Version May 2024
Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including tendinitis and tendon rupture, peripheral neuropathy, and CNS effects. Discontinue levofloxacin immediately and avoid the use of fluoroquinolones in patients who experience any of these serious adverse reactions. Because fluoroquinolones have been associated with serious adverse reactions, reserve levofloxacin for use in patients who have no alternative treatment options for the following indications: uncomplicated urinary tract infection, acute bacterial exacerbation of chronic bronchitis, and acute bacterial sinusitis.
Fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis. Avoid levofloxacin in patients with a known history of myasthenia gravis.
Anthrax:
Note: Consult public health officials for event-specific recommendations.
Inhalational (postexposure prophylaxis) (alternative agent) : Oral: 750 mg every 24 hours; duration depends on anthrax vaccine status and series completion, age, immune status, and pregnancy/breastfeeding status. For those who have not previously received an anthrax vaccine, duration ranges from 42 to 60 days (Ref). Some experts favor longer durations of prophylaxis (eg, total of 3 to 4 months) for patients who are immunocompromised or remain unvaccinated (Ref).
Note: Anthrax vaccine should also be administered to exposed individuals (Ref).
Cutaneous (without systemic involvement), treatment (off-label use) : Oral: 750 mg every 24 hours for 7 to 10 days after naturally acquired infection; treat for 60 days for bioterrorism-related cases. Note: Treat patients with extensive edema or cutaneous lesions of the head or neck with a parenteral regimen recommended for systemic involvement (Ref).
Systemic (with or without meningitis), treatment (alternative agent) (off-label use): IV: 750 mg every 24 hours, in combination with other appropriate agents for ≥2 to 3 weeks or until clinically stable, whichever is longer (Ref).
Note: Antitoxin should also be administered for patients with suspected systemic anthrax. Following the course of IV combination therapy for systemic anthrax infection (including meningitis), patients exposed to aerosolized spores require oral monotherapy to complete a total antimicrobial course of 60 days (Ref).
Bite wound infection, prophylaxis or treatment (animal or human bite) (alternative agent) (off-label use):
Oral, IV: 750 mg once daily, in combination with an agent appropriate for anaerobes. Duration of therapy is 3 to 5 days for prophylaxis (Ref); duration of treatment for established infection is typically 5 to 14 days and varies based on patient-specific factors, including clinical response (Ref).
Chronic obstructive pulmonary disease, acute exacerbation:
Note: Some experts reserve for outpatients with risk factors for poor outcomes (eg, ≥65 years of age, FEV1 <50% predicted, frequent exacerbations, significant comorbidities) or for inpatients without risk factors for Pseudomonas infection (Ref).
Oral, IV: 500 mg once daily (Ref) for 5 to 7 days (Ref); use 750 mg once daily if P. aeruginosa is suspected (Ref).
Diabetic foot infection (off-label use):
Note: When used as empiric therapy, levofloxacin should be used in combination with other appropriate agents.
Mild to moderate infection: Oral: 500 mg every 24 hours (750 mg every 24 hours if P. aeruginosa is suspected) (Ref).
Moderate to severe infection (alternative agent): IV: 750 mg every 24 hours (Ref).
Helicobacter pylori eradication (salvage regimen) (off-label use):
Note: Reserve use for levofloxacin susceptible isolates or if the population resistance rate is <15% (Ref).
Levofloxacin triple regimen: Oral: Levofloxacin 500 mg once daily, in combination with amoxicillin 750 mg 3 times daily, plus a double-dose proton pump inhibitor twice daily; continue regimen for 14 days (Ref).
Intra-abdominal infection, mild to moderate, community-acquired in patients without risk factors for resistance or treatment failure (off-label use):
Note: Empiric oral regimens may be appropriate for patients with mild to moderate infection. Other patients may be switched from IV to oral therapy when clinically improved and able to tolerate an oral diet (Ref).
Cholecystitis, acute: IV, Oral: 750 mg once daily (Ref); continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Ref). Note: The addition of anaerobic therapy (eg, metronidazole) is recommended if biliary-enteric anastomosis is present (Ref).
Other intra-abdominal infections (eg, perforated appendix, diverticulitis, intra-abdominal abscess):
Note: For acute diverticulitis, some experts suggest deferring antibiotics in otherwise healthy patients who are immunocompetent with mild disease (Ref).
IV, Oral: 750 mg once daily in combination with metronidazole. Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Ref). For diverticulitis or uncomplicated appendicitis managed without intervention, duration is 10 to 14 days (Ref); for perforated appendicitis managed with laparoscopic appendectomy, 2 to 4 days may be sufficient (Ref).
Neutropenia (chemotherapy-induced), antibacterial prophylaxis in high-risk patients anticipated to have an ANC ≤100 cells/mm3 for >7 days (off-label use):
Oral: 500 or 750 mg once daily (Ref). Some clinicians will provide antibacterial prophylaxis if ANC is anticipated to be <500 cells/mm3 for >7 days (Ref). For hematopoietic cell transplant recipients, begin at the time of stem cell infusion and continue until recovery of neutropenia or until initiation of empiric antibiotic therapy for neutropenic fever (Ref).
Odontogenic soft tissue infection, pyogenic (alternative agent) (off-label use):
Note: For patients unable to take beta-lactams (Chow 2022).
IV, Oral: 750 mg once daily in combination with metronidazole; continue until clinical resolution, typically for 7 to 14 days. Use in addition to appropriate surgical management (eg, drainage and/or extraction) (Chow 2022).
Osteomyelitis (off-label use):
Oral, IV: 750 mg once daily for ≥6 weeks (Ref).
Plague (Yersinia pestis):
Note: Consult public health officials for event-specific recommendations:
Treatment: Oral, IV: 750 mg every 24 hours for 7 to 14 days and for at least a few days after clinical resolution (Ref). For plague meningitis, use as part of an appropriate combination regimen (Ref).
Postexposure prophylaxis: Oral: 500 to 750 mg once daily for 7 days; use 750 mg once daily in patients who are pregnant (Ref).
Pneumonia:
Community-acquired pneumonia: Outpatients with comorbidities or inpatients:
Note: Some experts reserve fluoroquinolones for patients who cannot take other preferred regimens (Ref).
Oral, IV: 750 mg once daily. For inpatients with severe pneumonia or risk factors for methicillin-resistant Staphylococcus aureus, use as part of an appropriate combination regimen. Duration is for a minimum of 5 days; a longer course may be required for patients with an immunocompromising condition, severe or complicated infection, or for P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (Ref).
Hospital-acquired or ventilator-associated pneumonia :
Note: For empiric therapy, use in combination with other appropriate agents (Ref).
Oral, IV: 750 mg every 24 hours. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (Ref).
Prosthetic joint infection (off-label use):
Treatment:
Gram-negative bacilli: Oral, IV: 750 mg once daily (Ref).
Staphylococcus aureus, oral continuation therapy (following pathogen-specific IV therapy in patients undergoing 1-stage exchange or debridement with retention of prosthesis): Oral: 500 to 750 mg once daily in combination with rifampin; duration is a minimum of 3 months, depending on patient-specific factors (Ref).
Chronic suppressive therapy for gram-negative bacilli: Oral: 500 mg once daily (Ref).
Rhinosinusitis, acute bacterial (alternative agent):
Note: In uncomplicated acute bacterial rhinosinusitis, initial observation and symptom management without antibiotic therapy is appropriate in most patients. Reserve antibiotic therapy for poor follow-up or lack of improvement over the observation period (Ref). Due to risks associated with use, reserve fluoroquinolones for those who have no alternative treatment options (Ref).
Oral: 500 mg or 750 mg once daily for 5 to 7 days (Ref).
Salmonella (nontyphoidal) infection (alternative agent):
GI infection: Oral, IV: 500 mg once daily for 3 to 14 days (7 to 14 days in patients with HIV with a CD4 count ≥200 cells/mm3). Immunosuppressed patients (eg, patients with HIV and CD4 count <200 cells/mm3) require longer duration of treatment (eg, weeks to months) and may require a higher dose (eg, 750 mg once daily). Note: Reserve antibiotic treatment for patients with severe illness or at high risk of invasive disease (eg, extremes of age, immunosuppression); reserve parenteral therapy for those who cannot tolerate oral agents (Ref).
