Product Name
:
VENO-TAVOX
Chemical Name
:
Levofloxacin
Therapeutic Category
:
Antimicrobial
Pharmacologic Category
:
Antibiotic, Quinolone - Respiratory Fluoroquinolone
Pharmaceutical Form
:
Vial
Composition
:
Levofloxacin 500mg/100ml
Dosing
 
Dosing: Adult
Note: Sequential therapy (intravenous to oral) may be instituted based on prescriber's discretion.
Anthrax (inhalational): 500 mg every 24 hours for 60 days, beginning as soon as possible after exposure
Chronic bronchitis (acute bacterial exacerbation): Oral, I.V.: 500 mg every 24 hours for at least 7 days
Diverticulitis, peritonitis (unlabeled use): Oral, I.V.: 750 mg every 24 hours for 7-10 days; use adjunctive metronidazole therapy
Dysenteric enterocolitis, Shigella spp. (unlabeled use): Oral, I.V.: 500 mg every 24 hours for 3-5 days
Epididymitis, nongonococcal (unlabeled use): 500 mg once daily for 10 days
Gonococcal infection (unlabeled use): Oral, I.V.:
Cervicitis, urethritis: 250 mg for one dose with azithromycin or doxycycline; Note: As of April 2007, the CDC no longer recommends the use of fluoroquinolones for the treatment of uncomplicated gonococcal disease.
Disseminated infection: 250 mg I.V. once daily; 24 hours after symptoms improve may change to 500 mg orally every 24 hours to complete total therapy of 7 days; Note: As of April 2007, the CDC no longer recommends the use of fluoroquinolones for the treatment of more serious gonococcal disease, unless no other options exist and susceptibility can be confirmed via culture.
Intra-abdominal infection, complicated, community-acquired (in combination with metronidazole) (unlabeled use): I.V.: 750 mg once daily for 4-7 days (provided source controlled). Note: Avoid using in settings where E. coli susceptibility to fluoroquinolones is <90%.
Pelvic inflammatory disease (unlabeled use): 500 mg once daily for 14 days with or without adjunctive metronidazole; Note: The CDC recommends use only if standard cephalosporin therapy is not feasible and community prevalence of quinolone-resistant gonococcal organisms is low. Culture sensitivity must be confirmed.

Pneumonia:
Oral, I.V.:
Community-acquired: 500 mg every 24 hours for 7-14 days or 750 mg every 24 hours for 5 days (efficacy of 5-day regimen for MDRSP not established)
Nosocomial: 750 mg every 24 hours for 7-14 days
Prostatitis (chronic bacterial): Oral, I.V.: 500 mg every 24 hours for 28 days
Sinusitis (acute bacterial): Oral, I.V.: 500 mg every 24 hours for 10-14 days or 750 mg every 24 hours for 5 days
Skin and skin structure infections: Oral, I.V.:
Uncomplicated: 500 mg every 24 hours for 7-10 days
Complicated: 750 mg every 24 hours for 7-14 days
Traveler's diarrhea (unlabeled use): Oral, I.V.: 500 mg for one dose
Urinary tract infections: Oral, I.V.:
Uncomplicated: 250 mg once daily for 3 days
Complicated, including acute pyelonephritis: 250 mg once daily for 10 days or 750 mg once daily for 5 days

Dosing: Pediatric

Anthrax (inhalational, postexposure):  Oral, I.V.
Children ≥6 months and ≤50 kg: 8 mg/kg every 12 hours for 60 days (do not exceed 250 mg/dose), beginning as soon as possible after exposure
Children >50 kg : 500 mg every 24 hours for 60 days, beginning as soon as possible after exposure

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Normal renal function dosing of 750 mg/day:
Clcr 20-49 mL/minute: Administer 750 mg every 48 hours
Clcr 10-19 mL/minute: Administer 750 mg initial dose, followed by 500 mg every 48 hours
Hemodialysis (administer after hemodialysis on dialysis days)/peritoneal dialysis (PD): Administer 750 mg initial dose, followed by 500 mg every 48 hours
Normal renal function dosing of 500 mg/day:
Clcr 20-49 mL/minute: Administer 500 mg initial dose, followed by 250 mg every 24 hours
Clcr 10-19 mL/minute: Administer 500 mg initial dose, followed by 250 mg every 48 hours
Hemodialysis (administer after hemodialysis on dialysis days)/peritoneal dialysis (PD): Administer 500 mg initial dose, followed by 250 mg every 48 hours
Normal renal function dosing of 250 mg/day:
Clcr 20-49 mL/minute: No dosage adjustment required
Clcr 10-19 mL/minute: Administer 250 mg every 48 hours (except in uncomplicated UTI, where no dosage adjustment is required)
Hemodialysis (administer after hemodialysis on dialysis days)/peritoneal dialysis (PD): No information available.
Continuous renal replacement therapy (CRRT) (Heintz, 2009; Trotman, 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:
CVVH: Loading dose of 500-750 mg followed by 250 mg every 24 hours
CVVHD: Loading dose of 500-750 mg followed by 250-500 mg every 24 hours
CVVHDF: Loading dose of 500-750 mg followed by 250-750 mg every 24 hours
Use
 
