Moxifloxacin

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS and EXACERBATION OF MYASTHENIA GRAVIS Fluoroquinolones, including moxifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together [see Warnings and Precautions ( 5.1 )] , including: Tendinitis and tendon rupture [see Warnings and Precautions ( 5.2 )] Peripheral neuropathy [see Warnings and Precautions ( 5.3 )] Central nervous system effects [see Warnings and Precautions ( 5.4 )] Discontinue Moxifloxacin Injection immediately and avoid the use of fluoroquinolones, including Moxifloxacin Injection, in patients who experience any of these serious adverse reactions [see Warnings and Precautions ( 5.1 )] . Fluoroquinolones, including moxifloxacin, may exacerbate muscle weakness in patients with myasthenia gravis. Avoid Moxifloxacin Injection in patients with known history of myasthenia gravis [see Warnings and Precautions ( 5.5 )]. Because fluoroquinolones, including moxifloxacin, have been associated with serious adverse reactions [see Warnings and Precautions ( 5.1 to 5.14 )] , reserve Moxifloxacin Injection for use in patients who have no alternative treatment options for the following indications: Acute sinusitis [see Indications and Usage ( 1.5 )] Acute bacterial exacerbation of chronic bronchitis [see Indications and Usage ( 1.6 )] WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS and EXACERBATION OF MYASTHENIA GRAVIS See full prescribing Information for complete boxed warning Fluoroquinolones, including moxifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together ( 5.1 ) including: Tendinitis and tendon rupture ( 5.2 ) Peripheral neuropathy ( 5.3 ) Central nervous system effects ( 5.4 ) Discontinue Moxifloxacin Injection immediately and avoid the use of fluoroquinolones, including Moxifloxacin Injection, in patients who experience any of these serious adverse reactions. Fluoroquinolones, including moxifloxacin, may exacerbate muscle weakness in patients with myasthenia gravis. Avoid Moxifloxacin Injection in patients with known history of myasthenia gravis ( 5.5 ). Because fluoroquinolones, including moxifloxacin, have been associated with serious adverse reactions ( 5.1 to 5.14 ), reserve Moxifloxacin Injection for use in patients who have no alternative treatment options for the following indications: Acute bacterial sinusitis ( 1.5 ) Acute bacterial exacerbation of chronic bronchitis ( 1.6 )

5 WARNINGS AND PRECAUTIONS Prolongation of the QT interval and isolated cases of torsades de pointes has been reported. Avoid use in patients with known prolongation, hypokalemia, and with drugs that prolong the QT interval. ( 5.6 , 7.4 , 8.5 ). Use caution in patients with proarrhythmic conditions such as clinically significant bradycardia or acute myocardial ischemia. ( 5.6 ) Serious and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, may occur after first or subsequent doses. Discontinue moxifloxacin at the first sign of skin rash, jaundice or any other sign of hypersensitivity. ( 5.7 , 5.8 ) Clostridioides difficile -associated diarrhea: Evaluate if diarrhea occurs. ( 5.10 ) High sodium load: each unit dose contains 52.5 mEq (1,207 mg) of sodium. Avoid in patients with sodium restriction. ( 5.11 ) 5.1 Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects Fluoroquinolones, including Moxifloxacin Injection, have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to weeks after starting moxifloxacin. Patients of any age or without pre-existing risk factors have experienced these adverse reactions [see Warnings and Precautions ( 5.2 , 5.3 , 5.4 )] . Discontinue Moxifloxacin Injection immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including moxifloxacin, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones. 5.2 Tendinitis and Tendon Rupture Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of tendinitis and tendon rupture in all ages [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . This adverse reaction most frequently involves the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur within hours or days of starting moxifloxacin or as long as several months after completion of therapy. Tendinitis and tendon rupture can occur bilaterally. The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants. Other factors 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 also occurred in patients taking fluoroquinolones who do not have the above risk factors. Discontinue moxifloxacin 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 ( 6.2 ) and Patient Counseling Information ( 17 )]. Avoid fluoroquinolones, including moxifloxacin, in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture [see Adverse Reactions ( 6.1 )] . 