250 ML moxifloxacin 1.6 MG/ML Injection [Avelox]

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 ) 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 5.13) ] 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 5.13) ] 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. Culture and Susceptibility Testing Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing infection and to determine their susceptibility to moxifloxacin [see Clinical Pharmacology (12.4) ] . Therapy with moxifloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued. 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) ].

DOSAGE AND ADMINISTRATION Type of Infection Dose Every 24 hours Duration (days) Community Acquired Pneumonia ( 1.1 ) 400 mg 7 to 14 Uncomplicated Skin and Skin Structure Infections (SSSI) ( 1.2 ) 400 mg 7 Complicated SSSI ( 1.3 ) 400 mg 7 to 21 Complicated Intra-Abdominal Infections ( 1.4 ) 400 mg 5 to 14 Acute Bacterial Sinusitis ( 1.5 ) 400 mg 10 Acute Bacterial Exacerbation of Chronic Bronchitis ( 1.6 ) 400 mg 5 No dosage adjustment in patients with renal or hepatic impairment. ( 8.6 , 8.7 ) Moxifloxacin Injection: Slow Intravenous infusion over 60 minutes. Avoid rapid or bolus Intravenous infusion. ( 2.2 ) Do not mix with other medications in intravenous bag or in intravenous line. ( 2.2 ) 2.1 Dosage in Adult Patients The dose of Moxifloxacin Injection is 400 mg intravenously 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 a Due to the designated pathogens [see Indications and Usage ( 1 ), for IV use , see Use in Specific Populations ( 8.5 )] . b Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. Type of Infection a Dose Every 24 hours Duration b (days) Community Acquired Pneumonia ( 1.1 ) 400 mg 7 to 14 Uncomplicated Skin and Skin Structure Infections (SSSI) ( 1.2 ) 400 mg 7 Complicated SSSI ( 1.3 ) 400 mg 7 to 21 Complicated Intra-Abdominal Infections ( 1.4 ) 400 mg 5 to 14 Acute Bacterial Sinusitis ( 1.5 ) 400 mg 10 Acute Bacterial Exacerbation of Chronic Bronchitis ( 1.6 ) 400 mg 5 When switching from intravenous to oral formulation, no dosage adjustment is necessary [see Clinical Pharmacology ( 12.4 )] . Patients whose therapy is started with Moxifloxacin Injection may be switched to moxifloxacin tablets when clinically indicated at the discretion of the physician. 2.2 Administration Instructions Moxifloxacin Injection Solution for Infusion Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Moxifloxacin Injection should be administered by intravenous infusion only. It is not intended for intra-arterial, intramuscular, intrathecal, intraperitoneal, or subcutaneous administration. Moxifloxacin Injection should be administered by intravenous infusion over a period of 60 minutes by direct infusion or through a Y-type intravenous infusion set which may already be in place. Caution: rapid or bolus intravenous infusion must be avoided. Because only limited data are available on the compatibility of moxifloxacin intravenous injection with other intravenous substances, additives or other medications should not be added to Moxifloxacin Injection or infused simultaneously through the same intravenous line. If the same intravenous line or a Y-type line is used for sequential infusion of other drugs, or if the “piggyback” method of administration is used, the line should be flushed before and after infusion of Moxifloxacin Injection with an infusion solution compatible with moxifloxacin injection as well as with other drug(s) administered via this common line. Moxifloxacin Injection is compatible with the following intravenous solutions at ratios from 1:10 to 10:1 0.9% Sodium Chloride Injection, USP Sterile Water for Injection, USP 1 molar Sodium Chloride Injection 10% Dextrose for Injection, USP 5% Dextrose Injection, USP Lactated Ringer's for Injection 2.3 Preparation for Administration of Moxifloxacin Injection To prepare Moxifloxacin Injection premix in flexible bags: Close flow control clamp of administration set. Remove cover from port at bottom of container. Insert piercing pin from an appropriate transfer set (for example, one that does not require excessive force, such as ISO compatible administration set) into port with a gentle twisting motion until pin is firmly seated. NOTE: Refer to complete directions that have been provided with the administration set. Because the premix flexible bags are for single-dose only, any unused portion should be discarded.

