Levofloxacin in 5% Dextrose Injection: Indications, Dosage, Precautions, Adverse Effects
Россия
  • Россия
  • Украина

Levofloxacin in 5% Dextrose Injection - Product Information

Manufacture: Fresenius Kabi USA, LLC
Country: United States
Condition: Bacterial Infection, Bronchitis, Chronic (COPD), Inhalation Anthrax (Anthrax), Plague, Pneumonia, Pyelonephritis (Kidney Infections), Prostatitis, Sinusitis, Acute (Sinusitis), Skin and Structure Infection, Urinary Tract Infection
Class: Anti-infectives, Quinolones
Form: Liquid solution, Intravenous (IV)
Ingredients: Levofloxacin, hydrochloric acid, sodium hydroxide

Indications and Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of levofloxacin in 5% dextrose injection and other antibacterial drugs, levofloxacin in 5% dextrose injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Levofloxacin in 5% dextrose 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 in 5% dextrose injection is indicated when intravenous administration offers a route of administration advantageous to the patient (e.g., patient cannot tolerate an oral dosage form).

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]. 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.

Nosocomial Pneumonia

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].

Community-Acquired Pneumonia: 7 to 14 day Treatment Regimen

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 and Clinical Studies].

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.

Community-Acquired Pneumonia: 5-day Treatment Regimen

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 and Clinical Studies].

Acute Bacterial Sinusitis: 5-day and 10 to 14 day Treatment Regimens

Levofloxacin is indicated for the treatment of acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see Clinical Studies].

Acute Bacterial Exacerbation of Chronic Bronchitis

Levofloxacin is indicated for the treatment of acute bacterial exacerbation of chronic bronchitis due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis.

Complicated Skin and Skin Structure Infections

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].

Uncomplicated Skin and Skin Structure Infections

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.

Chronic Bacterial Prostatitis

Levofloxacin is indicated for the treatment of chronic bacterial prostatitis due to Escherichia coli, Enterococcus faecalis, or methicillin-susceptible Staphylococcus epidermidis [see Clinical Studies].

Complicated Urinary Tract Infections: 5-day Treatment Regimen

Levofloxacin is indicated for the treatment of complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis [see Clinical Studies].

Complicated Urinary Tract Infections : 10-day Treatment Regimen

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].

Acute Pyelonephritis: 5 or 10-day Treatment Regimen

Levofloxacin is indicated for the treatment of acute pyelonephritis caused by Escherichia coli, including cases with concurrent bacteremia [see Clinical Studies].

Uncomplicated Urinary Tract Infections

Levofloxacin is indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.

Inhalational Anthrax (Pos t-Expos ure)

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 and Clinical Studies].

Plague

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 and Clinical Studies].

Dosage and Administration

Dosage in Adult Patients with Normal Renal Function

The usual dose of levofloxacin in 5% dextrose 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].

Table 1: Dosage in Adult Patients with Normal Renal Function (creatinine clearance ≥ 50 mL/min)
Type of Infection* Dosed Every 24 hours Duration (days)
Nosocomial Pneumonia 750 mg 7 to 14
Community-Acquired Pneumonia‡ 500 mg 7 to 14
Community-Acquired Pneumonia§ 750 mg 5
Acute Bacterial Sinusitis 750 mg 5
500 mg 10 to 14
Acute Bacterial Exacerbation of Chronic Bronchitis 500 mg 7
Complicated Skin and Skin Structure Infections (SSSI) 750 mg 7 to 14
Uncomplicated SSSI 500 mg 7 to 10
Chronic Bacterial Prostatitis 500 mg 28
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) 750 mg 5
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)# 250 mg 10
Uncomplicated Urinary Tract Infection 250 mg 3
Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kgÞ,β
Pediatric patients < 50 kg and ≥ 6 months of ageÞ,β
500 mg
see Table 2 below
(2.2)
60β
60β
Plague, adult and pediatric patients > 50 kgα
Pediatric patients < 50 kg and ≥ 6 months of age
500 mg
See Table 2 below
(2.2)
10 to 14
10 to 14

* Due to the designated pathogens [see Indications and Usage].

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].

§ Due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Indications and Usage].

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].

β 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, Use in Specific Populations and Clinical Studies]. Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk.

α 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.

Dosage in Pediatric Patients

The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.

Table 2: Dos age 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].

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].

§ 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, Use in Specific Populations and Clinical Studies]. 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 Adjustment in Adults with Renal Impairment

Administer levofloxacin with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.

No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.

