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

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 tablets, USP [see Microbiology(12.4)]. Therapy with levofloxacin tablets, USP 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 tablets, USP. 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.

1.1 Nosocomial Pneumonia

Levofloxacin tablets, USP are indicated for the treatment of nosocomial pneumonia due to methicillinsusceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an antipseudomonal β-lactam is recommended [see Clinical Studies (14.1)].

1.2 Community-Acquired Pneumonia: 7-14 day Treatment Regimen

Levofloxacin tablets, USP are indicated for the treatment of community-acquired pneumonia due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multidrug-resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.2)].

MDRSP isolates are strains 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.

1.3 Community-Acquired Pneumonia: 5-day Treatment Regimen

Levofloxacin tablets, USP 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)].

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

Levofloxacin tablets, USP are indicated for the treatment of acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see Clinical Studies (14.4)].

1.5 Acute Bacterial Exacerbation of Chronic Bronchitis

Levofloxacin tablets, USP 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.

1.6 Complicated Skin and Skin Structure Infections

Levofloxacin tablets, USP 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)].

1.7 Uncomplicated Skin and Skin Structure Infections

Levofloxacin tablets, USP are 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.

1.8 Chronic Bacterial Prostatitis

Levofloxacin tablets, USP are indicated for the treatment of chronic bacterial prostatitis due to Escherichia coli, Enterococcus faecalis, or methicillin-susceptible Staphylococcus epidermidis [see Clinical Studies (14.6)].

1.9 Complicated Urinary Tract Infections: 5-day Treatment Regimen

Levofloxacin tablets, USP are indicated for the treatment of complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis [see Clinical Studies (14.7)].

1.10 Complicated Urinary Tract Infections: 10-day Treatment Regimen

Levofloxacin tablets, USP are 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)].

1.11 Acute Pyelonephritis: 5 or 10-day Treatment Regimen

Levofloxacin tablets, USP are indicated for the treatment of acute pyelonephritis caused by Escherichia coli, including cases with concurrent bacteremia [see Clinical Studies(14.7, 14.8)].].

1.12 Uncomplicated Urinary Tract Infections

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

1.13 Inhalational Anthrax (Post-Exposure)

Levofloxacin tablets, USP 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, USP are based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. Levofloxacin tablets, USP has not been tested in humans for the post-exposure prevention of inhalation anthrax. The safety of levofloxacin tablets, USP 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, USP therapy should only be used when the benefit outweighs the risk [see Dosage and Administration(2.1, 2.2) and Clinical Studies (14.9)].

1.14 Plague

Levofloxacin tablets, USP are 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 tablets, USP 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 [seeDosage and Administration (2.1, 2.2) and Clinical Studies (14.10)].

2.1 Dosage in Adult Patients with Normal Renal Function

The usual dose of Levofloxacin Tablet is 250 mg, 500 mg, or 750 mg administered orally every 24 hours, as indicated by infection and described in Table 1.

These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance <50 mL/min, adjustments to the dosing regimen are required [see Dosage and Administration (2.3)].

Table 1: Dosage in Adult Patients with Normal Renal Function (creatinine clearance ≥ 50 mL/min)>

*
Due to the designated pathogens [see Indications and Usage (1)].
†
Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.
‡
Due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Indications and Usage (1.2)].
§
Due to Streptococcus pneumoniae (excluding multi-drug-resistant strains [MDRSP]), Haemophilus influenzae,Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Indications and
Usage (1.3)].
¶
This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia.
#
This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli,
Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; and for AP due to E. coli.
Þ
Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)].
ß
The safety of levofloxacin in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)] Prolonged levofloxacin therapy in adults should only be used when the benefit outweighs the risk
à
Drug administration should begin as soon as possible after suspected or confirmed exposure to <em>Yersinia pestis</em>. Higher doses of levofloxacin typically used for treatment of pneumonia can be used for treatment of plague, if clinically indicated.

Type of Infection*
Dosed Every 24 hours
Duration (days)†
Nosocomial Pneumonia
750 mg
7–14
Community Acquired Pneumonia‡
500 mg
7–14
Community Acquired Pneumonia§
750 mg
5
Acute Bacterial Sinusitis
750 mg
5
500 mg
10–14
Acute Bacterial Exacerbation of Chronic Bronchitis
500 mg
7
Complicated Skin and Skin Structure Infections (SSSI)
750 mg
7–14
Uncomplicated SSSI
500 mg
7–10
Chronic Bacterial Prostatitis
500 mg
28
Complicated Urinary Tract Infection (cUTI) or
Acute Pyelonephritis (AP)¶
750 mg
5
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)#
250 mg
10
Uncomplicated Urinary Tract Infection
250 mg
3
Inhalational Anthrax (Post-Exposure), adult and
pediatric patients > 50 kg and ≥ 6 months of ageÞ,ß
Pediatric patients < 50 kg and ≥ 6 months of ageÞ,ß
500 mg

see Table 2 below (2.2) 60ß

60ß
Plague, adult and pediatric patients > 50 kg à
Pediatric patients < 50 kg and ≥ 6 months of age
500 mg
see Table 2 below (2.2) 10 to 14
10 to 14

2.2 Dosage in Pediatric Patients

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

*
Due to Bacillus anthracis [see Indications and Usage (1.13)] and Yersinia pestis [see Indications and Usage (1.14)].
†
Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.
‡
Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)]
§
The safety of levofloxacin in pediatric patients for durations of therapy beyond 14 has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9).] Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk.
¶
Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis.

