be discarded.
Stability of Levofloxacin Injection Following Dilution: Levofloxacin injection, when diluted in a compatible intravenous fluid to a concentration of 5 mg/mL, is stable for 72 hours when stored at or below 25°C (77°F) and for 14 days when stored under refrigeration at 5°C (41°F) in plastic intravenous containers. Solutions that are diluted in a compatible intravenous solution and frozen in glass bottles or plastic intravenous containers are stable for 6 months when stored at - 20°C (- 4°F). Thaw frozen solutions at room temperature 25°C (77°F) or in a refrigerator 8°C (46°F). Do not force thaw by microwave irradiation or water bath immersion. Do not refreeze after initial thawing.
Levofloxacin injection is contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see Warnings and Precautions (5.3)].
Fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and rupture of the Achilles tendon may require surgical repair. Tendinitis and tendon rupture in the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendon sites have also been reported. 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)].
Postmarketing 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)].
Convulsions, toxic psychoses, increased intracranial pressure (including pseudotumor cerebri) have been reported in patients receiving fluoroquinolones, including levofloxacin. Fluoroquinolones may also cause central nervous system stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, insomnia, and, rarely, suicidal thoughts or acts. These reactions may occur following the first dose. If these reactions occur in patients receiving levofloxacin, the drug should be discontinued and appropriate measures instituted. As with other fluoroquinolones, levofloxacin should be used with caution in patients with a known or suspected central nervous system (CNS) disorder that may predispose them to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose them to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction). [see Adverse Reactions (6); Drug Interactions (7.4,7.5); Patient Counseling Information (17.3)].
Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones, including levofloxacin. Levofloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation in order to prevent the development of an irreversible condition [see Adverse Reactions (6), Patient Counseling Information (17.3)].
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 Class IA (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)].
Levofloxacin is indicated in pediatric patients (6 months of age and older) only for the prevention of inhalational anthrax (post-exposure) and for plague [see Indications and Usage (1.13,1.14)]. An increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, and gait abnormality) compared to controls has been observed in pediatric patients receiving levofloxacin[see Use in Specific Populations (8.4)].
In immature rats and dogs, the oral and intravenous administration of levofloxacin resulted in increased osteochondrosis. Histopathological examination of the weight-bearing joints of immature dogs dosed with levofloxacin revealed persistent lesions of the cartilage. Other fluoroquinolones also produce similar erosions in the weight-bearing joints and other signs of arthropathy in immature animals of various species [see Animal Toxicology and/or Pharmacology (13.2)].
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)].
Hypotension has been associated with rapid or bolus intravenous infusion of levofloxacin. Levofloxacin should be infused slowly over 60 to 90 minutes, depending on dosage [see Dosage and Administration (2.5)].
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)].
System/Organ Class | Adverse Reaction | % (N = 7537) |
---|---|---|
* N = 7274 †N = 3758 (women) |
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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 |
---|---|
* N = 7274 |
|
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 pseudomembranous/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 leucopenia 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 Warnings 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/phototoxicity 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 |
The concomitant administration of a non-steroidal anti-inflammatory drug with a fluoroquinolone, including levofloxacin, may increase the risk of CNS stimulation and convulsive seizures [see Warnings and Precautions (5.6)].
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 coadministered. 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 cyclosporine was detected in a clinical study involving healthy volunteers. However, elevated serum levels of cyclosporine have been reported in the patient population when coadministered with some other fluoroquinolones. Levofloxacin Cmax and ke were slightly lower while Tmax and t½ were slightly longer in the presence of cyclosporine than those observed in other studies without concomitant medication. The differences, however, are not considered to be clinically significant. Therefore, no dosage adjustment is required for levofloxacin or cyclosporine when administered concomitantly.
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.
No significant effect of probenecid or cimetidine on the Cmax of levofloxacin was observed in a clinical study involving healthy volunteers. The AUC and t1/2 of levofloxacin were higher while CL/F and CLR were lower during concomitant treatment of levofloxacin with probenecid or cimetidine compared to levofloxacin alone. However, these changes do not warrant dosage adjustment for levofloxacin when probenecid or cimetidine is coadministered.
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.
