Levaquin (Levofloxacin)

LEVAQUIN®

Janssen-Ortho

Levofloxacin

Antibacterial

Action And Clinical Pharmacology: Levofloxacin is a synthetic broad spectrum antibacterial agent for oral and i.v. administration.

Levofloxacin is the l-isomer of the racemate, ofloxacin, a quinolone antibacterial agent. The antibacterial activity of ofloxacin resides primarily in the l-isomer. The mechanism of action of levofloxacin and other quinolone antibacterials involves inhibition of DNA gyrase (bacterial topoisomerase II), an enzyme required for DNA replication, transcription, repair and recombination.

Pharmacokinetics: Absorption: Oral: Levofloxacin is rapidly and essentially completely absorbed after oral administration. Peak plasma concentrations are usually attained 1 to 2 hours after oral dosing. The absolute bioavailability of a 500 mg oral dose of levofloxacin is approximately 99%. Levofloxacin pharmacokinetics are linear and predictable after single and multiple oral dosing regimens. Steady state is reached within 48 hours following a 500 mg once daily regimen. The peak and trough plasma concentrations attained following multiple once daily oral 500 mg regimens were approximately 5.7 µg/mL and 0.5 µg/mL respectively. There was no clinically significant effect of food on the extent of absorption of levofloxacin. Oral administration with food slightly prolongs the time to peak concentration by approximately 1 hour and slightly decreases the peak concentration by approximately 14%. Therefore, levofloxacin can be administered without regard to food.

I.V.: Following a single 60 minute i.v. infusion of 500 mg of levofloxacin to healthy volunteers, the mean peak plasma concentration attained was 6.2 g/mL. Levofloxacin pharmacokinetics are linear and predictable after single and multiple i.v. dosing regimens. Steady-state is reached within 48 hours following a 500 mg once daily regimen. The peak and trough plasma concentrations attained following multiple once daily i.v. 500 mg regimens were approximately 6.4 g/mL and 0.8 g/mL respectively.

The plasma concentration profile of levofloxacin after i.v. administration is similar and comparable in extent of exposure (AUC) to that observed for levofloxacin tablets when equal doses (mg/mg) are administered. Therefore, the oral and i.v. routes of administration can be considered interchangeable.

Distribution: The mean volume of distribution of levofloxacin generally ranges from 89 to 112 L after single and multiple 500 mg doses, indicating widespread distribution into body tissues. Levofloxacin penetrates into blister fluid. The blister fluid to plasma AUC ratio is approximately 1. Levofloxacin also penetrates into lung tissues. Lung tissue concentrations were generally 2- to 5-fold higher than plasma concentrations and ranged from approximately 2.4 to 11.3 g/g over a 24-hour period after a single 500 mg oral dose.

Levofloxacin is 24 to 38% bound to serum proteins across all species studied. Levofloxacin binding to serum proteins is independent of the drug concentration.

Metabolism: Levofloxacin is stereochemically stable in plasma and urine and does not invert metabolically to its enantiomer, D-ofloxacin. Levofloxacin undergoes limited metabolism in humans and is primarily excreted as unchanged drug (87%) in the urine within 48 hours.

Excretion: The major route of elimination of levofloxacin in humans is as unchanged drug in urine. The mean terminal plasma elimination half-life of levofloxacin ranges from approximately 6 to 8 hours following single or multiple doses of levofloxacin given orally or i.v.

Factors Influencing the Pharmacokinetics: Special Populations: Geriatrics: There are no significant differences in levofloxacin pharmacokinetics between young and elderly subjects when the subjects’ differences in creatinine clearance are taken into consideration. Drug absorption appears to be unaffected by age. Levofloxacin dose adjustment based on age alone is not necessary.

Children: The pharmacokinetics of levofloxacin in pediatric patients have not been studied.

Gender: There are no significant differences in levofloxacin pharmacokinetics between male and female subjects when subjects’ differences in creatinine clearance are taken into consideration. Dose adjustment based on gender alone is not necessary.

