Fluoroquinolones (oral)

Last Updated

Medications listed in the tables and non-FDA approved indications included in these retrospective criteria are not indicative of Vendor Drug Program formulary coverage.

  • Revision history
    • July 2022, June 2020; May 2018; Nov. 2015; Feb. 2014; June 2012; Oct. 2010; Sept. 2007; May 2007; Sept. 2006; Aug. 2006; Aug. 2003; Sept. 2002; Sept. 2001; Aug. 2000; Nov. 1999; Oct. 1999; Sept. 1999; Sept. 1998; Sept. 1997.
  • Initially developed
    • Oct. 1996

1.1. Adults

Maximum recommended adult daily doses for fluoroquinolones are summarized in Table 1. Prescribed dosages exceeding these recommendations will be reviewed.

Table 1. Adult Oral Fluoroquinolone Maximum Dosage Recommendations1-9
Drug Name Dosage Form/Strength Treatment Indication Maximum Recommended Dosage 
ciprofloxacin (Cipro®, generics) immediate-release (IR)#: 100 mg, 250 mg, 500 mg, 750 mg tablets; 250 mg/5 mL, 500 mg/5 mL suspension acute sinusitis 500 mg twice daily
    bone and joint infections 750 mg twice daily
    chronic bacterial prostatitis 500 mg twice daily
    complicated intra-abdominal infections (in combination with metronidazole) 500 mg twice daily
    complicated, uncomplicated skin/skin structure infections 750 mg twice daily
    infectious diarrhea 500 mg twice daily
    inhalational anthrax (post-exposure) 500 mg twice daily
    lower respiratory tract infections 750 mg twice daily
    moderate, complicated urinary tract infection (UTI) 500 mg twice daily
    plague 1500 mg/day
    typhoid fever 500 mg twice daily
    uncomplicated cervical, urethral gonococcal infections* 250 mg as single dose
    Uncomplicated UTI 250 mg twice daily
ciprofloxacin (Cipro® XR, generics) extended-release (ER)#:  500 mg, 1000 mg tablets acute uncomplicated pyelonephritis 1000 mg/day
    complicated UTI 1000 mg/day
    uncomplicated UTI 500 mg/day
delafloxacin (Baxdela®) 450 mg tablets acute bacterial skin/skin structure infections 450 mg twice daily
    community acquired bacterial pneumonia (CABP) 450 mg twice daily
gemifloxacin (Factive®) 320 mg tablets chronic bronchitis (acute bacterial exacerbation) 320 mg daily
    Community acquired pneumonia (CAP) 320 mg daily
levofloxacin (Levaquin®, generics) 250 mg, 500 mg, 750 mg tablets, 25 mg/mL solution acute bacterial sinusitis 750 mg once daily
    acute pyelonephritis 750 mg once daily
    chronic bacterial prostatitis 500 mg once daily
    chronic bronchitis (acute bacterial exacerbation) 500 mg once daily
    CAP 750 mg once daily
    complicated skin/skin structure infections 750 mg once daily
    inhalational anthrax 500 mg once daily
    mild/moderate complicated UTI 750 mg once daily
    nosocomial pneumonia 750 mg/day
    plague or plague prophylaxis 500 mg once daily
    uncomplicated skin/skin structure infections 500 mg once daily
    uncomplicated UTI 250 mg once daily
moxifloxacin (Avelox®, generics) 400 mg tablets acute bacterial sinusitis 400 mg once/day
    chronic bronchitis (acute bacterial exacerbation) 400 mg once/day
    CAP 400 mg once/day
    complicated intra-abdominal infections 400 mg once/day
    complicated skin/skin structure infections 400 mg once/day
    plague or plague prophylaxis 400 mg once/day
    uncomplicated skin/skin structure infections 400 mg once/day
ofloxacin (generics) 200 mg, 300 mg, 400 mg tablets acute pelvic inflammatory disease (PID)^ 400 mg twice daily
    acute, uncomplicated urethral, cervical gonorrhea* 400 mg as single dose
    chronic bronchitis (acute bacterial exacerbation) 400 mg twice daily
    CAP 400 mg twice daily
    complicated UTI 200 mg twice daily
    mixed infection of urethra, cervix due to C. trachomatis and N. gonorrhoeae* 300 mg twice daily
    nongonococcal cervicitis/urethritis due to Chlamydia trachomatis 300 mg twice daily
    prostatitis due to E. coli 300 mg twice daily
    uncomplicated cystitis due to E. coli or K. pneumoniae 200 mg twice daily
    uncomplicated cystitis due to other organisms 200 mg twice daily
    uncomplicated skin and skin structure infections 400 mg twice daily