Bacteremia: Oral, IV: 500 or 750 mg once daily for 14 days. Note: Immunosuppressed patients (eg, HIV-infected with CD4 count <200 cells/mm3) and those with an extraintestinal focus of infection warrant a longer duration of treatment (eg, weeks to months) (Ref).
Sexually transmitted infections:
Cervicitis/urethritis due to Chlamydia trachomatis (alternative agent) (off-label use): Oral: 500 mg once daily for 7 days (Ref).
Epididymitis, acute (off-label use):
Patients ≥35 years of age and who are at low risk for sexually transmitted diseases (ie, likely caused by enteric organisms): Oral: 500 mg once daily for 10 days. Note: In patients <35 years of age or who are at risk of sexually transmitted diseases, fluoroquinolones are not recommended due to widespread resistance of N. gonorrhoeae to these agents (Ref).
Males of any age who practice insertive anal sex (ie, likely caused by sexually transmitted Chlamydia trachomatis or N. gonorrhoeae, and enteric organisms): Oral: 500 mg once daily for 10 days, in combination with a single dose of ceftriaxone (Ref).
Pelvic inflammatory disease, outpatient therapy, mild to moderate disease (alternative agent) (off-label use) :
Note: Reserve for patients who cannot use first-line options and are at low risk for fluoroquinolone-resistant N. gonorrhoeae (eg, prevalence is <5% in the location where the infection was acquired) (Ref).
Oral: 500 mg once daily in combination with metronidazole for 14 days (Ref).
Skin and soft tissue infection:
Cellulitis or abscess (alternative agent):
Note: Reserve for patients who require broad spectrum therapy because of severe sepsis or immunocompromising condition who cannot take beta-lactams (Ref). For patients with severe sepsis, initial therapy with IV is recommended with transition to oral therapy when clinical improvement and sepsis resolution occurs (Ref).
Oral, IV: 750 mg once daily in combination with other appropriate agents. Treat for 5 to 14 days depending on severity and clinical response (Ref).
Surgical site incisional infection:
Intestinal or genitourinary tract surgery: IV: 750 mg every 24 hours in combination with metronidazole (Ref).
Perineum or axilla surgery: Oral, IV: 750 mg every 24 hours in combination with metronidazole (Ref).
S. maltophilia infection, multidrug-resistant (alternative agent) (off-label use): Oral, IV: 750 mg every 24 hours. For mild infection, may use as monotherapy; however, use with caution, as resistance may develop during therapy. For moderate to severe infection, administer as part of an appropriate combination regimen (Ref).
Surgical (preoperative) prophylaxis (alternative agent) (off-label use):
IV: 500 mg beginning 120 minutes prior to initial surgical incision; use in combination with other appropriate agents may be warranted (procedure dependent) (Ref). Note: Postoperative prophylaxis is not recommended for clean and clean-contaminated surgeries (Ref).
Tuberculosis, drug-resistant (off-label use):
Oral, IV: 750 mg to 1 g once daily in combination with additional appropriate antituberculosis agents (Ref).
Duration: Individualize based on rapidity of culture conversion, extent of disease, and patient-specific factors, including clinical response and toxicity (Ref).
Urinary tract infection:
Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection) (alternative agent): Note: Use is discouraged due to safety concerns and increasing resistance; reserve for those who have no alternative treatment options (Ref). However, for men who have severe symptoms or concern for early prostate involvement, some experts prefer fluoroquinolones (Ref).
Oral: 250 mg once daily for 3 days (females) (Ref) or 5 days (males) (Ref).
Urinary tract infection, complicated, (including pyelonephritis): Note: If the prevalence of fluoroquinolone resistance is >10%, an initial dose of a long-acting parenteral antimicrobial (eg, ceftriaxone) followed by oral therapy is recommended for outpatients (Ref).
Oral, IV: 750 mg once daily for 5 to 7 days (Ref).
Missed dose: Administer as soon as possible if ≥8 hours until next scheduled dose; otherwise, wait until next scheduled dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Oral, IV:
|
CrCl (mL/minute) |
If usual recommended dose is 250 mg every 24 hours |
If usual recommended dose is 500 mg every 24 hours |
If usual recommended dose is 750 mg every 24 hoursa |
|---|---|---|---|
|
aTreatment of tuberculosis: CrCl >30 mL/minute: No dosage adjustment necessary. CrCl <30 mL/minute or on hemodialysis/peritoneal dialysis: Administer 750 mg or 1 g 3 times per week (Ref). Patients receiving hemodialysis 3 times/week: Administer dose after hemodialysis on dialysis days. b Severe infections and GFRCKD-EPI >80 mL/minute/1.73 m2: Monte Carlo simulations suggest a dose of 500 mg every 12 hours may be necessary to obtain pharmacodynamic targets when minimum inhibitory concentration ≥0.5 mg/L (Ref). cWhen scheduled dose falls on a dialysis day, administer post dialysis (Ref). | |||
|
≥50 |
No dosage adjustment necessary |
No dosage adjustment necessary |
No dosage adjustment necessaryb |
|
20 to <50 |
No dosage adjustment necessary |
500 mg initial dose, then 250 mg every 24 hours |
750 mg every 48 hours |
|
<20 |
250 mg every 48 hours (except for uncomplicated UTI, where no dosage adjustment is required) |
500 mg initial dose, then 250 mg every 48 hours |
750 mg initial dose, then 500 mg every 48 hours |
|
Hemodialysis, intermittent (thrice weekly)c: Dialyzable (21% [4-hour dialysis session utilizing high-flux dialyzers]) (Ref) |
250 mg every 48 hours (Ref) |
500 mg initial dose, then either 250 mg every 48 hours (Ref) or 125 mg every 24 hours (Ref) (if daily dosing improves adherence (Ref)) |
750 mg initial dose, then either 500 mg every 48 hours (Ref) or 250 mg every 24 hours (if daily dosing improves adherence (Ref)) |
|
Peritoneal dialysis |
250 mg every 48 hours (Ref) |
500 mg initial dose, then either 250 mg every 48 hours (Ref) or 125 mg every 24 hours (if daily dosing improves adherence [expert opinion derived from Kanamori 2001]) |
750 mg initial dose, then either 500 mg every 48 hours (Ref) or 250 mg every 24 hours (if daily dosing improves adherence (Ref)) |
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2 ): Augmented renal clearance (ARC) is a condition that occurs in certain critically-ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Note: Dose based on expert opinion derived from Monte Carlo simulations only (Ref).
Oral, IV: 750 mg loading dose followed by 500 mg every 12 hours or 1 g every 24 hours.
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations assume high-flux dialyzers and flow rates of ~1,500 to 3,000 mL/hour, and minimal residual kidney function unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.
CVVH/CVVHD/CVVHDF: Oral, IV:
|
If usual recommended dose is 250 mg every 24 hours |
If usual recommended dose is 500 mg every 24 hours |
If usual recommended dose is 750 mg every 24 hours |
|---|---|---|
|
No dosage adjustment necessary (Ref) |
500 mg initial dose, then 250 mg every 24 hours (Ref) or 500 mg every 48 hours (Ref) |
750 mg initial dose, then 500 mg every 24 hours (Ref) or 750 mg every 48 hours (Ref) |
PIRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.
Oral, IV (dialysate flow rate 160 mL/minute, 8-hour session):
|
If usual recommended dose is 250 mg every 24 hours |
If usual recommended dose is 500 mg every 24 hours |
If usual recommended dose is 750 mg every 24 hours |
|---|---|---|
|
No dosage adjustment necessary (Ref) |
500 mg initial dose, then 250 mg every 24 hours (after PIRRT treatment when possible) (Ref) |
750 mg every 48 hours (after PIRRT treatment when possible) (Ref) |
IV, Oral: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, dosage adjustment unlikely due to limited hepatic metabolism.
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2, and 3 obesity (BMI ≥30 kg/m2):
IV, Oral: No dosage adjustment necessary (Ref). Dose adjustments based on CrCl in patients with obesity remain the most important approach to ensuring patients receive optimal drug exposure. In patients with BMI ≥40 kg/m2 and CrCl >110 mL/minute, consider using therapeutic drug monitoring (if available) or alternative treatment options (Ref). Refer to adult dosing for indication-specific doses.