Follow-up Period | Levofloxacin N = 1340 | Non-Fluoroquinolone* N = 893 | p-value† |
---|---|---|---|
* Non-Fluoroquinolone: ceftriaxone, amoxicillin/clavulanate, clarithromycin †2-sided Fisher’s Exact Test ‡ There were 1199 levofloxacin-treated and 804 non-fluoroquinolone-treated children who had a one-year evaluation visit. However, the incidence of musculoskeletal disorders was calculated using all reported events during the specified period for all children enrolled regardless of whether they completed the 1-year evaluation visit. |
|||
60 days
| 28 (2.1%) | 8 (0.9%) | p = 0.038 |
1 year‡
| 46 (3.4%) | 16 (1.8%) | p = 0.025 |
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)].
Levofloxacin is a member of the fluoroquinolone class of antibacterial agents [see Microbiology (12.4)].
Regimen | Cmax
(mcg/mL) | Tmax
(h) | AUC (mcg•h/mL) | CL/F1
(mL/min) | Vd/F2
(L) | t1/2
(h) | CLR
(mL/min) |
---|---|---|---|---|---|---|---|
1 clearance/bioavailability 2 volume of distribution/bioavailability 3 healthy males 18 to 53 years of age 4 60 min infusion for 250 mg and 500 mg doses, 90 min infusion for 750 mg dose 5 healthy male and female subjects 18 to 54 years of age 6 500 mg every 48 h for patients with moderate renal impairment (CLCR 20 to 50 mL/min) and infections of the respiratory tract or skin 7 dose-normalized values (to 500 mg dose), estimated by population pharmacokinetic modeling 8 healthy males 22 to 75 years of age 9 healthy females 18 to 80 years of age 10 young healthy male and female subjects 18 to 36 years of age 11 healthy elderly male and female subjects 66 to 80 years of age 12 healthy males and females 19 to 55 years of age. * Absolute bioavailability; F=0.99 ± 0.08 from a 500 mg tablet and F=0.99 ± 0.06 from a 750 mg tablet ND=not determined. |
|||||||
Single dose
| | | | | |
||
250 mg oral tablet3
| 2.8 ± 0.4 | 1.6 ± 1 | 27.2 ± 3.9 | 156 ± 20 | ND | 7.3 ± 0.9 | 142 ± 21 |
500 mg oral tablet3*
| 5.1 ± 0.8 | 1.3 ± 0.6 | 47.9 ± 6.8 | 178 ± 28 | ND | 6.3 ± 0.6 | 103 ± 30 |
500 mg oral solution12
| 5.8 ± 1.8 | 0.8 ± 0.7 | 47.8 ± 10.8 | 183 ± 40 | 112 ± 37.2 | 7 ± 1.4 | ND |
500 mg IV3
| 6.2 ± 1 | 1 ± 0.1 | 48.3 ± 5.4 | 175 ± 20 | 90 ± 11 | 6.4 ± 0.7 | 112 ± 25 |
750 mg oral tablet5*
| 9.3 ± 1.6 | 1.6 ± 0.8 | 101 ± 20 | 129 ± 24 | 83 ± 17 | 7.5 ± 0.9 | ND |
750 mg IV5
| 11.5 ± 44
| ND | 110 ± 40 | 126 ± 39 | 75 ± 13 | 7.5 ± 1.6 | ND |
Multiple dose
| | | | | |
||
500 mg every 24 h oral tablet3
| 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 24 h IV3
| 6.4 ± 0.8 | ND | 54.6 ± 11.1 | 158 ± 29 | 91 ± 12 | 7 ± 0.8 | 99 ± 28 |
500 mg or 250 mg every 24 h IV, patients with bacterial infection6
| 8.7 ± 47
| ND | 72.5 ± 51.27
| 154 ± 72 | 111 ± 58 | ND | ND |
750 mg every 24 h oral tablet5
| 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 24 h IV5
| 12.1 ± 4.14
| ND | 108 ± 34 | 126 ± 37 | 80 ± 27 | 7.9 ± 1.9 | ND |
500 mg oral tablet single dose, effects of gender and age:
| | | | | |
||
Male8
| 5.5 ± 1.1 | 1.2 ± 0.4 | 54.4 ± 18.9 | 166 ± 44 | 89 ± 13 | 7.5 ± 2.1 | 126 ± 38 |
Female9
| 7 ± 1.6 | 1.7 ± 0.5 | 67.7 ± 24.2 | 136 ± 44 | 62 ± 16 | 6.1 ± 0.8 | 106 ± 40 |
Young10
| 5.5 ± 1 | 1.5 ± 0.6 | 47.5 ± 9.8 | 182 ± 35 | 83 ± 18 | 6 ± 0.9 | 140 ± 33 |
Elderly11
| 7 ± 1.6 | 1.4 ± 0.5 | 74.7 ± 23.3 | 121 ± 33 | 67 ± 19 | 7.6 ± 2 | 91 ± 29 |
500 mg oral single dose tablet, patients with renal insufficiency:
| | | | | |
||
CLCR 50 to 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 to 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 | 263.5 ± 72.5 | 33 ± 8 | ND | 35 ± 5 | 13 ± 3 |
Hemodialysis
| 5.7 ± 1 | 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 |
Reports from the laboratory providing results of the standard single-disk susceptibility test with a 5 mcg levofloxacin disk should be interpreted according to the criteria outlined in Table 11.