Renal Insufficiency: Clearance of levofloxacin is reduced and plasma elimination half-life is prolonged in patients with impaired renal function (creatinine clearance £80 mL/min), and may require dosage adjustment in such patients to avoid accumulation. Neither hemodialysis nor continuous ambulatory peritoneal dialysis (CAPD) is effective in removal of levofloxacin from the body, indicating supplemental doses of levofloxacin are not required following hemodialysis or CAPD (see Precautions, Renal and Dosage).

Hepatic Insufficiency: Pharmacokinetics studies in hepatically impaired patients have not been conducted. Due to the limited extent of levofloxacin metabolism, the pharmacokinetics of levofloxacin are not expected to be affected by hepatic impairment.

Bacterial Infection: The pharmacokinetics of levofloxacin in patients with community-acquired bacterial infections are comparable to those observed in healthy subjects.

Indications And Clinical Uses: For the treatment of adults with bacterial infections caused by susceptible strains of the designated microorganisms in the infections listed.

Note: Since i.v. and oral formulations are interchangeable, i.v. administration is recommended only when it offers a route of administration advantageous to the patient (e.g., patient cannot tolerate oral dosage form).

Upper Respiratory Tract: Acute sinusitis (mild to moderate) due to S. pneumoniae, H. influenzae and M. catarrhalis.

Lower Respiratory Tract: Acute exacerbations of chronic bronchitis (mild to moderate) due to S. aureus, S. pneumoniae, H. influenzae, H. parainfluenzae and M. catarrhalis.

Community-acquired pneumonia (mild, moderate and severe* infections) due to S. aureus, S. pneumoniae, H. influenzae, H. parainfluenzae, K. pneumoniae, M. catarrhalis, C. pneumoniae, L. pneumophila and M. pneumoniae.

*Note: In 3 North American clinical studies, of 655 patients treated with levofloxacin for community-acquired pneumonia, 45 clinically and microbiologically evaluable patients were defined as severely ill by study criteria and met American Thoracic Society criteria for severe (American Thoracic Society, 1993). Clinical success (cure and improvement) was achieved in 98% of these 45 patients. Data on the treatment of patients with severe Legionella pneumonia is limited to one patient.

Skin and Skin Structure: Uncomplicated skin and skin structure infections (mild to moderate) due to S. aureus and S. pyogenes.

Complicated skin and skin structure infections (mild to moderate) due to E. faecalis, S. aureus, S. pyogenes, E. cloacae, E. coli, K. pneumoniae, P. mirabilis and P. aeruginosa.

Urinary Tract: Complicated urinary tract infections (mild to moderate) due to E. faecalis, E. cloacae, E. coli, K. pneumoniae, P. mirabilis and P. aeruginosa.

Acute pyelonephritis (mild to moderate) caused by E. coli.

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 continued.

As with other drugs in this class, some strains of P. aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin. Culture and susceptibility testing performed periodically during therapy will provide not only the therapeutic effect of the antimicrobial agent but also the possible emergence of bacterial resistance.

Contra-Indications: Persons with a history of hypersensitivity to levofloxacin, quinolone antimicrobial agents, or any other components of this product. Levofloxacin is also contraindicated in persons with a history of tendinitis or tendon rupture associated with the use of any member of the quinolone group of antimicrobial agents.

Manufacturers’ Warnings In Clinical States: The safety and efficacy of levofloxacin in children, adolescents (under the age of 18 years), pregnant women, and nursing mothers have not been established (see Precautions: Children, Pregnancy and Lactation).

The oral and i.v. administration of levofloxacin increased the incidence and severity of osteochondrosis in immature rats and dogs. Other quinolones also produce similar erosions in the weight bearing joints and other signs of arthropathy in immature animals of various species. Consequently, levofloxacin should not be used in pre-pubertal patients.