Legend:

  • # ciprofloxacin immediate-release and extended-release tablets are not interchangeable
  • * CDC no longer recommends fluoroquinolones for treatment of infections due to N. gonorrhoeae
  • ^ CDC no longer recommends fluoroquinolones for treating PID; may be considered in combination with metronidazole if parenteral therapy not feasible

1.2. Pediatrics

Fluoroquinolones are not drugs of choice in pediatric patients due to an increased incidence of musculoskeletal adverse reactions, including arthralgias and events related to surrounding joints and tissues10. However, ciprofloxacin and levofloxacin have been evaluated for use in pediatric patients and are FDA-approved for use in select circumstances. Recommended dosage guidelines for fluoroquinolones in pediatric patients are summarized in Table 2.

Table 2. Fluoroquinolone Recommended Dosage Guidelines in Pediatric Patients1-3,7
Drug Name Treatment Indication Maximum Recommended Dosage 
ciprofloxacin complicated urinary tract infection (UTI) or pyelonephritis 10-20 mg/kg orally every 12 hours (not to exceed 750 mg/dose)
  inhalational anthrax (postexposure prophylaxis) 15 mg/kg orally every 12 hours (not to exceed 500 mg/dose)
  plague 15 mg/kg orally every 8-12 hours (not to exceed 500 mg/dose)
levofloxacin inhalational anthrax (postexposure prophylaxis)

Greater than or equal to 6 months of age and less than 50 kg: 8 mg/kg orally every 12 hours (not to exceed 250 mg/dose)

Greater than or equal to 6 months of age and greater than 50 kg: 500 mg orally once daily

  plague

Greater than or equal to 6 months of age and less than 50 kg: 8 mg/kg orally every 12 hours (not to exceed 250 mg/dose)

Greater than or equal to 6 months of age and greater than 50 kg: 500 mg orally once daily

2. Duration of Therapy

Therapy duration for antibiotics like fluoroquinolones is based on the type and severity of infection. Recommendations for usual or documented therapy durations for adults are summarized in Table 3. However, severe or complicated infections may require prolonged therapy.