In patients with impaired renal function (creatinine clearance < 50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance [see Use in Specific Populations].

Table 3 shows how to adjust dose based on creatinine clearance.

Table 3: Dos age Adjus tment in Adult Patients with Renal Impairment (creatinine clearance < 50 mL/min)
Dosage in Normal
Renal Function
Every 24 hours
Creatinine
Clearance 20 to 49 mL/min
Creatinine Clearance 10 to 19 mL/min Hemodialys is or Chronic
Ambulatory Peritoneal
Dialys is (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

Drug Interaction with Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

Levofloxacin in 5% dextrose injection should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line [see Dosage and Administration].

Administration Instructions

Caution: Rapid or bolus intravenous infusion of levofloxacin has been associated with hypotension and must be avoided. Levofloxacin in 5% dextrose injection should be infused intravenously slowly over a period of not less than 60 or 90 minutes, depending on the dosage. Levofloxacin in 5% dextrose injection should be administered only by intravenous infusion. It is not for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.

Hydration for Patients Receiving Levofloxacin in 5% Dextrose Injection

Adequate hydration of patients receiving intravenous levofloxacin should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones [see Adverse Reactions and Patient Counseling Information].

Preparation of Intravenous Product

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Because only limited data are available on the compatibility of levofloxacin in 5% dextrose injection with other intravenous substances, additives or other medications should not be added to Levofloxacin Injection Premix Solution in Single-Use Flexible Containers or infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of levofloxacin in 5% dextrose injection with an infusion solution compatible with levofloxacin in 5% dextrose injection and with any other drug(s) administered via this common line.

Levofloxacin Injection Premix in Single-Use Flexible Containers (5 mg/mL)

Levofloxacin in 5% dextrose injection is supplied in flexible containers within a foil overwrap. These contain a premixed, ready to use levofloxacin solution in 5% dextrose (D5W) for single-use. The 50 mL premixed flexible container contains 250 mg/50 mL of levofloxacin solution. The 100 mL premixed flexible container contains 500 mg/100 mL of levofloxacin solution. The 150 mL premixed flexible container contains 750 mg/150 mL of levofloxacin solution. The concentration of each container is 5 mg/mL. No further dilution of these preparations is necessary. Because the premix flexible containers are for single-use only, any unused portion should be discarded.

Instructions for the Use of Levofloxacin Injection Premix in Single-Use Flexible Containers
  1. Tear outer wrap at the notch and remove solution container.
  2. Check the container for minute leaks by squeezing the inner bag firmly. If leaks are found, or if the seal is not intact, discard the solution, as the sterility may be compromised.
  3. Do not use if the solution is cloudy or a precipitate is present.
  4. Use sterile equipment.
  5. WARNING: Do not admix with other drugs or additives . Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.
Preparation for Administration
  1. Close flow control clamp of administration set.
  2. Remove cover from port at bottom of container.
  3. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated.

    NOTE: See full directions on adminis tration s et carton.

  4. Suspend container from hanger.
  5. Squeeze and release drip chamber to establish proper fluid level in chamber during infusion of Levofloxacin Injection Premix in Flexible Containers.
  6. Open flow control clamp to expel air from set. Close clamp.
  7. Regulate rate of administration with flow control clamp.

Dosage Forms and Strengths

Levofloxacin in 5% dextrose injection is supplied in single-use flexible containers for intravenous infusion, and is clear yellow to clear greenish-yellow in appearance.

  • 250 mg, in flexible container, 50 mL fill
  • 500 mg, in flexible container, 100 mL fill
  • 750 mg, in flexible container, 150 mL fill

Contraindications

Levofloxacin is contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see Warnings and Precautions].

Warnings and Precautions

Fluoroquinolones, including Levofloxacin in 5% Dextrose Injection, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 6 0 years of age, in patients taking cortico stero id drugs, and in patients with kidney, heart or lung transplants.


Fluoroquinolones, including Levofloxacin in 5% Dextrose Injection, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid Levofloxacin in 5% Dextrose Injection in patients with a known history of myasthenia gravis.

Tendinopathy and Tendon Rupture

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 and Patient Counseling Information].

Exacerbation of Myasthenia Gravis

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Post-marketing 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 and Patient Counseling Information].

Hypersensitivity Reactions

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 and Patient Counseling Information].

Other Serious and Sometimes Fatal Reactions

Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with fluoroquinolones, including levofloxacin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following:

  • fever, rash, or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson Syndrome);
  • vasculitis; arthralgia; myalgia; serum sickness;
  • allergic pneumonitis;
  • interstitial nephritis; acute renal insufficiency or failure;
  • hepatitis; jaundice; acute hepatic necrosis or failure;
  • anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic abnormalities.