5.3 Peripheral Neuropathy Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of 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 moxifloxacin. Symptoms may occur soon after initiation of moxifloxacin and may be irreversible in some patients [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6 , 6.1 , 6.2 )] . Discontinue moxifloxacin immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation. Avoid fluoroquinolones, including moxifloxacin, in patients who have previously experienced peripheral neuropathy [see Adverse Reactions ( 6.1 , 6.2 ) and Patient Counseling Information ( 17 )]. 5.4 Central Nervous System Effects Psychiatric Adverse Reactions Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of psychiatric adverse reactions, including: toxic psychosis, hallucinations, or paranoia; depression or suicidal thoughts or acts; anxiety, agitation, or nervousness; confusion, delirium, disorientation, or disturbances in attention; insomnia or nightmares; and memory impairment. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin, discontinue moxifloxacin immediately and institute appropriate measures [see Adverse Reactions ( 6.1 , 6.2 )]. Central Nervous System Adverse Reactions Fluoroquinolones, including moxifloxacin, have been associated with an increased risk of seizures (convulsions), increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremors. As with all fluoroquinolones, use moxifloxacin with caution in patients with known or suspected CNS disorders (for example, severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin, discontinue moxifloxacin immediately and institute appropriate measures [see Drug Interactions ( 7.3 ), Adverse Reactions ( 6.1 , 6.2 ) and Patient Counseling Information ( 17 )]. 5.5 Exacerbation of Myasthenia Gravis Fluoroquinolones, including moxifloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions, including deaths and requirement for ventilatory support, have been associated with fluoroquinolone use in patients with myasthenia gravis. Avoid moxifloxacin in patients with known history of myasthenia gravis [see Patient Counseling Information ( 17 )]. 5.6 QT Prolongation Moxifloxacin has been shown to prolong the QT interval of the electrocardiogram in some patients. Following oral dosing with 400 mg of moxifloxacin the mean (± SD) change in QTc from the pre-dose value at the time of maximum drug concentration was 6 msec (± 26) (n = 787). Following a course of daily intravenous dosing (400 mg; 1 hour infusion each day) the mean change in QTc from the Day 1 pre-dose value was 10 msec (± 22) on Day 1 (n = 667) and 7 msec (± 24) on Day 3 (n = 667). The drug should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia and patients receiving Class IA (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic agents, due to the lack of clinical experience with the drug in these patient populations. Pharmacokinetic studies between moxifloxacin and other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. An additive effect of moxifloxacin and these drugs cannot be excluded; therefore caution should be exercised when moxifloxacin is given concurrently with these drugs. In premarketing clinical trials, the rate of cardiovascular adverse events was similar in 798 moxifloxacin and 702 comparator treated patients who received concomitant therapy with drugs known to prolong the QTc interval. Moxifloxacin should be used with caution in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia, acute myocardial ischemia. The magnitude of QT prolongation may increase with increasing concentrations of the drug or increasing rates of infusion of the intravenous formulation. Therefore the recommended dose or infusion rate should not be exceeded. QT prolongation may lead to an increased risk for ventricular arrhythmias including torsades de pointes. No excess in cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin treatment in over 15,500 patients in controlled clinical studies, including 759 patients who were hypokalemic at the start of treatment, and there was no increase in mortality in over 18,000 moxifloxacin tablet treated patients in a postmarketing observational study in which ECGs were not performed. Elderly patients using Moxifloxacin Injection may be more susceptible to drug-associated QT prolongation [see Use in Specific Populations ( 8.5 )]. In addition, moxifloxacin should be used with caution in patients with mild, moderate, or severe liver cirrhosis [see Clinical Pharmacology ( 12.3 ) and Patient Counseling Information ( 17 )]. 5.7 Hypersensitivity Reactions Serious anaphylactic reactions, some following the first dose, have been reported in patients receiving fluoroquinolone therapy, including moxifloxacin. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Discontinue Moxifloxacin Injection at the first appearance of a skin rash or any other sign of hypersensitivity [see Warnings and Precautions ( 5.7 ), Adverse Reactions ( 6 ) and Patient Counseling Information ( 17 )]. 