Table 3. Adult Oral Fluoroquinolone Maximum Recommended Therapy Duration1-9
Drug Name Treatment Indication Maximum Therapy Duration
ciprofloxacin, IR acute sinusitis 10 days
  bone and joint infections 4 to 8 weeks
  chronic bacterial prostatitis 28 days
  complicated intra-abdominal infections (in combination with metronidazole) 7 to 14 days
  complicated, uncomplicated skin/skin structure infections 7 to 14 days
  infectious diarrhea 5 to 7 days
  inhalational anthrax (post-exposure) 60 days
  lower respiratory tract infections 7 to 14 days
ciprofloxacin, IR or ER moderate, complicated UTI 7 to 14 days
Ciprofloxacin, IR typhoid fever 10 days
  uncomplicated cervical, urethral gonococcal infections* single dose
ciprofloxacin, IR or ER uncomplicated UTI 3 days
delafloxacin acute bacterial skin/skin structure infections 5-14 days
  community acquired bacterial pneumonia (CABP) 5-10 days
gemifloxacin chronic bronchitis (acute bacterial exacerbation) 5 days
  CAP 5 to 7 days
levofloxacin acute bacterial sinusitis 10 to 14 days (500 mg dose); 5 days (750 mg dose)
  acute pyelonephritis 10 days (250 mg dose); 5 days (750 mg dose)
  chronic bacterial prostatitis 28 days
  chronic bronchitis (acute bacterial exacerbation) 7 days
  CAP 7 to 14 days (500 mg dose); 5 days (750 mg dose)
  complicated skin/skin structure infections 7 to 14 days (750 mg dose)
  inhalational anthrax 60 days+
  mild/moderate complicated UTI 10 days (250 mg dose); 5 days (750 mg dose)
  hospital acquired pneumonia 7 to 14 days
  plague or plague prophylaxis 10 to 14 days (500 mg dose; 750 mg dose considered if clinically warranted)
  uncomplicated skin/skin structure infections 7 to 10 days (500 mg dose)
  uncomplicated UTI 3 days (250 mg dose)
moxifloxacin acute bacterial sinusitis 10 days (5 to 7 days IDSA guidelines)
  chronic bronchitis (acute bacterial exacerbation) 5 days
  CAP 7 to 14 days
  complicated intra-abdominal infections 5 to 14 days
  complicated skin/skin structure infections 7 to 21 days
  plague or plague prophylaxis 10 to 14 days
  uncomplicated skin/skin structure infections 7 days
ofloxacin acute pelvic inflammatory disease (PID) 10 to 14 days^
  acute, uncomplicated urethral, cervical gonorrhea* (400 mg dose) 1 day
  chronic bronchitis (acute bacterial exacerbation) 10 days
  CAP 10 days
  complicated UTI 10 days
  mixed infection of urethra, cervix due to C. trachomatis and N. gonorrhoeae* 7 days
  nongonococcal cervicitis/urethritis due to Chlamydia trachomatis 7 days
  prostatitis due to E. coli 6 weeks
  uncomplicated cystitis due to E. coli or K. pneumoniae 3 days
  uncomplicated cystitis due to other organisms 7 days
  uncomplicated skin and skin structure infections 10 days

Legend:

  • +Levofloxacin safety greater than 28 days in adults and greater than 14 days in pediatric patients to manage anthrax has not been studied; use for greater than 28 days in adults and greater than 14 days in pediatrics when benefits outweigh risks
  • * CDC no longer recommends fluoroquinolones for treatment of infections due to N. gonorrhoeae
  • ^CDC no longer recommends fluoroquinolones for treating PID; may be considered in combination with metronidazole if parenteral therapy not feasible

Fluoroquinolone therapy duration in pediatric patients is summarized in Table 4.

Table 4. Pediatric Oral Fluoroquinolone Maximum Recommended Therapy Duration1-3,7

 

Drug Name

Treatment Indication Maximum Therapy Duration
ciprofloxacin UTI, pyelonephritis 10 to 21 days
  inhalational anthrax (postexposure prophylaxis) 60 days
  plague 14 days
levofloxacin inhalational anthrax (postexposure prophylaxis) 60 days+
  plague 10 to 14 days

Legend:

  • UTI = urinary tract infection
  • +Levofloxacin safety when used for longer than 14 days in pediatric patients has not been studied; use for greater than 14 days when benefit outweighs risk

3. Duplicative Therapy

The adjunctive use of two or more fluoroquinolones is not recommended. Additional therapeutic benefit is not realized when fluoroquinolones are administered in combination. Patient profiles containing concurrent prescriptions for multiple fluoroquinolones will be reviewed.

4. Drug-Drug Interactions

Patient profiles will be assessed to identify those drug regimens, which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for oral fluoroquinolones are summarized in Table 5. Only those drug-drug interactions classified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.