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-associat

CONTRAINDICATIONS Moxifloxacin ophthalmic solution is contraindicated in patients with a history of hypersensitivity to moxifloxacin, to other quinolones, or to any of the components in this medication. . Moxifloxacin ophthalmic solution is contraindicated in patients with a history of hypersensitivity to moxifloxacin, to other quinolones, or to any of the components in this medication. ( 4 )

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Moxifloxacin is a member of the fluoroquinolone class of anti-infective drugs [see Microbiology ( 12.4 )]. 12.3 Pharmacokinetics Plasma concentrations of moxifloxacin were measured in healthy adult male and female subjects who received bilateral topical ocular doses of moxifloxacin ophthalmic solution 3 times a day. The mean steady-state C max (2.7 ng/mL) and AUC 0-∞ (41.9 ng●hr/mL) values were 1600 and 1100 times lower than the mean C max and AUC reported after therapeutic 400 mg doses of moxifloxacin. The plasma half-life of moxifloxacin was estimated to be 13 hours. 12.4 Microbiology The antibacterial action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division. The mechanism of action for quinolones, including moxifloxacin, is different from that of macrolides, aminoglycosides, or tetracyclines. Therefore, moxifloxacin may be active against pathogens that are resistant to these antibiotics and these antibiotics may be active against pathogens that are resistant to moxifloxacin. There is no cross-resistance between moxifloxacin and the aforementioned classes of antibiotics. Cross-resistance has been observed between systemic moxifloxacin and some other quinolones. In vitro resistance to moxifloxacin develops via multiple-step mutations. Resistance to moxifloxacin occurs in vitro at a general frequency of between 1.8 x 10 -9 to less than 1 x 10 -11 for gram-positive bacteria. Moxifloxacin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the Indications and Usage section: Aerobic Gram-Positive Microorganisms Corynebacterium species* Micrococcus luteus* Staphylococcus aureus Staphylococcus epidermidis Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus warneri* Streptococcus pneumoniae Streptococcus viridans group Aerobic Gram-Negative Microorganisms Acinetobacter lwoffii* Haemophilus influenza Haemophilus parainfluenzae* Other Microorganisms Chlamydia trachomatis *Efficacy for this organism was studied in fewer than 10 infections. The following in vitro data are also available, but their clinical significance in ophthalmic infections is unknown . The safety and effectiveness of moxifloxacin ophthalmic solution in treating ophthalmological infections due to these microorganisms have not been established in adequate and well-controlled trials. The following organisms are considered susceptible when evaluated using systemic breakpoints. However, a correlation between the in vitro systemic breakpoint and ophthalmological efficacy has not been established. The list of organisms is provided as guidance only in assessing the potential treatment of conjunctival infections. Moxifloxacin exhibits in vitro minimal inhibitory concentrations (MICs) of 2 microgram/mL or less (systemic susceptible breakpoint) against most (greater than or equal to 90%) strains of the following ocular pathogens. Aerobic Gram-Positive Microorganisms Listeria monocytogenes Staphylococcus saprophyticus Streptococcus agalactiae Streptococcus mitis Streptococcus pyogenes Streptococcus Group C, G, and F Aerobic Gram-Negative Microorganisms Acinetobacter baumannii Acinetobacter calcoaceticus Citrobacter freundii Citrobacter koseri Enterobacter aerogenes Enterobacter cloacae Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Moraxella catarrhalis Morganella morganii Neisseria gonorrhoeae Proteus mirabilis Proteus vulgaris Pseudomonas stutzeri Anaerobic Microorganisms Clostridium perfringens Fusobacterium species Prevotella species Propionibacterium acnes Other Microorganisms Chlamydia pneumoniae Legionella pneumophila Mycobacterium avium Mycobacterium marinum Mycoplasma pneumoniae