LEVOFLOXACIN injection, solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

LEVOFLOXACIN (UNII: 6GNT3Y5LMF) (LEVOFLOXACIN ANHYDROUS - UNII:RIX4E89Y14)

Available from:

Baxter Healthcare Corporation

INN (International Name):

LEVOFLOXACIN

Composition:

LEVOFLOXACIN ANHYDROUS 25 mg in 1 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Levofloxacin Injection is indicated for the treatment of adults (≥18 years of age) with mild, moderate, and severe infections caused by susceptible isolates of the designated microorganisms in the conditions listed in this section. Levofloxacin Injection is indicated when intravenous administration offers a route of administration advantageous to the patient (e.g., patient cannot tolerate an oral dosage form). Levofloxacin is indicated for the treatment of nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus , Pseudomonas aeruginosa , Serratia marcescens , Escherichia coli , Klebsiella pneumoniae , Haemophilus influenzae , or Streptococcus pneumoniae . Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see Clinical Studies (14.1)] . Levofloxacin is indicated for the treatment of community-acquired pneumonia due to methicillin-susceptible Staphylococcus aureus , Streptococcus pneumoniae (including multi- drug-resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae , Haemophilus parainfluenzae , Klebsiella pneumoniae , Moraxella catarrhalis , Chlamydophila pneumoniae , Legionella pneumophila , or Mycoplasma pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.2)] . 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. Levofloxacin 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 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 is indicated for the treatment of uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to methicillin-susceptible Staphylococcus aureus , or Streptococcus pyogenes . Levofloxacin is indicated for the treatment of chronic bacterial prostatitis due to Escherichia coli , Enterococcus faecalis , or methicillin-susceptible Staphylococcus epidermidis [see Clinical Studies (14.6)] . Levofloxacin is indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis . The effectiveness of levofloxacin is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. Levofloxacin has not been tested in humans for the post-exposure prevention of inhalation anthrax. The 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 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)] . Levofloxacin 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 is indicated for the treatment of complicated urinary tract infections (mild to moderate) due to Enterococcus faecalis , Enterobacter cloacae , Escherichia coli , Klebsiella pneumoniae , Proteus mirabilis , or Pseudomonas aeruginosa [see Clinical Studies (14.8)] . Levofloxacin is indicated for the treatment of acute pyelonephritis caused by Escherichia coli , including cases with concurrent bacteremia [see Clinical Studies (14.7 , 14.8)] . Levofloxacin is indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli , Klebsiella pneumoniae , or Staphylococcus saprophyticus . Because fluoroquinolones, including levofloxacin, have been associated with serious adverse reactions [see Warnings and Precautions (5.1– 5.15 )] and for some patients uncomplicated urinary tract infection is self-limiting, reserve levofloxacin for treatment of uncomplicated urinary tract infections in patients who have no alternative treatment options. Levofloxacin is indicated for the treatment of acute bacterial exacerbation of chronic bronchitis (ABECB) due to methicillin-susceptible Staphylococcus aureus , Streptococcus pneumoniae , Haemophilus influenzae , Haemophilus parainfluenzae , or Moraxella catarrhalis . Because fluoroquinolones, including levofloxacin, have been associated with serious adverse reactions [see Warnings and Precautions (5.1– 5.15 )] and for some patients ABECB is self-limiting, reserve levofloxacin for treatment of ABECB in patients who have no alternative treatment options. Levofloxacin is indicated for the treatment of acute bacterial sinusitis (ABS) due to Streptococcus pneumoniae , Haemophilus influenzae , or Moraxella catarrhalis [see Clinical Studies (14.4)] . Because fluoroquinolones, including levofloxacin, have been associated with serious adverse reactions [see Warnings and Precautions (5.1– 5.15 )] and for some patients ABS is self-limiting, reserve levofloxacin for treatment of ABS in patients who have no alternative treatment options. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Levofloxacin and other antibacterial drugs, Levofloxacin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Culture and susceptibility testing Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin [see Microbiology (12.4)] . Therapy with levofloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be selected. As with other drugs in this class, some isolates of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin. Culture and susceptibility testing performed periodically during therapy will provide information about the continued susceptibility of the pathogens to the antimicrobial agent and also the possible emergence of bacterial resistance. Levofloxacin is contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see Warnings and Precautions (5.3)] . Pregnancy Category C. Levofloxacin was not teratogenic in rats at oral doses as high as 810 mg/kg/day which corresponds to 9.4 times the highest recommended human dose based upon relative body surface area, or at intravenous doses as high as 160 mg/kg/day corresponding to 1.9 times the highest recommended human dose based upon relative body surface area. The oral dose of 810 mg/kg/day to rats caused decreased fetal body weight and increased fetal mortality. No teratogenicity was observed when rabbits were dosed orally as high as 50 mg/kg/day which corresponds to 1.1 times the highest recommended human dose based upon relative body surface area, or when dosed intravenously as high as 25 mg/kg/day, corresponding to 0.5 times the highest recommended human dose based upon relative body surface area. There are, however, no adequate