Table 11: Susceptibility Test Interpretive Criteria for Levofloxacin
Pathogen
| Minimum Inhibitory Concentrations (mcg/mL)
| Disk Diffusion
(zone diameter in mm) |
||||
S
| I
| R
| S
| I
| R
|
|
Enterobacteriaceae
| ≤2 | 4 | ≥8 | ≥17 | 14 to 16 | ≤13 |
Enterococcus faecalis
| ≤2 | 4 | ≥8 | ≥17 | 14 to 16 | ≤13 |
Staphylococcus species | ≤2 | 4 | ≥8 | ≥17 | 14 to 16 | ≤13 |
Pseudomonas aeruginosa
| ≤2 | 4 | ≥8 | ≥17 | 14 to 16 | ≤13 |
Haemophilus influenzae
| ≤2 | --†
| -- | ≥17 | -- | -- |
Haemophilus parainfluenzae
| ≤2 | -- | -- | ≥17 | -- | -- |
Streptococcus pneumoniae
| ≤2 | 4 | ≥8 | ≥17 | 14 to 16 | ≤13 |
Streptococcus pyogenes
| ≤2 | 4 | ≥8 | ≥17 | 14 to 16 | ≤13 |
Yersinia pestis4
| ≤0.25 | -- | -- | -- | -- | -- |
Bacillus anthracis4
| ≤0.25 | -- | -- | -- | -- | -- |
S = Susceptible, I = Intermediate, R = Resistant
† The current absence of data on resistant isolates precludes defining any categories other than “Susceptible.” Isolates yielding MIC/zone diameter results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing.
A report of Susceptible indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of Intermediate indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where a high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of Resistant indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.
Quality Control
Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test.1,2,3,4 Standard levofloxacin powder should provide the range of MIC values noted in Table 12. For the diffusion technique using the 5 mcg disk, the criteria in Table 12 should be achieved.
Table 12: Quality Control Ranges for Susceptibility Testing
Microorganism
| Microorganism QC Number
| MIC
(mcg/mL) | Disk Diffusion
(zone diameter in mm) |
Enterococcus faecalis
| ATCC 29212 | 0.25 to 2 | -- |
Escherichia coli
| ATCC 25922 | 0.008 to 0.06 | 29 to 37 |
Escherichia coli
| ATCC 35218 | 0.015 to 0.06 | -- |
Haemophilus influenzae
| ATCC 49247 | 0.008 to 0.03 | 32 to 40 |
Pseudomonas aeruginosa
| ATCC 27853 | 0.5 to 4 | 19 to 26 |
Staphylococcus aureus
| ATCC 29213 | 0.06 to 0.5 | -- |
Staphylococcus aureus
| ATCC 25923 | -- | 25 to 30 |
Streptococcus pneumoniae
| ATCC 49619 | 0.5 to 2 | 20 to 25 |
Adult patients with clinically and radiologically documented nosocomial pneumonia were enrolled in a multicenter, randomized, open-label study comparing intravenous levofloxacin (750 mg once daily) followed by oral levofloxacin (750 mg once daily) for a total of 7 to 15 days to intravenous imipenem/cilastatin (500 to 1000 mg every 6 to 8 hours daily) followed by oral ciprofloxacin (750 mg every 12 hours daily) for a total of 7 to 15 days. Levofloxacin-treated patients received an average of 7 days of intravenous therapy (range: 1 to 16 days); comparator-treated patients received an average of 8 days of intravenous therapy (range: 1 to 19 days).