Rationale for recommendations: Levofloxacin is predominantly eliminated by the kidneys and is the most hydrophilic of the quinolones. Although there are limited data on the pharmacokinetics of levofloxacin in patients with BMI ≥30 kg/m2, the data suggest CrCl (particularly measured by Cockcroft-Gault equation) is the predominant patient factor guiding altered dosing (Ref). In one observational study in patients with BMI ≥40 kg/m2, levofloxacin AUC was not related to any body size metric; however, levofloxacin AUC was associated with CrCl (measured using Cockcroft-Gault with ideal body weight). A dose of 750 mg may be unlikely to achieve target endpoints in patients with BMI ≥40 kg/m2 and CrCl >110 mL/minute, especially organisms with higher minimum inhibitory concentrations (eg, Pseudomonas sp.) (Ref). A small pharmacokinetic study and a separate case study found no clear effects of obesity on levofloxacin dosing requirements, suggesting that weight-based dosing is not required (Ref).
Refer to adult dosing.
(For additional information see "Levofloxacin (systemic): Pediatric drug information")
Dosage guidance:
Dosage form information: Concentration of oral suspension may vary (commercially available or extemporaneous compounded); use caution.
Clinical considerations: In pediatric patients, fluoroquinolones are not routinely first-line therapy, but after assessment of risks and benefits, can be considered a reasonable alternative for situations where no safe and effective substitute is available (eg, multidrug resistance) or in situations where the only alternative is parenteral therapy and levofloxacin offers an oral therapy option (Ref).
General dosing, susceptible infection (Ref):
Infants ≥6 months, Children, and Adolescents:
6 months to <5 years: Oral, IV: 8 to 10 mg/kg/dose twice daily.
≥5 years: Oral, IV: 10 mg/kg/dose once daily; maximum dose: 750 mg/day.
Anthrax: Limited data available in infants <6 months of age: Note: Levofloxacin is not preferred therapy for any prophylaxis or treatment regimens; use should be considered when patients are unable to tolerate first-line therapy (eg, ciprofloxacin or others depending upon disease presentation). Although longer durations of therapy are recommended in guidelines in some cases based on risk:benefit assessments (eg, up to 60 days), specific safety data for levofloxacin in pediatric patients is limited to 14 days (Ref).
Infants, Children, and Adolescents:
Cutaneous, without systemic involvement; treatment (Ref): Appropriate for all strains regardless of penicillin susceptibility or if susceptibility unknown. Treatment duration: 7 to 10 days for naturally-acquired infection, and up to 60 days for biological weapon-related event.
<50 kg: Oral: 8 mg/kg/dose every 12 hours; maximum dose: 250 mg/dose.
≥50 kg: Oral: 500 mg every 24 hours.
Inhalational (postexposure prophylaxis) (Ref): Reserve levofloxacin use for penicillin-resistant strains or prior to susceptibility testing. Begin therapy as soon as possible after exposure.
<50 kg: Oral (preferred), IV: 8 mg/kg/dose every 12 hours for 60 days; maximum dose: 250 mg/dose.
≥50 kg: Oral (preferred), IV: 500 mg every 24 hours for 60 days.
Systemic anthrax (excluding meningitis); treatment (Ref): Note: A fluoroquinolone is appropriate for all strains regardless of penicillin susceptibility or if susceptibility unknown; ciprofloxacin is preferred.
Initial treatment: Use in combination with a protein synthesis inhibitor (eg, clindamycin); continue therapy for at least 14 days or longer until clinical criteria for stability are met.
<50 kg: IV: 10 mg/kg/dose every 12 hours; maximum dose: 250 mg/dose.
≥50 kg: IV: 500 mg every 24 hours.
Oral step-down therapy: Use in combination with a protein synthesis inhibitor (eg, clindamycin). Duration of therapy to complete treatment course is variable; some patients may require up to 60 days additional prophylaxis from onset of illness.
<50 kg: Oral: 8 mg/kg/dose every 12 hours; maximum dose: 250 mg/dose.
≥50 kg: Oral: 500 mg every 24 hours.
Systemic anthrax; disseminated infection including meningitis (or when meningitis cannot be ruled out):
Initial triple therapy: Use in combination with another bactericidal antimicrobial (beta-lactam or glycopeptide [depending on susceptibility]) and a protein synthesis inhibitor (eg, linezolid); continue therapy for at least 2 to 3 weeks or longer until clinical criteria for stability are met.
<50 kg: IV: 8 mg/kg/dose every 12 hours; maximum dose: 250 mg/dose.
≥50 kg: IV: 500 mg every 24 hours.
Oral step-down therapy: Use in combination with a protein synthesis inhibitor (eg, clindamycin). Duration of therapy to complete treatment course is variable; some patients may require up to 60 days additional prophylaxis from onset of illness.
<50 kg: Oral: 8 mg/kg/dose every 12 hours; maximum dose: 250 mg/dose.
≥50 kg: Oral: 500 mg every 24 hour.
Bacteremia prophylaxis in patients with acute myeloid leukemia (AML) or relapsed acute lymphocytic leukemia (ALL): Note: Recommended only during period when patient is severely neutropenic (ie, when absolute neutrophil count [ANC] is <500 cells/mm3) (Ref).
Infants ≥6 months and Children <5 years: Oral, IV: 10 mg/kg/dose every 12 hours (Ref).
Children ≥5 years and Adolescents: Oral, IV: 10 mg/kg/dose every 24 hours; maximum dose: 750 mg/dose (Ref).
Chlamydia trachomatis, urogenital infections: Adolescents: Oral: 500 mg every 24 hours for 7 days (Ref).
Cystic fibrosis pulmonary exacerbation: Limited data available (Ref):
Infants ≥6 months, Children, and Adolescents:
6 months to <5 years: Oral, IV: 10 mg/kg/dose twice daily.
≥5 years: Oral, IV: 10 mg/kg/dose once daily; maximum dose: 750 mg/day.
Epididymitis, nongonococcal: Adolescents: Oral: 500 mg once daily for 10 days (Ref).
Exit-site or tunnel infection, peritoneal dialysis catheter: Infants, Children, and Adolescents: Oral: 10 mg/kg/dose every 48 hours; maximum initial dose: 500 mg; maximum subsequent doses: 250 mg (Ref).
Mycobacterium avium Complex , severe or disseminated disease, HIV-exposed/-infected: Adolescents: Oral: 500 mg once daily in combination with other antibiotics (Ref).
Otitis media, acute (AOM) (alternative agent): Limited data available: Note: Not recommended for routine empiric use; may be considered for patients with severe penicillin allergy, persistent or recurrent infection, or resistant causative bacteria (Ref).
Infants ≥6 months and Children <5 years: Oral: 10 mg/kg/dose every 12 hours for 10 days (Ref).
Children ≥5 years and Adolescents: Oral: 10 mg/kg/dose every 24 hours for 10 days; maximum dose: 750 mg/dose (Ref).
Pelvic inflammatory disease: Adolescents: Oral: 500 mg once daily for 14 days with or without concomitant metronidazole; Note: Due to resistant organisms, the CDC recommends use as an alternative therapy only if standard parenteral cephalosporin therapy is not feasible and community prevalence, and individual risk of quinolone-resistant gonococcal organisms is low. Culture sensitivity must be confirmed (Ref).
Plague (Yersinia pestis), prophylaxis or treatment:
Infants ≥6 months, Children, and Adolescents: Note: Begin therapy as soon as possible after exposure:
<50 kg: Oral, IV: 8 mg/kg/dose every 12 hours for 10 to 14 days; maximum dose: 250 mg/dose.
≥50 kg: Oral, IV: 500 mg every 24 hours for 10 to 14 days.
Pneumonia, community-acquired (CAP) (Ref): Note: May consider addition of vancomycin or clindamycin to empiric therapy if community-acquired MRSA suspected. Levofloxacin is not the preferred agent for CAP but may be used as an alternative agent when necessary.
Typical pathogens (eg, H. influenzae, S. pneumoniae): Note: Oral administration is generally reserved for mild infections or step-down therapy.
