FDA label 26f29b41-dffd-e685-e063-6294a90a3a41

WARNING: WARNING: See full prescribing information for complete boxed 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 tablets 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 )].

5 WARNINGS AND PRECAUTIONS 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 ( 5.9 ) Prolongation of the QT interval and isolated cases of torsade de pointes have been reported. Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval ( 5.10 , 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 ); 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 Risk of Aortic Aneurysm and Dissection Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients. The cause for the increased risk has not been identified. In patients with a known aortic aneurysm or patients who are at greater risk for aortic aneurysms, reserve levofloxacin tablets for use only when there are no alternative antibacterial treatments available. 5.9 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 )]. 5.10 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 )]. 5.11 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 )]. 5.12 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 )]. 5.13 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 )]. 5.14 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 Wockhardt USA LLC., at 1-800-346-6854 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 ( 5.9 )] Prolongation of the QT Interval [see Warnings and Precautions ( 5.10 )] Musculoskeletal Disorders in Pediatric Patients [see Warnings and Precautions ( 5.11 )] Blood Glucose Disturbances [see Warnings and Precautions ( 5.12 )] Photosensitivity/Phototoxicity [see Warnings and Precautions ( 5.13 )] Development of Drug Resistant Bacteria [see Warnings and Precautions ( 5.14 )] 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 * N = 7274 † N = 3758 (women) System/Organ Class Adverse Reaction % (N=7537) 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) * N = 7274 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 ( 5.12 )] 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 ( 5.9 )] 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 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 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 ( 5.9 )] isolated reports of encephalopathy abnormal electroencephalogram (EEG) dysphonia pseudotumor cerebri [see Warnings 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 ( 5.10 )] 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 ( 5.13 )] 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

<table ID="ID393" width="100%"><caption>Table 4: Common ( &#x2265;1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin</caption><col width="32%"/><col width="53%"/><col width="13%"/><tfoot><tr><td align="left" colspan="3"><paragraph styleCode="Footnote">^*N = 7274 </paragraph></td></tr><tr><td align="left" colspan="3"><paragraph styleCode="Footnote">^&#x2020;N = 3758 (women) </paragraph></td></tr></tfoot><tbody><tr><td align="left" styleCode="Lrule Toprule Botrule Rrule" valign="top"><content styleCode="bold">System/Organ Class</content> </td><td align="left" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Adverse Reaction</content> </td><td align="center" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">%</content> <content styleCode="bold">(N=7537)</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Infections and Infestations</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">moniliasis </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Psychiatric Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">insomnia ^* <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID368">5.6</linkHtml>)] </content> </td><td align="center" styleCode=" Botrule Rrule" valign="top">4 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Nervous System Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">headache dizziness <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID368">5.6</linkHtml>)] </content> </td><td align="center" styleCode=" Botrule Rrule" valign="top">6 3 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Respiratory, Thoracic and</content> <content styleCode="bold">Mediastinal Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">dyspnea <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID360">5.3</linkHtml>)] </content> </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">nausea diarrhea constipation abdominal pain vomiting dyspepsia </td><td align="center" styleCode=" Botrule Rrule" valign="top">7 5 3 2 2 2 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Skin and Subcutaneous</content> <content styleCode="bold">Tissue Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">rash <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID360">5.3</linkHtml>)] </content> pruritus </td><td align="center" styleCode=" Botrule Rrule" valign="top">2 1 </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Reproductive System and</content> <content styleCode="bold">Breast Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">vaginitis </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 ^&#x2020; </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">General Disorders and</content> <content styleCode="bold">Administration Site Conditions</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">edema injection site reaction chest pain </td><td align="center" styleCode=" Botrule Rrule" valign="top">1 1 1 </td></tr></tbody></table>