Sexually Transmitted Diseases: Levofloxacin is not indicated for the treatment of syphilis or gonorrhea. Levofloxacin is not effective in the treatment of syphilis. Antimicrobial agents used in high doses for short periods of time to treat gonorrhea may mask or delay the symptoms of incubating syphilis. All patients with gonorrhea should have a serologic test for syphilis at the time of diagnosis. Patients treated with antimicrobial agents with limited or no activity against T. pallidum should have a follow-up serologic test for syphilis after 3 months.

Hypersensitivity 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, i.v. fluids, antihistamines, corticosteroids, pressor amines and airway management, as clinically indicated (see Adverse Effects.)

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 administration of levofloxacin should be discontinued immediately at the first appearance of a skin rash or any other sign of hypersensitivity and supportive measures instituted (see Adverse Effects.)

CNS and Psychiatric Effects: Convulsions and toxic psychoses have been reported in patients receiving quinolones, including levofloxacin. Quinolones may also cause increased intracranial pressure and CNS stimulation which may lead to tremors, restlessness, anxiety, lightheadedness, dizziness, confusion and 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 all 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., alcohol abuse, certain drug therapy such as NSAIDs and theophylline, renal dysfunction.) Levofloxacin should be used with caution in patients with unstable psychiatric illness (see Precautions, Drug Interactions and Adverse Effects).

Gastrointestinal Effects: 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 a toxin produced by C. 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 Effects).

Musculoskeletal Effects: Ruptures of the shoulder, hand and Achilles tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving quinolones. 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 (see Contraindications).

Precautions: Although levofloxacin is soluble, adequate hydration of patients receiving levofloxacin should be maintained to prevent the formation of a highly concentrated urine. Crystalluria has been observed rarely in patients receiving other quinolones when associated with high doses and an alkaline urine. Although crystalluria was not observed in clinical trials with levofloxacin, patients are encouraged to remain adequately hydrated.

As with any antimicrobial drug, periodic assessment of organ system functions, including renal, hepatic, and hematopoietic, is advisable during prolonged therapy (see Warnings and Adverse Effects).

I.V. Administration: Because rapid or bolus i.v. injection may result in hypotension, levofloxacin injection should only be administered by slow i.v. infusion over a period of 60 minutes (see Dosage).

Renal: In patients with impaired renal function (creatinine clearance 80 mL/min), adjustment of the dosage regimen may be necessary to avoid the accumulation of levofloxacin due to decreased clearance. 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 (see Dosage and Pharmacology).

Phototoxicity: 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., skin eruption) occurs.

Pregnancy: There are 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).

Lactation : Levofloxacin has not been measured in human milk. Based upon data from ofloxacin, it can be presumed that levofloxacin can 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 (see Warnings).

Children: Safety and effectiveness in children and adolescents below the age of 18 years have not been established. Levofloxacin like other quinolones, causes arthropathy and osteochondrosis in juvenile animals of several species (see Warnings).

Disturbances of Blood Glucose: 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, discontinue levofloxacin immediately and appropriate therapy should be initiated (see Drug Interactions and Adverse Effects).

Drug Interactions: Antacids, Sucralfate, Metal Cations, Multivitamins: Levaquin Tablets: Due to the chelation of levofloxacin by multivalent cations, concurrent administration of Levaquin tablets with antacids containing calcium, 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. These agents should be taken at least 2 hours before or 2 hours after levofloxacin tablet administration.

Levaquin Injection: There are no data concerning an interaction of i.v. quinolones with oral antacids, sucralfate, multivitamins, or metal cations. Levofloxacin should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same i.v. line (see Dosage, Preparation of Parenteral Products for 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, 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 theophylline dosage adjustments made, if appropriate, when levofloxacin is co-administered. Adverse reactions, including seizures, may occur with or without an elevation in serum theophylline level (see Warnings).

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. No significant change in prothrombin time was noted in the presence of levofloxacin. Similarly, no apparent effect of warfarin on levofloxacin absorption and disposition was observed. However, since some quinolones have been reported to enhance the effects of oral anticoagulant warfarin or its derivatives in the patient population, the prothrombin time or other suitable coagulation test should be closely monitored if a quinolone antimicrobial is administered concomitantly with warfarin or its derivatives.

