Levofloxacin

Warnings and Precautions, Hypersensitivity Reactions ( 5.7 ) 06/2024 Warnings and Precautions, Risk of Aortic Aneurysm and Dissection ( 5.9 ) 09/2024

1 INDICATIONS AND USAGE Levofloxacin Injection is indicated for the treatment of adults (≥18 years of age) with mild, moderate, and severe infections caused by susceptible isolates of the designated microorganisms in the conditions listed in this section. Levofloxacin Injection is indicated when intravenous administration offers a route of administration advantageous to the patient (e.g., patient cannot tolerate an oral dosage form). Levofloxacin is a fluoroquinolone antibacterial indicated in adults (≥18 years of age) with infections caused by designated, susceptible bacteria ( 1 , 12.4 ). • Pneumonia: Nosocomial ( 1.1 ) and Community Acquired ( 1.2 , 1.3 ) • Skin and Skin Structure Infections: Complicated ( 1.4 ) and Uncomplicated ( 1.5 ) • Chronic bacterial prostatitis ( 1.6 ) • Inhalational Anthrax, Post-Exposure ( 1.7 ) • Plague ( 1.8 ) • Urinary Tract Infections: Complicated ( 1.9 , 1.10 ) and Uncomplicated ( 1.12 ) • Acute Pyelonephritis ( 1.11 ) • Acute Bacterial Exacerbation of Chronic Bronchitis ( 1.13 ) • Acute Bacterial Sinusitis ( 1.14 ) Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of levofloxacin and other antibacterial drugs, levofloxacin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria ( 1.15 ). 1.1 Nosocomial Pneumonia Levofloxacin is indicated for the treatment of nosocomial pneumonia due to methicillin-susceptible Staphylococcus aureus , Pseudomonas aeruginosa , Serratia marcescens , Escherichia coli , Klebsiella pneumoniae , Haemophilus influenzae , or Streptococcus pneumoniae . Adjunctive therapy should be used as clinically indicated. Where Pseudomonas aeruginosa is a documented or presumptive pathogen, combination therapy with an anti-pseudomonal β-lactam is recommended [see Clinical Studies (14.1) ] . 1.2 Community-Acquired Pneumonia: 7–14 day Treatment Regimen Levofloxacin is indicated for the treatment of community-acquired pneumonia due to methicillin-susceptible Staphylococcus aureus , Streptococcus pneumoniae (including multi- drug-resistant Streptococcus pneumoniae [MDRSP]), Haemophilus influenzae , Haemophilus parainfluenzae , Klebsiella pneumoniae , Moraxella catarrhalis , Chlamydophila pneumoniae , Legionella pneumophila , or Mycoplasma pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.2) ] . MDRSP isolates are isolates resistant to two or more of the following antibacterials: penicillin (MIC ≥2 mcg/mL), 2 nd generation cephalosporins, e.g., cefuroxime, macrolides, tetracyclines and trimethoprim/sulfamethoxazole. 1.3 Community-Acquired Pneumonia: 5-day Treatment Regimen Levofloxacin is indicated for the treatment of community-acquired pneumonia due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae , Haemophilus parainfluenzae , Mycoplasma pneumoniae , or Chlamydophila pneumoniae [see Dosage and Administration (2.1) and Clinical Studies (14.3) ] . 1.4 Complicated Skin and Skin Structure Infections Levofloxacin is indicated for the treatment of complicated skin and skin structure infections due to methicillin-susceptible Staphylococcus aureus , Enterococcus faecalis , Streptococcus pyogenes , or Proteus mirabilis [see Clinical Studies (14.5) ] . 1.5 Uncomplicated Skin and Skin Structure Infections Levofloxacin is indicated for the treatment of uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to methicillin-susceptible Staphylococcus aureus , or Streptococcus pyogenes . 1.6 Chronic Bacterial Prostatitis Levofloxacin is indicated for the treatment of chronic bacterial prostatitis due to Escherichia coli , Enterococcus faecalis , or methicillin-susceptible Staphylococcus epidermidis [see Clinical Studies (14.6) ] . 1.7 Inhalational Anthrax (Post-Exposure) Levofloxacin is indicated for inhalational anthrax (post-exp …