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 and Patient Counseling Information].

Hepatotoxicity

Post-marketing reports of severe hepatotoxicity (including acute hepatitis and fatal events) have been received for patients treated with levofloxacin. No evidence of serious drug-associated hepatotoxicity was detected in clinical trials of over 7,000 patients. Severe hepatotoxicity generally occurred within 14 days of initiation of therapy and most cases occurred within 6 days. Most cases of severe hepatotoxicity were not associated with hypersensitivity [see Warnings and Precautions]. 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 and Patient Counseling Information].

Central Nervous System Effects

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, Drug Interactions and Patient Counseling Information].

Clostridium Difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including levofloxacin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated [see Adverse Reactions and Patient Counseling Information].

Peripheral Neuropathy

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. Symptoms may occur soon after initiation of levofloxacin and may be irreversible. Levofloxacin should be discontinued immediately 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 [see Adverse Reactions and Patient Counseling Information].

Prolongation of the QT Interval

Some fluoroquinolones, including levofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. Rare cases of torsades de pointes have been spontaneously reported during post-marketing 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, Use in Specific Populations and Patient Counseling Information].

Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals

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]. 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].

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].

Blood Glucose Disturbances

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, Drug Interactions and Patient Counseling Information].

Photosensitivity/Phototoxicity

Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, “V” area of the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of fluoroquinolones after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if photosensitivity/phototoxicity occurs [see Adverse Reactions and Patient Counseling Information].

Development of Drug-Resistant Bacteria

Prescribing levofloxacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria [see Patient Counseling Information].

Adverse Reactions

Serious and Otherwise Important Adverse Reactions

The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling:

  • Tendon Effects [see Warnings and Precautions]
  • Exacerbation of Myasthenia Gravis [see Warnings and Precautions]
  • Hypersensitivity Reactions [see Warnings and Precautions]
  • Other Serious and Sometimes Fatal Reactions [see Warnings and Precautions]
  • Hepatotoxicity [see Warnings and Precautions]
  • Central Nervous System Effects [see Warnings and Precautions]
  • Clostridium difficile-Associated Diarrhea [see Warnings and Precautions]
  • Peripheral Neuropathy that may be irreversible [see Warnings and Precautions]
  • Prolongation of the QT Interval [see Warnings and Precautions]
  • Musculoskeletal Disorders in Pediatric Patients [see Warnings and Precautions]
  • Blood Glucose Disturbances [see Warnings and Precautions]
  • Photosensitivity/Phototoxicity [see Warnings and Precautions]
  • Development of Drug-Resistant Bacteria [see Warnings and Precautions]

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].

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].

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below reflect exposure to levofloxacin in 7,537 patients in 29 pooled Phase 3 clinical trials. The population studied had a mean age of 50 years (approximately 74% of the population was < 65 years of age), 50% were male, 71% were Caucasian, 19% were Black. Patients were treated with levofloxacin for a wide variety of infectious diseases [see Indications and Usage]. Patients received levofloxacin doses of 750 mg once daily, 250 mg once daily, or 500 mg once or twice daily. Treatment duration was usually 3 to 14 days, and the mean number of days on therapy was 10 days.

The overall incidence, type and distribution of adverse reactions was similar in patients receiving levofloxacin doses of 750 mg once daily, 250 mg once daily, and 500 mg once or twice daily. Discontinuation of levofloxacin due to adverse drug reactions occurred in 4.3% of patients overall, 3.8% of patients treated with the 250 mg and 500 mg doses and 5.4% of patients treated with the 750 mg dose. The most common adverse drug reactions leading to discontinuation with the 250 and 500 mg doses were gastrointestinal (1.4%), primarily nausea (0.6%); vomiting (0.4%); dizziness (0.3%); and headache (0.2%). The most common adverse drug reactions leading to discontinuation with the 750 mg dose were gastrointestinal (1.2%), primarily nausea (0.6%), vomiting (0.5%); dizziness (0.3%); and headache (0.3%).

Adverse reactions occurring in ≥ 1% of levofloxacin-treated patients and less common adverse reactions, occurring in 0.1 to < 1% of levofloxacin-treated patients, are shown in Table 4 and Table 5, respectively. The most common adverse drug reactions (≥ 3%) are nausea, headache, diarrhea, insomnia, constipation, and dizziness.

