LEVOFLOXACIN
-
levofloxacin tablet, film coated
Greenstone LLC
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Levofloxacin tablets are indicated for the treatment of community-acquired pneumonia due to Streptococcus pneumoniae (excluding multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.3)].
Levofloxacin tablets are indicated for the treatment of acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see Clinical Studies (14.4)].
Levofloxacin tablets are 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 tablets are 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 tablets are indicated for the treatment of complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis [see Clinical Studies (14.7)].
Levofloxacin tablets are indicated for the treatment of acute pyelonephritis caused by Escherichia coli, including cases with concurrent bacteremia [see Clinical Studies (14.7, 14.8)].
Levofloxacin tablets are indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.
Levofloxacin tablets are indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis. The effectiveness of levofloxacin tablets is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. Levofloxacin tablets have not been tested in humans for the post-exposure prevention of inhalation anthrax. The safety of levofloxacin tablets 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 tablets therapy should only be used when the benefit outweighs the risk [see Dosage and Administration (2.1, 2.2) and Clinical Studies (14.9)].
Type of Infection1 | Dosed Every 24 hours | Duration (days)2 |
---|---|---|
1 Due to the designated pathogens [see Indications and Usage (1)]. 2 Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. 3 Due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Indications and Usage (1.2)]. 4 Due to Streptococcus pneumoniae (excluding multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Indications and Usage (1.3)]. 5 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. 6 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. 7 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)]. 8 The safety of levofloxacin tablets 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 tablets therapy should only be used when the benefit outweighs the risk. |
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Nosocomial Pneumonia | 750 mg | 7-14 |
Community Acquired Pneumonia3
| 500 mg | 7-14 |
Community Acquired Pneumonia4
| 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)5
| 750 mg | 5 |
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)6
| 250 mg | 10 |
Uncomplicated Urinary Tract Infection | 250 mg | 3 |
Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kg and ≥ 6 months of age7,8
Pediatric patients < 50 kg and ≥ 6 months of age7,8 | 500 mg see Table 2 below (2.2) | 608
608 |
1 Due to Bacillus anthracis [see Indications and Usage (1.13)]
2 Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. 3 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)] 4 The safety of levofloxacin tablets 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 tablets therapy should only be used when the benefit outweighs the risk. |
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Type of Infection1
| Dose | Freq. Once every | Duration2
|
Inhalational Anthrax (post-exposure)3, 4
| |||
Pediatric patients > 50 kg and ≥ 6 months of age | 500 mg | 24 hr | 60 days4
|
Pediatric patients < 50 kg and ≥ 6 months of age | 8 mg/kg (not to exceed 250 mg per dose) | 12 hr | 60 days4
|
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) |
---|---|---|---|
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 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)].
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)].
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)].
System/Organ Class | Adverse Reaction | % (N = 7537) |
---|---|---|
a N = 7274 b N = 3758 (women) |
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Infections and Infestations
| moniliasis | 1 |
Psychiatric Disorders
| insomniaa
[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 | 1b
|
General Disorders and
Administration Site Conditions | edema injection site reaction chest pain | 1 1 1 |
System/Organ Class | Adverse Reaction |
---|---|
a 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 nightmarea [see Warnings and Precautions (5.6)] sleep disordera anorexia abnormal dreaminga |
Nervous System Disorders
| tremor convulsions [see Warnings and Precautions (5.6)] paresthesia [see Warnings and Precautions (5.8)] vertigo hypertonia hyperkinesias abnormal gait somnolencea 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 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 |
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 |
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 coadministered [see Warnings and Precautions (5.11); Adverse Reactions (6.2), Patient Counseling Information (17.4)].
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.
Follow-up Period | Levofloxacin N = 1340 | Non-Fluoroquinolonea
N = 893 | p-valueb |
---|---|---|---|
a Non-Fluoroquinolone: ceftriaxone, amoxicillin/clavulanate, clarithromycin b 2-sided Fisher’s Exact Test c 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. |
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60 days
| 28 (2.1%) | 8 (0.9%) | p = 0.038 |
1 yearc
| 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)].