2 DOSAGE AND ADMINISTRATION • Dosage in patients with normal renal function ( 2.1 ) Type of Infection Dose Every 24 hours Duration (days) Nosocomial Pneumonia ( 1.1 ) 750 mg 7-14 Community Acquired Pneumonia ( 1.2 ) 500 mg 7-14 Community Acquired Pneumonia ( 1.3 ) 750 mg 5 Complicated Skin and Skin Structure Infections (SSSI) ( 1.4 ) 750 mg 7-14 Uncomplicated SSSI ( 1.5 ) 500 mg 7-10 Chronic Bacterial Prostatitis ( 1.6 ) 500 mg 28 Inhalational Anthrax (Post-Exposure) ( 1.7 ) Adults and Pediatric Patients > 50 kg 500 mg 60 Pediatric Patients 50 kg 500 mg 10 to 14 Pediatric Patients 50 kg ¶ , # Pediatric patients 50 kg Þ Pediatric patients 50 kg 500 mg 24 hr 60 days § Pediatric patients 50 kg 500 mg 24 hr 10 to 14 days Pediatric patients < 50 kg and ≥ 6 months of age 8 mg/kg (not to exceed 250 mg per dose) 12 hr 10 to 14 days * Due to Bacillus anthracis [see Indications and Usage (1.13) ] and Yersinia pestis [see Indications and Usage (1.14) ] . † Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. ‡ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis . This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9) ] § The safety of levofloxacin in pediatric patients for durations of therapy beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions ( 5.11 ), Use in Specific Populations (8.4) , and Clinical Studies (14.9) ] . Prolonged levofloxacin therapy should only be used when the benefit outweighs the risk. ¶ Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis . 2.3 Dosage Adjustment in Adults with Renal Impairment Administer levofloxacin with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced. No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min. In patients with impaired renal function (creatinine clearance < 50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance [see Use in Specific Populations (8.6) ]. Table 3 shows how to adjust dose based on creatinine clearance. Table 3: Dosage Adjustment in Adult Patients with Renal Impairment (creatinine clearance <50 mL/min) Dosage in Normal Renal Function Every 24 hours Creatinine Clearance 20 to 49 mL/min Creatinine Clearance 10 to 19 mL/min Hemodialysis or Chronic Ambulatory Peritoneal Dialysis (CAPD) 750 mg 750 mg every 48 hours 750 mg initial dose, then 500 mg every 48 hours 750 mg initial dose, then 500 mg every 48 hours 500 mg 500 mg initial dose, then 250 mg every 24 hours 500 mg initial dose, then 250 mg every 48 hours 500 mg initial dose, then 250 mg every 48 hours 250 mg No dosage adjustment required 250 mg every 48 hours. If treating uncomplicated UTI, then no dosage adjustment is required No information on dosing adjustment is available 2.4 Drug Interaction with Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins Levofloxacin Injection Levofloxacin Injection should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line [see Dosage and Administration (2.6) ] . 2.5 Administration Instructions Levofloxacin Injection Caution: Rapid or bolus intravenous infusion of levofloxacin has been associated with hypotension and must be avoided. Levofloxacin Injection should be infused intravenously slowly over a period of not less than 60 or 90 minutes, depending on the dosage. Levofloxacin Injection should be administered only by intraveno …