Infants ≥6 months and Children <5 years: Oral, IV: 8 to 10 mg/kg/dose every 12 hours; maximum daily dose: 750 mg/day.
Children ≥5 years and Adolescents ≤16 years: Oral, IV: 8 to 10 mg/kg/dose once every 24 hours; maximum daily dose: 750 mg/day.
Atypical pathogens (eg, Mycoplasma pneumonia or Chlamydia ssp):
IV:
Infants ≥6 months and Children <5 years: IV: 8 to 10 mg/kg/dose every 12 hours; maximum daily dose: 750 mg/day.
Children ≥5 years and Adolescents ≤16 years: IV: 8 to 10 mg/kg/dose once every 24 hours; maximum daily dose: 750 mg/day.
Oral: Mild infection/step-down therapy: Adolescents with skeletal maturity: Oral: 500 mg once daily.
Rhinosinusitis, acute bacterial: Note: Recommended in the following types of patients: Type I penicillin allergy, after failure of initial therapy or in patients at risk for antibiotic resistance (eg, daycare attendance, age <2 years, recent hospitalization, antibiotic use within the past month) (Ref).
Children and Adolescents: Oral, IV: 10 to 20 mg/kg/day divided every 12 to 24 hours for 10 to 14 days; maximum daily dose: 500 mg/day.
Surgical prophylaxis: Children and Adolescents: IV: 10 mg/kg as a single dose 120 minutes prior to procedure; maximum dose: 500 mg/dose; Note: While fluoroquinolones have been associated with an increased risk of tendinopathy/tendon rupture in all ages, use of these agents for single-dose prophylaxis is generally safe (Ref).
Tuberculosis (TB), multidrug-resistant: Limited data available: Note: Use in combination with at least 3 to 4 additional anti-TB agents (overall multidrug regimen dependent upon susceptibility profile/patterns) (Ref):
Infants, Children, and Adolescents: Oral: 15 to 20 mg/kg/dose once daily; usual maximum daily dose: 1,000 mg/day; higher doses (1,250 to 1,500 mg/day) have been reported in adults (Ref).
Urethritis, nongonococcal: Adolescents: Oral: 500 mg every 24 hours for 7 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: IV, Oral: The following adjustments have been recommended (Ref). Note: Renally adjusted dose recommendations are based on doses of 5 to 10 mg/kg/dose every 12 hours in ages ≤5 years and 5 to 10 mg/kg/dose every 24 hours in ages >5 years.
GFR ≥30 mL/minute/1.73 m2: No adjustment necessary
GFR 10 to 29 mL/minute/1.73 m2: 5 to 10 mg/kg/dose every 24 hours
GFR <10 mL/minute/1.73 m2: 5 to 10 mg/kg/dose every 48 hours
Intermittent hemodialysis: 5 to 10 mg/kg/dose every 48 hours; not removed by hemodialysis; supplemental levofloxacin doses are not required
Peritoneal dialysis (PD): 5 to 10 mg/kg/dose every 48 hours; not removed by peritoneal dialysis; supplemental levofloxacin doses are not required
Continuous renal replacement therapy (CRRT): 10 mg/kg/dose every 24 hours
There are no dosage adjustments provided in the manufacturer's labeling; has not been studied; however, dosage adjustment unlikely to be necessary due to limited hepatic metabolism.
Fluoroquinolones have been associated with aortic aneurysm and aortic dissection with risk of aortic aneurysm higher than aortic dissection. Overall risk with levofloxacin may be higher than ciprofloxacin and moxifloxacin (Ref).
Mechanism : Time-related; upregulation of matrix metalloproteinase (MMP) enzymes capable of damaging components of the extracellular matrix, including collagen and elastin (Ref). MMP-2 and MMP-9 have been shown to play a role in development of aneurysms via degradation of collagen fibril (Ref). May also have a direct effect on the viability of chondrocytes and tenocytes responsible for collagen synthesis, due to generation of reactive oxygen species, caspase activation, and apoptosis (Ref).
Onset: Delayed in most cases. Studies evaluating risk generally evaluated the time period of 60 days after the initiation of fluoroquinolone therapy (Ref).
Risk factors:
• Older adults with peripheral vascular disease or a history of aneurysms, atherosclerosis, hypertension, or genetic conditions predisposing to aortic aneurysm (eg, Marfan syndrome, Ehlers-Danlos syndrome) (Ref)
• Longer courses of therapy (>14 days) (Ref)
• Severe emotional or physical stress has been correlated to the onset of pain (Ref)
Arthropathy, or joint disease, has been observed in both animal and pediatric human studies following treatment with fluoroquinolone antibiotics, including levofloxacin (Ref). In a pooled safety data analysis of ~2,500 pediatric patients, musculoskeletal events including arthralgia were observed more frequently at 2 months and 12 months after treatment with levofloxacin than comparative treatment; no physical joint abnormalities were observed (Ref). Long-term follow-up (up to 5 years) of ~200 of the initial patients demonstrated no difference in musculoskeletal adverse events including ongoing arthropathy, between levofloxacin and comparator (Ref). Arthropathy and arthralgias appear to resolve after discontinuation of treatment with no long-term sequelae (Ref). Though the true incidence is unknown, arthropathy and arthralgia are considered to be infrequent, but potentially serious adverse reactions.
Mechanism: Unknown; several hypotheses have been proposed including inhibition of mitochondria DNA synthesis in immature chondrocytes, direct toxic effect of fluoride on cartilage, magnesium chelation and subsequent deficiency in cartilage, and defective proteoglycan and procollagen synthesis with decreased incorporation of tritiated thymidine by chondrocytes (Ref).
Onset: Varied; may occur within a day of initiation or months following discontinuation (Ref).
Risk factors:
• Higher doses (Ref)
• Prolonged exposure (Ref)
Fluoroquinolones have been associated with a range of psychiatric and neurologic effects, from dizziness and restlessness to toxic psychosis (Ref). More common reactions include confusion, agitation, insomnia, and drowsiness. More severe reactions, including delusions, hallucinations, suicidal ideation, suicidal tendencies, and toxic psychosis are less common (Ref). Neuroexcitation may include seizure in some patients (Ref).
Mechanism: GABA binding disruption, NMDA binding alterations, and increased excitatory neurotransmitters (Ref). Mitochondrial dysfunction has been hypothesized to contribute (Ref).
Onset: Varied; neuroexcitatory phenomena generally occur in the first week of therapy, often after 2 to 3 days (Ref).
Risk factors:
• Older adults (Ref)
• Kidney impairment with unadjusted or higher doses (Ref)
• Concurrent therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with enhanced neuroexcitation (less risk with levofloxacin) (Ref)
• Concurrent theophylline (less risk with levofloxacin) (Ref)
• History of seizures, seizure disorders, CNS disorders, or concurrent therapy with medications known to lower seizure threshold may increase risk of seizures (Ref)
• History of or risk factor for mental illness (eg, depression)
Clostridioides difficile infection (CDI), including Clostridioides difficile associated diarrhea and Clostridioides difficile colitis, has been reported.
Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).
Risk factors:
• Antibiotic exposure (highest risk factor) (Ref)
• Type of antibiotic (fluroquinolones among the highest risk) (Ref)
• Long durations in a hospital or other health care setting (recent or current) (Ref)
• Older adults (Ref)
• Immunocompromised conditions (Ref)
• A serious underlying condition (Ref)
• GI surgery/manipulation (Ref)
• Antiulcer medications (eg, proton pump inhibitors and H2 blockers) (Ref)
• Chemotherapy (Ref)
Hyperglycemia and hypoglycemia have been associated with the use of fluoroquinolones, including levofloxacin.
Mechanism: Increase in insulin release via blockade of adenosine triphosphate-sensitive potassium channels in the pancreatic beta cells, but the significance at clinical concentrations has been questioned (Ref). Additionally, effects on gluconeogenesis, glucose transport (via expression of GLUT-1), and mitochondrial dysfunction have been implicated (Ref).
Onset: Varied; corresponds to the initiation of therapy but may be delayed by 2 to 3 days. Events requiring emergent care or hospitalization occurred between day 3 and day 10 of therapy (Ref).
