MOXIFLOXACIN HYDROCHLORIDE

1 INDICATIONS AND USAGE Moxifloxacin tablets are a fluoroquinolone antibacterial indicated for treating infections in adults 18 years of age and older caused by designated susceptible bacteria, in the conditions listed below: • Community Acquired Pneumonia (1.1) • Skin and Skin Structure Infections: Uncomplicated (1.2) and Complicated (1.3) • Complicated Intra-Abdominal Infections (1.4) • Plague (1.5) • Acute Bacterial Sinusitis (1.6) • Acute Bacterial Exacerbation of Chronic Bronchitis (1.7) To reduce the development of drug-resistant bacteria and maintain the effectiveness of moxifloxacin tablets and other antibacterial drugs. Moxifloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. (1.8) 1.1 Community Acquired Pneumonia Moxifloxacin tablets are indicated in adult patients for the treatment of Community Acquired Pneumonia caused by susceptible isolates of Streptococcus pneumoniae (including multi-drug resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Clinical Studies (14.3)]. MDRSP isolates are isolates resistant to two or more of the following antibacterial drugs: penicillin (minimum inhibitory concentrations [MIC] greater than or equal to 2 mcg/mL), 2nd generation cephalosporins (for example, cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole. 1.2 Uncomplicated Skin and Skin Structure Infections Moxifloxacin tablets are indicated in adult patients 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 (14.4)]. 1.3 Complicated Skin and Skin Structure Infections Moxifloxacin tablets are indicated in adult patients 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 (14.5)]. 1.4 Complicated Intra-Abdominal Infections Moxifloxacin tablets are indicated in adult patients for the treatment of Complicated Intra-Abdominal Infections (cIAI) 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 (14.6)]. 1.5 Plague Moxifloxacin tablets are indicated in adult patients for the treatment of plague, including pneumonic and septicemic plague, due to susceptible isolates of Yersinia pestis and prophylaxis of plague in adult patients. Efficacy studies of moxifloxacin could not be conducted in humans with plague for feasibility reasons. Therefore, this indication is based on an efficacy study conducted in animals only [see Clinical Studies (14.7)]. 1.6 Acute Bacterial Sinusitis Moxifloxacin tablets are indicated in adult patients for the treatment of acute bacterial sinusitis (ABS) caused by susceptible isolates of Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis [see Clinical Studies (14.1)]. Because fluoroquinolones, including moxifloxacin tablets, 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 tablets for treatment of ABS in patients who have no alternative treatment options. 1.7 Acute Bacterial Exacerbation of Chronic Bronchitis Moxifloxacin tablets are indicated in adult patients 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 (14.2)]. Because fluoroquinolones, including moxifloxacin tablets, 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 tablets for treatment of ABECB in patients who have no alternative treatment options. 1.8 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of moxifloxacin tablets and other antibacterial drugs, moxifloxacin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

2 DOSAGE AND ADMINISTRATION The dose of moxifloxacin is 400 mg (orally) once every 24 hours. The duration of therapy depends on the type of infection. 2.1 Dosage in Adult Patients The dose of moxifloxacin is 400 mg (orally) once every 24 hours. The duration of therapy depends on the type of infection as described in Table 1 . Table 1: Dosage and Duration of Therapy in Adult Patients Type of Infection a Dose Every 24 hours Duration b (days) a) Due to the designated pathogens [see Indications and Usage (1) , . b) Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. c) Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Acute Bacterial Sinusitis (1.1) 400 mg 10 Acute Bacterial Exacerbation of Chronic Bronchitis (1.2) 400 mg 5 Community Acquired Pneumonia 400 mg 7-14 Uncomplicated Skin and Skin Structure Infections (SSSI ) (1.4) 400 mg 7 Complicated SSSI (1.5) 400 mg 7-21 Complicated Intra-Abdominal Infections (1.6) 400 mg 5-14 Conversion of Intravenous to Oral Dosing in Adults Intravenous formulation is indicated when it offers a route of administration advantageous to the patient (for example, patient cannot tolerate an oral dosage form). When switching from intravenous to oral formulation, no dosage adjustment is necessary. Patients whose therapy is started with moxifloxacin hydrochloride IV may be switched to moxifloxacin hydrochloride tablets when clinically indicated at the discretion of the physician. 2.2 Important Administration Instructions With Multivalent Cations Administer moxifloxacin tablets at least 4 hours before or 8 hours after products containing magnesium, aluminum, iron or zinc, including antacids, sucralfate, multivitamins and didanosine buffered tablets for oral suspension or the pediatric powder for oral solution [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. With Food Moxifloxacin tablets can be taken with or without food, drink fluids liberally. Missed Doses If a dose is missed, it should be taken anytime but not later than 8 hours prior to the next scheduled dose. If less than 8 hours remain before the next dose, the missed dose should not be taken and treatment should be continued as prescribed with the next scheduled dose. Double doses should not be taken to compensate for a missed dose.