5.8 Other Serious and Sometimes Fatal Adverse Reactions Other serious and sometimes fatal adverse reactions, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including moxifloxacin. 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 (for example, 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 Discontinue Moxifloxacin Injection immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and supportive measures instituted [see Patient Counseling Information ( 17 ) and Adverse Reactions ( 6.2 )]. 5.9 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 Moxifloxacin Injection for use only when there are no alternative antibacterial treatments available. 5.10 Clostridioides Difficile -Associated Diarrhea Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including moxifloxacin, 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 ( 6.1 ) and Patient Counseling Information ( 17 )]. 5.11 High Sodium Load Each unit dose of Moxifloxacin Injection contains 52.5 mEq (1,207 mg) of sodium. Avoid use of Moxifloxacin Injection in patients with congestive heart failure, elderly, and those with restricted sodium intake [see Use in Specific Populations ( 8.5 ), Description ( 11 )] . 5.12 Arthropathic Effects in Animals The oral administration of moxifloxacin caused lameness in immature dogs. Histopathological examination of the weight-bearing joints of these dogs revealed permanent lesions of the cartilage. Related quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature animals of various species [see Nonclinical Toxicology ( 13.2 )]. 5.13 Blood Glucose Disturbances As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with moxifloxacin. In moxifloxacin-treated patients, dysglycemia occurred predominantly in elderly diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (for example, sulfonylurea) or with insulin. Severe cases of hypoglycemia resulting in coma or death have been reported. In diabetic patients, careful monitoring of blood glucose is recommended [see Adverse Reactions ( 6.1 )]. If a hypoglycemic reaction occurs, discontinue moxifloxacin and initiate appropriate therapy immediately [see Adverse Reactions ( 6.1 ), Drug Interactions ( 7.2 ) and Patient Counseling Information ( 17 )] . 5.14 Photosensitivity/Phototoxicity Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as exaggerated sunburn reactions (for example, 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 quinolone antibiotics after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Drug therapy should be discontinued if phototoxicity occurs [see Adverse Reactions ( 6.2 ) and Clinical Pharmacology ( 12.3 )]. 5.15 Development of Drug Resistant Bacteria Prescribing moxifloxacin 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 )].

6 ADVERSE REACTIONS The following serious and otherwise important adverse reactions are discussed in greater detail in the Warnings and Precautions section of the label: Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects [see Warnings and Precautions ( 5.1 )] Tendinitis and Tendon Rupture [see Warnings and Precautions ( 5.2 )] Peripheral Neuropathy [see Warnings and Precautions ( 5.3 )] Central Nervous System Effects [see Warnings and Precautions ( 5.4 )] Exacerbation of Myasthenia Gravis [see Warnings and Precautions ( 5.5 )] QT Prolongation [see Warnings and Precautions ( 5.6 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.7 )] Other Serious and Sometimes Fatal Adverse Reactions [see Warnings and Precautions ( 5.8 )] Clostridioides Difficile -Associated Diarrhea [see Warnings and Precautions ( 5.10 )] Blood Glucose Disturbances [see Warnings and Precautions ( 5.13 )] Photosensitivity/Phototoxicity [see Warnings and Precautions ( 5.14 )] Development of Drug Resistant Bacteria [see Warnings and Precautions ( 5.15 )] Most common reactions (≥ 3%) were nausea, diarrhea, headache, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials 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 moxifloxacin in 14,981 patients in 71 active controlled Phase II - IV clinical trials in different indications [see Indications and Usage ( 1 )] . The population studied had a mean age of 50 years (approximately 73% of the population was < 65 years of age), 50% were male, 63% were Caucasian, 12% were Asian and 9% were Black. Patients received moxifloxacin 400 mg once daily PO, IV, or sequentially (IV followed by PO). Treatment duration was usually 6 to 10 days, and the mean number of days on therapy was 9 days. Discontinuation of moxifloxacin due to adverse events occurred in 5% of patients overall, 4.1% of patients treated with 400 mg PO, 3.9% with 400 mg IV and 8.2% with sequential therapy 400 mg PO/IV. The most common adverse events leading to discontinuation with the 400 mg PO doses were nausea (0.8%), diarrhea (0.5%), dizziness (0.5%), and vomiting (0.4%). The