Risk factors:
• Patients with diabetes are at highest risk; however, cases in patients without diabetes have been reported (Ref)
• Concurrent therapy with hypoglycemic agents, including insulin (Ref)
Liver injury/drug-induced liver injury: May cause liver injury (hepatotoxicity); both cholestatic and hepatocellular patterns are represented in reported clinical presentations (Ref). Published reports include at least 1 fatal case (Ref).
Mechanism: Immunologic reactions account for many events; direct toxicity related to mitochondrial dysfunction and increased oxidative stress may also be responsible for some reactions (Ref).
Onset: Varied; acute liver injury generally occurred within 14 days of initiation (most cases within 6 days) range of 1 to 39 days.
Risk factors:
• Most fatal events occurred in patients ≥65 years of age
Hypersensitivity reactions include anaphylaxis, nonimmune anaphylaxis (previously called anaphylactoid reactions) (Ref) and delayed cutaneous reactions.
Delayed cutaneous reactions include severe dermatologic reactions, acute generalized exanthematous pustulosis , drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Ref). Less severe reactions include fixed drug eruption and bullous pemphigoid reactions (Ref).
Immunologically mediated organ-specific reactions include pancreatitis, interstitial nephritis, hemolytic anemia, thrombocytopenia, and some cases of hepatitis (Ref).
Mechanism: Nonimmune anaphylaxis results from binding directly to specific receptors (MGPRX2) on mast cells and basophils, causing direct stimulation of histamine release (and other mediators) (Ref). Importantly, these cases may occur without prior exposure. In other cases, anaphylaxis may be mediated by IgE, formed with prior exposure to the drug (Ref).
Delayed reactions are mediated by activated T cells. Chemical activation of fluoroquinolones was not required for immune reactions to occur, which implies direct activation (pharmacologic interaction) without covalent binding to host proteins/hapten formation (Ref).
Onset: Anaphylaxis (nonimmune and immune): Rapid; may occur within an hour of administration (Ref). Other reactions, particularly various maculopapular cutaneous reactions or organ-specific reactions: Varied; occur after days to weeks of therapy (Ref).
Risk factors:
• Nonimmune anaphylaxis may be dose and/or infusion rate related (concentration-related) (Ref).
Fluoroquinolones, including levofloxacin, may cause an exacerbation of myasthenia gravis. Disease exacerbations vary in severity from muscular weakness to severe compromise (myasthenic crisis characterized by acute respiratory failure) (Ref).
Mechanism: Neuromuscular blockade is the most frequently cited mechanism, although alterations in mitochondrial energy production has also been suggested as a contributing mechanism (Ref).
Onset: Rapid; Within hours of the initiation of therapy with a fluoroquinolone (Ref).
Risk factors:
• Patients with myasthenia gravis (diagnosed and undiagnosed) (Ref).
Fluoroquinolones have been associated with peripheral neuropathy and other effects, including axonal neuropathy and Guillain-Barré syndrome (GBS) (Ref). Associated with many types of disturbances of special senses, including several case reports indicating a very slow recovery and/or permanent state of disability (Ref).
Mechanism: Mitochondrial effects related to reactive oxygen species and apoptotic changes (Ref).
Onset: Varied; may present as early as the first day of therapy (Ref).
Risk factors:
• Males (Ref)
• Older adults (>60 years of age) (Ref)
• Duration of therapy (Ref)
• Type 1 diabetes may also be a risk factor (data are limited) (Ref)
• History of peripheral neuropathy
Phototoxicity/skin photosensitivity account for a proportion of the overall cutaneous adverse reactions (Ref). Hyperpigmentation (brown-grey) in areas exposed to sunlight has also been reported with levofloxacin (Ref). Levofloxacin is considered a lower risk among the fluoroquinolone class (Ref).
Mechanism: Non-dose-related; immunologic. Reactive intermediates are generated by ultraviolet exposure and attach to proteins of Langerhans cells, triggering immune reactions (Ref).
Onset: Rapid; in a study with ofloxacin, occurred within 24 hours of initiation and sun exposure (Ref).
Risk factors:
• Duration and intensity of sun exposure
• Cystic fibrosis (Ref)
• Prior phototoxic reaction to another fluoroquinolone (Ref)
Fluoroquinolones may be associated with prolonged QT interval on ECG and ventricular arrhythmias, such as torsades de pointes (TdP). Levofloxacin may have a lower risk than other fluoroquinolones, particularly moxifloxacin (Ref). Change in QTc from baseline for moxifloxacin was found to be +16.34 to 17.83 ms, while the change with levofloxacin was +3.53 to 4.88 ms (Ref).
Mechanism: May alter the rapid delayed rectifier potassium current, resulting in prolonged repolarization (Ref). Prolonged repolarization can alter action potentials in cardiac cells and promote arrhythmogenic activity (Ref).
Onset: Varied; effect is concentration dependent, initially observed at supra-therapeutic doses (Ref). High dose or accumulation may influence timing/concentrations.
Risk factors:
Drug-induced QTc prolongation/ TdP (in general)
• Females (Ref)
• Age >65 years (Ref)
• Structural heart disease (eg, history of myocardial infarction or heart failure) (Ref)
• History of drug-induced TdP (Ref)
• Genetic defects of cardiac ion channels (Ref)
• Congenital long QT syndrome (Ref)
• Baseline QT interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)
• Electrolyte disturbances (eg, hypocalcemia, hypokalemia, hypomagnesemia) (Ref)
• Bradycardia (Ref)
• Hepatic impairment (Ref)
• Kidney impairment (Ref)
• Loop diuretic use (Ref)
• Sepsis (Ref)
• Concurrent administration of multiple medications (≥ 2) that prolong the QT interval or increase drug interactions that increase serum drug concentrations of QT prolonging medications (Ref)
May cause tendinopathy or rupture of tendon. Achilles is most commonly cited, but inflammation/rupture of many other tendons (including hand, rotator cuff, biceps, and thumb) has been reported (Ref).
Mechanism: Dose and time-related; upregulation of MMPs capable of damaging components of the extracellular matrix, including collagen and elastin (Ref). Direct effect on the viability of chondrocytes and tenocytes responsible for collagen synthesis, due to generation of reactive oxygen species, and caspase activation and apoptosis (Ref).
Onset: Varied; per the manufacturer's labeling, tendinopathy or tendon rupture may occur within hours or days of initiation or may be delayed for several months after discontinuation.