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

2.3 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 (8.6)].

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

Table 3: Dosage Adjustment 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 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

2.4 Drug Interaction With Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

Levofloxacin Tablets

Levofloxacin Tablets should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine chewable/buffered tablets or the pediatric powder for oral solution [see Drug Interactions (7.1) and Patient Counseling Information (17.2)] .

2.5 Administration Instructions

Food and Levofloxacin Tablets

Levofloxacin Tablets can be administered without regard to food.

Hydration for Patients Receiving Levofloxacin Tablets

Adequate hydration of patients receiving oral levofloxacin should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones [see Adverse Reactions (6.1) and Patient Counseling Information (17.2)].

Levofloxacin is contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see Warnings and Precautions (5.3)].

5.1 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 ( 6.3 ); Patient Counseling Information ( 17.3 )]

5.2 Exacerbation of Myasthenia Gravis

Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid levofloxacin in patients with a known history of myasthenia gravis [see Adverse Reactions (6.3); Patient Counseling Information (17.3)].

5.3 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 (6); Patient Counseling Information (17.3)].

5.4 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 (6); Patient Counseling Information (17.3)].

5.5 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 (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)].

5.6 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 (6); Drug Interactions (7.4, 7.5); Patient Counseling Information (17.3)].

5.7 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 (6.2), Patient Counseling Information (17.3)].

5.8 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 (6), Patient Counseling Information (17.3)].

5.9 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 torsade de pointes have been spontaneously reported during postmarketing surveillance in patients receiving fluoroquinolones, including levofloxacin. Levofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving ClassIA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval [see Adverse Reactions (6.3), Use in Specific Populations (8.5), and Patient Counseling Information (17.3)].

5.10 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 (1.13, 1.14)]. An increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, and gait abnormality) compared to controls has been observed in pediatric patients receiving levofloxacin [seeUse in Specific Populations (8.4 )].

In immature rats and dogs, the oral and intravenous administration of levofloxacin resulted in increased osteochondrosis. Histopathological examination of the weight-bearing joints of immature dogs dosed with levofloxacin revealed persistent lesions of the cartilage. Other fluroquinolones also produce similar erosions in the weight-bearing joints and other signs of arthropathy in immature animals of various species [see Animal Toxicology and/or Pharmacology (13.2)].

5.11 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 (6.2); Drug Interactions (7.3); Patient Counseling Information (17.4)]

5.12 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 (6.3); Patient Counseling Information (17.3)].

5.13 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 (17.1)].

6.1 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 (5.1)]

Exacerbation of Myasthenia Gravis [see Warnings andPrecautions (5.2)]
Hypersensitivity Reactions [see Warnings and Precautions (5.3)]
Other Serious and Sometimes Fatal Reactions [see Warnings and Precautions (5.4)]
Hepatotoxicity [see Warnings and Precautions (5.5)]
Central Nervous System Effects [see Warnings andPrecautions (5.6)]
Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.7)]
Peripheral Neuropathy that may be irreversible [see Warnings and Precautions (5.8)]
Prolongation of the QT Interval [see Warnings and Precautions (5.9)]
Musculoskeletal Disorders in Pediatric Patients [see Warnings and Precautions (5.10)]
Blood Glucose Disturbances [see Warnings and Precautions (5.11)]
Photosensitivity/Phototoxicity [see Warnings and Precautions (5.12)]
Development of Drug Resistant Bacteria [see Warnings and Precautions (5.13)]

Crystalluria and cylindruria have been reported with quinolones, including levofloxacin. Therefore, adequate hydration of patients receiving levofloxacin should be maintained to prevent the formation of a highly concentrated urine [see Dosage and Administration (2.5)].

6.2 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 7537 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 (1)]. Patients received levofloxacin doses of 750 mg once daily, 250 mg once daily, or 500 mg once or twice daily. Treatment duration was usually 3–14 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 ClassSystem/Organ Class Adverse ReactionAdverse Reaction %
(N=7537)%
(N=7537)
System/Organ Class Adverse Reaction %
(N=7537)

*
N=7274
†
N=3758 (women)

Infections and Infestations
moniliasis
1

Psychiatric Disorders
insomnia*[see Warnings and Precautions (5.6)]
4

Nervous System Disorders
headache
dizziness [see Warnings and Precautions (5.6)]
6
3

Respiratory, Thoracic and Mediastinal Disorders
dyspnea [see Warnings and Precautions (5.3)]
1