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 Cmax and ke were slightly lower while Tmax and t1/2 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 t1/2 of levofloxacin were 27 to 38% and 30% higher, respectively, while CL/F and CLR were 21 to 35% lower during concomitant treatment with probenecid or cimetidine compared to levofloxacin alone. Although the differences were statistically significant, the changes were not high enough to warrant dosage adjustment for levofloxacin when probenecid or cimetidine is co-administered.

NSAIDs: The concomitant administration of a NSAID with a quinolone, including levofloxacin, may increase the risk of CNS stimulation and convulsive seizures (see Warnings: CNS and Psychiatric Effects).

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 including levofloxacin are co-administered.

Zidovudine: Levofloxacin absorption and disposition in HIV-infected subjects with or without concomitant zidovudine treatment were similar. Therefore, no dosage adjustment for levofloxacin appears to be required when co-administered with zidovudine. The effect of levofloxacin on zidovudine pharmacokinetics has not been studied.

Adverse Reactions: In North American Phase 2 and 3 Clinical Trials involving 3 158 subjects the incidence of treatment emergent adverse events in patients treated with levofloxacin was 41.2% which was comparable to controls. The majority of adverse events were considered to be mild to moderate with 4.7% of patients considered to have severe adverse events. Among patients receiving multiple dose therapy, 3.7% discontinued therapy with levofloxacin due to adverse experiences. The incidence of adverse reactions which were considered to be probably or definitely related to treatment with levofloxacin was 6.2%.

In clinical trials, the adverse events in Table II were characterized as probably or definitely related to drug therapy for patients receiving multiple doses of levofloxacin.

In clinical trials, the most frequently reported adverse events occurring in >2% of the study population regardless of drug relationship, were: nausea 6.6%, injection site reaction 5.6%, diarrhea 5.4%, headache 5.4%, constipation 3.1%, i.v. injection site pain 2.7%, dizziness 2.5%, insomnia 2.9% and vomiting 2.1%.

Events occurring at a frequency lower than 0.3% regardless of drug relationship but considered medically important include: Cardiovascular: angina pectoris, arrhythmia, atrial and ventricular fibrillation, bradycardia, cardiac arrest, cardiomyopathy, circulatory failure, coronary thrombosis, embolism-blood clot, heart block, hypotension, palpitations, phlebitis, postural hypotension, syncope, supraventricular tachycardia, thrombosis (arterial).

CNS/Psychiatric: abnormal co-ordination, abnormal dreaming, aggressive reaction, cerebrovascular disorder, coma, confusion, convulsions (seizures), delirium, depression, emotional lability, hallucination, impaired concentration, manic reaction, mental deficiency, paralysis, paranoia, sleep disorders, speech disorder, stupor, vertigo.

Gastrointestinal: esophagitis, gastrointestinal hemorrhage, pseudomembranous colitis, stomatitis.

Hematopoietic: abnormal platelets, anemia, granulocytopenia, leukocytosis, leukopenia, lymphadenopathy, thrombocytopenia, WBC abnormal (not otherwise specified).

Liver/Biliary/Pancreas: abnormal hepatic function, hepatic coma, increased LDH, jaundice, pancreatitis.

Metabolic: dehydration, aggravated diabetes mellitus, hypoglycemia, hyperkalemia, weight decrease.

Musculoskeletal: arthritis, muscle weakness, rhabdomyolysis, tendinitis.

Renal/Urinary: abnormal renal function, acute renal failure.

Respiratory: ARDS, asthma.

Special Senses: abnormal vision, diplopia.

Skin/Hypersensitivity: anaphylactoid reaction, erythema nodosum, photosensitivity.

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.

Laboratory abnormalities seen in ³2% of the patients receiving multiple doses of levofloxacin: decreased glucose 2.4% and decreased lymphocytes 2.2%. It is not known whether these abnormalities were caused by the drug or the underlying condition being treated.

