Cipro Zithromax Antibiotics

Levaquin Injection, Levaquin Tablets, Levaquin in 5% Dextrose Injection(Ortho-McNeil)

DESCRIPTION
LEVAQUIN® (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.
The chemical structure is:

Aerobic gram-negative microorganisms
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Haemophilus parainfluenzae
Klebsiella pneumoniae
Legionella pneumophila
Moraxella catarrhalis
Proteus mirabilis
Pseudomonas aeruginosa
Serratia marcescens
As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin.
Other microorganisms
Chlamydia pneumoniae
Mycoplasma pneumoniae
The following in vitro data are available, but their clinical significance is unknown .
Levofloxacin exhibits in vitro minimum inhibitory concentrations (MIC values) of 2 µg/mL or less against most (>/=90%) strains of the following microorganisms; however, the safety and effectiveness of levofloxacin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled trials.
Aerobic gram-positive microorganisms
Staphylococcus epidermidis (methicillin-susceptible strains)
Streptococcus (Group C/F)
Streptococcus (Group G)
Streptococcus agalactiae
Streptococcus milleri
Viridans group streptococci
Aerobic gram-negative microorganisms
Acinetobacter baumannii
Acinetobacter lwoffii
Bordetella pertussis
Citrobacter (diversus) koseri
Citrobacter freundii
Enterobacter aerogenes
Enterobacter sakazakii
Klebsiella oxytoca
Morganella morganii
Pantoea (Enterobacter) agglomerans
Proteus vulgaris
Providencia rettgeri
Providencia stuartii
Pseudomonas fluorescens
Anaerobic gram-positive microorganisms
Clostridium perfringens
Susceptibility Tests
Susceptibility testing for levofloxacin should be performed, as it is the optimal predictor of activity.
Dilution techniques: Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MIC values). These MIC values provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC values should be determined using a standardized procedure. Standardized procedures are based on a dilution method 1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of levofloxacin powder. The MIC values should be interpreted according to the following criteria:
For testing Enterobacteriaceae , Enterococci, Staphylococcus species, and Pseudomonas aeruginosa:
MIC (µg/mL) Interpretation
< /=2 Susceptible (S)
4 Intermediate (I)
> /=8 Resistant (R)

For testing Haemophilus influenzae and Haemophilus parainfluenzae: a
MIC (µg/mL) Interpretation
< /=2 Susceptible (S)
a These interpretive standards are applicable only to broth microdilution susceptibility testing with Haemophilus influenzae and Haemophilus parainfluenzae using Haemophilus Test Medium. 1

INDICATIONS AND USAGE
LEVAQUIN Tablets/Injection are indicated for the treatment of adults (>/=18 years of age) with mild, moderate, and severe infections caused by susceptible strains of the designated microorganisms in the conditions listed below. LEVAQUIN Injection is indicated when intravenous administration offers a route of administration advantageous to the patient (e.g., patient cannot tolerate an oral dosage form). Please see DOSAGE AND ADMINISTRATION for specific recommendations.
Acute maxillary sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.
Acute bacterial exacerbation of chronic bronchitis due to Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, or Moraxella catarrhalis.
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 (beta)-lactam is recommended. (See CLINICAL STUDIES .)
Community-acquired pneumonia due to Staphylococcus aureus, Streptococcus pneumoniae (including penicillin-resistant strains, MIC value for penicillin >/=2 µg/mL), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae . (See CLINICAL STUDIES .)
Complicated skin and skin structure infections due to methicillin-susceptible Staphylococcus aureus, Enterococcus faecalis, Streptococcus pyogenes, or Proteus mirabilis.
Uncomplicated skin and skin structure infections (mild to moderate) including abscesses, cellulitis, furuncles, impetigo, pyoderma, wound infections, due to Staphylococcus aureus or Streptococcus pyogenes.
Complicated urinary tract infections (mild to moderate) due to Enterococcus faecalis, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Pseudomonas aeruginosa.
Acute pyelonephritis (mild to moderate) caused by Escherichia coli.
Uncomplicated urinary tract infections (mild to moderate) due to Escherichia coli, Klebsiella pneumoniae, or Staphylococcus saprophyticus.