most common adverse event leading to discontinuation with the 400 mg IV dose was rash (0.5%). The most common adverse events leading to discontinuation with the 400 mg IV/PO sequential dose were diarrhea (0.5%) and pyrexia (0.4%). Adverse reactions occurring in ≥ 1% of moxifloxacin-treated patients and less common adverse reactions, occurring in 0.1 to < 1% of moxifloxacin-treated patients, are shown in Table 2 and Table 3 , respectively. The most common adverse drug reactions (≥ 3%) are nausea, diarrhea, headache, and dizziness. Table 2: Common (≥1%) Adverse Reactions Reported in Active-Controlled Clinical Trials with Moxifloxacin a MedDRA Version 12.0 System Organ Class Adverse Reactions a % (N=14,981) Blood and Lymphatic System Disorders Anemia 1.1 Gastrointestinal Disorders Nausea 6.9 Diarrhea 6 Vomiting 2.4 Constipation 1.9 Abdominal pain 1.5 Abdominal pain upper 1.1 Dyspepsia 1 General Disorders and Administration Site Conditions Pyrexia 1.1 Investigations Alanine aminotransferase increased 1.1 Metabolism and Nutritional Disorder Hypokalemia 1 Nervous System Disorders Headache 4.2 Dizziness 3 Psychiatric Disorders Insomnia 1.9 Table 3: Less Common (0.1 to < 1%) Adverse Reactions Reported in Active-Controlled Clinical Trials with Moxifloxacin (N=14,981) a MedDRA Version 12.0 System Organ Class Adverse Reactions a Blood and Lymphatic System Disorders Thrombocythemia Eosinophilia Neutropenia Thrombocytopenia Leukopenia Leukocytosis Cardiac Disorders Atrial fibrillation Palpitations Tachycardia Cardiac failure congestive Angina pectoris Cardiac failure Cardiac arrest Bradycardia Ear and Labyrinth Disorders Vertigo Tinnitus Eye Disorders Vision blurred Gastrointestinal Disorders Dry mouth Abdominal discomfort Flatulence Abdominal distention Gastritis Gastroesophageal reflux disease General Disorders and Administration Site Conditions Fatigue Chest pain Asthenia Edema peripheral Pain Malaise System Organ Class Adverse Reactions a Infusion site extravasation Edema Chills Chest discomfort Facial pain Hepatobiliary Disorders Hepatic function abnormal Infections and Infestations Vulvovaginal candidiasis Oral candidiasis Vulvovaginal mycotic infection Candidiasis Vaginal infection Oral fungal infection Fungal infection Gastroenteritis Investigations Aspartate aminotransferase increased Gamma-glutamyltransferase increased Blood alkaline phosphatase increased Hepatic enzyme increased Electrocardiogram QT prolonged Blood lactate dehydrogenase increased Platelet count increased Blood amylase increased Blood glucose increased Lipase increased Hemoglobin decreased Blood creatinine increased Transaminases increased White blood cell count increased Blood urea increased Liver function test abnormal Hematocrit decreased Prothrombin time prolonged Eosinophil count increased Activated partial thromboplastin time prolonged Blood bilirubin increased Blood triglycerides increased Blood uric acid increased Blood pressure increased Metabolism and Nutrition Disorders Hyperglycemia Anorexia Hypoglycemia Hyperlipidemia Decreased appetite Dehydration Musculoskeletal and Connective Tissue Disorders Back pain Pain in extremity Arthralgia Myalgia Muscle spasms Musculoskeletal chest pain Musculoskeletal pain Nervous System Disorders Dysgeusia Somnolence Tremor Lethargy System Organ Class Adverse Reactions a Paresthesia Tension headache Hypoesthesia Syncope Psychiatric Disorders Anxiety Confusional state Agitation Depression Nervousness Restlessness Hallucination Disorientation Renal and Urinary Disorders Renal failure Dysuria Renal failure acute Reproductive System and Breast Disorders Vulvovaginal pruritus Respiratory, Thoracic, and Mediastinal Disorders Dyspnea Asthma Wheezing Bronchospasm Skin and Subcutaneous Tissue Disorders Rash Pruritus Hyperhidrosis Erythema Urticaria Dermatitis allergic Night sweats Vascular Disorders Hypertension Hypotension Phlebitis Laboratory Changes Changes in laboratory parameters, without regard to drug relationship, which are not listed above and which occurred in ≥ 2% of patients and at an incidence greater than in controls included: increases in MCH, neutrophils, WBCs, PT ratio, ionized calcium, chloride, albumin, globulin, bilirubin; decreases in hemoglobin, RBCs, neutrophils, eosinophils, basophils, PT ratio, glucose, pO 2 , bilirubin, and amylase. It cannot be determined if any of the above laboratory abnormalities were caused by the drug or the underlying condition being treated. 