Postmarketing Adverse Reactions: Additional serious adverse events reported with levofloxacin regardless of drug relationship include: agranulocytosis, allergic pneumonitis, amnesia, anaphylactic shock, anaphylactoid reaction, angioedema, aplastic anemia, apnea, DIC, dysphonia, EEG abnormal, encephalopathy, eosinophilia, erythema multiforme, glomerulonephritis, hemolytic anemia, hepatitis, interstitial pneumonia, interstitial nephritis, laryngeal edema, liver failure, multi-system organ failure, myositis, nephrosis, pancytopenia, Stevens-Johnson syndrome, thrombocytopenic purpura, tendon rupture, toxic epidermal necrolysis and vasodilation.

Symptoms And Treatment Of Overdose: Symptoms and Treatment: 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: The dosage of levofloxacin tablets and i.v. for Patients with Normal Renal Function (i.e., CLCR>80 mL/min). For patients with altered renal function (i.e., CLCR80 mL/min), see the Patients with Impaired Renal Function subsection. The dose of levofloxacin i.v. should be administered by slow infusion over 60 minutes.

Patients with Impaired Renal Function: On the basis of the altered levofloxacin disposition pharmacokinetics in subjects with impaired renal function, dose adjustment is recommended for patients with impaired renal function (see Pharmacology, Renal Insufficiency).

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.

Tablets: Levofloxacin can be administered without regard to food. Doses should be administered at least 2 hours before or 2 hours after antacids containing magnesium or aluminum, sucralfate, metal cations such as iron, and multivitamin preparations with zinc.

I.V.: Caution: Rapid or bolus i.v. infusion must be avoided. Levofloxacin injection should be infused i.v. slowly over a period of not less than 60 minutes. The injection should only be administered by i.v. infusion. It is not for i.m., intrathecal, intraperitoneal, or s.c. administration (see Precautions).

Single-use vials require dilution prior to administration. The concentration of the resulting diluted solution should be 5 mg/mL prior to administration (see Preparation of Patenteral Products for Administration).

This parenteral 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 parenteral solution. Since the vials are for single-use only, any unused portion remaining in the vial should be discarded. When used for split dosing, 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 and Storage).

Since only limited data are available on the compatibility of levofloxacin i.v. injection with other i.v. substances, additives or other medications should not be added to the injection in single-use vials or infused simultaneously through the same i.v. line. If the same i.v. line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of levofloxacin injection with an infusion solution compatible with levofloxacin injection and with any other drug(s) administered via this common line.

Preparation of Parenteral Products for Administration: Single-use Vials: The injection is supplied in single-use vials containing a concentrated levofloxacin solution with the equivalent of 500 mg of levofloxacin in water for injection. The 20 mL vials contain 25 mg of levofloxacin/mL. These single-use vials must be further diluted with an appropriate solution prior to i.v. administration (see Compatible Intravenous Solutions). The concentration of the resulting diluted solution should be 5 mg/mL prior to administration.

As with all parenteral products, i.v. admixture should be inspected visually for clarity, discoloration, particulate matter, precipitate, and leakage prior to administration whenever solution and container permit. 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 parenteral solution. Since the vials are for single-use only, any unused portion remaining in the vial should be discarded. When used for split dosing, 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 and Storage).

Since only limited data are available on the compatibility of levofloxacin i.v. injection with other i.v. substances, additives or other medications should not be added to the injection in single-use vials or infused simultaneously through the same i.v. line. If the same i.v. line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of levofloxacin injection with an infusion solution compatible with levofloxacin injection and with any other drug(s) administered via this common line.

For example, to prepare a 500-mg dose using the 20 mL vial (25 mg/mL), withdraw 20 mL and dilute with a compatible i.v. solution to a total volume of 100 mL.

Premix in Single-use Flexible Containers: The injection is also supplied in 100 mL flexible containers containing a premixed, ready-to-use levofloxacin solution in D5W for single-use. The fill volume is either 50 or 100 mL. No further dilution of this preparation is necessary. Each 100 mL Premix flexible container already contains a dilute solution with the equivalent of 500 mg of levofloxacin (5 mg/mL) in 5% Dextrose (D5W).