4 CONTRAINDICATIONS Moxifloxacin tablets are contraindicated in persons with a history of hypersensitivity to moxifloxacin or any member of the quinolone class of antibacterials [see Warnings and Precautions (5.8)]. Known hypersensitivity to moxifloxacin hydrochloride tablets or other quinolones. (4, 5.4)

5 WARNINGS AND PRECAUTIONS Prolongation of the QT interval and isolated cases of torsade de pointes has been reported. Avoid use in patients with known prolongation, proarrhythmic conditions such as clinically significant bradycardia or acute myocardial ischemia, hypokalemia, hypomagnesemia, and with drugs that prolong the QT interval. (5.6, 7.5, 8.5) Hypersensitivity and other serious reactions: Serious and sometimes fatal reactions, including anaphylactic reactions, may occur after first or subsequent doses of moxifloxacin hydrochloride. Discontinue moxifloxacin hydrochloride at 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) 5.1 Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects Fluoroquinolones, including moxifloxacin hydrochloride, 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 hydrochloride. 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 hydrochloride immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including moxifloxacin hydrochloride, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones. 5.2 Tendinitis and Tendon Rupture Fluoroquinolones, including moxifloxacin hydrochloride, have been associated with an increased risk of tendinitis and tendon rupture in all ages [see Warnings and Precautions (5.1) and Adverse Reactions (6.2)]. 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 hydrochloride immediately 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. Avoid fluoroquinolones, including moxifloxacin hydrochloride, in patients who have a history of tendon disorders or who have experienced tendinitis or tendon rupture [see Adverse Reactions (6.2)]. 5.3 Peripheral Neuropathy Fluoroquinolones, including moxifloxacin hydrochloride, 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 hydrochloride. Symptoms may occur soon after initiation of moxifloxacin hydrochloride and may be irreversible in some patients [see Warnings and Precautions (5.1) and Adverse Reactions (6.1, 6.2)]. Discontinue moxifloxacin hydrochloride 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 hydrochloride, in patients who have previously experienced peripheral neuropathy. 5.4 Central Nervous System Effects Psychiatric Adverse Reactions Fluoroquinolones, including moxifloxacin hydrochloride, 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; memory impairment. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving moxifloxacin hydrochloride, discontinue moxifloxacin hydrochloride immediately and institute appropriate measures [see Adverse Reactions (6.1, 6.2)]. Central Nervous System Adverse Reactions Fluoroquinolones, including moxifloxacin hydrochloride, 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 hydrochloride 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 hydrochloride, discontinue moxifloxacin hydrochloride immediately and institute appropriate measures [see Drug Interactions (7.4) Adverse Reactions (6.1, 6.2), and Patient Counseling Information (17)]. 5.5 Exacerbation of Myasthenia Gravis Fluoroquinolones, including moxifloxacin hydrochloride, 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 hydrochloride in patients with known history of myasthenia gravis. 5.6 QT Prolongation Moxifloxacin hydrochloride has been shown to prolong the QT interval of the electrocardiogram in some patients. Following oral dosing with 400 mg of moxifloxacin hydrochloride 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). Avoid moxifloxacin hydrochloride in patients with the following risk factors due to the lack of clinical experience with the drug in these patient populations: Known prolongation of the QT interval Ventricular arrhythmias including torsade de pointes because QT prolongation may lead to an increased risk for these conditions Ongoing proarrhythmic conditions, such as clinically significant bradycardia and acute myocardial ischemia, Uncorrected hypokalemia or hypomagnesemia Class IA (for example, quinidine, procainamide) or Class III (for example, amiodarone, sotalol) antiarrhythmic agents Other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants Elderly patients using intravenous moxifloxacin hydrochloride may be more susceptible to drug-associated QT prolongation [see Use In Specific Populations (8.5)]. In patients with mild, moderate, or severe liver cirrhosis, metabolic disturbances associated with hepatic insufficiency may lead to QT prolongation. Monitor ECG in patients with liver cirrhosis treated with moxifloxacin hydrochloride [see Clinical Pharmacology (12.3)]. 