Appropriate culture and susceptibility tests should be performed before treatment in order to isolate and identify organisms causing the infection and to determine their susceptibility to levofloxacin. Therapy with levofloxacin may be initiated before results of these tests are known; once results become available, appropriate therapy should be selected.
As with other drugs in this class, some strains of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin. Culture and susceptibility testing performed periodically during therapy will provide information about the continued susceptibility of the pathogens to the antimicrobial agent and also the possible emergence of bacterial resistance.
CONTRAINDICATIONS
Levofloxacin is contraindicated in persons with a history of hypersensitivity to levofloxacin, quinolone antimicrobial agents, or any other components of this product.
WARNINGS
THE SAFETY AND EFFICACY OF LEVOFLOXACIN IN PEDIATRIC PATIENTS, ADOLESCENTS (UNDER THE AGE OF 18 YEARS), PREGNANT WOMEN, AND NURSING WOMEN HAVE NOT BEEN ESTABLISHED . (See PRECAUTIONS : Pediatric Use , Pregnancy , and Nursing Mothers subsections.)
In immature rats and dogs, the oral and intravenous administration of levofloxacin increased the incidence and severity of osteochondrosis. Other fluoroquinolones also produce similar erosions in the weight bearing joints and other signs of arthropathy in immature animals of various species. (See ANIMAL PHARMACOLOGY .)
Convulsions and toxic psychoses have been reported in patients receiving quinolones, including levofloxacin. Quinolones may also cause increased intracranial pressure and central nervous system stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, nightmares, insomnia, and, rarely, suicidal thoughts or acts. These reactions may occur following the first dose. If these reactions occur in patients receiving levofloxacin, the drug should be discontinued and appropriate measures instituted. As with other quinolones, levofloxacin should be used with caution in patients with a known or suspected CNS disorder that may predispose to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction.) (See PRECAUTIONS : General , Information for Patients , Drug Interactions and ADVERSE REACTIONS .)
Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving therapy with quinolones, including levofloxacin. These reactions often occur following the first dose. Some reactions have been accompanied by cardiovascular collapse, hypotension/shock, seizure, loss of consciousness, tingling, angioedema (including tongue, laryngeal, throat, or facial edema/swelling), airway obstruction (including bronchospasm, shortness of breath, and acute respiratory distress), dyspnea, urticaria, itching, and other serious skin reactions. Levofloxacin should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity. Serious acute hypersensitivity reactions may require treatment with epinephrine and other resuscitative measures, including oxygen, intravenous fluids, antihistamines, corticosteroids, pressor amines, and airway management, as clinically indicated. (See PRECAUTIONS and ADVERSE REACTIONS .)
Serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain etiology, have been reported rarely in patients receiving therapy with quinolones, including levofloxacin. These events may be severe and generally occur following the administration of multiple doses. Clinical manifestations may include one or more of the following: fever, rash or severe dermatologic reactions (e.g., 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. The drug should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity and supportive measures instituted. (See PRECAUTIONS : Information for Patients and ADVERSE REACTIONS .)
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including levofloxacin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of any antibacterial agent.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of "antibiotic-associated colitis."
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile colitis. (See ADVERSE REACTIONS .)
Ruptures of the shoulder, hand, or Achilles tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones, including levofloxacin. Post-marketing surveillance reports indicate that this risk may be increased in patients receiving concomitant corticosteroids, especially in the elderly. Levofloxacin should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should rest and refrain from exercise until the diagnosis of tendinitis or tendon rupture has been confidently excluded. Tendon rupture can occur during or after therapy with quinolones, including levofloxacin.
PRECAUTIONS
General
Because a rapid or bolus intravenous injection may result in hypotension, LEVOFLOXACIN INJECTION SHOULD ONLY BE ADMINISTERED BY SLOW INTRAVENOUS INFUSION OVER A PERIOD OF 60 OR 90 MINUTES DEPENDING ON THE DOSAGE. (See DOSAGE AND ADMINISTRATION .)
Although levofloxacin is more soluble than other quinolones, adequate hydration of patients receiving levofloxacin should be maintained to prevent the formation of a highly concentrated urine.