This parenteral drug product should be inspected visually for clarity, discoloration, particulate matter, precipitate and leakage 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 i.v. injection with other i.v. substances, additives or other medications should not be added to levofloxacin injection in flexible containers or infused simultaneously through the same i.v. line. If the same i.v. line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of levofloxacin Injection with an infusion solution compatible with levofloxacin 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: 1. Tear outer wrap at the notch and remove solution container. 2. 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. 3. Do not use if the solution is cloudy or a precipitate is present. 4. Use sterile equipment. 5. 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: 1. Close flow control clamp of administration set. 2. Remove cover from port at bottom of container. 3. 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. 4. Suspend container from hanger. 5. Squeeze and release drip chamber to establish proper fluid level in chamber during infusion of the injection in Premix Flexible Containers. 6. Open flow control clamp to expel air from set. Close clamp. 7. Regulate rate of administration with flow control clamp.

Stability and Storage: Tablets: Store at controlled room temperature (15 to 30°C) in well-closed containers.

Injection: When stored under recommended conditions, the injection, as supplied in 20 mL vials and 100 mL flexible containers, is stable through the expiration date printed on the label.

Single-use vials should be stored at 2 to 30°C and protected from light.

Premix in flexible containers should be stored at 2 to 25°C; however, brief exposure up to 40°C does not adversely affect the product. Avoid excessive heat and protect from freezing and light.

Stability of Injection Following Dilution: The injection, when diluted in a compatible i.v. fluid to a concentration of 5 mg/mL, is stable for 24 hours when stored at or below 25°C and for 72 hours when stored under refrigeration at 5°C in plastic i.v. containers. Solutions that are diluted in a compatible i.v. solution and frozen in glass bottles or plastic i.v. containers are stable for 6 months when stored at -20°C. Thaw frozen solutions at room temperature (25°C) or in a refrigerator (8°C). Do not force thaw by microwave irradiation or water bath immersion. Do not refreeze after initial thawing.

Availability And Storage: Injection: 5 mg/mL: Each mL of sterile, non-pyrogenic premixed, ready-to-use solution contains: levofloxacin 5 mg in 5% Dextrose (D5W). pH: 3.8 to 5.8. Solutions of hydrochloric acid and/or sodium hydroxide may have been added to adjust the pH. Preservative-free. Single-use flexible containers of 100 mL with a fill volume of 50 or 100 mL, cases of 12.

No further dilution of this preparation is necessary. Consequently, each 100 mL premix flexible container with a fill volume of either 50 or 100 mL already contains a dilute solution with the equivalent of either 250 or 500 mg of levofloxacin (5 mg/mL) in 5% Dextrose (D5W).

25 mg/mL: Each mL of sterile, clear yellow to greenish-yellow solution contains: levofloxacin 25 mg in water for injection. pH: 3.8 to 5.8. Solution may contain hydrochloric acid and/or sodium hydroxide for pH adjustment. Preservative-free. Single-use vials of 20 mL, cartons of 1. Single-use vials require dilution prior to administration. See Dosage, Preparation for Administration.

Tablets: 250 mg: Each modified rectangular, film-coated, terra cotta pink tablet contains: levofloxacin 250 mg. Nonmedicinal ingredients: crospovidone, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, synthetic red iron oxide and titanium dioxide. Bottles of 50.

500 mg: Each modified rectangular, film-coated, peach tablet contains: levofloxacin 500 mg. Nonmedicinal ingredients: crospovidone, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, synthetic red and yellow oxides and titanium dioxide. Bottles of 50.

LEVAQUIN® Janssen-Ortho Levofloxacin Antibacterial

Connected Diseases :

Bacterial Infections

Description: Bacterial infections include a huge group of diseases caused by microorganisms – bacteria. These are small unicellular microorganisms that have a strong cell wall…