6.2 Postmarketing Experience Table 4 lists adverse reactions that have been identified during post-approval use of moxifloxacin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Table 4: Postmarketing Reports of Adverse Drug Reactions System/Organ Class Adverse Reaction Blood and Lymphatic System Disorders Agranulocytosis Pancytopenia [see Warnings and Precautions ( 5.8 )] Cardiac Disorders Ventricular tachyarrhythmias (including in very rare cases cardiac arrest and torsades de pointes, and usually in patients with concurrent severe underlying proarrhythmic conditions) Ear and Labyrinth Disorders Hearing impairment, including deafness (reversible in majority of cases) Eye Disorders Vision loss (especially in the course of CNS reactions, transient in majority of cases) Hepatobiliary Disorders Hepatitis (predominantly cholestatic) Hepatic failure (including fatal cases) Jaundice Acute hepatic necrosis [see Warnings and Precautions ( 5.8 )] Immune System Disorders Anaphylactic reaction Anaphylactic shock Angioedema (including laryngeal edema) [see Warnings and Precautions ( 5.7 , 5.8 )] Musculoskeletal and Connective Tissue Disorders Tendon rupture [see Warnings and Precautions ( 5.2 )] Nervous System Disorders Altered coordination Abnormal gait [see Warnings and Precautions ( 5.3 )] Myasthenia gravis (exacerbation of) [see Warnings and Precautions ( 5.5 )] Muscle weakness Peripheral neuropathy (that may be irreversible), polyneuropathy [see Warnings and Precautions ( 5.3 )] Psychiatric Disorders Psychotic reaction (very rarely culminating in self- injurious behavior, such as suicidal ideation/thoughts or suicide attempts [see Warnings and Precautions ( 5.4 )] Renal and Urinary Disorders Renal dysfunction Interstitial nephritis [see Warnings and Precautions ( 5.8 )] Respiratory, Thoracic and Mediastinal Disorders Allergic pneumonitis [see Warnings and Precautions ( 5.8 )] Skin and Subcutaneous Tissue Disorders Photosensitivity/phototoxicity reaction [see Warnings and Precautions ( 5.14 )] Stevens-Johnson syndrome Toxic epidermal necrolysis [see Warnings and Precautions ( 5.8 )]

<table ID="t2" width="100%"><caption>Table 2: Common (&#x2265;1%) Adverse Reactions Reported in Active-Controlled Clinical Trials with Moxifloxacin </caption><col width="52.167%" align="left"/><col width="33.233%" align="left"/><col width="14.600%" align="left"/><tfoot><tr><td colspan="3" align="left" valign="top"><paragraph styleCode="footnote">^a MedDRA Version 12.0 </paragraph></td></tr></tfoot><tbody><tr><td align="left" valign="top" styleCode="Toprule Botrule Lrule Rrule"> <content styleCode="bold">System Organ Class</content></td><td align="left" valign="top" styleCode="Toprule Botrule Rrule"> <content styleCode="bold">Adverse Reactions</content><content styleCode="bold">^a</content></td><td align="center" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">% (N=14,981)</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Blood and Lymphatic System Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Anemia </td><td align="center" valign="top" styleCode="Botrule Rrule">1.1 </td></tr><tr><td rowspan="7" align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Gastrointestinal Disorders</content></td><td align="left" valign="top" styleCode="Rrule">Nausea </td><td align="center" valign="top" styleCode="Rrule">6.9 </td></tr><tr><td align="left" valign="top" styleCode="Rrule">Diarrhea </td><td align="center" valign="top" styleCode="Rrule">6 </td></tr><tr><td align="left" valign="top" styleCode="Rrule">Vomiting </td><td align="center" valign="top" styleCode="Rrule">2.4 </td></tr><tr><td align="left" valign="top" styleCode="Rrule">Constipation </td><td align="center" valign="top" styleCode="Rrule">1.9 </td></tr><tr><td align="left" valign="top" styleCode="Rrule">Abdominal pain </td><td align="center" valign="top" styleCode="Rrule">1.5 </td></tr><tr><td align="left" valign="top" styleCode="Rrule">Abdominal pain upper </td><td align="center" valign="top" styleCode="Rrule">1.1 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Rrule">Dyspepsia </td><td align="center" valign="top" styleCode="Botrule Rrule">1 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">General Disorders and Administration Site Conditions</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Pyrexia </td><td align="center" valign="top" styleCode="Botrule Rrule">1.1 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Investigations</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Alanine aminotransferase increased </td><td align="center" valign="top" styleCode="Botrule Rrule">1.1 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Metabolism and Nutritional Disorder</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Hypokalemia </td><td align="center" valign="top" styleCode="Botrule Rrule">1 </td></tr><tr><td rowspan="2" align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Nervous System Disorders</content></td><td align="left" valign="top" styleCode="Rrule">Headache </td><td align="center" valign="top" styleCode="Rrule">4.2 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Rrule">Dizziness </td><td align="center" valign="top" styleCode="Botrule Rrule">3 </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Psychiatric Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Insomnia </td><td align="center" valign="top" styleCode="Botrule Rrule">1.9 </td></tr></tbody></table>