Risk factors:
• Age >60 years (Ref)
• Corticosteroid therapy (Ref)
• Kidney failure (Ref)
• Diabetes mellitus (Ref)
• Previous tendon disorders (eg, rheumatoid arthritis) (Ref)
• Solid organ transplant recipients (Ref)
• Strenuous physical activity (Ref)
• Longer duration of therapy and higher dosages (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Cardiovascular: Chest pain (1%), edema (1%)
Dermatologic: Pruritus (1%), skin rash (2%)
Gastrointestinal: Abdominal pain (2%), constipation (3%), diarrhea (5%), dyspepsia (2%), nausea (7%), vomiting (2%)
Genitourinary: Vaginitis (1%)
Infection: Candidiasis (1%)
Local: Injection site reaction (1%)
Nervous system: Dizziness (3%), headache (6%), insomnia (4%)
Respiratory: Dyspnea (1%)
<1%:
Cardiovascular: Palpitations, phlebitis, syncope, ventricular arrhythmia, ventricular tachycardia
Dermatologic: Urticaria
Endocrine & metabolic: Hyperglycemia, hyperkalemia, hypoglycemia
Gastrointestinal: Anorexia, Clostridioides difficile colitis, esophagitis, gastritis, gastroenteritis, glossitis, pancreatitis, stomatitis
Genitourinary: Genital candidiasis
Hematologic & oncologic: Anemia, granulocytopenia, thrombocytopenia
Nervous system: Abnormal dreams, abnormal gait, agitation, anxiety, confusion, depression, drowsiness, hallucination, hypertonia, nightmares, paresthesia, seizure, vertigo
Neuromuscular & skeletal: Arthralgia, hyperkinetic muscle activity, myalgia, skeletal pain, tremor
Renal: Acute kidney injury
Respiratory: Epistaxis
Postmarketing:
Cardiovascular: Aortic aneurysm (rare: <1%) (Meng 2018; Pasternak 2018), aortic dissection (rare: <1%) (Meng 2018; Pasternak 2018), hypersensitivity angiitis, hypotension, prolonged QT interval on ECG (rare: <1%) (Teng 2019), tachycardia (rare: <1%), torsades de pointes (rare: <1%) (Teng 2019), vasodilation
Dermatologic: Acute generalized exanthematous pustulosis, erythema multiforme, hyperpigmentation (rare: <1%) (Connors 2018), phototoxicity (rare: <1%), skin photosensitivity (rare: <1%), Stevens-Johnson syndrome, toxic epidermal necrolysis
Gastrointestinal: Ageusia, Clostridioides difficile associated diarrhea, dysgeusia
Genitourinary: Casts in urine, crystalluria
Hematologic & oncologic: Agranulocytosis, aplastic anemia, eosinophilia, hemolytic anemia, increased INR, leukopenia, pancytopenia, prolonged prothrombin time, thrombotic thrombocytopenic purpura
Hepatic: Hepatic failure, hepatotoxicity (idiosyncratic; rare: <1%) (Chalasani 2014; Gulen 2015; Schloss 2018)
Hypersensitivity: Anaphylactic shock, anaphylaxis, angioedema, fixed drug eruption, nonimmune anaphylaxis, serum sickness
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Charfi 2015)
Nervous system: Abnormal electroencephalogram, altered sense of smell, anosmia, delirium, disorientation, disturbance in attention, encephalopathy (rare), exacerbation of myasthenia gravis, Guillain-Barre syndrome (rare: <1%) (Ali 2014), increased intracranial pressure, memory impairment, nervousness, paranoid ideation, peripheral neuropathy (rare: <1%; may be irreversible), psychosis, restlessness, suicidal ideation, suicidal tendencies, toxic psychosis, voice disorder
Neuromuscular & skeletal: Muscular paralysis (musculospiral) (Pan 2017), rhabdomyolysis, rupture of tendon (less frequent: ≥1% to <4%) (van der Linden 2002), tendinopathy (less frequent: ≥1% to <4%) (van der Linden 2002)
Ophthalmic: Blurred vision, decreased visual acuity, diplopia, scotoma, uveitis
Otic: Hypoacusis, tinnitus
Renal: Interstitial nephritis
Respiratory: Bronchospasm, hypersensitivity pneumonitis
Miscellaneous: Fever, multi-organ failure
Hypersensitivity to levofloxacin, any component of the formulation, or other quinolones
Canadian labeling: Additional contraindications (not in US labeling): History of tendinopathy or tendon rupture associated with use of any quinolone antimicrobial agent
Concerns related to adverse effects:
• Superinfection: Prolonged use may result in fungal or bacterial superinfection.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required.
Special populations:
• Older adult: Adverse effects (eg, hepatotoxicity, tendon rupture, QT changes, aortic dissection) may be increased in the elderly.
• G6PD deficiency: Hemolytic reactions may (rarely) occur with fluoroquinolone use in patients with G6PD deficiency (Luzzatto 2020).
• Pediatric: Safety of use in pediatric patients for >14 days of therapy has not been studied; increased incidence of musculoskeletal disorders (eg, arthralgia, tendon rupture) has been observed in children.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
In pediatric patients, fluoroquinolones are not routinely first-line therapy, but after assessment of risks and benefits, can be considered a reasonable alternative for situations where no safe and effective substitute is available (eg, multidrug resistance) or in situations where the only alternative is parenteral therapy and levofloxacin offers an oral therapy option (AAP [Jackson 2016]).
Concentration of oral suspension may vary (commercially available or extemporaneous compound); use caution. Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous [preservative free]:
Generic: 250 mg/50 mL (50 mL); 500 mg/100 mL (100 mL); 750 mg/150 mL (150 mL); 25 mg/mL (20 mL, 30 mL [DSC])
Solution, Oral:
Generic: 25 mg/mL (100 mL, 200 mL, 480 mL)
Tablet, Oral:
Levaquin: 500 mg [DSC], 750 mg [DSC]
Generic: 250 mg, 500 mg, 750 mg
Yes
Solution (levoFLOXacin in D5W Intravenous)
250 mg/50 mL (per mL): $0.04 - $0.18
500 mg/100 mL (per mL): $0.03 - $0.15
750 mg/150 mL (per mL): $0.02 - $0.10
Solution (levoFLOXacin Intravenous)
25 mg/mL (per mL): $2.20
Solution (levoFLOXacin Oral)
25 mg/mL (per mL): $3.21
Tablets (levoFLOXacin Oral)
250 mg (per each): $16.81 - $17.53
500 mg (per each): $19.27 - $20.09
750 mg (per each): $36.07 - $36.12
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 5 mg/mL (50 mL, 100 mL, 150 mL); 5-5 MG/ML-% (50 mL, 100 mL, 150 mL)
Tablet, Oral:
Generic: 250 mg, 500 mg, 750 mg
Oral: Tablets may be administered without regard to meals. Oral solution should be administered at least 1 hour before or 2 hours after meals. Maintain adequate hydration of patient to prevent crystalluria. Administer at least 2 hours before or 2 hours after antacids containing magnesium or aluminum, sucralfate, metal cations (eg, iron), multivitamin preparations with zinc, or didanosine chewable/buffered tablets or the pediatric powder for solution.
IV: Infuse 250 to 500 mg IV solution over 60 minutes; infuse 750 mg IV solution over 90 minutes. Too rapid of infusion can lead to hypotension. Avoid administration through an intravenous line with a solution containing multivalent cations (eg, magnesium, calcium). Maintain adequate hydration of patient to prevent crystalluria or cylindruria.
Oral: Maintain adequate hydration to prevent crystalluria or cylindruria. Administer at least 2 hours before or 2 hours after antacids containing magnesium or aluminum, sucralfate, metal cations (eg, iron), multivitamin preparations with zinc, or didanosine chewable/buffered tablets or the pediatric powder for solution.
Tablets: May administer without regard to meals.
Oral solution: Administer 1 hour before or 2 hours after meals.
Missed dose: Administer as soon as possible if ≥8 hours until next scheduled dose; otherwise, wait until next scheduled dose.
Parenteral: Administer by slow IV infusion over 60 to 90 minutes (250 to 500 mg over 60 minutes; 750 mg over 90 minutes); avoid rapid or bolus IV infusion due to risk of hypotension. Avoid administration through an intravenous line with a solution containing multivalent cations (eg, magnesium, calcium). Maintain adequate hydration to prevent crystalluria or cylindruria; not for IM, SubQ, or intrathecal administration.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Levaquin tablets: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020634s073lbl.pdf#page=54
Treatment of community-acquired pneumonia, including multidrug-resistant strains of Streptococcus pneumoniae (MDRSP); nosocomial pneumonia; chronic obstructive pulmonary disease, acute exacerbation; rhinosinusitis, acute bacterial (ABRS); prostatitis (chronic bacterial); urinary tract infection (uncomplicated or complicated); acute pyelonephritis; skin and soft tissue infections (uncomplicated or complicated); inhalational anthrax (postexposure) to reduce incidence or disease progression; prophylaxis and treatment of plague due to Yersinia pestis
Limitations of use: Because fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions (eg, tendinopathy and tendon rupture, peripheral neuropathy, CNS effects), reserve levofloxacin for use in patients who have no alternative treatment options for acute exacerbation of chronic bronchitis, acute bacterial sinusitis, and uncomplicated urinary tract infections.