and well-controlled studies in pregnant women. Levofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Based on data on other fluoroquinolones and very limited data on levofloxacin, it can be presumed that levofloxacin will be excreted in human milk. Because of the potential for serious adverse reactions from levofloxacin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species. [see Warnings and Precautions (5.12) and Animal Toxicology and/or Pharmacology (13.2)] . Pharmacokinetics following intravenous administration The pharmacokinetics of levofloxacin following a single intravenous dose were investigated in pediatric patients ranging in age from six months to 16 years. Pediatric patients cleared levofloxacin faster than adult patients resulting in lower plasma exposures than adults for a given mg/kg dose [see Clinical Pharmacology (12.3) and Clinical Studies (14.9)] . Inhalational Anthrax (Post-Exposure) Levofloxacin is indicated in pediatric patients 6 months of age and older, for inhalational anthrax (post-exposure). The risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate. The safety of levofloxacin in pediatric patients treated for more than 14 days has not been studied [see Indications and Usage (1.7) , Dosage and Administration (2.2) and Clinical Studies (14.9)] . Plague Levofloxacin is indicated in pediatric patients, 6 months of age and older, for treatment of plague, including pneumonic and septicemic plague due to Yersinia pestis (Y. pestis ) and prophylaxis for plague. Efficacy studies of levofloxacin could not be conducted in humans with pneumonic plague for ethical and feasibility reasons. Therefore, approval of this indication was based on an efficacy study conducted in animals. The risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate [see Indications and Usage (1.8) , Dosage and Administration (2.2) and Clinical Studies (14.10)]. Safety and effectiveness in pediatric patients below the age of six months have not been established. Adverse Events In clinical trials, 1534 children (6 months to 16 years of age) were treated with oral and intravenous levofloxacin. Children 6 months to 5 years of age received levofloxacin 10 mg/kg twice a day and children greater than 5 years of age received 10 mg/kg once a day (maximum 500 mg per day) for approximately 10 days. A subset of children in the clinical trials (1340 levofloxacin-treated and 893 non-fluoroquinolone-treated) enrolled in a prospective, long-term surveillance study to assess the incidence of protocol-defined musculoskeletal disorders (arthralgia, arthritis, tendinopathy, gait abnormality) during 60 days and 1 year following the first dose of the study drug. Children treated with levofloxacin had a significantly higher incidence of musculoskeletal disorders when compared to the non-fluoroquinolone-treated children as illustrated in Table 9. Follow-up Period Levofloxacin N = 1340 Non-Fluoroquinolone N = 893 * p-value † 60 days 28 (2.1%) 8 (0.9%) p = 0.038 1 year ‡ 46 (3.4%) 16 (1.8%) p = 0.025 Arthralgia was the most frequently occurring musculoskeletal disorder in both treatment groups. Most of the musculoskeletal disorders in both groups involved multiple weight-bearing joints. Disorders were moderate in 8/46 (17%) children and mild in 35/46 (76%) levofloxacin-treated children and most were treated with analgesics. The median time to resolution was 7 days for levofloxacin-treated children and 9 for non-fluoroquinolone-treated children (approximately 80% resolved within 2 months in both groups). No child had a severe or serious disorder and all musculoskeletal disorders resolved without sequelae. Vomiting and diarrhea were the most frequently reported adverse events, occurring in similar frequency in the levofloxacin-treated and non-fluoroquinolone-treated children. In addition to the events reported in pediatric patients in clinical trials, events reported in adults during clinical trials or post-marketing experience [see Adverse Reactions (6)] may also be expected to occur in pediatric patients. Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with a fluoroquinolone such as levofloxacin. This risk is further increased in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported. Caution should be used when prescribing levofloxacin to elderly patients especially those on corticosteroids. Patients should be informed of this potential side effect and advised to discontinue levofloxacin and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur [see Boxed Warning ; Warnings and Precautions (5.2) ; and Adverse Reactions (6.3)] . In Phase 3 clinical trials, 1,945 levofloxacin-treated patients (26%) were ≥ 65 years of age. Of these, 1,081 patients (14%) were between the ages of 65 and 74 and 864 patients (12%) were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Severe, and sometimes fatal, cases of hepatotoxicity have been reported post-marketing in association with levofloxacin. The majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. Levofloxacin should be discontinued immediately if the patient develops signs and symptoms of hepatitis [see Warnings and Precautions (5.9) ] . Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients [see Warnings and Precautions (5.8)] . Elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, precaution should be taken when using levofloxacin with concomitant drugs that can result in prolongation of the QT interval (e.g., Class IA or Class III antiarrhythmics) or in patients with risk factors for torsade de pointes (e.g., known QT prolongation, uncorrected hypokalemia) [see Warnings and Precautions (5.11) ] . The pharmacokinetic properties of levofloxacin in younger adults and elderly adults do not differ significantly when creatinine clearance is taken into consideration. However, since the drug is known to be substantially excreted by the kidney, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Clinical Pharmacology (12.3)] . 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)] . Pharmacokinetic studies in hepatically impaired patients have not been conducted. Due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment.