Treatment of community-acquired pneumonia, including multidrug resistant strains of S. pneumoniae (MDRSP); nosocomial pneumonia; chronic bronchitis (acute bacterial exacerbation); acute bacterial sinusitis; prostatitis, urinary tract infection (uncomplicated or complicated); acute pyelonephritis; skin or skin structure infections (uncomplicated or complicated); reduce incidence or disease progression of inhalational anthrax (postexposure)
Use - Unlabeled/Investigational
Diverticulitis, enterocolitis (Shigella spp), epididymitis (nongonococcal), gonococcal infections, complicated intra-abdominal infections (in combination with metronidazole), Legionnaires' disease, peritonitis, PID
Note: As of April 2007, the CDC no longer recommends the use of fluoroquinolones for the treatment of gonococcal disease.
Adverse Reactions
 
1% to 10%:
Cardiovascular: Chest pain (1%), edema (1%)
Central nervous system: Headache (6%), insomnia (4%), dizziness (3%), fatigue (1%), pain (1%)
Dermatologic: Rash (2%), pruritus (1%)
Gastrointestinal: Nausea (7%), diarrhea (5%), constipation (3%), abdominal pain (2%), dyspepsia (2%), vomiting (2%)
Genitourinary: Vaginitis (1%)
Local: Injection site reaction (1%)
Respiratory: Pharyngitis (4%), dyspnea (1%)
Miscellaneous: Moniliasis (1%)
<1% (Limited to important or life-threatening): Acute renal failure, agitation, agranulocytosis; allergic reaction (including anaphylaxis, angioedema, pneumonitis rash, pneumonitis, and serum sickness); anaphylactoid reaction, arrhythmia (including atrial/ventricular tachycardia/fibrillation and torsade de pointes), aplastic anemia, arthralgia, ascites, bradycardia, bronchospasm, carcinoma, cardiac failure, cholecystitis, cholelithiasis, confusion, depression, EEG abnormalities, encephalopathy, eosinophilia, erythema multiforme, GI hemorrhage, granulocytopenia, hallucination, heart block, hemolytic anemia, hemoptysis, hepatic failure (some fatal), hepatitis, hyper-/hypoglycemia, hyperkalemia, hyperkinesias, hyper-/hypotension, infection, INR increased, intestinal obstruction, intracranial hypertension, involuntary muscle contractions, jaundice, leukocytosis, leukopenia, leukorrhea, lymphadenopathy, MI, migraine, multiple organ failure, myalgia, myasthenia gravis exacerbation, nephritis (interstitial), palpitation, pancreatitis, pancytopenia, paralysis, paresthesia, peripheral neuropathy, photosensitivity (<0.1%), pleural effusion, pneumonitis, postural hypotension, prothrombin time increased/decreased, pseudomembraneous colitis, psychosis, pulmonary edema, pulmonary embolism, purpura, QTc prolongation, respiratory depression, rhabdomyolysis, seizure, skin disorder, somnolence, speech disorder, Stevens-Johnson syndrome, stupor, suicide attempt/ideation, syncope, tendonitis, tendon rupture, tongue edema, toxic epidermal necrolysis, transaminases increased, thrombocythemia, thrombocytopenia, tremor, urticaria, WBC abnormality
Contraindications
 
Hypersensitivity to levofloxacin, any component of the formulation, or other quinolones
Warnings / Precautions Drug
 