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. In premarketing clinical trials, the rate of cardiovascular adverse reactions was similar in 798 moxifloxacin hydrochloride and 702 comparator treated patients who received concomitant therapy with drugs known to prolong the QTc interval. No excess in cardiovascular morbidity or mortality attributable to QTc prolongation occurred with moxifloxacin hydrochloride 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. 5.7 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 in patients receiving therapy with fluoroquinolones, including moxifloxacin hydrochloride. These reactions 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 hydrochloride immediately at the first appearance of a skin rash, jaundice, or any other sign of hypersensitivity and institute supportive measures. 5.8 Hypersensitivity Reactions Serious anaphylactic reactions, some following the first dose, have been reported in patients receiving fluoroquinolone therapy, including moxifloxacin hydrochloride. Some reactions were accompanied by cardiovascular collapse, acute myocardial ischemia with or without myocardial infarction, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Discontinue moxifloxacin hydrochloride at the first appearance of a skin rash or any other sign of hypersensitivity [see Warnings and Precautions (5.7) and Adverse Reactions (6.1, 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 hydrochloride 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 hydrochloride, 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 antibacterial 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. 5.11 Arthropathic Effects in Animals In immature dogs, oral administration of moxifloxacin hydrochloride caused lameness. 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)]. 5.12 Blood Glucose Disturbances As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported with moxifloxacin hydrochloride. In moxifloxacin hydrochloride-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. If a hypoglycemic reaction occurs, discontinue moxifloxacin hydrochloride and initiate appropriate therapy immediately [see Adverse Reactions (6.1), Drug Interactions (7.3)] and Patient Counseling Information (17). 5.13 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 fluoroquinolones, including moxifloxacin hydrochloride, after sun or UV light exposure. Therefore, excessive exposure to these sources of light should be avoided. Moxifloxacin hydrochloride should be discontinued if phototoxicity occurs [see Clinical Pharmacology (12.2)]. 5.14 Development of Drug Resistant Bacteria Prescribing moxifloxacin hydrochloride 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.

7 DRUG INTERACTIONS Interacting Drug Interaction Multivalent cation-containing products including: antacids, sucralfate, multivitamins Decreased moxifloxacin hydrochloride absorption. Take moxifloxacin tablet at least 4 hours before or 8 hours after these products. ( 2.2 , 7.1 , 12.3 ) Warfarin Anticoagulant effect of warfarin may be enhanced. Monitor prothrombin time/INR, watch for bleeding. ( 6.4 , 7.2 , 12.3 ) Class IA and Class III antiarrhythmics: Proarrhythmic effect may be enhanced. Avoid concomitant use. ( 5.3 , 7.5 ) Antidiabetic agents Carefully monitor blood glucose ( 5.10 , 7.3 ) 7.1 Antacids, Sucralfate, Multivitamins and Other Products Containing Multivalent Cations Fluoroquinolones, including moxifloxacin hydrochloride, form chelates with alkaline earth and transition metal cations. Oral administration of moxifloxacin hydrochloride with antacids containing aluminum or magnesium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as didanosine buffered tablets for oral suspension or the pediatric powder for oral solution, may substantially interfere with the absorption of moxifloxacin hydrochloride, resulting in systemic concentrations considerably lower than desired. Therefore, moxifloxacin hydrochloride should be taken at least 4 hours before or 8 hours after these agents [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. 