Criteria for Outpatient Use Guidelines >>Fluoroquinolones

Criteria for Outpatient Use Guidelines

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Fluoroquinolones

[Developed, October 1996; Revised, September 1997; September 1998; September 1999; October 1999; November 1999; August 2000; September 2001; September 2002; August 2003; August 2006; September 2006; May 2007; September 2007; October 2010 ]

Information on indications for use or diagnosis is assumed to be unavailable.All criteria may be applied retrospectively; prospective application is indicated with [*].

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1.*Dosage

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

TABLE 1
Fluoroquinolones - Maximum Dosage Recommendations (Adults)
DRUG	MAXIMUM DAILY DOSE
ciprofloxacin (Cipro®)	1500 mg/day
gemifloxacin (Factive®)	320 mg/day
levofloxacin (Levaquin®)	750 mg/day
lomefloxacin (Maxaquin®)	400 mg/day
moxifloxacin (Avelox®)	400 mg/day
norfloxacin (Noroxin®)	800 mg/day
ofloxacin (Floxin®)	800 mg/day

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 tissues. 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 Patients
DRUG	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):10-15 mg/kg orally every 12 hours (not to exceed 500mg/dose) inhalational/systemic/cutaneous anthrax:following IV therapy, 10-15 mg/kg orally every 12 hours (not to exceed 500 mg/dose) cystic fibrosis:20 mg/kg orally every 12 hours (not to exceed 1 g/dose)
levofloxacin	inhalational anthrax (postexposure prophylaxis): > 6 months of age and < 50 kg: 8 mg/kg orally every 12 hours (not to exceed 250 mg/dose) > 6 months of age and > 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. Health care providers should remain cognizant that neither gemifloxacin nor moxifloxacin is approved for use in managing urinary tract infections. Patient profiles documenting moxifloxacin or gemifloxacin use for UTIs will be reviewed.

TABLE 3
Fluoroquinolones - Recommended Maximum Duration of Therapy in Adults
DRUG	RECOMMENDED THERAPY DURATION
ciprofloxacin^*	acute sinusitis - 10 days chronic bacterial prostatitis – 28 days bone and joint infections - 4 to 6 weeks, or longer lower respiratory tract infections – 14 days complicated skin/skin structure infections - 14 days uncomplicated skin/skin structure infections - 14 days moderate, complicated UTI - 14 days uncomplicated UTI - 3 days complicated intra-abdominal infections – 14 days infectious diarrhea - 7 days typhoid fever - 10 days uncomplicated cervical, urethral gonococcal infections – single dose inhalational anthrax (post-exposure) – 60 days
gemifloxacin	chronic bronchitis (acute exacerbation) - 5 days community-acquired pneumonia – 5 to 7 days
levofloxacin	acute maxillary sinusitis - 14 days (500 mg dose); 5 days (750 mg dose) chronic bronchitis (acute exacerbation) - 7 days community acquired pneumonia - 14 days (500 mg dose); 5 days (750 mg dose) nosocomial pneumonia - 14 days complicated skin/skin structure infections - 14 days uncomplicated skin/skin structure infections - 10 days complicated UTI - 10 days (250 mg dose); 5 days (750 mg dose) uncomplicated UTI - 3 days (250 mg dose) acute pyelonephritis - 10 days (250 mg dose); 5 days (750 mg dose) chronic bacterial prostatitis – 28 days inhalational anthrax – 60 days+
lomefloxacin	chronic bronchitis (acute exacerbation) - 10 days uncomplicated UTI due to K. pneumoniae, P. mirabilis, or S. saprophyticus - 10 days uncomplicated UTI due to E. coli in females - 3 days
moxifloxacin	acute bacterial sinusitis - 10 days chronic bronchitis (acute exacerbation) - 5 days community-acquired pneumonia - 14 days complicated intra-abdominal infections – 14 days complicated skin/skin structure infections - 21 days uncomplicated skin/skin structure infections - 7 days
norfloxacin	uncomplicated UTI due to E. coli, K. pneumoniae, or P. mirabilis - 3 days uncomplicated UTI due to other organisms - 10 days complicated UTI - 21 days prostatitis due to E. coli - 28 days uncomplicated urethral and cervical gonorrhea – single dose
ofloxacin	chronic bronchitis (acute exacerbation) - 10 days uncomplicated skin and skin structure infections - 10 days uncomplicated cystitis due to E. coli or K. pneumoniae - 3 days uncomplicated cystitis due to other organisms - 7 days complicated UTI - 10 days (may require up to 14 days in some clinical situations) prostatitis due to E. coli - 6 weeks community-acquired pneumonia – 10 days acute pelvic inflammatory disease – 14 days acute, uncomplicated urethral, cervical gonorrhea – (400 mg dose) 1 day mixed infection of urethra, cervix due to C. trachomatis and N. gonorrhoeae – 7 days