Anthrax; Bite wound infection, prophylaxis or treatment (animal or human bite); Cervicitis or urethritis due to Chlamydia trachomatis infection; Diabetic foot infection; Epididymitis, acute; Helicobacter pylori eradication; Intra-abdominal infection, mild to moderate, community-acquired in patients without risk factors for resistance or treatment failure; Neutropenia (chemotherapy-induced), antibacterial prophylaxis; Odontogenic soft tissue infection, pyogenic; Osteomyelitis; Pelvic inflammatory disease; Prostatitis (acute bacterial); Prosthetic joint infection; Salmonella (nontyphoidal) infection; Shigella infection; Stenotrophomonas maltophilia infection, multidrug-resistant; Surgical (preoperative) prophylaxis; Tuberculosis
Levaquin may be confused with Levoxyl, Levsin/SL, Lovenox
LevoFLOXacin may be confused with levETIRAcetam, levodopa, Levophed, levothyroxine
Levaquin [Argentina, Brazil, US, Venezuela] may be confused with Lariam brand name for mefloquine [multiple international markets]
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Blood Glucose Lowering Effects: Quinolones may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Amiodarone: Levofloxacin-Containing Products (Systemic) may enhance the QTc-prolonging effect of Amiodarone. Risk X: Avoid combination
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Amphetamines: May enhance the cardiotoxic effect of Quinolones. Risk C: Monitor therapy
Antacids: May decrease the absorption of Quinolones. Of concern only with oral administration of quinolones. Management: Avoid concurrent administration of quinolones and antacids to minimize the impact of this interaction. Recommendations for optimal dose separation vary by specific quinolone; see full monograph for details. Risk D: Consider therapy modification
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Calcium Salts: May decrease the absorption of Quinolones. Of concern only with oral administration of both agents. Management: Consider administering an oral quinolone at least 2 hours before or 6 hours after the dose of oral calcium to minimize this interaction. Monitor for decreased therapeutic effects of quinolones during coadministration. Risk D: Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Quinolones. Specifically, the risk of tendonitis and tendon rupture may be increased. Risk C: Monitor therapy
Dabrafenib: QT-prolonging Quinolone Antibiotics (Moderate Risk) may enhance the QTc-prolonging effect of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Delamanid: May enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). QT-prolonging Quinolone Antibiotics (Moderate Risk) may enhance the QTc-prolonging effect of Delamanid. Management: Avoid concomitant use of delamanid and quinolone antibiotics if possible. If coadministration is considered to be unavoidable, frequent monitoring of electrocardiograms throughout the full delamanid treatment period should occur. Risk D: Consider therapy modification
Didanosine: Quinolones may decrease the serum concentration of Didanosine. Didanosine may decrease the serum concentration of Quinolones. 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
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Fluorouracil Products: QT-prolonging Quinolone Antibiotics (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Haloperidol: May enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Hydroxychloroquine: May enhance the hyperglycemic effect of Levofloxacin-Containing Products (Systemic). Hydroxychloroquine may enhance the hypoglycemic effect of Levofloxacin-Containing Products (Systemic). Hydroxychloroquine may enhance the QTc-prolonging effect of Levofloxacin-Containing Products (Systemic). Risk C: Monitor therapy
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Iron Preparations: May decrease the serum concentration of Quinolones. Management: Give oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome-, 3 h for gemi-, and 2 h for enox-, levo-, nor-, oflox-, peflox, or nalidixic acid) oral iron. Risk D: Consider therapy modification
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Lanthanum: May decrease the serum concentration of Quinolones. Management: Administer oral quinolone antibiotics at least one hour before or four hours after lanthanum. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Magnesium Salts: May decrease the serum concentration of Quinolones. Management: Administer oral quinolones several hours before (4 h for moxi/pe/spar/enox-, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome/pe/enox-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral magnesium salts. Risk D: Consider therapy modification
Methadone: Levofloxacin-Containing Products (Systemic) may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Methylphenidate: May enhance the cardiotoxic effect of Quinolones. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Quinolones. Specifically, polyvalent cations in multivitamin products may decrease the absorption of orally administered quinolone antibiotics. Management: Administer oral quinolones at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (ie, calcium, iron, magnesium, selenium, zinc). Monitor for decreased quinolone efficacy. Risk D: Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Quinolones. Specifically, minerals in the multivitamin/mineral product may impair absorption of quinolone antibiotics. Management: Administer oral quinolones at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (ie, calcium, iron, magnesium, selenium, zinc). Monitor for decreased therapeutic effects of quinolones. Risk D: Consider therapy modification
Mycophenolate: Quinolones may decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy
Nadifloxacin: May enhance the adverse/toxic effect of Quinolones. Risk X: Avoid combination
Nonsteroidal Anti-Inflammatory Agents: May enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Risk C: Monitor therapy
Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Polyethylene Glycol-Electrolyte Solution: May decrease the absorption of Quinolones. Management: Give oral quinolones at least 2 hours before or at least 6 hours after polyethylene glycol-electrolyte solutions that contain magnesium sulfate (Suflave brand). Other products without magnesium do not require dose separation. Risk D: Consider therapy modification
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Probenecid: May decrease the excretion of Quinolones. Specifically, probenecid may decreased the renal excretion of quinolone antibiotics. Probenecid may increase the serum concentration of Quinolones. Risk C: Monitor therapy
QT-prolonging Antidepressants (Moderate Risk): QT-prolonging Quinolone Antibiotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Quinolone Antibiotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IA Antiarrhythmics (Highest Risk): Levofloxacin-Containing Products (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-prolonging Quinolone Antibiotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class III Antiarrhythmics (Highest Risk): Levofloxacin-Containing Products (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid combination
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of Levofloxacin-Containing Products (Systemic). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Quinolone Antibiotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Highest Risk): Levofloxacin-Containing Products (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Quinolone Antibiotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of other QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): QT-prolonging Quinolone Antibiotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Quinolone Antibiotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Strontium Ranelate: May decrease the serum concentration of Quinolones. Management: In order to minimize any potential impact of strontium ranelate on quinolone antibiotic concentrations, it is recommended that strontium ranelate treatment be interrupted during quinolone therapy. Risk X: Avoid combination
Sucralfate: May decrease the serum concentration of Quinolones. Management: Avoid concurrent administration of quinolones and sucralfate to minimize the impact of this interaction. Recommendations for optimal dose separation vary by specific quinolone. Risk D: Consider therapy modification
Tacrolimus (Systemic): LevoFLOXacin (Systemic) may enhance the QTc-prolonging effect of Tacrolimus (Systemic). LevoFLOXacin (Systemic) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Quinolones may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Zinc Salts: May decrease the serum concentration of Quinolones. Management: Give oral quinolones at several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome-, 3 h for gemi-, and 2 h for enox-, levo-, nor-, pe- or ofloxacin or nalidixic acid) oral zinc salts. Risk D: Consider therapy modification
Administration with food prolonged time to peak by ~1 hour and decreased the peak concentration by ~14% and ~25% for the tablet and oral solution, respectively. Management: Tablet may be administered without regard to food; oral solution should be administered at least 1 hour before or 2 hours after food.
Levofloxacin crosses the placenta and can be detected in the amniotic fluid and cord blood (Ozyüncü 2010a; Ozyüncü 2010b).
Based on available data, an increased risk of major birth defects, miscarriage, or other adverse fetal and maternal outcomes have not been observed following levofloxacin use during pregnancy (Acar 2019; Yefet 2018; Ziv 2018).
Levofloxacin is an alternative agent for treatment of drug-resistant tuberculosis. Tuberculosis (TB) disease (active TB) is associated with adverse fetal outcomes, including intrauterine growth restriction, low birth weight, preterm birth, and perinatal death (Esmail 2018; Miele 2020), as well as adverse maternal outcomes, including increased risks for anemia and cesarean delivery. Placental transmission may rarely occur with active maternal disease (Miele 2020). Data are limited for use of second-line drugs in pregnancy (ie, fluroquinolones). Individualized regimens should be utilized to treat multidrug-resistant tuberculosis in pregnant patients; evidence to support a specific regimen is not available. Based on susceptibility testing, levofloxacin may be used to treat multidrug-resistant TB during pregnancy when needed (ATS/CDC/ERS/IDSA [Nahid 2019]; HHS [OI adult 2020]; WHO 2020).
Levofloxacin is approved to reduce the incidence or disease progression of inhalational anthrax (postexposure). Untreated anthrax infection during pregnancy is associated with preterm labor, fetal distress, and fetal loss. However, levofloxacin is not the preferred fluoroquinolone for the prophylaxis or treatment of anthrax in pregnant and postpartum patients (Meaney-Delman 2014).