7.2 Warfarin Fluoroquinolones, including moxifloxacin hydrochloride, have been reported to enhance the anticoagulant effects of warfarin or its derivatives in the patient population. In addition, infectious disease and its accompanying inflammatory process, age, and general status of the patient are risk factors for increased anticoagulant activity. Therefore the prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if moxifloxacin hydrochloride is administered concomitantly with warfarin or its derivatives [see Adverse Reactions (6.2) and Clinical Pharmacology (12.3)]. 7.3 Antidiabetic Agents Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with fluoroquinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered. If a hypoglycemic reaction occurs, moxifloxacin hydrochloride should be discontinued and appropriate therapy should be initiated immediately. [See Warnings and Precautions (5.10) , Adverse Reactions (6.2) , and Patient Counseling Information (17) .] 7.4 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) The concomitant administration of a nonsteroidal anti-inflammatory drug (NSAID) with a fluoroquinolone, including moxifloxacin hydrochloride, may increase the risks of CNS stimulation and convulsions [see Warnings and Precautions (5.4)]. 7.5 Drugs that Prolong QT There is limited information available on the potential for a pharmacodynamic interaction in humans between moxifloxacin hydrochloride and other drugs that prolong the QTc interval of the electrocardiogram. Sotalol, a Class III antiarrhythmic, has been shown to further increase the QTc interval when combined with high doses of intravenous (IV) moxifloxacin in dogs. Therefore, moxifloxacin hydrochloride should be avoided with Class IA and Class III antiarrhythmics. [See Warnings and Precautions (5.3) , Nonclinical Toxicology (13.2) , and Patient Counseling Information (17) .]

6 ADVERSE REACTIONS Most common reactions (≥3%) were nausea, diarrhea, headache, and dizziness. (6.2) To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-361-3993 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 reactions are discussed in greater detail in the warnings and precautions section of the label: Tendinopathy and Tendon Rupture [see Warnings and Precautions (5.1) ] QT Prolongation [see Warnings and Precautions (5.3) ] Hypersensitivity Reactions [see Warnings and Precautions (5.4) ] Other Serious and Sometimes Fatal Reactions [see Warnings and Precautions (5.5) ] Central Nervous System Effects [see Warnings and Precautions (5.6) ] Clostridium difficile -Associated Diarrhea [see Warnings and Precautions (5.7) ] Peripheral Neuropathy that may be irreversible [see Warnings and Precautions (5.8) ] Blood Glucose Disturbances [see Warnings and Precautions (5.10) ] Photosensitivity/Phototoxicity [see Warnings and Precautions (5.11) ] Development of Drug Resistant Bacteria [see Warnings and Precautions (5.12) ] 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 moxifloxacin hydrochloride in 14981 patients in 71 active controlled Phase II to 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%), pyrexia (0.4%). Adverse reactions occurring in ≥1% of moxifloxacin hydrochloride-treated patients and less common adverse reactions, occurring in 0.1 to <1% of moxifloxacin hydrochloride-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 Hydrochloride System Organ Class Adverse Reactions a % (N=14,981) a) MedDRA Version 12.0 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 Disorders 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 Hydrochloride (N=14,981) System Organ Class Adverse Reactions a a) MedDRA Version 12.0 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 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 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, which are not listed above and which occurred in 2% or more of patients and at an incidence greater than in controls included: increases in mean corpuscular hemoglobin (MCH), neutrophils, white blood cells (WBCs), prothrombin time (PT) ratio, ionized calcium, chloride, albumin, globulin, bilirubin; decreases in hemoglobin, red blood cells (RBCs), neutrophils, eosinophils, basophils, glucose, oxygen partial pressure (pO2), 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. 