Overall, in the clinically and microbiologically evaluable population, adjunctive therapy was empirically initiated at study entry in 56 of 93 (60.2%) patients in the levofloxacin arm and 53 of 94 (56.4%) patients in the comparator arm. The average duration of adjunctive therapy was 7 days in the levofloxacin arm and 7 days in the comparator. In clinically and microbiologically evaluable patients with documented Pseudomonas aeruginosa infection, 15 of 17 (88.2%) received ceftazidime (N=11) or piperacillin/tazobactam (N=4) in the levofloxacin arm and 16 of 17 (94.1%) received an aminoglycoside in the comparator arm. Overall, in clinically and microbiologically evaluable patients, vancomycin was added to the treatment regimen of 37 of 93 (39.8%) patients in the levofloxacin arm and 28 of 94 (29.8%) patients in the comparator arm for suspected methicillin-resistant S. aureus infection.
Clinical success rates in clinically and microbiologically evaluable patients at the posttherapy visit (primary study endpoint assessed on day 3 to 15 after completing therapy) were 58.1% for levofloxacin and 60.6% for comparator. The 95% CI for the difference of response rates (levofloxacin minus comparator) was [-17.2, 12]. The microbiological eradication rates at the posttherapy visit were 66.7% for levofloxacin and 60.6% for comparator. The 95% CI for the difference of eradication rates (levofloxacin minus comparator) was [-8.3, 20.3]. Clinical success and microbiological eradication rates by pathogen are detailed in Table 13.
Table 13: Clinical Success Rates and Bacteriological Eradication Rates (Nosocomial Pneumonia)
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)/3 (75) | 7 | 5 (71.4)/4 (57.1) |
* Methicillin-susceptible S. aureus
† See above text for use of combination therapy
‡ The observed differences in rates for the clinical and microbiological outcomes may reflect other factors that were not accounted for in the studyAdult inpatients and outpatients with a diagnosis of community-acquired bacterial pneumonia were evaluated in 2 pivotal clinical studies. In the first study, 590 patients were enrolled in a prospective, multi-center, unblinded randomized trial comparing levofloxacin 500 mg once daily orally or intravenously for 7 to 14 days to ceftriaxone 1 to 2 grams intravenously once or in equally divided doses twice daily followed by cefuroxime axetil 500 mg orally twice daily for a total of 7 to 14 days. Patients assigned to treatment with the control regimen were allowed to receive erythromycin (or doxycycline if intolerant of erythromycin) if an infection due to atypical pathogens was suspected or proven. Clinical and microbiologic evaluations were performed during treatment, 5 to 7 days posttherapy, and 3 to 4 weeks posttherapy. Clinical success (cure plus improvement) with levofloxacin at 5 to 7 days posttherapy, the primary efficacy variable in this study, was superior (95%) to the control group (83%). The 95% CI for the difference of response rates (levofloxacin minus comparator) was [-6, 19]. In the second study, 264 patients were enrolled in a prospective, multi-center, non-comparative trial of 500 mg levofloxacin administered orally or intravenously once daily for 7 to 14 days. Clinical success for clinically evaluable patients was 93%. For both studies, the clinical success rate in patients with atypical pneumonia due to Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila were 96%, 96%, and 70%, respectively. Microbiologic eradication rates across both studies are presented in Table 14.
Table 14: Bacteriological Eradication Rates Across 2 Community Acquired Pneumonia Clinical Studies
Pathogen
| No. Pathogens
| Bacteriological 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 |
Community-Acquired Pneumonia Due to Multi-Drug Resistant Streptococcus pneumoniae
Levofloxacin was effective for the treatment of community-acquired pneumonia caused by multi-drug resistant Streptococcus pneumoniae (MDRSP). MDRSP isolates are isolates resistant to two or more of the following antibacterials: penicillin (MIC ≥2 mcg/mL), 2nd generation cephalosporins (e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/ sulfamethoxazole). Of 40 microbiologically evaluable patients with MDRSP isolates, 38 patients (95%) achieved clinical and bacteriologic success at post-therapy. The clinical and bacterial success rates are shown in Table 15.