Product summary:

Levofloxacin Injection is supplied in single-use vials. Each vial contains a concentrated solution with the equivalent of 500 mg of levofloxacin in 20 mL vials. 25 mg/mL, 20 mL vials (NDC 36000-045-01) Levofloxacin Injection in Single-Use Vials should be stored at controlled room temperature and protected from light. Levofloxacin Injection in Single-Use Vials is manufactured for Baxter Healthcare Corporation, Deerfield, IL 60015 USA by Baxter Pharmaceuticals India Private Ltd, Ahmedabad 382213, India. Levofloxacin Injection in 5% Dextrose (Premix) is supplied as a single-use, premixed solution in flexible containers. Each bag contains a dilute solution with the equivalent of 250, 500, or 750 mg of levofloxacin, respectively, in 5% Dextrose (D5W). 5 mg/mL (250 mg), 50 mL filled in 100 mL flexible container (NDC 36000-046-24) 5 mg/mL (500 mg), 100 mL filled in 100 mL flexible container, (NDC 36000-047-24) 5 mg/mL (750 mg), 150 mL filled in 250 mL flexible container, (NDC 36000-048-24) Levofloxacin Injection in 5% Dextrose (Premix) in Flexible Containers should be stored at 20° - 25°C (68° - 77°F) [See USP Controlled Room Temperature] . Avoid excessive heat and protect from freezing and light. Levofloxacin Injection in 5% Dextrose (Premix) is manufactured for Baxter Healthcare Corporation, Deerfield, IL 60015 USA by Baxter Pharmaceuticals India Private Ltd, Ahmedabad 382213, India. Keep out of reach of children.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