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. |
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Single dose
| | | | | |
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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
| | | | | |
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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:
| | | | | |
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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:
| | | | | |
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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 |
Pathogen | Minimum Inhibitory Concentrations (mcg/mL) | Disk Diffusion (zone diameter in mm) |
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---|---|---|---|---|---|---|
S | I | R | S | I | R | |
S = Susceptible, I = Intermediate, R = Resistant a These interpretive standards are applicable only to broth microdilution susceptibility testing with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium.1 b The current absence of data on resistant strains precludes defining any categories other than “Susceptible.” Strains yielding MIC/zone diameter results suggestive of a “nonsusceptible” category should be submitted to a reference laboratory for further testing. c These interpretive standards are applicable only to disk diffusion susceptibility testing with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium.2 d These interpretive standards are applicable only to broth microdilution susceptibility tests using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood. e These zone diameter standards for Streptococcus spp. including S. pneumoniae apply only to tests performed using Mueller-Hinton agar supplemented with 5% sheep blood and incubated in 5% CO2. |
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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
| ≤2a
| --b
| --b
| ≥17c
| --b
| --b
|
Haemophilus parainfluenzae
| ≤2a
| --b
| --b
| ≥17c
| --b
| --b
|
Streptococcus pneumoniae
| ≤2d
| 4d
| ≥8d
| ≥17e
| 14-16e
| ≤13e
|
Streptococcus pyogenes
| ≤2 | 4 | ≥8 | ≥17 | 14-16 | ≤13 |
Microorganism | Microorganism QC Number | MIC (mcg/mL) | Disk Diffusion (zone diameter in mm) |
---|---|---|---|
a This quality control range is applicable to only H. influenzae ATCC 49247 tested by a broth microdilution procedure using Haemophilus Test Medium (HTM).1
b This quality control range is applicable to only H. influenzae ATCC 49247 tested by a disk diffusion procedure using Haemophilus Test Medium (HTM).2 c This quality control range is applicable to only S. pneumoniae ATCC 49619 tested by a broth microdilution procedure using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood. d This quality control range is applicable to only S. pneumoniae ATCC 49619 tested by a disk diffusion procedure using Mueller-Hinton agar supplemented with 5% sheep blood and incubated in 5% CO2. **Careful maintenance of this organism is required as the strain may lose its plasmid. |
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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 – 0.03a
| 32 – 40b
|
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 – 2c
| 20 – 25d
|
Pathogen | N | Levofloxacin No. (%) of Patients Microbiologic/ Clinical Outcomes | N | Imipenem/Cilastatin No. (%) of Patients Microbiologic/ Clinical Outcomes |
---|---|---|---|---|
a Methicillin-susceptible S. aureus
b See above text for use of combination therapy c The observed differences in rates for the clinical and microbiological outcomes may reflect other factors that were not accounted for in the study |
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MSSAa
| 21 | 14 (66.7)/13 (61.9) | 19 | 13 (68.4)/15 (78.9) |
P. aeruginosab
| 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. pneumoniaec
| 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) |
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 |
Screening Susceptibility | Clinical Success | Bacteriological Successc | ||
---|---|---|---|---|
n/Na | % | n/Nb | % | |
a n=the number of microbiologically evaluable patients who were clinical successes; N=number of microbiologically evaluable patients in the designated resistance group. b n=the number of MDRSP isolates eradicated or presumed eradicated in microbiologically evaluable patients; N=number of MDRSP isolates in a designated resistance group. c 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. |
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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 |
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%) |
Penicillin susceptible S. pneumoniae
| 19/20 |
Haemophilus influenzae
| 12/12 |
Haemophilus parainfluenzae
| 10/10 |
Mycoplasma pneumoniae
| 26/27 |
Chlamydophila pneumoniae
| 13/15 |
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. |
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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%) |
Pathogen | Levofloxacin (N = 136) | Ciprofloxacin (N = 125) | ||
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N | Eradication | N | Eradication | |
* Eradication rates shown are for patients who had a sole pathogen only; mixed cultures were excluded. |
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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%) |
a 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. b 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). |
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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] |
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n/N | % | n/N | % | Levofloxacin- Ciprofloxacin |
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mITT Populationa
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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 Populationb
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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 | Microbiologic Eradication Rate (n/N) | % |
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* 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. |
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Escherichia coli*
| 155/172 | 90 |
Klebsiella pneumoniae
| 20/23 | 87 |
Proteus mirabilis
| 12/12 | 100 |
a 1 to 9 days posttherapy for 30% of subjects enrolled prior to a protocol amendment; 5 to 12 days posttherapy for 70% of subjects. b The mITT population included patients who had a pathogen isolated at baseline. Patients with missing response were counted as failures in this analysis. c The Microbiologically Evaluable population included mITT patients who met protocol-specified evaluability criteria. |
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| Levofloxacin 250 mg once daily for 10 days | Ciprofloxacin 500 mg twice daily for 10 days |
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n/N | % | n/N | % |
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mITT Populationb
| 174/209 | 83.3 | 184/219 | 84 |
Microbiologically Evaluable Populationc
| 164/177 | 92.7 | 159/171 | 93 |
LEVOFLOXACIN
levofloxacin tablet, film coated |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
ANDA | ANDA201043 | 06/20/2011 |
LEVOFLOXACIN
levofloxacin tablet, film coated |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
ANDA | ANDA201043 | 06/20/2011 |
LEVOFLOXACIN
levofloxacin tablet, film coated |
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Marketing Information | |||
Marketing Category | Application Number or Monograph Citation | Marketing Start Date | Marketing End Date |
ANDA | ANDA201043 | 06/20/2011 |
Labeler - Greenstone LLC (825560733) |
Revised: 12/2011 Greenstone LLC