Levofloxacin (levofloxacin 500 mg) Dailymed

2 Dosage And Administration

• •Dosage in patients with normal renal function (2.1)

Type of Infection	Dose Every 24 hours	Duration (days)
Nosocomial Pneumonia (1.1)	750 mg	7 to 14
Community Acquired Pneumonia (1.2)	500 mg	7 to 14
Community Acquired Pneumonia (1.3)	750 mg	5
Acute Bacterial Sinusitis (1.4)	750 mg	5
	500 mg	10 to 14
Acute Bacterial Exacerbation of Chronic Bronchitis (1.5)	500 mg	7
Complicated Skin and Skin Structure Infections (SSSI) (1.6)	750 mg	7 to 14
Uncomplicated SSSI (1.7)	500 mg	7 to 10
Chronic Bacterial Prostatitis (1.8)	500 mg	28
Complicated Urinary Tract Infection (1.9) or Acute Pyelonephritis (1.11)	750 mg	5
Complicated Urinary Tract Infection (1.10) or Acute Pyelonephritis (1.11)	250 mg	10
Uncomplicated Urinary Tract Infection (1.12)	250 mg	3
Inhalational Anthrax (Post-Exposure) (1.13) Adults and Pediatric Patients > 50 kg Pediatric Patients < 50 kg and ≥ 6 months of age	500 mg 8 mg/kg BID (not to exceed 250 mg/dose)	60 60
Plague (1.14) Adults and Pediatric Patients > 50 kg Pediatric Patients < 50 kg and ≥ 6 months of age	500 mg 8 mg/kg BID (not to exceed 250 mg/dose)	10 to 14 10 to 14

• • Adjust dose for creatinine clearance < 50 mL/min (2.3, 8.6, 12.3)

2.1 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)].

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

Type of Infection Due to the designated pathogens [see Indications and Usage (1)].	Dosed Every 24 hours	Duration (days) Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.
Nosocomial Pneumonia	750 mg	7 to 14
Community Acquired PneumoniaDue 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 pneumonia [see Indications and Usage (1.2)].	500 mg	7 to 14
Community Acquired PneumoniaDue to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae or Chlamydophila pneumoniae [see Indications and Usage (1.3)].	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)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.	750 mg	5
Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)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.	250 mg	10
Uncomplicated Urinary Tract Infection	250 mg	3
Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kgDrug 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 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 should only be used when the benefit outweighs the risk. Pediatric patients < 50 kg and ≥ 6 months of age	500 mg see Table 2 below (2.2)	60  60
Plague, adult and pediatric patients > 50 kgDrug 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. 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

Type of Infection Due to Bacillus anthracis [see Indications and Usage (1.13)] and Yersinia pestis [see Indications and Usage (1.14)].	Dose	Freq. Once Every	Duration Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.
Inhalational Anthrax (post-exposure)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 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 should only be used when the benefit outweighs the risk.
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
PlagueDrug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis.
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 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.

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 should be administered at least 2 hours before or 2 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 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)].

• •Risk of tendinitis and tendon rupture is increased. This risk is further increased in older patients usually over 60 years of age, in patients taking corticosteroids, and in patients with kidney, heart or lung transplants. Discontinue if pain or inflammation in a tendon occurs (5.1, 8.5).
• •May exacerbate muscle weakness in persons with myasthenia gravis. Avoid use in patients with a known history of myasthenia gravis (5.2).
• •Anaphylactic reactions and allergic skin reactions, serious, occasionally fatal, may occur after first dose (4, 5.3).
• •Hematologic (including agranulocytosis, thrombocytopenia), and renal toxicities may occur after multiple doses (5.4).
• •Hepatotoxicity: Severe, and sometimes fatal, hepatoxicity has been reported. Discontinue immediately if signs and symptoms of hepatitis occur (5.5).
• •Central nervous system effects, including convulsions, anxiety, confusion, depression and insomnia may occur after the first dose. Use with caution in patients with known or suspected disorders that may predispose them to seizures or lower the seizure threshold. Increased intracranial pressure (pseudotumor cerebri) has been reported (5.6).
• • Clostridium difficile-associated colitis: Evaluate if diarrhea occurs (5.7).
• •Peripheral neuropathy: Discontinue immediately if symptoms occur in order to prevent irreversibility (5.8).
• •Prolongation of the QT interval and isolated cases of Torsades de pointes have been reported. Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval (5.9, 8.5).

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) and 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. 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 (6.3) and 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) and 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) and 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) and 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, light-headedness, 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) and Patient Counseling Information (17.3)].

5.7 -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 2 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) and 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) and 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 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 (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 [see Use 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 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)].

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) and 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, bulering, 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) and 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 Adverse Reactions

The most common reactions (≥ 3%) were nausea, headache, diarrhea, insomnia, constipation and dizziness (6.2).

To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc. toll free at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 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 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 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 (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 mg 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	insomniaN = 7,274 [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	1N = 3,758 (women)
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 = 7,537)

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 nightmareN = 7,274 [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 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.

6.3 Post-Marketing Experience

Table 6 uls 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 (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 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 Torsades de pointes electrocardiogram QT prolonged [see Warnings and Precautions (5.9)] tachycardia
Vascular Disorders	vasodilatation
Respiratory, Thoracic and Mediastinal Disorders	isolated reports of allergic pneumonitis [see Warnings and Precautions (5.4)]
Hepatobiliary Disorders	hepatic failure (including fatal cases) hepatitis jaundice [see Warnings and Precautions (5.4, 5.5)]
Skin and Subcutaneous Tissue Disorders	bullous eruptions to include:     Stevens-Johnson Syndrome     toxic epidermal necrolysis     erythema multiforme [see Warnings and Precautions (5.4)] photosensitivity/phototoxicity reaction [see Warnings and Precautions (5.12)] leukocytoclastic vasculitis
Musculoskeletal and Connective Tissue Disorders	tendon rupture [see Warnings and Precautions (5.1)] muscle injury, including rupture rhabdomyolysis
Renal and Urinary Disorders	interstitial nephritis [see Warnings and Precautions (5.4)]
General Disorders and Administration Site Conditions	multi-organ failure pyrexia
Investigations	prothrombin time prolonged international normalized ratio prolonged muscle enzymes increased