Fluoroquinolones (oral)
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. Dosage
1.1. Adults
Maximum recommended adult daily doses for fluoroquinolones are summarized in Table 1. Prescribed dosages exceeding these recommendations will be reviewed.
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.
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.
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.
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.
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
- 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.
- 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).
- Ciprofloxacin tablets (Cipro®) package insert. Bayer Healthcare Pharmaceuticals, Inc., November 2021.
- Ciprofloxacin extended-release tablets (Cipro® XR) package insert. Mylan Pharmaceuticals, Inc., May 2019.
- Delafloxacin tablets (Baxdela®) package insert. Melinta Therapeutics, LLC. June 2021.
- Gemifloxacin tablets (Factive®) package insert. Merus Labs International, Inc., August 2016.
- Levofloxacin tablets (Levaquin®) package insert. Cipla USA Inc., July 2020.
- Moxifloxacin tablets (Avelox®) package insert. Bayer Healthcare Pharmaceuticals Inc., July 2016.
- Ofloxacin tablets package insert. Dr. Reddy’s Laboratories Limited, December 2018.
- 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).