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 |
* One patient had a respiratory isolate that was resistant to tetracycline, cefuroxime, macrolides and TMP/SMX and intermediate to penicillin and a blood isolate that was intermediate to penicillin and cefuroxime and resistant to the other classes. The patient is included in the database based on respiratory isolate.
† n=the number of microbiologically evaluable patients who were clinical successes; N=number of microbiologically evaluable patients in the designated resistance group.
‡ n=the number of MDRSP isolates eradicated or presumed eradicated in microbiologically evaluable patients; N=number of MDRSP isolates in a designated resistance group.
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 the higher dose and shorter course of levofloxacin, 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.
Clinical success rates (cure plus improvement) in the clinically evaluable population were 90.9% in the levofloxacin 750 mg group and 91.1% in the levofloxacin 500 mg group. The 95% CI for the difference of response rates (levofloxacin 750 minus levofloxacin 500) was [-5.9, 5.4]. In the clinically evaluable population (31 to 38 days after enrollment) pneumonia was observed in 7 out of 151 patients in the levofloxacin 750 mg group and 2 out of 147 patients in the levofloxacin 500 mg group. Given the small numbers observed, the significance of this finding cannot be determined statistically. The microbiological efficacy of the 5-day regimen was documented for infections listed in Table 17.
Table 17: Bacteriological Eradication Rates (Community-Acquired Pneumonia)
S. pneumoniae
| 19/20 (95%) |
Haemophilus influenzae
| 12/12 (100%) |
Haemophilus parainfluenzae
| 10/10 (100%) |
Mycoplasma pneumoniae
| 26/27 (96%) |
Chlamydophila pneumoniae
| 13/15 (87%) |
Levofloxacin is approved for the treatment of acute bacterial sinusitis (ABS) using either 750 mg by mouth x 5 days or 500 mg by mouth once daily x 10 to 14 days. To evaluate the safety and efficacy of a high dose short course of levofloxacin, 780 outpatient adults with clinically and radiologically determined acute bacterial sinusitis were evaluated in a double-blind, randomized, prospective, multicenter study comparing levofloxacin 750 mg by mouth once daily for five days to levofloxacin 500 mg by mouth once daily for 10 days.
Clinical success rates (defined as complete or partial resolution of the pre-treatment signs and symptoms of ABS to such an extent that no further antibiotic treatment was deemed necessary) in the microbiologically evaluable population were 91.4% (139/152) in the levofloxacin 750 mg group and 88.6% (132/149) in the levofloxacin 500 mg group at the test-of-cure (TOC) visit (95% CI [-4.2, 10] for levofloxacin 750 mg minus levofloxacin 500 mg).
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.
Pathogen | Levofloxacin 750 mg x 5 days | Levofloxacin 500 mg x 10 days |
---|---|---|
* Note: Forty percent of the subjects in this trial had specimens obtained by sinus endoscopy. The efficacy data for subjects whose specimen was obtained endoscopically were comparable to those presented in the above table. |
||
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%) |
Adult patients with a clinical diagnosis of prostatitis and microbiological culture results from urine sample collected after prostatic massage (VB3) or expressed prostatic secretion (EPS) specimens obtained via the Meares-Stamey procedure were enrolled in a multicenter, randomized, double-blind study comparing oral levofloxacin 500 mg, once daily for a total of 28 days to oral ciprofloxacin 500 mg, twice daily for a total of 28 days. The primary efficacy endpoint was microbiologic efficacy in microbiologically evaluable patients. A total of 136 and 125 microbiologically evaluable patients were enrolled in the levofloxacin and ciprofloxacin groups, respectively. The microbiologic eradication rate by patient infection at 5 to 18 days after completion of therapy was 75% in the levofloxacin group and 76.8% in the ciprofloxacin group (95% CI [-12.58, 8.98] for levofloxacin minus ciprofloxacin). The overall eradication rates for pathogens of interest are presented in Table 19.