3 DOSAGE FORMS AND STRENGTHS Levofloxacin injection: Single-Use Vials of concentrated solution for dilution for intravenous infusion, clear yellow to clear greenish-yellow in appearance • 20 mL vial of 25 mg/mL levofloxacin solution, equivalent to 500 mg of levofloxacin. Levofloxacin Injection in 5% Dextrose (Premix) in Single-Use Flexible Containers for intravenous infusion: • 100 mL container, fill volume 50 mL (equivalent to 250 mg levofloxacin) • 100 mL container, fill volume 100 mL (equivalent to 500 mg levofloxacin) • 250 mL container, fill volume 150 mL (equivalent to 750 mg levofloxacin) Formulation ( 3 ) Strength Injection: single-use vials for dilution 500 mg in 20 mL Injection: premix single-use flexible containers 250 mg in 50 mL 500 mg in 100 mL 750 mg in 150 mL

4 CONTRAINDICATIONS Levofloxacin injection is contraindicated in persons with known hypersensitivity to levofloxacin, or other quinolone antibacterials [see Warnings and Precautions (5.3) ]. Known hypersensitivity to levofloxacin injection or other quinolones (4 , 5.7 )

6 ADVERSE REACTIONS The most common reactions (≥ 3%) were nausea, headache, diarrhea, insomnia, constipation and dizziness ( 6.2 ). To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-877-233-2001, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Serious and Otherwise Important Adverse Reactions The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling: Disabling and Potentially Irreversible Serious Adverse Reactions [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 ) ] Other Serious and Sometimes Fatal Reactions [see WARNINGS AND PRECAUTIONS ( 5.6 ) ] Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS ( 5.7 ) ] Risk of Aortic Aneurysm and Dissection [see WARNINGS AND PRECAUTIONS ( 5.8 ) ] Hepatotoxicity [see WARNINGS AND PRECAUTIONS ( 5.9 ) ] Clostridium difficile -Associated Diarrhea [see WARNINGS AND PRECAUTIONS ( 5.10 ) ] Prolongation of the QT Interval [see WARNINGS AND PRECAUTIONS ( 5.11 ) ] Musculoskeletal Disorders in Pediatric Patients [see WARNINGS AND PRECAUTIONS ( 5.12 ) ] 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 ) ] Hypotension has been associated with rapid or bolus intravenous infusion of levofloxacin. Levofloxacin should be infused slowly over 60 to 90 minutes, depending on dosage [see DOSAGE AND ADMINISTRATION ( 2.5 ) ]. Crystalluria and cylindruria have been reported with quinolones, including levofloxacin. Therefore, adequate hydration of patients receiving levofloxacin should be maintained to prevent the formation of a highly concentrated urine [see DOSAGE AND ADMINISTRATION ( 2.5 ) ]. 6.2 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to levofloxacin in 7537 patients in 29 pooled Phase 3 clinical trials. The population studied had a mean age of 50 years (approximately 74% of the population was < 65 years of age), 50% were male, 71% were Caucasian, 19% were Black. Patients were treated with levofloxacin for a wide variety of infectious diseases [see INDICATIONS AND USAGE ( 1 ) ]. Patients received levofloxacin doses of 750 mg once daily, 250 mg once daily, or 500 mg once or twice daily. Treatment duration was usually 3–14 days, and the mean number of days on therapy was 10 days. The overall incidence, type and distribution of adverse reactions was similar in patients receiving levofloxacin doses of 750 mg once daily, 250 mg once daily, and 500 mg once or twice daily. Discontinuation of levofloxacin due to adverse drug reactions occurred in 4.3% of patients overall, 3.8% of patients treated with the 250 mg and 500 mg doses and 5.4% of patients treated with the 750 mg dose. The most common adverse drug reactions leading to discontinuation with the 250 and 500 mg doses were gastrointestinal (1.4%), primarily nausea (0.6%); vomiting (0.4%); dizziness (0.3%); and headache (0.2%). The most common adverse drug reactions leading to discontinuation with the 750 mg dose were gastrointestinal (1.2%), primarily nausea (0.6%), vomiting (0.5%); dizziness (0.3%); and headache (0.3%). Adverse reactions occurring in ≥ 1% of levofloxacin-treated patients and less common adverse reactions, occurring in 0.1 to < 1% of levofloxacin-treated patients, are shown in Table 4 and Table 5 , respectively. Th …