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. 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 CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION .)
Moderate to severe phototoxicity reactions have been observed in patients exposed to direct sunlight while receiving drugs in this class. Excessive exposure to sunlight should be avoided. However, in clinical trials with levofloxacin, phototoxicity has been observed in less than 0.1% of patients. Therapy should be discontinued if phototoxicity (e.g., a skin eruption) occurs.
As with other quinolones, levofloxacin should be used with caution in any patient with a known or suspected CNS disorder that may predispose to seizures or lower the seizure threshold (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold (e.g., certain drug therapy, renal dysfunction). (See WARNINGS and Drug Interactions .)
As with other quinolones, disturbances of blood glucose, including symptomatic hyper- and hypoglycemia, have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycemic agent (e.g., glyburide/glibenclamide) or with insulin. In these patients, careful monitoring of blood glucose is recommended. If a hypoglycemic reaction occurs in a patient being treated with levofloxacin, levofloxacin should be discontinued immediately and appropriate therapy should be initiated immediately. (See Drug Interactions and ADVERSE REACTIONS .)
Some quinolones, including levofloxacin, have been associated with prolongation of the QT interval on the electrocardiogram and infrequent cases of arrhythmia. During post-marketing surveillance, rare cases of torsades de pointes have been reported in patients taking levofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. The risk of arrhythmias may be reduced by avoiding concurrent use with other drugs that prolong the QT interval including class Ia or class III antiarrhythmic agents; in addition, use of levofloxacin in the presence of risk factors for torsades de pointes such as hypokalemia, significant bradycardia, and cardiomyopathy should be avoided.
As with any potent antimicrobial drug, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, is advisable during therapy. (See WARNINGS and ADVERSE REACTIONS .)
Information for Patients
Patients should be advised:
to drink fluids liberally;
that antacids containing magnesium, or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or Videx® (didanosine), chewable/buffered tablets or the pediatric powder for oral solution should be taken at least two hours before or two hours after oral levofloxacin administration. (See Drug Interactions );
that oral levofloxacin can be taken without regard to meals;
that levofloxacin may cause neurologic adverse effects (e.g., dizziness, lightheadedness) and that patients should know how they react to levofloxacin before they operate an automobile or machinery or engage in other activities requiring mental alertness and coordination. (See WARNINGS and ADVERSE REACTIONS );
to discontinue treatment and inform their physician if they experience pain, inflammation, or rupture of a tendon, and to rest and refrain from exercise until the diagnosis of tendinitis or tendon rupture has been confidently excluded;
that levofloxacin may be associated with hypersensitivity reactions, even following the first dose, and to discontinue the drug at the first sign of a skin rash, hives or other skin reactions, a rapid heartbeat, difficulty in swallowing or breathing, any swelling suggesting angioedema (e.g., swelling of the lips, tongue, face, tightness of the throat, hoarseness), or other symptoms of an allergic reaction. (See WARNINGS and ADVERSE REACTIONS );
to avoid excessive sunlight or artificial ultraviolet light while receiving levofloxacin and to discontinue therapy if phototoxicity (i.e., skin eruption) occurs;
that if they are diabetic and are being treated with insulin or an oral hypoglycemic agent and a hypoglycemic reaction occurs, they should discontinue levofloxacin and consult a physician. (See PRECAUTIONS : General and Drug Interactions .);
that concurrent administration of warfarin and levofloxacin has been associated with increases of the International Normalized Ratio (INR) or prothrombin time and clinical episodes of bleeding. Patients should notify their physician if they are taking warfarin.
that convulsions have been reported in patients taking quinolones, including levofloxacin, and to notify their physician before taking this drug if there is a history of this condition.
Drug Interactions
Antacids, Sucralfate, Metal Cations, Multivitamins
LEVAQUIN Tablets: While the chelation by divalent cations is less marked than with other quinolones, concurrent administration of LEVAQUIN Tablets with antacids containing magnesium, or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc may interfere with the gastrointestinal absorption of levofloxacin, resulting in systemic levels considerably lower than desired. Tablets with antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamins preparations with zinc or Videx® (didanosine), chewable/buffered tablets or the pediatric powder for oral solution may substantially interfere with the gastrointestinal absorption of levofloxacin, resulting in systemic levels considerably lower than desired. These agents should be taken at least two hours before or two hours after levofloxacin administration.