Table 4: Common (≥ 1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin
System/Organ Class Adverse Reaction %
(N =
7,537)
Infections and Infestations moniliasis 1
Psychiatric Disorders insomnia* [see Warnings and Precautions] 4
Nervous System Disorders headache
dizziness [see Warnings and Precautions]
6
3
Respiratory, Thoracic and Mediastinal
Disorders
dyspnea [see Warnings and Precautions] 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]
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

* N = 7,274

N = 3,758 (women)

Table 5: Less Common (0.1 to 1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin (N=7,537)
System/Organ Class Adverse Reaction
Infections and Infestations genital moniliasis
Blood and Lymphatic System Disorders anemia
thrombocytopenia
granulocytopenia [see Warnings and Precautions]
Immune System Disorders allergic reaction [see Warnings and Precautions]
Metabolism and Nutrition Disorders hyperglycemia
hypoglycemia [see Warnings and Precautions]
hyperkalemia
Psychiatric Disorders anxiety
agitation
confusion
depression
hallucination
nightmare* [see Warnings and Precautions]
sleep disorder*
anorexia
abnormal dreaming*
Nervous System Disorders tremor
convulsions [see Warnings and Precautions]
paresthesia [see Warnings and Precautions]
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]
Hepatobiliary Disorders abnormal hepatic function
increased hepatic enzymes
increased alkaline phosphatase
Skin and Subcutaneous Tissue
Disorders
urticaria [see Warnings and Precautions]
Musculos keletal and Connective Tissue
Disorders
arthralgia
tendinitis [see Warnings and Precautions]
myalgia
skeletal pain
Renal and Urinary Disorders abnormal renal function
acute renal failure [see Warnings and Precautions]

* N = 7,274

In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been noted in patients undergoing treatment with quinolones, including levofloxacin. The relationship of the drugs to these events is not presently established.

Post-marketing Experience

Table 6 lists adverse reactions that have been identified during post-approval use of levofloxacin. Because these reactions are reported voluntarily from a population of uncertain size, reliably estimating their frequency or establishing a causal relationship to drug exposure is not always possible.

Table 6: Post-marketing Reports of Adverse Drug Reactions
System/Organ Class Adverse Reaction
Blood and Lymphatic System
Disorders
pancytopenia
aplastic anemia
leukopenia
hemolytic anemia [see Warnings and Precautions]
eosinophilia
Immune System Disorders hypersensitivity reactions, sometimes fatal including:
 anaphylactic/anaphylactoid reactions
 anaphylactic shock
 angioneurotic edema
 serum sickness [see Warnings and Precautions]
Psychiatric Disorders psychosis
paranoia
isolated reports of suicide attempt and suicidal ideation [see Warnings and Precautions]
Nervous System Disorders exacerbation of myasthenia gravis [see Warnings and Precautions]
anosmia
ageusia
parosmia
dysgeusia
peripheral neuropathy (may be irreversible) [see Warnings and Precautions]
isolated reports of encephalopathy
abnormal electroencephalogram (EEG)
dysphonia
pseudotumor cerebri [see Warnings and Precautions]
Eye Disorders uveitis
vision disturbance, including diplopia
visual acuity reduced
vision blurred
scotoma
Ear and Labyrinth Disorders hypoacusis
tinnitus
Cardiac Disorders isolated reports of torsades de pointes
electrocardiogram QT prolonged [see Warnings and Precautions]
tachycardia
Vascular Disorders vasodilatation
Respiratory, Thoracic and
Medias tinal Disorders
isolated reports of allergic pneumonitis [see Warnings and Precautions]
Hepatobiliary Disorders hepatic failure (including fatal cases)
hepatitis
jaundice [see Warnings and Precautions]
Skin and Subcutaneous Tissue
Disorders
bullous eruptions to include:
 Stevens-Johnson Syndrome
 toxic epidermal necrolysis
 erythema multiforme [see Warnings and Precautions]
photosensitivity/phototoxicity reaction [see Warnings and Precautions]
 leukocytoclastic vasculitis
Musculoskeletal and Connective
Tissue Disorders
tendon rupture [see Warnings and Precautions]
muscle injury, including rupture
rhabdomyolysis
Renal and Urinary Disorders interstitial nephritis [see Warnings and Precautions]
General Disorders and
Administration Site Conditions
multi-organ failure
pyrexia
Investigations prothrombin time prolonged
international normalized ratio prolonged
muscle enzymes increased

Drug Interactions

Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

There are no data concerning an interaction of intravenous fluoroquinolones with oral antacids, sucralfate, multivitamins, didanosine, or metal cations. However, no fluoroquinolone should be coadministered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line [see Dosage and Administration].