<table ID="ID394" width="100%"><caption>Table 5: Less Common (0.1 to 1%) Adverse Reactions Reported in Clinical Trials with Levofloxacin (N=7537)</caption><col width="33%"/><col width="66%"/><tfoot><tr><td align="left" colspan="2"><paragraph styleCode="Footnote">^*N = 7274 </paragraph></td></tr></tfoot><tbody><tr><td align="left" styleCode="Lrule Toprule Botrule Rrule"><content styleCode="bold">System/Organ Class</content> </td><td align="left" styleCode=" Toprule Botrule Rrule"><content styleCode="bold">Adverse Reaction</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Infections and Infestations</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">genital moniliasis </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Blood and Lymphatic System Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">anemia thrombocytopenia granulocytopenia <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID362">5.4</linkHtml>)] </content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Immune System Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">allergic reaction <content styleCode="italics">[See Warnings and Precautions ( <linkHtml href="#ID360">5.3</linkHtml>, <linkHtml href="#ID362">5.4</linkHtml>)] </content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Metabolism and</content> <content styleCode="bold">Nutrition Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">hyperglycemia hypoglycemia <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID378">5.12</linkHtml>)] </content> hyperkalemia </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Psychiatric Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">anxiety agitation confusion depression hallucination nightmare ^* <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID368">5.6</linkHtml>)] </content> sleep disorder ^* anorexia abnormal dreaming ^* </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Nervous System Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">tremor convulsions <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID368">5.6</linkHtml>)] </content> paresthesia <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID372">5.9</linkHtml>)] </content> vertigo hypertonia hyperkinesias abnormal gait somnolence ^* syncope </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Respiratory, Thoracic and</content> <content styleCode="bold">Mediastinal Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">epistaxis </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Cardiac Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">cardiac arrest palpitation ventricular tachycardia ventricular arrhythmia </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Vascular Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">phlebitis </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Gastrointestinal Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">gastritis stomatitis pancreatitis esophagitis gastroenteritis glossitis pseudomembranous/ <content styleCode="italics">C. difficile</content>colitis <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID370">5.7</linkHtml>)] </content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Hepatobiliary Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">abnormal hepatic function increased hepatic enzymes increased alkaline phosphatase </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Skin and Subcutaneous</content> <content styleCode="bold">Tissue Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">urticaria <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID360">5.3</linkHtml>)] </content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Musculoskeletal and</content> <content styleCode="bold">Connective Tissue Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">arthralgia tendinitis <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID356">5.1</linkHtml>)] </content> myalgia skeletal pain </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Renal and Urinary Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">abnormal renal function acute renal failure <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID362">5.4</linkHtml>)] </content> </td></tr></tbody></table>

<table ID="ID397" width="100%"><caption>Table 6: Postmarketing Reports Of Adverse Drug Reactions</caption><col width="33%"/><col width="66%"/><tbody><tr><td align="left" styleCode="Lrule Toprule Botrule Rrule" valign="top"><content styleCode="bold">System/Organ Class</content> </td><td align="left" styleCode=" Toprule Botrule Rrule" valign="top"><content styleCode="bold">Adverse Reaction</content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Blood and Lymphatic System Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">pancytopenia aplastic anemia leukopenia hemolytic anemia <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID362">5.4</linkHtml>)] </content> eosinophilia </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Immune System Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">hypersensitivity reactions, sometimes fatal including: anaphylactic/anaphylactoid reactions anaphylactic shock angioneurotic edema serum sickness <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID360">5.3</linkHtml>, <linkHtml href="#ID362">5.4</linkHtml>)] </content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Psychiatric Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">psychosis paranoia isolated reports of suicide attempt and suicidal ideation <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID368">5.6</linkHtml>)] </content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Nervous System Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">exacerbation of myasthenia gravis <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID358">5.2</linkHtml>)] </content> anosmia ageusia parosmia dysgeusia peripheral neuropathy (may be irreversible) <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID372">5.9</linkHtml>)] </content> isolated reports of encephalopathy abnormal electroencephalogram (EEG) dysphonia pseudotumor cerebri <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID368">5.6</linkHtml>)] </content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Eye Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">Uveitis vision disturbance, including diplopia visual acuity reduced vision blurred scotoma </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Ear and Labyrinth Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">hypoacusis tinnitus </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Cardiac Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">isolated reports of torsade de pointes electrocardiogram QT prolonged <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID374">5.10</linkHtml>)] </content> tachycardia </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Vascular Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">vasodilatation </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Respiratory, Thoracic and</content> <content styleCode="bold">Mediastinal Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">isolated reports of allergic pneumonitis <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID362">5.4</linkHtml>)] </content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Hepatobiliary Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">hepatic failure (including fatal cases) hepatitis jaundice <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID362">5.4</linkHtml>), ( <linkHtml href="#ID366">5.5</linkHtml>)] </content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">bullous eruptions to include: Stevens-Johnson Syndrome toxic epidermal necrolysis erythema multiforme <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID362">5.4</linkHtml>)] </content> photosensitivity/phototoxicity reaction <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID380">5.13</linkHtml>)] </content> leukocytoclastic vasculitis </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Musculoskeletal and</content> <content styleCode="bold">Connective Tissue Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">tendon rupture <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID356">5.1</linkHtml>)] </content> muscle injury, including rupture rhabdomyolysis </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Renal and Urinary Disorders</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">interstitial nephritis <content styleCode="italics">[see Warnings and Precautions ( <linkHtml href="#ID362">5.4</linkHtml>)] </content> </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">General Disorders and</content> <content styleCode="bold">Administration Site Conditions</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">multi-organ failure pyrexia </td></tr><tr><td align="left" styleCode="Lrule Botrule Rrule" valign="top"><content styleCode="bold">Investigations</content> </td><td align="left" styleCode=" Botrule Rrule" valign="top">prothrombin time prolonged international normalized ratio prolonged muscle enzymes increased </td></tr></tbody></table>