6.3 Postmarketing Experience Table 4 lists adverse reactions that have been identified during post-approval use of moxifloxacin hydrochloride. Because these events 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 (5.5) ] Cardiac Disorders Ventricular tachyarrhythmias (including in very rare cases cardiac arrest and torsade 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 (5.5) ] Immune System Disorders Anaphylactic reaction Anaphylactic shock Angioedema (including laryngeal edema) [see Warnings and Precautions (5.4 , 5.5) ] Musculoskeletal and Connective Tissue Disorders Tendon rupture [see Warnings and Precautions (5.1) ] Nervous System Disorders Altered coordination Abnormal gait [see Warnings and Precautions (5.8) ] Myasthenia gravis (exacerbation of) [see Warnings and Precautions (5.2) ] Muscle weakness Peripheral neuropathy (that may be irreversible), polyneuropathy [see Warnings and Precautions (5.8) ] Psychiatric Disorders Psychotic reaction (very rarely culminating in self-injurious behavior, such as suicidal ideation/thoughts or suicide attempts [see Warnings and Precautions (5.6) ] Renal and Urinary Disorders Renal dysfunction Interstitial nephritis [see Warnings and Precautions (5.5) ] Respiratory, Thoracic and Mediastinal Disorders Allergic pneumonitis [see Warnings and Precautions (5.5) ] Skin and Subcutaneous Tissue Disorders Photosensitivity/phototoxicity reaction [see Warnings and Precautions (5.11) ] Stevens-Johnson syndrome Toxic epidermal necrolysis [see Warnings and Precautions (5.5) ] To report SUSPECTED ADVERSE REACTIONS contact AvKARE at 1-855-361-3993; email drugsafety@avkare.com ; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

8.1 Pregnancy Risk Summary There are no available human data establishing a drug associated risk with the use of moxifloxacin. Based on animal studies with moxifloxacin, moxifloxacin hydrochloride may cause fetal harm. Moxifloxacin did not cause fetal malformations when administered to pregnant rats (IV and oral), rabbits (IV), and monkeys (oral) at exposures that were 0.24 to 2.5 times of those at the human clinical dose (400 mg/day moxifloxacin hydrochloride). However, when moxifloxacin was administered to rats and rabbits during pregnancy and throughout lactation (rats only) at doses associated with maternal toxicity, decreased neonatal body weights, increased incidence of skeletal variations (rib and vertebra combined), and increased fetal loss were observed (see Data). Advise pregnant women of the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Animal reproductive and development studies were done in rats, rabbits and cynomolgus macaques. Moxifloxacin did not cause fetal malformations when administered to pregnant rats during organogenesis (gestation days 6 to 17) at oral doses as high as 500 mg/kg/day or 0.24 times the maximum recommended human dose based on systemic exposure (AUC), but decreased fetal body weights and slightly delayed fetal skeletal development were observed. Intravenous administration of 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) to pregnant rats resulted in maternal toxicity and a marginal effect on fetal and placental weights and the appearance of the placenta (Gestation days 6 to 17). Fetal malformations were not observed at intravenous doses as high as 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) in litters of pregnant rats that received moxifloxacin during organogenesis (Gestation days 6 to 17). Intravenous administration of 20 mg/kg/day (approximately equal to the maximum recommended human oral dose based upon systemic exposure) to pregnant rabbits during organogenesis (gestation days 6 to 20) resulted in decreased fetal body weights and delayed fetal skeletal ossification. When rib and vertebral malformations were combined, there was an increased fetal and litter incidence of these effects in rabbits. Signs of maternal toxicity in rabbits at this dose included mortality, abortions, marked reduction of food consumption, decreased water intake, body weight loss and hypoactivity. Fetal malformations were not observed when pregnant cynomolgus macaques were given oral doses as high as 100 mg/kg/day (2.5 times the maximum recommended human dose based upon systemic exposure) during organogenesis (gestation days 20 to 50). An increased incidence of smaller fetuses was observed at 100 mg/kg/day in macaques. In a pre- and postnatal development study conducted in rats given oral doses from Gestation day 6, throughout gestation and rearing to Postpartum day 21, effects observed at 500 mg/kg/day (0.24 times the maximum recommended human dose based on systemic exposure (AUC)) included slight increases in duration of pregnancy and prenatal loss, reduced pup birth weight and decreased neonatal survival. Treatment-related maternal mortality occurred during gestation at 500 mg/kg/day in this study.