LEVAQUIN Injection: There are no data concerning an interaction of intravenous quinolones with oral antacids, sucralfate, multivitamins, Videx® (didanosine), or metal cations. However, no quinolone should be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line. (See DOSAGE AND ADMINISTRATION .)
Theophylline: No significant effect of levofloxacin on the plasma concentrations, AUC, and other disposition parameters for theophylline was detected in a clinical study involving 14 healthy volunteers. Similarly, no apparent effect of theophylline on levofloxacin absorption and disposition was observed. However, concomitant administration of other quinolones 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 : General .)
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. There have been reports during the post-marketing 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.
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 quinolones. 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, however, are not considered to be clinically significant. Therefore, no dosage adjustment is required for levofloxacin or cyclosporine when administered concomitantly.
Digoxin: No significant effect of levofloxacin on the peak plasma concentrations, AUC, and other disposition parameters for digoxin was detected in a clinical study involving healthy volunteers. Levofloxacin absorption and disposition kinetics were similar in the presence or absence of digoxin. Therefore, no dosage adjustment for levofloxacin or digoxin is required when administered concomitantly.
Probenecid and Cimetidine: No significant effect of probenecid or cimetidine on the rate and extent of levofloxacin absorption was observed in a clinical study involving healthy volunteers. The AUC and t 1/2 of levofloxacin were 27-38% and 30% higher, respectively, while CL/F and CL R were 21-35% lower during concomitant treatment with probenecid or cimetidine compared to levofloxacin alone. Although these differences were statistically significant, the changes were not high enough to warrant dosage adjustment for levofloxacin when probenecid or cimetidine is co-administered.
Non-steroidal anti-inflammatory drugs: The concomitant administration of a non-steroidal anti-inflammatory drug with a quinolone, including levofloxacin, may increase the risk of CNS stimulation and convulsive seizures. (See WARNINGS and PRECAUTIONS : General .)
Antidiabetic agents: Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when these agents are co-administered.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a lifetime bioassay in rats, levofloxacin exhibited no carcinogenic potential following daily dietary administration for 2 years; the highest dose (100 mg/kg/day) was 1.4 times the highest recommended human dose (750 mg) based upon relative body surface area. Levofloxacin did not shorten the time to tumor development of UV-induced skin tumors in hairless albino (Skh-1) mice at any levofloxacin dose level and was therefore not photo-carcinogenic under conditions of this study. Dermal levofloxacin concentrations in the hairless mice ranged from 25 to 42 µg/g at the highest levofloxacin dose level (300 mg/kg/day) used in the photo-carcinogenicity study. By comparison, dermal levofloxacin concentrations in human subjects receiving 750 mg of levofloxacin averaged approximately 11.8 µg/g at Cmax.
Levofloxacin was not mutagenic in the following assays; Ames bacterial mutation assay ( S. typhimurium and E. coli ), CHO/HGPRT forward mutation assay, mouse micronucleus test, mouse dominant lethal test, rat unscheduled DNA synthesis assay, and the mouse sister chromatid exchange assay. It was positive in the in vitro chromosomal aberration (CHL cell line) and sister chromatid exchange (CHL/IU cell line) assays.
Levofloxacin caused no impairment of fertility or reproductive performance in rats at oral doses as high as 360 mg/kg/day, corresponding to 4.2 times the highest recommended human dose based upon relative body surface area and intravenous doses as high as 100 mg/kg/day, corresponding to 1.2 times the highest recommended human dose based upon relative body surface area.
Pregnancy: Teratogenic Effects. 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. (See WARNINGS .)
Nursing Mothers
Levofloxacin has not been measured in human milk. Based upon data from ofloxacin, 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.
Pediatric Use
Safety and effectiveness in pediatric patients and adolescents below the age of 18 years have not been established. Quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species. (See WARNINGS .)