Table 5. Oral Fluoroquinolone Drug-Drug Interactions2-9
Target Drug Interacting Drug Interaction Recommendation Clinical Significance Level#
ciprofloxacin drugs metabolized by CYP1A2 (e.g., alosetron, caffeine, clozapine, duloxetine, mexiletine, ropinirole, tizanidine) concurrent administration ciprofloxacin, a known CYP1A2 inhibitor, with drugs metabolized by CYP1A2 may result in increased serum levels of drugs metabolized by CYP1A2 and potentially increased pharmacologic/adverse effects if combination necessary, monitor for increased adverse effects; alternative FQ that does not affect CYP1A2 enzymes may be considered contraindicated,  major, moderate (DrugReax) 2-major, 3-moderate (CP)
ciprofloxacin methotrexate co-administration may result in reduced methotrexate renal tubular transport and potential for increased methotrexate levels and increased pharmacologic/adverse effects measure methotrexate concentrations and observe patients for increased adverse effects moderate (DrugReax) 3-moderate (CP)
ciprofloxacin mycophenolate concurrent administration may decrease mycophenolic acid concentrations monitor response to therapy when ciprofloxacin is started or stopped moderate (DrugReax) 3-moderate (CP)
ciprofloxacin phenytoin concurrent use may result in increased or decreased phenytoin concentrations ; mechanism unknown measure phenytoin concentrations and observe patients for increased or decreased pharmacologic  effects moderate (DrugReax) 3-moderate (CP)
ciprofloxacin phosphodiesterase type 5 (PDE5) inhibitors concurrent administration may increase PDE5 inhibitor plasma levels and risk of adverse reactions during coadministration, consider lower dose of PDE5 inhibitor or withholding PDE5 inhibitor in patients at high risk of developing PDE5 inhibitor adverse reactions moderate (DrugReax)
ciprofloxacin probenecid co-administration may result in increased serum ciprofloxacin levels due to probenecid inhibition of renal tubular secretion monitor patients for increased ciprofloxacin adverse effects moderate (DrugReax) 4-minor (CP)
ciprofloxacin theophyllines adjuvant administration may result in decreased theophylline clearance and potential for increased serum theophylline levels and enhanced pharmacologic/toxic effects as ciprofloxacin interferes with theophylline clearance if adjunctive therapy necessary, closely monitor theophylline levels and observe for increased adverse effects; may consider alternative FQ that does not interfere with theophylline clearance major (DrugReax) 3-moderate (CP)
ciprofloxacin tizanidine (Ziaflex®) combined administration may result in enhanced tizanidine pharmacologic effects and/or adverse effects (e.g., sedation, hypotension) due to ciprofloxacin inhibition of CYP1A2-mediated tizanidine metabolism avoid concurrent administration; use alternative spasticity medication contraindicated  (DrugReax) 1-severe (CP)
fluoroquinolones (FQ) antacids simultaneous administration may result in reduced absorption/bioavailability and clinical effectiveness of the FQ due to chelation of the antacid cations with the quinolone molecule avoid concurrent administration; give FQ 2 hours before or 6 hours after giving antacids; may consider H2 receptor antagonist as alternative to antacids (e.g., ranitidine) in some clinical situations moderate (DrugReax) 2-major (CP)
FQ antidiabetic agents adjunctive administration may result in altered blood glucose levels and increased risk for hypo- or hyperglycemia monitor serum glucose levels closely with concurrent administration major (DrugReax) 3-moderate (CP)
FQ corticosteroids concurrent therapy may increase risk for tendon rupture, especially in patients over 60 years of age discontinue FQ therapy with any signs of tendon inflammation or pain moderate (DrugReax) 3-moderate (CP)
FQ didanosine (Videx®) oral solution didanosine buffers consist of magnesium-aluminum cations; concomitant administration with FQ may result in reduced FQ absorption/ bioavailability and clinical effectiveness due to chelation of the antacid cations with the quinolone molecule avoid concurrent administration; give FQ 2 hours before or 6 hours after giving didanosine moderate (DrugReax) 2-major (CP)
FQ iron salts (including iron in multivitamins) iron salts may bind FQ in GI tract forming insoluble, unabsorbable complexes with resultant reduced FQ serum concentrations/pharmacologic effects avoid concurrent administration; give FQ 2 hours before or 6 hours after giving drugs containing iron moderate (DrugReax) 2-major (CP)
FQ nonsteroidal anti-inflammatory drugs (NSAIDs) concurrent administration may increase risk of central nervous system (CNS) stimulation and convulsive seizures administer cautiously together and monitor patients closely for increased CNS adverse effects moderate (DrugReax) 3-moderate (CP)
FQ QTc interval-prolonging medications (e.g., class IA, III anti-arrhythmics, tricyclic antidepressants, clozapine, cyclobenzaprine, macrolide antibiotics, cisapride, ziprasidone) concurrent administration may increase risk of significant cardiotoxicity (e.g., life-threatening arrhythmias, cardiac arrest) as FQ may cause QTc interval prolongation and, rarely, torsades de pointes adjunctive administration should be avoided contraindicated, major (DrugReax) 1-severe, 2-major (CP)
FQ sevelamer (Renagel®) concurrent administration may cause decreased FQ bioavailability and potential for reduced pharmacologic effects avoid concurrent administration; administer FQ 1 hour before or 3 hours after sevelamer moderate (DrugReax) 2-major (CP)
FQ sucralfate concurrent administration may result in decreased FQ efficacy due to FQ chelation by sucralfate in GI tract avoid concurrent administration; give FQ 2 hours before or 6 hours after giving sucralfate moderate (DrugReax) 2-major (CP)
FQ warfarin concomitant administration may result in enhanced hypoprothrombinemic effects and increased bleeding risk;  mechanism of this interaction not identified; changes in PT/INR may occur 2-16 days after addition of FQ to warfarin therapy if combination cannot be avoided, monitor PT/INR closely and observe for increased adverse effects major (DrugReax) 2-major (CP)
FQ zinc salts, calcium zinc salts or calcium may bind FQ in GI tract forming insoluble, unabsorbable complexes with resultant reduced FQ serum concentrations/ pharmacologic effects avoid concurrent administration; give FQ 2 hours before or 6 hours after giving drugs containing zinc moderate (DrugReax)
select FQ (ciprofloxacin, levofloxacin) cyclosporine adjunctive administration has resulted in transiently increased serum creatinine levels and/or increased cyclosporine levels monitor serum creatinine and cyclosporine levels; observe patients for cyclosporine adverse effects moderate (DrugReax)