7 DRUG INTERACTIONS Interacting Drug Interaction Multivalent cation - containing products including antacids, metal cations or didanosine Absorption of levofloxacin is decreased when the tablet or oral solution formulation is taken within 2 hours of these products. Do not co-administer the intravenous formulation in the same IV line with a multivalent cation, e.g., magnesium ( 2.4 , 7.1 ) Warfarin Effect may be enhanced. Monitor prothrombin time, INR, watch for bleeding ( 7.2 ) Antidiabetic agents Carefully monitor blood glucose ( 5.12 , 7.3 ) 7.1 Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins Levofloxacin Injection There are no data concerning an interaction of intravenous fluoroquinolones with oral antacids, sucralfate, multivitamins, didanosine, or metal cations. However, no fluoroquinolone should be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line [see DOSAGE AND ADMINISTRATION ( 2.5 ) ]. 7.2 Warfarin No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for R- and S- warfarin was detected in a clinical study involving healthy volunteers. Similarly, no apparent effect of warfarin on levofloxacin absorption and disposition was observed. However, there have been reports during the postmarketing experience in patients that levofloxacin enhances the effects of warfarin. Elevations of the prothrombin time in the setting of concurrent warfarin and levofloxacin use have been associated with episodes of bleeding. Prothrombin time, International Normalized Ratio (INR), or other suitable anticoagulation tests should be closely monitored if levofloxacin is administered concomitantly with warfarin. Patients should also be monitored for evidence of bleeding [see ADVERSE REACTIONS ( 6.3 ) ; PATIENT COUNSELING INFORMATION ( 17 ) ]. 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 [see WARNINGS AND PRECAUTIONS ( 5.13 ) ; ADVERSE REACTIONS ( 6.2 ) ; PATIENT COUNSELING INFORMATION ( 17 ) ]. 7.4 Non-Steroidal Anti-Inflammatory Drugs The concomitant administration of a non-steroidal anti-inflammatory drug with a fluoroquinolone, including levofloxacin, may increase the risk of CNS stimulation and convulsive seizures [see WARNINGS AND PRECAUTIONS ( 5.4 ) ]. 7.5 Theophylline No significant effect of levofloxacin on the plasma concentrations, AUC, and other disposition parameters for theophylline was detected in a clinical study involving healthy volunteers. Similarly, no apparent effect of theophylline on levofloxacin absorption and disposition was observed. However, concomitant administration of other fluoroquinolones with theophylline has resulted in prolonged elimination half-life, elevated serum theophylline levels, and a subsequent increase in the risk of theophylline-related adverse reactions in the patient population. Therefore, theophylline levels should be closely monitored and appropriate dosage adjustments made when levofloxacin is co‐administered. Adverse reactions, including seizures, may occur with or without an elevation in serum theophylline levels [see WARNINGS AND PRECAUTIONS ( 5.4 ) ]. 7.6 Cyclosporine No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for cyclosporine was detected in a clinical study involving healthy volunteers. However, elevated serum levels of cyclosporine have been reported in the patient population when co-administered with some other fluoroquinolones. Levofloxacin C max and k e were slightly lower while T max and t 1⁄2 were slightly longer in the presence of cyclosporine than those observed in other studies without concomitant medication. The differences …