Geriatric Use
In phase 3 clinical trials, 1,190 levofloxacin-treated patients (25%) were >/=65 years of age. Of these, 675 patients (14%) were between the ages of 65 and 74 and 515 patients (11%) were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
The pharmacokinetic properties of levofloxacin in younger adults and elderly adults do not differ significantly when creatinine clearance is taken into consideration. However since the drug is known to be substantially excreted by the kidney, the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
ADVERSE REACTIONS
The incidence of drug-related adverse reactions in patients during Phase 3 clinical trials conducted in North America was 6.2%. Among patients receiving levofloxacin therapy, 4.1% discontinued levofloxacin therapy due to adverse experiences. The overall incidence, type and distribution of adverse events was similar in patients receiving levofloxacin doses of 750 mg once daily compared to patients receiving doses from 250 mg once daily to 500 mg twice daily.
In clinical trials, the following events were considered likely to be drug-related in patients receiving levofloxacin:
nausea 1.3%, diarrhea 1.0%, vaginitis 0.7%, insomnia 0.4%, abdominal pain 0.4%, flatulence 0.3%, pruritus 0.3%, dizziness 0.3%, dyspepsia 0.3%, rash 0.3%, genital moniliasis 0.2%, taste perversion 0.2%, vomiting 0.2%, constipation 0.1%, fungal infection 0.1%, genital pruritis 0.1%, headache 0.1%, moniliasis 0.1%, nervousness 0.1%, rash erythematous 0.1%, urticaria 0.1%.
In clinical trials, the following events occurred in >3% of patients, regardless of drug relationship:
nausea 7.0%, headache 6.1%, diarrhea 5.7%, insomnia 4.5%, injection site reaction 3.5%, constipation 3.3%.
In clinical trials, the following events occurred in 1 to 3% of patients, regardless of drug relationship:
dizziness 2.6%, abdominal pain 2.5%, dyspepsia 2.3%, vomiting 2.4%, vaginitis 1.8%, injection site pain 1.7%, flatulence 1.4%, pain 1.4%, pruritus 1.3%, sinusitis 1.3%, chest pain 1.2%, fatigue 1.3%, rash 1.4%, back pain 1.1%, injection site inflammation 1.1%, rhinitis 1.0%, taste perversion 1.0%.
In clinical trials, the following events, of potential medical importance, occurred at a rate of 0.1% to 1.0%, regardless of drug relationship:
Autonomic Nervous System Disorders: Postural hypotension
Body as a Whole - General Disorders: Asthenia, fever, malaise, rigors, substernal chest pain, syncope, enlarged abdomen, allergic reaction, headache, hot flashes, edema, influenza-like symptoms, leg pain, multiple organ failure
Cardiovascular Disorders, General: Cardiac failure, circulatory failure, hypertension, hypotension, postural hypotension
Central and Peripheral Nervous System Disorders: Abnormal coordination, coma, convulsions (seizures), hyperkinesia, hypertonia, hypoesthesia, involuntary muscle contractions, paresthesia, paralysis, speech disorder, stupor, tremor, vertigo, encephalopathy abnormal gait, leg cramps, intracranial hypertension
Gastro-Intestinal System Disorders: Dry mouth, dysphagia, gastroenteritis, G.I. hemorrhage, pancreatitis, pseudomembranous colitis, tongue edema, gastritis, gastroesophageal reflux, melena, esophagitis, stomatitis
Hearing and Vestibular Disorders: Earache, tinnitus
Heart Rate and Rhythm Disorders: Arrhythmia, atrial fibrillation, bradycardia, cardiac arrest, palpitation, supraventricular tachycardia, ventricular tachycardia, tachycardia
Liver and Biliary System Disorders: Elevated bilirubin, abnormal hepatic function, cholelithiasis, jaundice, hepatic failure
Metabolic and Nutritional Disorders: Hypomagnesemia, thirst, aggravated diabetes mellitus, dehydration, hyperglycemia, hyperkalemia, hypoglycemia, hypokalemia
Musculo-Skeletal System Disorders: Arthralgia, arthritis, arthrosis, pathological fracture, myalgia, osteomyelitis, synovitis, tendinitis
Myo, Endo, Pericardial and Valve Disorders: Angina pectoris, myocardial infarction
Neoplasms: Carcinoma
Other Special Senses Disorders: Parosmia, taste perversion
Platelet, Bleeding and Clotting Disorders: Pulmonary embolism, hematoma, epistaxis, purpura, thrombocytopenia
