FULL PRESCRIBING INFORMATION
Warning
Fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants [see Warnings and Precautions (5.1)].
Fluoroquinolones, including levofloxacin, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid levofloxacin in patients with a known history of myasthenia gravis [see Warnings and Precautions (5.2)].
Fluoroquinolones, including levofloxacin, are associated with an increased risk of tendinitis and tendon rupture in all ages. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants [see Warnings and Precautions (5.1)].
Fluoroquinolones, including levofloxacin, may exacerbate muscle weakness in persons with myasthenia gravis. Avoid levofloxacin in patients with a known history of myasthenia gravis [see Warnings and Precautions (5.2)].
Indications and Usage for Levofloxacin Tablets
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Levofloxacin Tablets and other antibacterial drugs, Levofloxacin Tablets 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 are indicated for the treatment of adults (≥18 years of age) with mild, moderate, and severe infections caused by susceptible strains of the designated microorganisms in the conditions listed in this section. Levofloxacin injection is indicated when intravenous administration offers a route of administration advantageous to the patient (e.g., patient cannot tolerate an oral dosage form).
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 Clinical Pharmacology (12.4)]. Therapy with Levofloxacin Tablets 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 strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with Levofloxacin Tablets. 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 Tablets are indicated for the treatment of nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, or Streptococcus pneumoniae. Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see Clinical Studies (14.1)].
Community-Acquired Pneumonia: 7 to 14 day Treatment Regimen
Levofloxacin Tablets are indicated for the treatment of community-acquired pneumonia due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.2)].
MDRSP isolates are 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.
Community-Acquired Pneumonia: 5-day Treatment Regimen
Levofloxacin Tablets are indicated for the treatment of community-acquired pneumonia due to Streptococcus pneumoniae (excluding multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.3)].
Acute Bacterial Sinusitis: 5-day and 10 to 14 day Treatment Regimens
Levofloxacin Tablets are indicated for the treatment of acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see Clinical Studies (14.4)].
Acute Bacterial Exacerbation of Chronic Bronchitis
Levofloxacin Tablets are indicated for the treatment of acute bacterial exacerbation of chronic bronchitis due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis.
Complicated Skin and Skin Structure Infections
Levofloxacin Tablets are indicated for the treatment of complicated skin and skin structure infections due to methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, or Proteus mirabilis [see Clinical Studies (14.5)].
Uncomplicated Skin and Skin Structure Infections
Levofloxacin Tablets 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.
Chronic Bacterial Prostatitis
Levofloxacin Tablets 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)].
Complicated Urinary Tract Infections: 5-day Treatment Regimen
Levofloxacin Tablets are indicated for the treatment of complicated urinary tract infections due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis [see Clinical Studies (14.7)].
Complicated Urinary Tract Infections: 10-day Treatment Regimen
Levofloxacin Tablets 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)].
Acute Pyelonephritis: 5 or 10-day Treatment Regimen
Levofloxacin Tablets are indicated for the treatment of acute pyelonephritis caused by Escherichia coli, including cases with concurrent bacteremia [see Clinical Studies (14.7, 14.8)].
Uncomplicated Urinary Tract Infections
Levofloxacin Tablets are indicated for the treatment of uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.
Inhalational Anthrax (Post-Exposure)
Levofloxacin Tablets are indicated for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis. The effectiveness of Levofloxacin Tablets is based on plasma concentrations achieved in humans, a surrogate endpoint reasonably likely to predict clinical benefit. Levofloxacin Tablets have not been tested in humans for the post-exposure prevention of inhalation anthrax. The safety of Levofloxacin Tablets in adults for durations of therapy beyond 28 days or in pediatric patients for durations of therapy beyond 14 days has not been studied. Prolonged Levofloxacin Tablets therapy should only be used when the benefit outweighs the risk [see Dosage and Administration (2.1, 2.2) and Clinical Studies (14.9)].
Levofloxacin Tablets Dosage and Administration
Dosage in Adult Patients with Normal Renal Function
The usual dose of Levofloxacin Tablets 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)].
| Type of Infection1 | Dosed Every 24 hours | Duration (days)2 |
|---|---|---|
| 1 Due to the designated pathogens [see Indications and Usage (1)]. 2 Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. 3 Due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Indications and Usage (1.2)]. 4 Due to Streptococcus pneumoniae (excluding multi-drug-resistant strains [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Indications and Usage (1.3)]. 5 This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia. 6 This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; and for AP due to E. coli. 7 Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)]. 8 The safety of Levofloxacin Tablets in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged Levofloxacin Tablets therapy should only be used when the benefit outweighs the risk. | ||
| Nosocomial Pneumonia | 750 mg | 7-14 |
| Community Acquired Pneumonia3 | 500 mg | 7-14 |
| Community Acquired Pneumonia4 | 750 mg | 5 |
| Acute Bacterial Sinusitis | 750 mg | 5 |
| 500 mg | 10-14 | |
| Acute Bacterial Exacerbation of Chronic Bronchitis | 500 mg | 7 |
| Complicated Skin and Skin Structure Infections (SSSI) | 750 mg | 7-14 |
| Uncomplicated SSSI | 500 mg | 7-10 |
| Chronic Bacterial Prostatitis | 500 mg | 28 |
| Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)5 | 750 mg | 5 |
| Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)6 | 250 mg | 10 |
| Uncomplicated Urinary Tract Infection | 250 mg | 3 |
| Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kg and ≥ 6 months of age7,8 Pediatric patients < 50 kg and ≥ 6 months of age7,8 | 500 mg see Table 2 below (2.2) | 608 608 |
Dosage in Pediatric Patients
The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.