Boxed Warnings:
• Myasthenia gravis: See “Disease-related concerns” below.
• Tendon inflammation/rupture: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Altered cardiac conduction: Fluoroquinolones may prolong QTc interval; avoid use in patients with a history of QTc prolongation, uncorrected hypokalemia, hypomagnesemia, or concurrent administration of other medications known to prolong the QT interval (including Class Ia and Class III antiarrhythmics, cisapride, erythromycin, antipsychotics, and tricyclic antidepressants).
• CNS stimulation: Tremor, restlessness, confusion, and very rarely hallucinations or seizures may occur; use with caution in patients with known or suspected CNS disorder. Discontinue in patients who experience significant CNS adverse effects (eg, dizziness, hallucinations, suicidal ideations or actions).
• Glucose regulation: Fluoroquinolones have been associated with the development of serious, and sometimes fatal, hypoglycemia. These events have occurred most often in elderly patients with diabetes, but have also been reported in patients without a prior history of diabetes. Prompt identification and treatment of hypoglycemia is essential. Individual quinolones may differ in their potential to cause this effect. It was most evident with gatifloxacin (no longer marketed as systemic formulation). Hyperglycemia has also been associated with the use of fluoroquinolones. Patients should be monitored closely for signs/symptoms of disordered glucose regulation.
• Hepatotoxicity: Unrelated to hypersensitivity, severe hepatotoxicity (including acute hepatitis and fatalities) has been reported. Elderly patients may be at greater risk. Discontinue therapy immediately if signs and symptoms of hepatitis occur.
• Hypersensitivity reactions: Severe hypersensitivity reactions, including anaphylaxis, have occurred with quinolone therapy. The spectrum of these reactions can vary widely; reactions may present as typical allergic symptoms (eg, itching, urticaria, rash, edema) after a single dose, or may manifest as severe idiosyncratic dermatologic (eg, Stevens-Johnson, toxic epidermal necrolysis), vascular (eg, vasculitis), pulmonary (eg, pneumonitis), renal (eg, nephritis), hepatic (eg, hepatic failure or necrosis), and/or hematologic (eg, anemia, cytopenias) events, usually after multiple doses. Prompt discontinuation of drug should occur if skin rash or other symptoms arise.
• Peripheral neuropathy: The use of quinolones has been linked to peripheral neuropathy (rare); discontinue if symptoms of sensory or sensorimotor neuropathy occur.
• Phototoxicity: Avoid excessive sunlight and take precautions to limit exposure (eg, loose fitting clothing, sunscreen); may cause moderate-to-severe phototoxicity reactions. Discontinue use if photosensitivity occurs.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Tendon inflammation/rupture: [U.S. Boxed Warning]: There have been reports of tendon inflammation and/or rupture with quinolone antibiotics; risk may be increased with concurrent corticosteroids, organ transplant recipients, and in patients >60 years of age. Rupture of the Achilles tendon sometimes requiring surgical repair has been reported most frequently; but other tendon sites (eg, rotator cuff, biceps) have also been reported. Strenuous physical activity may be an independent risk factor for tendonitis. Discontinue at first sign of tendon inflammation or pain. May occur even after discontinuation of therapy.
Disease-related concerns:
• Myasthenia gravis: [U.S. Boxed Warning]: May exacerbate muscle weakness related to myasthenia gravis. Cases of severe exacerbations, including the need for ventilatory support and deaths have been reported; avoid use in patients with myasthenia gravis.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required. May increase risk of tendon rupture.
• Rheumatoid arthritis: Use with caution in patients with rheumatoid arthritis; may increase risk of tendon rupture.
• Seizures: Use with caution in individuals at risk of seizures (CNS disorders or concurrent therapy with medications which may lower seizure threshold). Potential for seizures, although very rare, may be increased with concomitant NSAID therapy.
Special populations:
• Elderly: Adverse effects (eg, hepatotoxicity, tendon rupture, QT changes) may be increased in the elderly.
• G6PD deficiency: Hemolytic reactions may (rarely) occur with quinolone use in patients with latent or actual G6PD deficiency.
• Pediatrics: Systemic use is only recommended in children <18 years of age for the prevention of inhalational anthrax (postexposure); increased incidence of musculoskeletal disorders (eg, arthralgia, tendon rupture) has been observed in children.
Interactions
 