5. References

  1. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc; 2022. Available at: http://www.clinicalpharmacology-ip.com.ezproxy.lib.utexas.edu. Accessed May 17th, 2022.
  2. IBM Micromedex® DRUGDEX® (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com.libproxy.uthscsa.edu/  (cited: May 17th, 2022).
  3. Ciprofloxacin tablets (Cipro®) package insert. Bayer Healthcare Pharmaceuticals, Inc., November 2021.
  4. Ciprofloxacin extended-release tablets (Cipro® XR) package insert. Mylan Pharmaceuticals, Inc., May 2019.
  5. Delafloxacin tablets (Baxdela®) package insert. Melinta Therapeutics, LLC. June 2021.
  6. Gemifloxacin tablets (Factive®) package insert. Merus Labs International, Inc., August 2016.
  7. Levofloxacin tablets (Levaquin®) package insert. Cipla USA Inc., July 2020.
  8. Moxifloxacin tablets (Avelox®) package insert. Bayer Healthcare Pharmaceuticals Inc., July 2016.
  9. Ofloxacin tablets package insert. Dr. Reddy’s Laboratories Limited, December 2018.
  10. Jackson MA, Schutze GE, for the Committee on Infectious Diseases. The use of systemic and topical fluoroquinolones. Pediatrics. 2016;138(5):e1-e13 (doi: 10.1542/peds.2016-2706).