1 INDICATIONS AND USAGE Moxifloxacin Injection is a fluoroquinolone antibacterial drug indicated for treating infections in adults ≥ 18 years of age caused by designated, susceptible bacteria.

( 1 , 12.4 ) Community Acquired Pneumonia ( 1.1 ) Skin and Skin Structure Infections: Uncomplicated ( 1.2 ) and Complicated ( 1.3 ) Complicated Intra-Abdominal Infections ( 1.4 ) Acute Bacterial Sinusitis ( 1.5 ) Acute Bacterial Exacerbation of Chronic Bronchitis ( 1.6 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of Moxifloxacin Injection and other antibacterial drugs, Moxifloxacin Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

( 1.7 ) 1.1 Community Acquired Pneumonia Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Community Acquired Pneumonia caused by susceptible isolates of Streptococcus pneumoniae (including multi-drug resistant isolates*), Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae .

* MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates previously known as PRSP (Penicillin-resistant S.

pneumoniae ), and are isolates resistant to two or more of the following antibiotics: penicillin (minimum inhibitory concentrations [MIC] ≥ 2 mcg/mL), 2nd generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole [see Clinical Studies ( 14.2 )] .

1.2 Uncomplicated Skin and Skin Structure Infections Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Uncomplicated Skin and Skin Structure Infections caused by susceptible isolates of methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes [see Clinical Studies ( 14.5 )].

1.3 Complicated Skin and Skin Structure Infections Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Complicated Skin and Skin Structure Infections caused by susceptible isolates of methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae [see Clinical Studies ( 14.6 )].

1.4 Complicated Intra-Abdominal Infections Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Complicated Intra-Abdominal Infections including polymicrobial infections such as abscess caused by susceptible isolates of Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron, or Peptostreptococcus species [see Clinical Studies ( 14.7 )] .

1.5 Acute Bacterial Sinusitis Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Acute Bacterial Sinusitis (ABS) caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae , or Moraxella catarrhalis [see Clinical Studies ( 14.4 )] .

Because fluoroquinolones, including Moxifloxacin Injection, have been associated with serious adverse reactions [see Warnings and Precautions ( 5.1 to 5.14 )] and for some patients ABS is self-limiting, reserve Moxifloxacin Injection for treatment of ABS in patients who have no alternative treatment options.

1.6 Acute Bacterial Exacerbation of Chronic Bronchitis Moxifloxacin Injection is indicated in adults (18 years of age or older) for the treatment of Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB) caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus, or Moraxella catarrhalis [see Clinical Studies ( 14.1 )].

Because fluoroquinolones, including Moxifloxacin Injection, have been associated with serious adverse reactions [see Warnings and Precautions ( 5.1 to 5.14 )] and for some patients ABECB is self-limiting, reserve Moxifloxacin Injection for treatment of ABECB in patients who have no alternative treatment options.

1.7 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of Moxifloxacin Injection and other antibacterial drugs, Moxifloxacin Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.

In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

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 )]