8 USE IN SPECIFIC POPULATIONS • Geriatrics : Severe hepatotoxicity has been reported. The majority of reports describe patients 65 years of age or older ( 5.8 , 8.5, 17 ). May have increased risk of tendinopathy (including rupture), especially with concomitant corticosteroid use (5.2, 8.5, 17). May be more susceptible to prolongation of the QT interval. ( 5.11 , 8.5 , 17 ). • Pediatrics : Musculoskeletal disorders (arthralgia, arthritis, tendinopathy, and gait abnormality) seen in more Levofloxacin- treated patients than in comparator. Shown to cause arthropathy and osteochondrosis in juvenile animals ( 5.12 , 8.4, 13.2 ). Safety in pediatric patients treated for more than 14 days has not been studied. Risk-benefit appropriate only for the treatment of inhalational anthrax (post-exposure) ( 1.7 , 2.2 , 8.4 , 14.9 ) and plague ( 1.8, 2.2, 8.4 , 14.10 ) 8.1 Pregnancy Pregnancy Category C. Levofloxacin was not teratogenic in rats at oral doses as high as 810 mg/kg/day which corresponds to 9.4 times the highest recommended human dose based upon relative body surface area, or at intravenous doses as high as 160 mg/kg/day corresponding to 1.9 times the highest recommended human dose based upon relative body surface area. The oral dose of 810 mg/kg/day to rats caused decreased fetal body weight and increased fetal mortality. No teratogenicity was observed when rabbits were dosed orally as high as 50 mg/kg/day which corresponds to 1.1 times the highest recommended human dose based upon relative body surface area, or when dosed intravenously as high as 25 mg/kg/day, corresponding to 0.5 times the highest recommended human dose based upon relative body surface area. There are, however, no adequate and well-controlled studies in pregnant women. Levofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 8.3 Nursing Mothers Based on data on other fluoroquinolones and very limited data on Levofloxacin, it can be presumed that levofloxacin will be excreted in human milk. Because of the potential for serious adverse reactions from Levofloxacin in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use Quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species [see Warnings and Precautions (5.12) and Animal Toxicology and/or Pharmacology (13.2) ] . Pharmacokinetics following intravenous administration The pharmacokinetics of levofloxacin following a single intravenous dose were investigated in pediatric patients ranging in age from six months to 16 years. Pediatric patients cleared levofloxacin faster than adult patients resulting in lower plasma exposures than adults for a given mg/kg dose [see Clinical Pharmacology (12.3) and Clinical Studies (14.9) ] . Inhalational Anthrax (Post-Exposure) Levofloxacin is indicated in pediatric patients 6 months of age and older, for inhalational anthrax (post-exposure). The risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate. The safety of levofloxacin in pediatric patients treated for more than 14 days has not been studied [see Indications and Usage (1.7) , Dosage and Administration (2.2) and Clinical Studies (14.9) ] . Plague Levofloxacin is indicated in pediatric patients, 6 months of age and older, for treatment of plague, including pneumonic and septicemic plague due to Yersinia pestis (Y. pestis) and prophylaxis for plague. Efficacy studies of Levofloxacin could not be conducted in humans with pneumonic plague for ethical and feasibility reasons. Therefore, approval of this indication was based on an efficacy study conducted in animals. The risk-benefit assessment indicates that administration of levofloxacin to pediatric patients is appropriate [see Indications and Usage (1.8) , Dosage and Administration (2.2) a …

12.1 Mechanism of Action Levofloxacin is a member of the fluoroquinolone class of antibacterial agents [see Microbiology ( 12.4 ) ] .