Warfarin

No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for R- and S- warfarin was detected in a clinical study involving healthy volunteers. Similarly, no apparent effect of warfarin on levofloxacin absorption and disposition was observed. However, there have been reports during the post-marketing experience in patients that levofloxacin enhances the effects of warfarin. Elevations of the prothrombin time in the setting of concurrent warfarin and levofloxacin use have been associated with episodes of bleeding. Prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if levofloxacin is administered concomitantly with warfarin. Patients should also be monitored for evidence of bleeding [see Adverse Reactions and Patient Counseling Information].

Anti-diabetic Agents

Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones and an anti-diabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered [see Warnings and Precautions, Adverse Reactions and Patient Counseling Information].

Non-Steroidal Anti-Inflammatory Drugs

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].

Theophylline

No significant effect of levofloxacin on the plasma concentrations, AUC, and other disposition parameters for theophylline was detected in a clinical study involving healthy volunteers. Similarly, no apparent effect of theophylline on levofloxacin absorption and disposition was observed. However, concomitant administration of other fluoroquinolones with theophylline has resulted in prolonged elimination half-life, elevated serum theophylline levels, and a subsequent increase in the risk of theophylline-related adverse reactions in the patient population. Therefore, theophylline levels should be closely monitored and appropriate dosage adjustments made when levofloxacin is co-administered. Adverse reactions, including seizures, may occur with or without an elevation in serum theophylline levels [see Warnings and Precautions].

Cyclosporine

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.

Digoxin

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.

Probenecid and Cimetidine

No significant effect of probenecid or cimetidine on the Cmax of levofloxacin was observed in a clinical study involving healthy volunteers. The AUC and t½ 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 co-administered.

Interactionswith Laboratory or Diagnostic Testing

Some fluoroquinolones, including levofloxacin, may produce false-positive urine screening results for opiates using commercially available immunoassay kits. Confirmation of positive opiate screens by more specific methods may be necessary.

Use in Specific Populations

Pregnancy

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.

Nursing Mothers

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.

Pediatric Use

Quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species [see Warnings and Precautions and Animal Toxicology and/or Pharmacology].

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 and Clinical Studies].

Inhalational Anthrax (Post-Exposure)

Levofloxacin is indicated in pediatric patients 6 months of age and older, for inhalational anthrax (postexposure). 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, Dosage and Administration and Clinical Studies].

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, Dosage and Administration and Clinical Studies].

Safety and effectiveness in pediatric patients below the age of six months have not been established.

Adverse Events

In clinical trials, 1,534 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 (1,340 levofloxacin-treated and 893 non-fluoroquinolonetreated) enrolled in a prospective, long-term surveillance study to assess the incidence of protocoldefined 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 nonfluoroquinolone-treated children as illustrated in Table 7.

Table 7: Incidence of Musculoskeletal Disorders in Pediatric Clinical Trial
Follow-up Period Levofloxacin
N = 1,340
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

* Non-Fluoroquinolone: ceftriaxone, amoxicillin/clavulanate, clarithromycin

2-sided Fisher’s Exact Test

There were 1,199 levofloxacin-treated and 804 non-fluoroquinolone-treated children who had a oneyear 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.

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] may also be expected to occur in pediatric patients.

Geriatric Use

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; and Adverse Reactions].

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].

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 torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia) [see Warnings and Precautions].

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].

Renal Impairment

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].

Hepatic Impairment

Pharmacokinetic studies in hepatically impaired patients have not been conducted. Due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment.

Overdosage

In the event of an acute overdosage, the stomach should be emptied. The patient should be observed and appropriate hydration maintained. Levofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis.

Levofloxacin exhibits a low potential for acute toxicity. Mice, rats, dogs and monkeys exhibited the following clinical signs after receiving a single high dose of levofloxacin: ataxia, ptosis, decreased locomotor activity, dyspnea, prostration, tremors, and convulsions. Doses in excess of 1,500 mg/kg orally and 250 mg/kg IV produced significant mortality in rodents.

How Supplied/Storage and Handling

Levofloxacin Injection Pre-Mixed Solution, Single-Use in Flexible Container

Levofloxacin in 5% Dextrose Injection 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).