| 1 Due to Bacillus anthracis [see Indications and Usage (1.13)] 2 Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. 3 Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)] 4 The safety of Levofloxacin Tablets in pediatric patients for durations of therapy beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged Levofloxacin Tablets therapy should only be used when the benefit outweighs the risk. | |||
| Type of Infection1 | Dose | Freq. Once every | Duration2 |
| Inhalational Anthrax (post-exposure)3, 4 | |||
| Pediatric patients > 50 kg and ≥ 6 months of age | 500 mg | 24 hr | 60 days4 |
| Pediatric patients < 50 kg and ≥ 6 months of age | 8 mg/kg (not to exceed 250 mg per dose) | 12 hr | 60 days4 |
Dosage Adjustment in Adults with Renal Impairment
Administer Levofloxacin Tablets 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.
| 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 |
Drug Interaction With Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins
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)].
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 Tablets 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)].
Dosage Forms and Strengths
Levofloxacin Tablets, 250 mg are terra pink colored capsule shaped, biconvex film-coated tablets, debossed with ‘13’ on one side and ‘T’ on the other side.
Levofloxacin Tablets, 500 mg are peach colored capsule shaped, biconvex film-coated tablets, debossed with ‘12’ on one side and ‘T’ on the other side.
Levofloxacin Tablets, 750 mg are white capsule shaped, biconvex film-coated tablets, debossed with ‘11’ on one side and ‘T’ on the other side.
Contraindications
Levofloxacin Tablets are contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see Warnings and Precautions (5.3)].
Warnings and Precautions
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)].
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)].
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)].
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)].
Hepatotoxicity
Postmarketing reports of severe hepatotoxicity (including acute hepatitis and fatal events) have been received for patients treated with levofloxacin. No evidence of serious drug-associated hepatotoxicity was detected in clinical trials of over 7,000 patients. Severe hepatotoxicity generally occurred within 14 days of initiation of therapy and most cases occurred within 6 days. Most cases of severe hepatotoxicity were not associated with hypersensitivity [see Warnings and Precautions (5.4)]. The majority of fatal hepatotoxicity reports occurred in patients 65 years of age or older and most were not associated with hypersensitivity. Levofloxacin should be discontinued immediately if the patient develops signs and symptoms of hepatitis [see Adverse Reactions (6); Patient Counseling Information (17.3)].
Central Nervous System Effects
Convulsions, and toxic psychoses, increased intracranial pressure (including pseudotumor cerebri) have been reported in patients receiving fluoroquinolones, including levofloxacin. Fluoroquinolones may also 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)].
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)].
Peripheral Neuropathy
Rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in patients receiving fluoroquinolones, including levofloxacin. Levofloxacin should be discontinued if the patient experiences symptoms of neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation in order to prevent the development of an irreversible condition [see Adverse Reactions (6), Patient Counseling Information (17.3)].
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 Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. Elderly patients may be more susceptible to drug-associated effects on the QT interval [see Adverse Reactions (6.3), Use in Specific Populations (8.5), and Patient Counseling Information (17.3)].
Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals
Levofloxacin is indicated in pediatric patients (≥6 months of age) only for the prevention of inhalational anthrax (post-exposure) [see Indications and Usage (1.13)]. An increased incidence of musculoskeletal disorders (arthralgia, arthritis, tendinopathy, and gait abnormality) compared to controls has been observed in pediatric patients receiving levofloxacin [see Use in Specific Populations (8.4)].
In immature rats and dogs, the oral administration of levofloxacin resulted in increased osteochondrosis. Histopathological examination of the weight-bearing joints of immature dogs dosed with levofloxacin revealed persistent lesions of the cartilage. Other fluoroquinolones also produce similar erosions in the weight-bearing joints and other signs of arthropathy in immature animals of various species [see Animal Toxicology and/or Pharmacology (13.2)].
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)].
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)].
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)].
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 (5.1)]
- Exacerbation of Myasthenia Gravis [see Warnings and Precautions (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 and Precautions (5.6)]
- Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.7)]
- Peripheral Neuropathy [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)].