*Manufacturer recommends continuing therapy at least 2 days after signs and symptoms of infection have disappeared, except for inhalational anthrax
+Levofloxacin safety in adults for longer than 28 days to manage anthrax has not been studied; use for> 28 days when benefit outweighs risk.
** CDC no longer recommends fluoroquinolones for treatment of infections due to N. gonorrhoeae

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

TABLE 4
Fluoroquinolones – Therapy Duration in Pediatric Patients
DRUG	RECOMMENDED THERAPY DURATION
ciprofloxacin	UTI, pyelonephritis – 10 - 21 days inhalational anthrax (postexposure prophylaxis) – 60 days
levofloxacin	inhalational anthrax (postexposure prophylaxis) – 60 days+

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 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
Fluoroquinolone Drug-Drug Interactions
Target Drug	Interacting Drug	Interaction	Recommendations	Clinical Significance Level
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 (Clinical Pharmacology) 1 (DIF)
fluoroquinolones (FQ)	QTc interval-prolonging medications (e.g., class I, III anti-arrhythmics, tricyclic antidepressants, clozapine, cyclobenzaprine)	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	major (DrugReax) 2-major (Clinical Pharmacology)
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	major (DrugReax) 2-major (Clinical Pharmacology) 2 (DIF)
select FQ (ciprofloxacin, norfloxacin)	drugs metabolized by CYP1A2 (e.g., alosetron, mexiletine, duloxetine)	concurrent administration of select FQ that are known CYP1A2 inhibitors 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	major, moderate (DrugReax) 2-major, 3-moderate (Clinical Pharmacology) 2 (DIF)
select FQ (ciprofloxacin, norfloxacin)	theophyllines	adjuvant administration may result in decreased theophylline clearance and potential for increased serum theophylline levels and enhanced pharmacologic/toxic effects as select FQ interfere 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 (Clinical Pharmacology) 2 (DIF)
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 (Clinical Pharmacology)
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 (Clinical Pharmacology) 2 (DIF)
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 (Clinical Pharmacology) 2 (DIF)
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	moderate (DrugReax) 2-major (Clinical Pharmacology) 1 (DIF)
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 (Clinical Pharmacology) 2 (DIF)
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 (Clinical Pharmacology) 2 (DIF)
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 (Clinical Pharmacology)
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 (Clinical Pharmacology)
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 (Clinical Pharmacology) 4 (DIF)
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	3-moderate (Clinical Pharmacology)
select FQ (ciprofloxacin, levofloxacin, norfloxacin)	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) 4-minor (Clinical Pharmacology) 4 (DIF)
select FQ (ciprofloxacin, gemifloxacin, norfloxacin	probenecid	co-administration may result in increased serum FQ levels due to probenecid inhibition of renal tubular secretion	monitor patients for increased FQ adverse effects	moderate (DrugReax) 4-minor (Clinical Pharmacology)

References

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Ciprofloxacin tablets, oral suspension (Cipro®) package insert. Bayer Healthcare Pharmaceuticals, Inc., April 2009.
Gemifloxacin tablets (Factive®) package insert. Cornerstone Therapeutics Inc., April 2010.
Levofloxacin tablets, oral solution (Levaquin®) package insert. Ortho-McNeil-Janssen Pharmaceuticals, Inc., July 2009.
Moxifloxacin tablets (Avelox®) package insert. Bayer Healthcare Pharmaceuticals, Inc., March 2010.
Norfloxacin tablets (Noroxin®) package insert. Merck & Co., Inc., February 2010.
Didanosine pediatric powder for oral solution (Videx®) package insert. Bristol-Myers Squibb, July 2010.
Owens RC. QT Prolongation with antimicrobial agents: Understanding the significance. Drugs 2004;64:1091-1124.
Mehlhorn AJ, Brown DA. Safety concerns with fluoroquinolones. Ann Pharmacother. 2007;41(11):1859-66.
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Prepared by:Drug Information Service, The University of Texas Health Science Center at San Antonio, and the College of Pharmacy, The University of Texas at Austin.