Table 19: Bacteriological Eradication Rates (Chronic Bacterial Prostatitis)
Pathogen
| Levofloxacin (N = 136)
| Ciprofloxacin (N = 125)
|
||
N
| Eradication
| N
| Eradication
|
|
E. coli
| 15 | 14 (93.3%) | 11 | 9 (81.8%) |
E. faecalis
| 54 | 39 (72.2%) | 44 | 33 (75%) |
S. epidermidis*
| 11 | 9 (81.8%) | 14 | 11 (78.6%) |
* Eradication rates shown are for patients who had a sole pathogen only; mixed cultures were excluded.
Eradication rates for S. epidermidis when found with other copathogens are consistent with rates seen in pure isolates.
Clinical success (cure + improvement with no need for further antibiotic therapy) rates in microbiologically evaluable population 5 to 18 days after completion of therapy were 75% 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 to 45 days after completion of therapy) rates were 66.7% for the levofloxacin-treated patients and 76.9% for the ciprofloxacin-treated patients (95% CI [-23.4, 2.89] for levofloxacin minus 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 |
|
*The mITT population included patients who received study medication and who had a positive (≥105 CFU/mL) urine culture with no more than 2 uropathogens at baseline. Patients with missing response were counted as failures in this analysis. †The Microbiologically Evaluable population included patients with a confirmed diagnosis of cUTI or AP, a causative organism(s) at baseline present at ≥ 105 CFU/mL, a valid test-of-cure urine culture, no pathogen isolated from blood resistant to study drug, no premature discontinuation or loss to follow-up, and compliance with treatment (among other criteria). |
|||||
mITT Population*
|
|||||
Overall (cUTI or AP) | 252/333 | 75.7 | 239/318 | 75.2 | 0.5 (-6.1, 7.1) |
cUTI | 168/230 | 73 | 157/213 | 73.7 | |
AP | 84/103 | 81.6 | 82/105 | 78.1 | |
Microbiologically Evaluable Population†
|
|||||
Overall (cUTI or AP) | 228/265 | 86 | 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 | Bacteriological Eradication Rate (n/N) | % |
---|---|---|
* The predominant organism isolated from patients with AP was E. coli: 91% (63/69) eradication in AP and 89% (92/103) in patients with cUTI. |
||
Escherichia coli*
| 155/172 | 90 |
Klebsiella pneumoniae
| 20/23 | 87 |
Proteus mirabilis
| 12/12 | 100 |
Levofloxacin 250 mg once daily for 10 days | Ciprofloxacin 500 mg twice daily for 10 days |
|||
---|---|---|---|---|
n/N | % | n/N | % | |
* 1 to 9 days posttherapy for 30% of subjects enrolled prior to a protocol amendment; 5 to 12 days posttherapy for 70% of subjects. †The mITT population included patients who had a pathogen isolated at baseline. Patients with missing response were counted as failures in this analysis. ‡ The Microbiologically Evaluable population included mITT patients who met protocol-specified evaluability criteria. |
||||
mITT Population†
| 174/209 | 83.3 | 184/219 | 84 |
Microbiologically Evaluable Population‡
| 164/177 | 92.7 | 159/171 | 93 |
See FDA-Approved Medication Guide (17.6)
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.
MEDICATION GUIDE
LEVOFLOXACIN INJECTION
for Intravenous Use
Read this Medication Guide before you start taking levofloxacin 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?
Levofloxacin, a fluoroquinolone antibiotic, can cause serious side effects. Some of these serious side effects could result in death.
If you have any of the following serious side effects while you take levofloxacin, get medical help right away. Talk with your healthcare provider about whether you should continue to take levofloxacin.
1. Tendon rupture or swelling of the tendon (tendinitis).
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 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. You may need a different antibiotic that is not a fluoroquinolone to treat your infection.
2. Worsening of myasthenia gravis (a problem that causes muscle weakness). Fluoroquinolones like levofloxacin 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.
What is levofloxacin?
Levofloxacin is a fluoroquinolone antibiotic medicine used in adults age 18 years or older to treat certain infections caused by certain germs called bacteria. These bacterial infections include:
Studies of levofloxacin for use in the treatment of plague and anthrax were done in animals only, because plague and anthrax could not be studied in people.