Untreated plague (Yersinia pestis) infection in pregnant patients may result in hemorrhage (including postpartum hemorrhage), maternal and fetal death, preterm birth, and stillbirth. Limited data suggest maternal-fetal transmission of Y. pestis can occur if not treated. Pregnant patients should be treated for Y. pestis; parenteral antibiotics are preferred for initial treatment when otherwise appropriate. Levofloxacin is one of the fluoroquinolones recommended for use (in combination with an aminoglycoside) for treating pregnant patients with bubonic, pharyngeal, pneumonic, or septicemic plague. Recommendations for treating pregnant patients with plague meningitis are the same as in nonpregnant patients. Levofloxacin may also be used for pre- and postexposure prophylaxis in pregnant patients exposed to Y. pestis (CDC [Nelson 2021]).
Antibiotics other than levofloxacin are recommended for the treatment of uncomplicated urinary tract infections and pyelonephritis during pregnancy (Betschart 2020).
Levofloxacin is present in breast milk.
Breast milk concentrations were measured in a woman receiving levofloxacin for treatment of a septic knee. Therapy was started as levofloxacin 500 mg/day IV for 9 days, followed by 14 days of oral therapy. A total of 26 breast milk samples were taken starting 10 days after the initiation of therapy and continuing after therapy was completed. During therapy, breast milk was expressed, but not fed to her preterm infant (27 weeks estimated gestation age). Steady-state peak milk concentration was 8.2 mcg/mL and occurred 5 hours after the dose. The half-life in the breast milk was approximately 7 hours, but small amounts were still detectable in the milk 65 hours after the last dose (Cahill 2005). Using a milk concentration of 8.2 mcg/mL, the estimated exposure to the breast-feeding infant would be 1.23 mg/kg/day (relative infant dose [RID] 6% based on a therapeutic infant dose of 20 mg/kg/day). In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).
Levofloxacin may be considered for use in breastfeeding patients requiring antibiotics for inhalational anthrax (postexposure); according to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. However, patients with active cutaneous anthrax lesions on the breast should avoid direct infant contact; feeding from the affected breast should be avoided until 48 hours after the appropriate antibiotic therapy (Meaney-Delman 2014).
For other indications, the manufacturer does not recommend use of levofloxacin in breastfeeding patients during therapy or for 2 days after the last levofloxacin dose due to concerns of potential serious adverse reactions; alternatively, lactating patients can pump and discard breast milk during therapy and for 2 days after the last levofloxacin dose. The risk of articular damage in breastfed infants exposed to other quinolones (ie, ciprofloxacin) is considered low even in children receiving high therapeutic doses. Therefore, some sources do not consider maternal use of these agents to be a reason to discontinue breastfeeding as long as the infant is monitored for GI symptoms (eg, diarrhea) that could occur following antibiotic exposure (Kaplan 2015). Other sources recommend avoiding quinolone antibiotics if alternative agents are available (WHO 2002).
The risk for transmission of plague (Yersinia pestis) via breast milk is considered low. Patients with pneumonic plague can breastfeed if both the mother and infant are receiving antibiotic treatment or the infant is receiving postexposure prophylaxis, considering the risk of exposure to the drug via breast milk. If the infant is not being treated, breast milk should be expressed for at least 48 hours of maternal antibiotic therapy to limit person-to-person contact with the infant. The expressed breast milk may be given to the infant. Once maternal clinical improvement is observed, direct breastfeeding may resume (CDC [Nelson 2021]).
In general, antibiotics that are present in breast milk may cause non–dose-related modification of bowel flora. Monitor infants for GI disturbances (WHO 2002).
Tablets may be taken without regard to meals. Oral solution should be administered on an empty stomach (at least 1 hour before or 2 hours after a meal).
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, altered mental status, signs and symptoms of tendinopathy (tendon pain, swelling, inflammation, or rupture) or peripheral neuropathy; signs and symptoms of disordered glucose regulation (especially in patients with diabetes mellitus); rash; signs and symptoms of hypersensitivity reaction.
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.
Absorption: Rapid and complete; levofloxacin oral tablet and solution formulations are bioequivalent
Distribution: Widely distributed in the body, including blister fluid, skin tissue, macrophages, prostate, and lung tissue; CSF concentrations ~15% of serum concentrations
Vd: (Chien 2005):
Infants ≥6 months, Children, and Adolescents ≤16 years: Mean range: 1.44 to 1.57 L/kg; reported values not statistically different between pediatric age subgroups; distribution not age-dependent
Adults: 1.27 L/kg
Protein binding: ~24% to 38%; primarily to albumin
Metabolism: Minimally hepatic
Bioavailability: ~99%
Half-life elimination:
Infants ≥6 months and Children ≤5 years: ~4 hours (Chien 2005)
Children 5 to 10 years: 4.8 hours (Chien 2005)
Children 10 to 12 years: 5.4 hours (Chien 2005)
Children 12 to 16 years: 6 hours (Chien 2005)
Adults: ~6 to 8 hours
Adults, renal impairment: 27 ± 10 hours (CrCl 20 to 49 mL/minute); 35 ± 5 hours (CrCl <20 mL/minute)
Time to peak, serum: Oral: 1 to 2 hours
Excretion: Urine (~87% as unchanged drug, <5% as metabolites); feces (<4%)
Clearance: IV (Chien 2005):
Infants and Children 6 months to 2 years: 0.35 ± 0.13 L/hour/kg
Children 2 to 5 years: 0.32 ± 0.08 L/hour/kg
Children 5 to 10 years: 0.25 ± 0.05 L/hour/kg
Children 10 to 12 years: 0.19 ± 0.05 L/hour/kg
Children 12 to 16 years: 0.18 ± 0.03 L/hour/kg
Adults: 0.15 ± 0.02 L/hour/kg
Renal impairment: Cl is reduced and half-life prolonged in patients with CrCl less than 50 mL/minute.
Anti-infective considerations:
Parameters associated with efficacy:
Concentration dependent, associated with AUC24/minimum inhibitory concentration (MIC), goal: >87 (90% positive predictive value for pathogen eradication) (Cojutti 2017; Drusano 2004); and Cmax (peak)/MIC, goal ≥12 (clinical and microbiologic cures) (Abdul-Aziz 2020; Preston 1998). Note: In critically ill patients, some experts recommend AUC24/MIC goal >125 to 250 (Abdul-Aziz 2020).
Organism specific:
S. pneumoniae: AUC24/MIC ≥30 (bactericidal) (Ambrose 2001; Garrison 2003; Lacy 1999; Lister 1999).
Mycobacterium tuberculosis: AUC24/MIC ≥146 (bacteriostatic at 24 hours) (Deshpande 2018).
Pseudomonas aeruginosa: AUC24/MIC ≥80 (bactericidal) (Griffith 2006).
Expected drug exposure in patients with normal renal function:
AUC:
Adults (multiple dose): AUC24:
500 mg daily: Oral: 47.5 ± 6.7 mg•hour/L; IV: 54.6 ± 11.1 mg•hour/L.
750 mg daily: Oral: 90.7 ± 17.6 mg•hour/L; IV: 108 ± 34 mg•hour/L.
Cmax (peak):
Pediatric patients:
7 mg/kg (single dose) (Chien 2005):
Infants and children 6 months to <5 years of age: Oral: 4.21 to 4.56 mg/L; IV: 5.19 to 6.02 mg/L.
Children and adolescents 5 to 16 years of age: Oral: 3.99 to 4.76 mg/L; IV: 6.12 to 7.3 mg/L.
15 mg/kg daily (steady state) (Thee 2014):
Infants and children <6 years of age: Oral: Median: 6.86 to 7 mg/L (interquartile range: 4.69 to 8.06 mg/L).
Children 6 to 8 years of age: Oral: Median: 4.98 mg/L (interquartile range: 4.52 to 7.48 mg/L).
Adults (multiple dose):
500 mg daily: Oral: 5.7 ± 1.4 mg/L; IV: 6.4 ± 0.8 mg/L.
750 mg daily: Oral: 8.6 ± 1.9 mg/L; IV: 12.1 ± 4.1 mg/L.
Postantibiotic effect: Bacterial killing continues after levofloxacin concentration falls below the MIC of targeted pathogen and varies based on the organism; generally, 1 to 3 hours (Fu 1992; Houston 1994; Licata 1997; Spangler 1998).
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