LEVOFLOXACIN- LEVOFLOXACIN INJECTION, SOLUTION
Baxter Healthcare Corporation
----------
MEDICATION GUIDE
LEVOFLOXACIN (LEE voe FLOX a sin) INJECTION, 25 mg/mL and
LEVOFLOXACIN (LEE voe FLOX a sin) INJECTION in 5% Dextrose
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 can happen at
the same time and could result in death.
If you have any of the following serious side effects while you take
levofloxacin, you should stop taking
levofloxacin immediately and get medical help right away.
1. Tendon rupture or swelling of the tendon (tendinitis).
•
Tendon problems can happen in people of all ages who take
levofloxacin. Tendons are tough cords
of tissue that connect muscles to bones.
Some tendon problems include pain, swelling, tears, and swelling of
tendons including the back of
the ankle (Achilles), shoulder, hand, or other tendon sites.
•
The risk of getting tendon problems while you take levofloxacin is
higher if you:
•
are over 60 years of age
•
are taking steroids (corticosteroids)
•
have had a kidney, heart or lung transplant.
•
Tendon problems can happen in people who do not have the above risk
factors when they take
levofloxacin.
•
Other reasons that can increase your risk of tendon problems can
include:
•
physical activity or exercise
•
kidney failure
•
tendon problems in the past, such as in people with rheumatoid
arthritis (RA)
•
Stop taking levofloxacin immediately and get medical help right away
at the first sign of tendon
pain, swelling or inflammation. Avoid exercise and using the affected
area.
The most common area of pain and swelling is the Achilles tendon at
the back of y

Summary of Product characteristics

LEVOFLOXACIN- LEVOFLOXACIN INJECTION, SOLUTION
BAXTER HEALTHCARE CORPORATION
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LEVOFLOXACIN SAFELY AND EFFECTIVELY. SEE FULL
PRESCRIBING INFORMATION FOR LEVOFLOXACIN INJECTION, 25 MG/ML AND
LEVOFLOXACIN INJECTION IN 5% DEXTROSE, 5
MG /ML.
INITIAL U.S. APPROVAL: 1996
WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON
RUPTURE,
PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS AND EXACERBATION
OF
MYASTHENIA GRAVIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
FLUOROQUINOLONES, INCLUDING LEVOFLOXACIN, HAVE BEEN ASSOCIATED WITH
DISABLING AND POTENTIALLY
IRREVERSIBLE SERIOUS ADVERSE REACTIONS THAT HAVE OCCURRED TOGETHER
(5.1), INCLUDING:
•
•
•
DISCONTINUE LEVOFLOXACIN IMMEDIATELY AND AVOID THE USE OF
FLUOROQUINOLONES, INCLUDING LEVOFLOXACIN, IN
PATIENTS WHO EXPERIENCE ANY OF THESE SERIOUS ADVERSE REACTIONS (5.1)
FLUOROQUINOLONES, INCLUDING LEVOFLOXACIN, MAY EXACERBATE MUSCLE
WEAKNESS IN PATIENTS WITH MYASTHENIA
GRAVIS. AVOID LEVOFLOXACIN IN PATIENTS WITH A KNOWN HISTORY OF
MYASTHENIA GRAVIS _[SEE WARNINGS AND_
_PRECAUTIONS (5.5)]_.
BECAUSE FLUOROQUINOLONES, INCLUDING LEVOFLOXACIN, HAVE BEEN ASSOCIATED
WITH SERIOUS ADVERSE REACTIONS
(5.1–5.15), RESERVE LEVOFLOXACIN FOR USE IN PATIENTS WHO HAVE NO
ALTERNATIVE TREATMENT OPTIONS FOR THE
FOLLOWING INDICATIONS:
•
•
•
INDICATIONS AND USAGE
Levofloxacin is a fluoroquinolone antibacterial indicated in adults
(≥18 years of age) with infections caused by designated,
susceptible bacteria (1_, _12.4).
•
•
•
•
•
•
•
•
•
Usage
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 (1.15).
DOSAGE AND ADMINISTRATION
•
TYPE OF INFECTION
DOSE EVERY 24 HOURS
DURATION
(DAYS)
Nosocomial Pneumonia (1.1)
750 mg
7-