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Antacids: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of quinolones. Exceptions: Sodium Bicarbonate. Risk D: Consider therapy modification
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Calcium Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Calcium Chloride. Risk D: Consider therapy modification
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Corticosteroids (Systemic): Quinolone Antibiotics may enhance the adverse/toxic effect of Corticosteroids (Systemic). Risk of tendon-related side effects, including tendonitis and rupture, may be enhanced. Risk C: Monitor therapy
Didanosine: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after didanosine. Monitor for decreased therapeutic effects of quinolones, particularly if doses cannot be separated as recommended. This does not apply to unbuffered enteric coated didanosine. Risk D: Consider therapy modification
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Insulin: May enhance the hyperglycemic effect of Quinolone Antibiotics. Insulin may enhance the hypoglycemic effect of Quinolone Antibiotics. Risk C: Monitor therapy
Iron Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Exceptions: Ferric Gluconate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Risk D: Consider therapy modification
Lanthanum: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolone antibiotics at least two hours before or after lanthanum. Risk D: Consider therapy modification
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Magnesium Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Risk D: Consider therapy modification
Mycophenolate: Quinolone Antibiotics may decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Nonsteroidal Anti-Inflammatory Agents: May enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolone Antibiotics. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolone Antibiotics. Risk C: Monitor therapy
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Quinolone Antibiotics. Risk C: Monitor therapy
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QUEtiapine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Quinapril: May decrease the serum concentration of Quinolone Antibiotics. Management: Separate doses of quinapril and oral quinolones by at least 2 hours in order to reduce the risk of interaction. Monitor for reduced efficacy of the quinolone if these products are used concomitantly. Risk D: Consider therapy modification
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Sevelamer: May decrease the absorption of Quinolone Antibiotics. Risk D: Consider therapy modification
Sucralfate: May decrease the serum concentration of Quinolone Antibiotics. Management: Administer oral quinolones at least 2 hours before or 6 hours after the sucralfate dose. Greater separation of doses may further lessen the risk for a significant interaction. Risk D: Consider therapy modification
Sulfonylureas: Quinolone Antibiotics may enhance the hypoglycemic effect of Sulfonylureas. This appears to be particularly concerning early in the course of combination therapy. Quinolone Antibiotics may diminish the hypoglycemic effect of Sulfonylureas. With longer-term combination, there is a greater risk of hyperglycemia. Risk C: Monitor therapy
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination
Varenicline: Quinolone Antibiotics may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of levofloxacin or other quinolone antibiotics, particulary in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Risk C: Monitor therapy
Vemurafenib: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Vemurafenib. Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Quinolone Antibiotics may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Zinc Salts: May decrease the absorption of Quinolone Antibiotics. Of concern only with oral administration of both agents. Risk D: Consider therapy modification
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Pregnancy
 
C
Pregnancy Implications
Adverse events have been observed in some animal studies; therefore, the manufacturer classifies levofloxacin as pregnancy category C. Levofloxacin crosses the placenta. Quinolone exposure during human pregnancy has been reported with other agents (see Ciprofloxacin, Ofloxacin, and Norfloxacin monographs). To date, no specific teratogenic effect or increased pregnancy risk has been identified; however, because of concerns of cartilage damage in immature animals exposed to quinolones and the limited levofloxacin specific data, levofloxacin should only be used during pregnancy if a safer option is not available.
Lactation
 
Enters breast milk/not recommended
Breast-Feeding Considerations
Based on data from a case report, small amounts of levofloxacin are excreted in breast milk. Breast-feeding is not recommended by the manufacturer. Levofloxacin is the L-isomer of ofloxacin. Ofloxacin has also been shown to have minimal concentrations in human milk. Nondose-related effects could include modification of bowel flora.
Monitoring Parameters
 
Evaluation of organ system functions (renal, hepatic, and hematopoietic) is recommended periodically during therapy; the possibility of crystalluria should be assessed; WBC and signs of infection
Mechanism of Action
 
As the S(-) enantiomer of the fluoroquinolone, ofloxacin, levofloxacin, inhibits DNA-gyrase in susceptible organisms thereby inhibits relaxation of supercoiled DNA and promotes breakage of DNA strands. DNA gyrase (topoisomerase II), is an essential bacterial enzyme that maintains the superhelical structure of DNA and is required for DNA replication and transcription, DNA repair, recombination, and transposition.
Pharmacodynamics / Kinetics
 
Absorption: Rapid and complete
Distribution: Vd: 74-112 L; CSF concentrations ~15% of serum levels; high concentrations are achieved in prostate, lung, and gynecological tissues, sinus, saliva
Protein binding: ~24% to 38%; primarily to albumin
Metabolism: Minimally hepatic
Bioavailability: ~99%
Half-life elimination: ~6-8 hours
Time to peak, serum: Oral: 1-2 hours
Excretion: Urine (~87% as unchanged drug, <5% as metabolites); feces (<4%)