Psychiatric Disorders: Abnormal dreaming, agitation, anorexia, anxiety, confusion, depression, hallucination, nervousness, paranoia, sleep disorder, somnolence
Red Blood Cell Disorders: Anemia
Reproductive Disorders: Dysmenorrhea, leukorrhea
Resistance Mechanism Disorders: Abscess, herpes simplex, bacterial infection, viral infection, moniliasis, otitis media, sepsis, fungal infection
Respiratory System Disorders: Bronchitis, epistaxis, pharyngitis, rhinitis, upper respiratory tract infection, asthma, coughing, dyspnea, hemoptysis, hypoxia, pleural effusion, respiratory insufficiency
Skin and Appendages Disorders: Rash, dry skin, genital pruritus, increased sweating, skin disorder, skin exfoliation, skin ulceration, urticaria
Urinary System Disorders: Urinary tract infection, abnormal renal function, acute renal failure, hematuria
Vascular (Extracardiac) Disorders: Cerebrovascular disorder, phlebitis, purpura, thrombophlebitis (deep)
Vision Disorders: Abnormal vision, conjunctivitis
White Cell and RES Disorders: Granulocytopenia, leukocytosis, lymphadenopathy, WBC abnormal
(not otherwise specified)

In clinical trials using multiple-dose therapy, ophthalmologic abnormalities, including cataracts and multiple punctate lenticular opacities, have been noted in patients undergoing treatment with other quinolones. The relationship of the drugs to these events is not presently established.
Crystalluria and cylindruria have been reported with other quinolones.
The following markedly abnormal laboratory values appeared in >2% of patients receiving levofloxacin. It is not known whether these abnormalities were caused by the drug or the underlying condition being treated.
Blood Chemistry: decreased glucose (2.2%)
Hematology: decreased lymphocytes (2.4%)
Post-Marketing Adverse Reactions
Additional adverse events reported from worldwide post-marketing experience with levofloxacin include:
allergic pneumonitis, anaphylactic shock, anaphylactoid reaction, dysphonia, abnormal EEG, encephalopathy, eosinophilia, erythema multiforme, hemolytic anemia, multi-system organ failure, increased International Normalized Ratio (INR)/prothrombin time, Stevens-Johnson Syndrome, tendon rupture, torsades de pointes, vasodilation.
OVERDOSAGE
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 1500 mg/kg orally and 250 mg/kg i.v. produced significant mortality in rodents. 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.
DOSAGE AND ADMINISTRATION
LEVAQUIN Injection should only be administered by intravenous infusion. It is not for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.
CAUTION: RAPID OR BOLUS INTRAVENOUS INFUSION 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. (See PRECAUTIONS .)
Single-use vials require dilution prior to administration. (See PREPARATION FOR ADMINISTRATION .)
The usual dose of LEVAQUIN Tablets or Injection is 250 mg or 500 mg administered orally or by slow infusion over 60 minutes every 24 hours, or 750 mg administered orally or by slow infusion over 90 minutes every 24 hours, as indicated by infection and described in the following dosing chart. These recommendations apply to patients with normal renal function (i.e., creatinine clearance > 80 mL/min). For patients with altered renal function see the Patients with Impaired Renal Function subsection. Oral doses should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or Videx® (didanosine), chewable/buffered tablets or the pediatric powder for oral solution.
Patients with Normal Renal Function Infection * Unit Dose Freq. Duration ** Daily Dose
Acute Bacterial Exacerbation of Chronic Bronchitis 500 mg q24h 7 days 500 mg
Nosocomial Pneumonia 750 mg q24h 7-14 days 750 mg
Comm. Acquired Pneumonia 500 mg q24h 7-14 days 500 mg
Acute Maxillary Sinusitis 500 mg q24h 10-14 days 500 mg
Complicated SSSI 750 mg q24h 7-14 days 750 mg
Uncomplicated SSSI 500 mg q24h 7-10 days 500 mg
Complicated UTI 250 mg q24h 10 days 250 mg
Acute pyelonephritis 250 mg q24h 10 days 250 mg
Uncomplicated UTI 250 mg q24h 3 days 250 mg
* DUE TO THE DESIGNATED PATHOGENS (See INDICATIONS AND USAGE .)
**Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician.

Patients with Impaired Renal Function Renal Status Initial Dose Subsequent Dose
Acute Bacterial Exacerbation of Chronic Bronchitis/
Comm. Acquired Pneumonia/Acute Maxillary Sinusitis/
Uncomplicated SSSI
CL CR from 50 to 80 mL/min No dosage adjustment required
CL CR from 20 to 49 mL/min 500 mg 250 mg q24h
CL CR from10 to 19 mL/min 500 mg 250 mg q48h
Hemodialysis 500 mg 250 mg q48h
CAPD 500 mg 250 mg q48h
Complicated SSSI/Nosocomial Pneumonia
CL CR from 50 to 80 mL/min No dosage adjustment required
CL CR from 20 to 49 mL/min 750 mg 750 mg q48h
CL CR from 10 to 19 mL/min 750 mg 500 mg q48h
Hemodialysis 750 mg 500 mg q48h
CAPD 750 mg 500 mg q48h
Complicated UTI/Acute Pyelonephritis
CL CR >/=20 mL/min No dosage adjustment required
CL CR from 10 to 19 mL/min 250 mg 250 mg q48h
Uncomplicated UTI No dosage adjustment required
CL CR =creatinine clearances
CAPD=chronic ambulatory peritoneal dialysis

When only the serum creatinine is known, the following formula may be used to estimate creatinine clearance.
Men: Creatinine Clearance (mL/min) =
Weight (kg) × (140 - age)
72 × serum creatinine (mg/dL)
Women: 0.85 × the value calculated for men.

The serum creatinine should represent a steady state of renal function.
Preparation of Levofloxacin Injection for Administration
LEVAQUIN Injection in Single-Use Vials: LEVAQUIN Injection is supplied in single-use vials containing a concentrated levofloxacin solution with the equivalent of 500 mg (20 mL vial) and 750 mg (30 mL vial) of levofloxacin in Water for Injection, USP. The 20 mL and 30 mL vials each contain 25 mg of levofloxacin/mL. THESE LEVAQUIN INJECTION SINGLE-USE VIALS MUST BE FURTHER DILUTED WITH AN APPROPRIATE SOLUTION PRIOR TO INTRAVENOUS ADMINISTRATION. (See COMPATIBLE INTRAVENOUS SOLUTIONS .) The concentration of the resulting diluted solution should be 5 mg/mL prior to administration.
This intravenous drug product should be inspected visually for particulate matter prior to administration. Samples containing visible particles should be discarded.
Since no preservative or bacteriostatic agent is present in this product, aseptic technique must be used in preparation of the final intravenous solution. Since the vials are for single-use only, any unused portion remaining in the vial should be discarded. When used to prepare two 250 mg doses from the 20 mL vial containing 500 mg of levofloxacin, the full content of the vial should be withdrawn at once using a single-entry procedure, and a second dose should be prepared and stored for subsequent use. (See Stability of LEVAQUIN Injection Following Dilution .)
Since only limited data are available on the compatibility of levofloxacin intravenous injection with other intravenous substances, additives or other medications should not be added to LEVAQUIN Injection in single-use vials or infused simultaneously through the same intravenous line . If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of LEVAQUIN Injection with an infusion solution compatible with LEVAQUIN Injection and with any other drug(s) administered via this common line.
Prepare the desired dosage of levofloxacin according to the following chart:
Desired
Dosage Strength From Appropriate Vial,
Withdraw Volume Volume of
Diluent Infusion
Time
250 mg 10 mL (20 mL Vial) 40 mL 60 min
500 mg 20 mL (20 mL Vial) 80 mL 60 min
750 mg 30 mL (30 mL Vial) 120 mL 90 min

For example, to prepare a 500 mg dose using the 20 mL vial (25 mg/mL), withdraw 20 mL and dilute with a compatible intravenous solution to a total volume of 100 mL.