<table ID="t3" width="100%"><caption>Table 3: Less Common (0.1 to &lt; 1%) Adverse Reactions Reported in Active-Controlled Clinical Trials with Moxifloxacin (N=14,981) </caption><col width="51.900%" align="left"/><col width="48.100%" align="left"/><tfoot><tr><td colspan="2" align="left" valign="top"><paragraph styleCode="footnote">^a MedDRA Version 12.0 </paragraph></td></tr></tfoot><tbody><tr><td align="left" valign="top" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">System Organ Class</content></td><td align="left" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Adverse Reactions</content><content styleCode="bold">^a</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Blood and Lymphatic System Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Thrombocythemia Eosinophilia Neutropenia Thrombocytopenia Leukopenia Leukocytosis </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Cardiac Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Atrial fibrillation Palpitations Tachycardia Cardiac failure congestive Angina pectoris Cardiac failure Cardiac arrest Bradycardia </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Ear and Labyrinth Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Vertigo Tinnitus </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Eye Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Vision blurred </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Gastrointestinal Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Dry mouth Abdominal discomfort Flatulence Abdominal distention Gastritis Gastroesophageal reflux disease </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">General Disorders and Administration Site Conditions</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Fatigue Chest pain Asthenia Edema peripheral Pain Malaise </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">System Organ Class</content></td><td align="left" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">Adverse Reactions</content><content styleCode="bold">^a</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule">Infusion site extravasation Edema Chills Chest discomfort Facial pain </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Hepatobiliary Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Hepatic function abnormal </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Infections and Infestations</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Vulvovaginal candidiasis Oral candidiasis Vulvovaginal mycotic infection Candidiasis Vaginal infection Oral fungal infection Fungal infection Gastroenteritis </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Investigations</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Aspartate aminotransferase increased Gamma-glutamyltransferase increased Blood alkaline phosphatase increased Hepatic enzyme increased Electrocardiogram QT prolonged Blood lactate dehydrogenase increased Platelet count increased Blood amylase increased Blood glucose increased Lipase increased Hemoglobin decreased Blood creatinine increased Transaminases increased White blood cell count increased Blood urea increased Liver function test abnormal Hematocrit decreased Prothrombin time prolonged Eosinophil count increased Activated partial thromboplastin time prolonged Blood bilirubin increased Blood triglycerides increased Blood uric acid increased Blood pressure increased </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Metabolism and Nutrition Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Hyperglycemia Anorexia Hypoglycemia Hyperlipidemia Decreased appetite Dehydration </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Musculoskeletal and Connective Tissue Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Back pain Pain in extremity Arthralgia Myalgia Muscle spasms Musculoskeletal chest pain Musculoskeletal pain </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Nervous System Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Dysgeusia Somnolence Tremor Lethargy </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">System Organ Class</content></td><td align="left" valign="top" styleCode="Botrule Rrule"><content styleCode="bold">Adverse Reactions</content><content styleCode="bold">^a</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"/><td align="left" valign="top" styleCode="Botrule Rrule">Paresthesia Tension headache Hypoesthesia Syncope </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Psychiatric Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Anxiety Confusional state Agitation Depression Nervousness Restlessness Hallucination Disorientation </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Renal and Urinary Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Renal failure Dysuria Renal failure acute </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Reproductive System and Breast Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Vulvovaginal pruritus </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Respiratory, Thoracic, and Mediastinal Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Dyspnea Asthma Wheezing Bronchospasm </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Rash Pruritus Hyperhidrosis Erythema Urticaria Dermatitis allergic Night sweats </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Vascular Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Hypertension Hypotension Phlebitis </td></tr></tbody></table>

<table ID="t4" width="100%"><caption>Table 4: Postmarketing Reports of Adverse Drug Reactions </caption><col width="49.200%" align="left"/><col width="50.800%" align="left"/><tbody><tr><td align="left" valign="top" styleCode="Toprule Botrule Lrule Rrule"><content styleCode="bold">System/Organ Class</content></td><td align="left" valign="top" styleCode="Toprule Botrule Rrule"><content styleCode="bold">Adverse Reaction</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Blood and Lymphatic System Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Agranulocytosis Pancytopenia <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s29">5.8</linkHtml>)]</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Cardiac Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Ventricular tachyarrhythmias (including in very rare cases cardiac arrest and torsades de pointes, and usually in patients with concurrent severe underlying proarrhythmic conditions) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Ear and Labyrinth Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Hearing impairment, including deafness (reversible in majority of cases) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Eye Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Vision loss (especially in the course of CNS reactions, transient in majority of cases) </td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Hepatobiliary Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Hepatitis (predominantly cholestatic) Hepatic failure (including fatal cases) Jaundice Acute hepatic necrosis <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s29">5.8</linkHtml>)]</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Immune System Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Anaphylactic reaction Anaphylactic shock Angioedema (including laryngeal edema) <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s28">5.7</linkHtml>, <linkHtml href="#s29">5.8</linkHtml>)]</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Musculoskeletal and Connective Tissue Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Tendon rupture <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s21">5.2</linkHtml>)]</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Nervous System Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Altered coordination Abnormal gait <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s22">5.3</linkHtml>)]</content> Myasthenia gravis (exacerbation of) <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s26">5.5</linkHtml>)]</content> Muscle weakness Peripheral neuropathy (that may be irreversible), polyneuropathy <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s22">5.3</linkHtml>)]</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Psychiatric Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Psychotic reaction (very rarely culminating in self- injurious behavior, such as suicidal ideation/thoughts or suicide attempts <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s23">5.4</linkHtml>)]</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Renal and Urinary Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Renal dysfunction Interstitial nephritis <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s29">5.8</linkHtml>)]</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Respiratory, Thoracic and Mediastinal Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Allergic pneumonitis <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s29">5.8</linkHtml>)]</content></td></tr><tr><td align="left" valign="top" styleCode="Botrule Lrule Rrule"><content styleCode="bold">Skin and Subcutaneous Tissue Disorders</content></td><td align="left" valign="top" styleCode="Botrule Rrule">Photosensitivity/phototoxicity reaction <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s35">5.14</linkHtml>)]</content> Stevens-Johnson syndrome Toxic epidermal necrolysis <content styleCode="italics">[see Warnings and Precautions (<linkHtml href="#s29">5.8</linkHtml>)]</content></td></tr></tbody></table>