11 DESCRIPTION Levofloxacin is a synthetic broad-spectrum antibacterial agent for oral and intravenous administration. Chemically, levofloxacin, a chiral fluorinated carboxyquinolone, is the pure (-)-(S)-enantiomer of the racemic drug substance ofloxacin. The chemical name is (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid hemihydrate. Figure 1: The Chemical Structure of Levofloxacin The empirical formula is C 18 H 20 FN 3 O 4 ∙ 1⁄2 H 2 O and the molecular weight is 370.38. Levofloxacin is a light yellowish-white to yellow-white crystal or crystalline powder. The molecule exists as a zwitterion at the pH conditions in the small intestine. The data demonstrate that from pH 0.6 to 5.8, the solubility of levofloxacin is essentially constant (approximately 100 mg/mL). Levofloxacin is considered soluble to freely soluble in this pH range, as defined by USP nomenclature. Above pH 5.8, the solubility increases rapidly to its maximum at pH 6.7 (272 mg/mL) and is considered freely soluble in this range. Above pH 6.7, the solubility decreases and reaches a minimum value (about 50 mg/mL) at a pH of approximately 6.9. Levofloxacin has the potential to form stable coordination compounds with many metal ions. This in vitro chelation potential has the following formation order: Al +3 >Cu +2 >Zn +2 >Mg +2 >Ca +2 . Excipients and Description of Dosage Forms The appearance of Levofloxacin Injection may range from a clear yellow to a clear greenish-yellow solution. This does not adversely affect product potency. Levofloxacin Injection in Single-Use Vials is a sterile, preservative-free aqueous solution of levofloxacin in Water for Injection, with pH ranging from 3.8 to 5.8. Levofloxacin Injection in 5% Dextrose (Premix) in Single-Use Flexible Containers is a sterile, preservative-free aqueous solution of levofloxacin with pH ranging from 3.8 to 5.8. This is a dilute, non-pyrogenic, nearly isotonic premixed solution that contains levofloxacin in 5% Dextrose (D W). Solutions of hydrochloric acid and sodium hydroxide may have been added to adjust the pH. The flexible container is fabricated from specially formulated non-plasticized, thermoplastic copolyester (CR3). The amount of water that can permeate from the container into the overwrap is insufficient to affect the solution significantly. Solutions in contact with the flexible container can leach out certain of the container’s chemical components in very small amounts within the expiration period. The suitability of the container material has been confirmed by tests in animals according to USP biological tests for plastic containers. Figure 1

10 OVERDOSAGE In the event of an acute overdosage, the stomach should be emptied. The patient should be observed and appropriate hydration maintained. Levofloxacin is not efficiently removed by hemodialysis or peritoneal dialysis. Levofloxacin exhibits a low potential for acute toxicity. Mice, rats, dogs and monkeys exhibited the following clinical signs after receiving a single high dose of levofloxacin: ataxia, ptosis, decreased locomotor activity, dyspnea, prostration, tremors, and convulsions. Doses in excess of 1,500 mg/kg orally and 250 mg/kg IV produced significant mortality in rodents.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 Levofloxacin Injection, Single-Use Vials Levofloxacin Injection is supplied in single-use vials. Each vial contains a concentrated solution with the equivalent of 500 mg of levofloxacin in 20 mL vials. AIN00228 25 mg/mL, 20 mL vials (NDC 36000-045-01) Levofloxacin Injection in Single-Use Vials should be stored at controlled room temperature and protected from light. Levofloxacin Injection in Single-Use Vials is manufactured for Baxter Healthcare Corporation, Deerfield, IL 60015 USA by Baxter Pharmaceuticals India Private Ltd, Ahmedabad 382213, India. 16.2 Levofloxacin Injection in 5% Dextrose (Premix), Single-Use in Flexible Container Levofloxacin Injection in 5% Dextrose (Premix) is supplied as a single-use, premixed solution in flexible containers. Each bag contains a dilute solution with the equivalent of 250, 500, or 750 mg of levofloxacin, respectively, in 5% Dextrose (D5W). AIN00233 5 mg/mL (250 mg), 50 mL filled in 100 mL flexible container (NDC 36000-046-24) AIN00232 5 mg/mL (500 mg), 100 mL filled in 100 mL flexible container, (NDC 36000-047-24) AIN00231 5 mg/mL (750 mg), 150 mL filled in 250 mL flexible container, (NDC 36000-048-24) Levofloxacin Injection in 5% Dextrose (Premix) in Flexible Containers should be stored at 20° - 25°C (68° - 77°F) [See USP Controlled Room Temperature] . Avoid excessive heat and protect from freezing and light. Levofloxacin Injection in 5% Dextrose (Premix) is manufactured for Baxter Healthcare Corporation, Deerfield, IL 60015 USA by Baxter Pharmaceuticals India Private Ltd, Ahmedabad 382213, India. Keep out of reach of children.