Compatible Intravenous Solutions: Any of the following intravenous solutions may be used to prepare a 5 mg/mL levofloxacin solution with the approximate pH values:
Intravenous Fluids Final pH of
LEVAQUIN Solution
0.9% Sodium Chloride
Injection, USP 4.71
5% Dextrose Injection, USP 4.58
5% Dextrose/0.9% NaCl Injection 4.62
5% Dextrose in Lactated Ringers 4.92
Plasma-Lyte® 56/5% Dextrose Injection 5.03
5% Dextrose, 0.45% Sodium Chloride, and 0.15% Potassium Chloride Injection 4.61
Sodium Lactate Injection (M/6) 5.54

LEVAQUIN Injection Premix in Single-Use Flexible Containers: LEVAQUIN Injection is also supplied in flexible containers containing a premixed, ready-to-use levofloxacin solution in D 5 W for single-use. The fill volume is either 50 or 100 mL for the 100 mL flexible container or 150 mL for the 150 mL container. NO FURTHER DILUTION OF THESE PREPARATIONS ARE NECESSARY. Consequently each 50 mL, 100 mL, and 150 mL premix flexible container already contains a dilute solution with the equivalent of 250 mg, 500 mg, and 750 mg of levofloxacin, respectively (5 mg/mL) in 5% Dextrose (D 5 W).
This parenteral drug product should be inspected visually for particulate matter prior to administration. Samples containing visible particles should be discarded.
Since the premix flexible containers are for single-use only, any unused portion should be discarded.
Since only limited data are available on the compatibility of levofloxacin intravenous injection with other intravenous substances, additives or other medications should not be added to LEVAQUIN Injection in flexible containers or infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of LEVAQUIN Injection with an infusion solution compatible with LEVAQUIN Injection and with any other drug(s) administered via this common line.
Instructions for the Use of LEVAQUIN Injection Premix in Flexible Containers
To open:
Tear outer wrap at the notch and remove solution container.
Check the container for minute leaks by squeezing the inner bag firmly. If leaks are found, or if the seal is not intact, discard the solution, as the sterility may be compromised.
Do not use if the solution is cloudy or a precipitate is present.
Use sterile equipment.
WARNING: Do not use flexible containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.
Preparation for administration:
Close flow control clamp of administration set.
Remove cover from port at bottom of container.
Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. NOTE: See full directions on administration set carton.
Suspend container from hanger.
Squeeze and release drip chamber to establish proper fluid level in chamber during infusion of LEVAQUIN Injection in Premix Flexible Containers.
Open flow control clamp to expel air from set. Close clamp.
Regulate rate of administration with flow control clamp.
Stability of LEVAQUIN Injection as Supplied
When stored under recommended conditions, LEVAQUIN Injection, as supplied in 20 mL and 30 mL vials, or 100 mL and 150 mL flexible containers, is stable through the expiration date printed on the label.
Stability of LEVAQUIN Injection Following Dilution
LEVAQUIN Injection, when diluted in a compatible intravenous fluid to a concentration of 5 mg/mL, is stable for 72 hours when stored at or below 25°C (77°F) and for 14 days when stored under refrigeration at 5°C (41°F) in plastic intravenous containers. Solutions that are diluted in a compatible intravenous solution and frozen in glass bottles or plastic intravenous containers are stable for 6 months when stored at -20°C (-4°F). THAW FROZEN SOLUTIONS AT ROOM TEMPERATURE 25°C (77°F) OR IN A REFRIGERATOR 8°C (46°F). DO NOT FORCE THAW BY MICROWAVE IRRADIATION OR WATER BATH IMMERSION. DO NOT REFREEZE AFTER INITIAL THAWING.
HOW SUPPLIED
LEVAQUIN Tablets
LEVAQUIN (levofloxacin) Tablets are supplied as 250, 500, and 750 mg modified rectangular, film-coated tablets. LEVAQUIN Tablets are packaged in bottles and in unit-dose blister strips.