Levofloxacin is also used to treat children who are 6 months of age or older and may have breathed in anthrax germs, have plague, or been exposed to plague germs.
It is not known if levofloxacin is safe and effective in children under 6 months of age.
The safety and effectiveness in children treated with levofloxacin for more than 14 days is not known.
Who should not take levofloxacin?
Do not take levofloxacin if you have ever had a severe allergic reaction to an antibiotic known as a fluoroquinolone, or if you are allergic to levofloxacin or any of the ingredients in levofloxacin injection. See the end of this leaflet for a complete list of ingredients in levofloxacin injection.
What should I tell my healthcare provider before taking levofloxacin?
Before you take levofloxacin, tell your healthcare provider if you:
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.
Levofloxacin and other medicines can affect each other causing side effects.
Especially tell your healthcare provider if you take:
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?
Taking all of your levofloxacin doses will help make sure that all of the bacteria are killed. Taking all of your levofloxacin doses will help you lower the chance that the bacteria will become resistant to levofloxacin. If your infection does not get better while you take levofloxacin, it may mean that the bacteria causing your infection may be resistant to levofloxacin. If your infection does not get better, call your healthcare provider. If your infection does not get better, levofloxacin and other similar antibiotic medicines may not work for you in the future.
What should I avoid while taking levofloxacin?
What are the possible side effects of levofloxacin?
Levofloxacincan cause serious side effects, including:
Allergic reactions can happen in people taking fluoroquinolones, including levofloxacin, even after only 1 dose. Stop taking levofloxacin and get emergency medical help right away if you have any of the following symptoms of a severe allergic reaction:
Skin rash may happen in people taking levofloxacin, even after only 1 dose. Stop taking levofloxacin at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to levofloxacin.
Stop taking levofloxacin and tell your healthcare provider right away if you have 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 (a liver problem).
Central Nervous System (CNS) side effects may happen as soon as after taking the first dose of levofloxacin. Talk to your healthcare provider right away if you get any of these side effects, or other changes in mood or behavior:
Pseudomembranous colitis can happen with many antibiotics, including levofloxacin. Call your healthcare provider right away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. You may have stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after you have finished your antibiotic.
Damage to the nerves in arms, hands, legs, or feet can happen in people taking fluoroquinolones, including levofloxacin. 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 may need to be stopped to prevent permanent nerve damage.
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 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:
Increased chance of problems with joints and tissues around joints in children can happen. Tell your child’s healthcare provider if your child has any joint problems during or after treatment with levofloxacin.
People who take levofloxacin 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 taking levofloxacin, stop taking levofloxacin and call your healthcare provider right away. Your antibiotic medicine may need to be changed.
See “What should I avoid while taking levofloxacin?”
The most common side effects of levofloxacin include:
In children 6 months and older who take levofloxacin to treat anthrax disease or plague, vomiting is also common.
Low blood pressure can happen when levofloxacin is given too fast by IV injection. Tell your healthcare provider if you feel dizzy or faint during a treatment with levofloxacin injection.
Levofloxacin 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 of levofloxacin. 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?
Keep levofloxacin and all medicines out of the reach of children.
General information about the safe and effective use of levofloxacin
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use levofloxacin for a condition for which it is not prescribed. Do not give levofloxacin 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. If you would like more information about levofloxacin, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about levofloxacin that is written for healthcare professionals.
For more information call 1-866-850-2876.
What are the ingredients in levofloxacin injection?
Active ingredient: levofloxacin.
Inactive ingredients: water for injection. Levofloxacin for injection single-use vials do not contain any preservatives.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Manufactured for:
AuroMedics Pharma LLC
6 Wheeling Road
Dayton, NJ 08810
Manufactured by:
Aurobindo Pharma Limited
IDA, Pashamylaram - 502307
AP., India
Issued: May 2012
LEVOFLOXACIN
levofloxacin injection, solution, concentrate |
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LEVOFLOXACIN
levofloxacin injection, solution, concentrate |
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Labeler - AuroMedics Pharma LLC (968961354) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
Aurobindo Pharma Limited | 918917626 | API MANUFACTURE(55150-156, 55150-157) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
Aurobindo Pharma Limited | 650498244 | ANALYSIS(55150-156, 55150-157), MANUFACTURE(55150-156, 55150-157) |