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 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.
| System/Organ Class | Adverse Reaction | % (N = 7537) |
|---|---|---|
| a N = 7274 b N = 3758 (women) | ||
| Infections and Infestations | moniliasis | 1 |
| Psychiatric Disorders | insomniaa [see Warnings and Precautions (5.6)] | 4 |
| Nervous System Disorders | headache dizziness [see Warnings and Precautions (5.6)] | 6 3 |
| Respiratory, Thoracic and Mediastinal Disorders | dyspnea [see Warnings and Precautions (5.3)] | 1 |
| Gastrointestinal Disorders | nausea diarrhea constipation abdominal pain vomiting dyspepsia | 7 5 3 2 2 2 |
| Skin and Subcutaneous Tissue Disorders | rash [see Warnings and Precautions (5.3)] pruritus | 2 1 |
| Reproductive System and Breast Disorders | vaginitis | 1b |
| General Disorders and Administration Site Conditions | edema injection site reaction chest pain | 1 1 1 |
| System/Organ Class | Adverse Reaction |
|---|---|
| a N = 7274 | |
| Infections and Infestations | genital moniliasis |
| Blood and Lymphatic System Disorders | anemia thrombocytopenia granulocytopenia [see Warnings and Precautions (5.4)] |
| Immune System Disorders | allergic reaction [see Warnings and Precautions (5.3, 5.4)] |
| Metabolism and Nutrition Disorders | hyperglycemia hypoglycemia [see Warnings and Precautions (5.11)] hyperkalemia |
| Psychiatric Disorders | anxiety agitation confusion depression hallucination nightmarea [see Warnings and Precautions (5.6)] sleep disordera anorexia abnormal dreaminga |
| Nervous System Disorders | tremor convulsions [see Warnings and Precautions (5.6)] paresthesia [see Warnings and Precautions (5.8)] vertigo hypertonia hyperkinesias abnormal gait somnolencea syncope |
| Respiratory, Thoracic and Mediastinal Disorders | epistaxis |
| Cardiac Disorders | cardiac arrest palpitation ventricular tachycardia ventricular arrhythmia |
| Vascular Disorders | phlebitis |
| Gastrointestinal Disorders | gastritis stomatitis pancreatitis esophagitis gastroenteritis glossitis pseudomembranous/C. difficile colitis [see Warnings and Precautions (5.7)] |
| Hepatobiliary Disorders | abnormal hepatic function increased hepatic enzymes increased alkaline phosphatase |
| Skin and Subcutaneous Tissue Disorders | urticaria [see Warnings and Precautions (5.3)] |
| Musculoskeletal and Connective Tissue Disorders | arthralgia tendinitis [see Warnings and Precautions (5.1)] myalgia skeletal pain |
| Renal and Urinary Disorders | abnormal renal function acute renal failure [see Warnings and Precautions (5.4)] |
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.
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.
| System/Organ Class | Adverse Reaction |
|---|---|
| Blood and Lymphatic System Disorders | pancytopenia aplastic anemia leucopenia hemolytic anemia [see Warnings and Precautions (5.4)] eosinophilia |
| Immune System Disorders | hypersensitivity reactions, sometimes fatal including: anaphylactic/anaphylactoid reactions anaphylactic shock angioneurotic edema serum sickness [see Warnings and Precautions (5.3, 5.4)] |
| Psychiatric Disorders | psychosis paranoia isolated reports of suicide attempt and suicidal ideation [see Warnings and Precautions (5.6)] |
| Nervous System Disorders | exacerbation of myasthenia gravis [see Warnings and Precautions (5.2)] anosmia ageusia parosmia dysgeusia peripheral neuropathy [see Warnings and Precautions (5.8)] isolated reports of encephalopathy abnormal electroencephalogram (EEG) dysphonia pseudotumor cerebri [see Warnings and Precautions (5.6)] |
| Eye Disorders | vision disturbance, including diplopia visual acuity reduced vision blurred scotoma |
| Ear and Labyrinth Disorders | hypoacusis tinnitus |
| Cardiac Disorders | isolated reports of torsade de pointes electrocardiogram QT prolonged [see Warnings and Precautions (5.9)] tachycardia |
| Vascular Disorders | vasodilatation |
| Respiratory, Thoracic and Mediastinal Disorders | isolated reports of allergic pneumonitis [see Warnings and Precautions (5.4)] |
| Hepatobiliary Disorders | hepatic failure (including fatal cases) hepatitis jaundice [see Warnings and Precautions (5.4, 5.5)] |
| Skin and Subcutaneous Tissue Disorders | bullous eruptions to include: Stevens-Johnson Syndrome toxic epidermal necrolysis erythema multiforme [see Warnings and Precautions (5.4)] photosensitivity/phototoxicity reaction [see Warnings and Precautions (5.12)] leukocytoclastic vasculitis |
| Musculoskeletal and Connective Tissue Disorders | tendon rupture [see Warnings and Precautions (5.1)] muscle injury, including rupture rhabdomyolysis |
| Renal and Urinary Disorders | interstitial nephritis [see Warnings and Precautions (5.4)] |
| General Disorders and Administration Site Condi |
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