Gastrointestinal Disorders
nausea
diarrhea
constipation
abdominal pain
vomiting
dyspepsia
7
5
3
2
2
2

Skin and Subcutaneous Tissue Disorders
rash [see Warnings and Precautions (5.3)]
pruritus
2
1

Reproductive System and Breast Disorders
vaginitis
1†

General Disorders and Administration Site Conditions
edema
injection site reaction
chest pain
1
1
1

Table 5: Less Common (0.1 to 1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin (N=7537) System/Organ ClassSystem/Organ Class Adverse ReactionAdverse Reaction
System/Organ Class Adverse Reaction
Infections and Infestations
genital moniliasis
Blood and Lymphatic System Disorders
anemia
thrombocytopenia
granulocytopenia
[see Warnings and Precautions (5.4)]
Immune System Disorders
allergic reaction [See Warnings and Precautions (5.3,5.4)]
Metabolism and Nutrition Disorders
hyperglycemia
hypoglycemia
[see Warnings and Precautions (5.11)]
hyperkalemia
Psychiatric Disorders
anxiety
agitation
confusion
depression
hallucination
nightmare*
[see Warnings and Precautions (5.6)]
sleep disorder*
anorexia
abnormal dreaming*
Nervous System Disorders
tremor
convulsions
[see Warnings and Precautions (5.6)]
paresthesia [see Warnings and Precautions (5.8)]
vertigo
hypertonia
hyperkinesias
abnormal gait
somnolence*
syncope
Respiratory, Thoracic and Mediastinal Disorders
epistaxis
Cardiac Disorders
cardiac arrest
palpitation
ventricular tachycardia
ventricular arrhythmia
Vascular Disorders
phlebitis
Gastrointestinal Disorders
gastritis
stomatitis
pancreatitis
esophagitis
gastroenteritis
glossitis
pseudomembraneous/ C. difficile colitis [see Warnings and Precautions (5.7)]
Hepatobiliary Disorders
abnormal hepatic function
increased hepatic enzymes
increased alkaline phosphatase
Skin and Subcutaneous Tissue Disorders
urticaria [see Warnings and Precautions (5.3)]
Musculoskeletal and Connective Tissue Disorders
arthralgia
tendinitis
[see Warnings and Precautions (5.1)]
myalgia
skeletal pain
Renal and Urinary Disorders
abnormal renal function
acute renal failure [see Warnings and Precautions (5.4)]

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.

6.3 Postmarketing 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: Postmarketing Reports Of Adverse Drug Reactions

System/Organ ClassSystem/Organ Class Adverse ReactionAdverse Reaction
System/Organ Class Adverse Reaction
Blood and Lymphatic System Disorders
pancytopenia
aplastic anemia
leukopenia
hemolytic anemia
[see Warnings and Precautions (5.4)]
eosinophilia
Immune System Disorders
hypersensitivity reactions, sometimes fatal including:
anaphylactic/anaphylactoid reactions
anaphylactic shock
angioneurotic edema
serum sickness
[see Warnings and Precautions (5.3,5.4)]
Psychiatric Disorders
psychosis
paranoia
isolated reports of suicide attempt and suicidal ideation
[see Warnings and Precautions (5.6)]
Nervous System Disorders
Exacerbation of myasthenia gravis [see Warnings and Precautions (5.2)]
anosmia
ageusia
parosmia
dysgeusia
peripheral neuropathy (may be irreversible) [see Warnings and Precautions (5.8)]
isolated reports of encephalopathy
abnormal electroencephalogram (EEG)
dysphonia
pseudotumor cerebri [see Warning and Precautions (5.6)]
Eye Disorders
Uveitis
vision disturbance, including diplopia
visual acuity reduced
vision blurred
scotoma
Ear and Labyrinth Disorders
hypoacusis
tinnitus
Cardiac Disorders
isolated reports of torsade de pointes
electrocardiogram QT prolonged
[see Warnings and Precautions (5.9)]
tachycardia
Vascular Disorders
vasodilatation
Respiratory, Thoracic and Mediastinal Disorders
isolated reports of allergic pneumonitis [see Warnings and Precautions (5.4)]
Hepatobiliary Disorders
hepatic failure (including fatal cases)
hepatitis
jaundice
[see Warnings and Precautions 5.4, 5.5)]

Skin and Subcutaneous Tissue Disorders

bullous eruptions to include:
Stevens-Johnson Syndrome
toxic epidermal necrolysis
erythema multiforme
[see Warnings and Precautions (5.4)]
photosensitivity/photoxicity reaction [see Warnings and Precautions (5.12)]
leukocytoclastic vasculitis
Musculoskeletal and Connective Tissue Disorders
tendon rupture [see Warnings and Precautions (5.1)]
muscle injury, including rupture
rhabdomyolysis
Renal and Urinary Disorders
interstitial nephritis [see Warnings and Precautions (5.4)]
General Disorders and Administration Site Conditions
multi-organ failure
pyrexia
Investigations
prothrombin time prolonged
international normalized ratio prolonged
muscle enzymes increased