Product
No.
NDC
No.
Strength
315550 63323-355-50 5 mg per mL 250 mg, in flexible container, 50 mL fill.
315565 63323-355-65 5 mg per mL 500 mg, in flexible container, 100 mL fill.
315560 63323-355-60 5 mg per mL 750 mg, in flexible container, 150 mL fill.

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Avoid excessive heat and protect from freezing and light.

The container closure is not made with natural rubber latex. Non-PVC, Non-DEHP, Sterile.

Patient Counseling Information

See Consumer Medicine Information

Antibacterial Resistance

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.

Administration with Fluids

Patients should drink fluids liberally while taking levofloxacin to avoid formation of a highly concentrated urine and crystal formation in the urine.

Serious and Potentially Serious Adverse Reactions

Patients should be informed of the following serious adverse reactions that have been associated with levofloxacin or other fluoroquinolone use:

  • Tendon Disorders: Patients should contact their healthcare provider if they experience pain, swelling, or inflammation of a tendon, or weakness or inability to use one of their joints; rest and refrain from exercise; and discontinue levofloxacin treatment. The risk of severe tendon dis orders with fluoroquinolones is higher in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants.
  • Exacerbation of Myasthenia Gravis: Patients should inform their physician of any history of myasthenia gravis. Patients should notify their physician if they experience any symptoms of muscle weakness, including respiratory difficulties.
  • Hypersensitivity Reactions: Patients should be informed that levofloxacin can cause hypersensitivity reactions, even following the first dose. Patients should discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (e.g., swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction.
  • Hepatotoxicity: Severe hepatotoxicity (including acute hepatitis and fatal events) has been reported in patients taking levofloxacin. Patients should inform their physician and be instructed to discontinue levofloxacin treatment immediately if they experience any signs or symptoms of liver injury including: loss of appetite, nausea, vomiting, fever, weakness, tiredness, right upper quadrant tenderness, itching, yellowing of the skin and eyes, light colored bowel movements or dark colored urine.
  • Convulsions: Convulsions have been reported in patients taking fluoroquinolones, including levofloxacin. Patients should notify their physician before taking this drug if they have a history of convulsions.
  • Neurologic Adverse Effects (e.g., dizziness, lightheadedness, increased intracranial pressure): Patients should know how they react to levofloxacin before they operate an automobile or machinery or engage in other activities requiring mental alertness and coordination. Patients should notify their physician if persistent headache with or without blurred vision occurs.
  • Diarrhea: Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.
  • Peripheral Neuropathies: Patients should be informed that peripheral neuropathy has been associated with levofloxacin use. Symptoms may occur soon after initiation of therapy and may be irreversible. If symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness develop, patients should immediately discontinue treatment and contact their physician.
  • Prolongation of the QT Interval: Patients should inform their physician of any personal or family history of QT prolongation or proarrhythmic conditions such as hypokalemia, bradycardia, or recent myocardial ischemia; if they are taking any Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) anti-arrhythmic agents. Patients should notify their physicians if they have any symptoms of prolongation of the QT interval, including prolonged heart palpitations or a loss of consciousness.
  • Musculoskeletal Disorders in Pediatric Patients: Parents should inform their child's physician if their child has a history of joint-related problems before taking this drug. Parents of pediatric patients should also notify their child's physician of any tendon or joint-related problems that occur during or following levofloxacin therapy [see Warnings and Precautions and Use in Specific Populations].
  • Photosensitivity/Phototoxicity: Patients should be advised that photosensitivity/phototoxicity has been reported in patients receiving fluoroquinolone antibiotics. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while taking fluoroquinolones. If patients need to be outdoors when taking fluoroquinolones, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. If a sunburn-like reaction or skin eruption occurs, patients should contact their physician.

Drug Interactions with Insulin, Oral Hypoglycemic Agents, and Warfarin

Patients should be informed that if they are diabetic and are being treated with insulin or an oral hypoglycemic agent and a hypoglycemic reaction occurs, they should discontinue levofloxacin and consult a physician.

Patients should be informed that concurrent administration of warfarin and levofloxacin has been associated with increases of the International Normalized Ratio (INR) or prothrombin time and clinical episodes of bleeding. Patients should notify their physician if they are taking warfarin, be monitored for evidence of bleeding, and also have their anticoagulation tests closely monitored while taking warfarin concomitantly.

Plague and Anthrax Studies

Patients given levofloxacin for these conditions should be informed that efficacy studies could not be conducted in humans for ethical and feasibility reasons. Therefore, approval for these conditions was based on efficacy studies conducted in animals.

The brand names mentioned in this document are the trademarks of their respective owners.