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Fluoroquinolones:

Ciprofloxacin (Cipro ®) Gatifloxacin (Tequin ®)
Levofloxacin (Levaquin ®) Moxifloxacin (Avelox ®)
Norfloxacin (Noroxin ®) Ofloxacin (Floxin ®)

Ciprofloxacin (Cipro ®) top of page icon

Overview:
Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive organisms. The bactericidal action of ciprofloxacin results from inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination. The mechanism of action of quinolones, including ciprofloxacin, is different from that of other antimicrobial agents such as beta-lactams, macrolides, tetracyclines, or aminoglycosides; therefore, organisms resistant to these drugs may be susceptible to ciprofloxacin. There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials.

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Oral:
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DOSAGE AND ADMINISTRATION - ADULTS
Ciprofloxacin tablets should be administered orally to adults as described in the Dosage Guidelines table.

The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative organism, the integrity of the patient’s host-defense mechanisms, and the status of renal function and hepatic function.

The duration of treatment depends upon the severity of infection. The usual duration is 7 to 14 days; however, for severe and complicated infections more prolonged therapy may be required. Ciprofloxacin should be administered at least 2 hours before or 6 hours after magnesium/aluminum antacids, or sucralfate, Videx ®* (didanosine) chewable/buffered tablets or pediatric powder for oral solution, other highly buffered drugs, or other products containing calcium, iron or zinc.


ADULT DOSAGE GUIDELINES

*used in conjunction with metronidazole

Generally ciprofloxacin should be continued for at least 2 days after the signs and symptoms of infection have disappeared, except for inhalational anthrax (post-exposure).

**Drug administration should begin as soon as possible after suspected or confirmed exposure. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit.5 For a discussion of ciprofloxacin serum concentrations in various human populations, see INHALATIONAL ANTHRAX –ADDITIONALINFORMATION.

 Infection  Severity  Dose  Frequency Usual Durations
Urinary Tract     Acute Uncomplicated 250 mg q 12 h 3 days
Mild/Moderate 250 mg   q 12 h 7 to 14 days
Severe/Complicated   500 mg   q 12 h   7 to 14 days
Chronic Bacterial Prostatitis   Mild/Moderate   500 mg   q 12 h   28 days  
Lower Respiratory Tract   Mild/Moderate   Severe/Complicated 500 mg   q 12 h   7 to 14 days  
750 mg q 12 h 7 to 14 days
Acute Sinusitis Mild/Moderate 500 mg q 12 h 10 days
Skin and Skin Structure   Mild/Moderate   Severe/Complicated 500 mg   q 12 h   7 to 14 days  
750 mg q 12 h 7 to 14 days
Bone and Joint   Mild/Moderate 500 mg q 12 h greater than or equal 4 to 6 weeks
Severe/Complicated   750 mg   q 12 h greater than or equal 4 to 6 weeks
Intra-Abdominal* Complicated 500 mg q 12 h 7 to 14 days
Infectious Diarrhea   Mild/Moderate/Severe   500 mg   q 12 h   5 to 7 days  
Typhoid Fever   Mild/Moderate   500 mg   q 12 h   10 days  
Urethral and Cervical Gonococcal Infections Uncomplicated 250 mg   single dose single dose
Inhalational anthrax (post-exposure)**   500 mg q 12 h   60 days

 

Conversion of I.V. to Oral Dosing in Adults

Patients whose therapy is started with ciprofloxacin I.V. may be switched to Ciprofloxacin Tablets when clinically indicated at the discretion of the physician (see CLINICAL PHARMACOLOGY and table below for the equivalent dosing regimens).
Equivalent AUC Dosing Regimens
Ciprofloxacin Oral Dosage Equivalent Ciprofloxacin I.V. Dosage
250 mg Tablet q 12 h 200 mg I.V. q 12 h
500 mg Tablet q 12 h 400 mg I.V. q 12 h
750 mg Tablet q 12 h 400 mg I.V. q 8 h

Adults with Impaired Renal Function

Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternate pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction. The following table provides dosage guidelines for use in patients with renal impairment:
RECOMMENDED STARTING AND MAINTENANCE DOSES FOR PATIENTS WITH IMPAIRED RENAL FUNCTION
Creatinine Clearance (mL/min) Dose
> 50 See Usual Dosage
30 to 50 250 to 500 mg q 12 h
5 to 29 250 to 500 mg q 18 h

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Adults: I.V.:
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Bone/joint infections:
Mild to moderate: 400 mg every 12 hours for 4-6 weeks
Severe or complicated: 400 mg every 8 hours for 4-6 weeks
Lower respiratory tract, skin/skin structure infections:
Mild to moderate: 400 mg every 12 hours for 7-14 days
Severe or complicated: 400 mg every 8 hours for 7-14 days
Febrile neutropenia (with piperacillin): 400 mg every 8 hours for 7-14 days
Intra-abdominal infection (with metronidazole): 400 mg every 12 hours for 7-14 days
Nosocomial pneumonia (mild to moderate to severe): 400 mg every 8 hours for 10-14 days
Prostatitis (chronic, bacterial): 400 mg every 12 hours for 28 days
Sinusitis (acute): 400 mg every 12 hours for 10 days
Urinary tract infection:
Mild to moderate: 200 mg every 12 hours for 7-14 days
Severe or complicated: 400 mg every 12 hours for 7-14 days


Elderly: No adjustment needed in patients with normal renal function


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Renal Dosing:
[CRCL >30 ]: no changes .
[5-30 ]: (IV): 200-400mg q18-24h or give 200mg q12h.
(Oral): 250 q12h or, 250-500mg q18 to 24 hours.

Hemodialysis: (IV): 200-400mg q24h or 200mg q12h. Schedule dose after dialysis on dialysis days. (Oral): 250mg q12h or 250-500mg q24h. Schedule dose after dialysis on dialysis days.

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SUPPLIED
Infusion, [premixed in D5W] (Cipro®): 200 mg (100 mL); 400 mg (200 mL) [latex free]
Injection, solution (Cipro®): 10 mg/mL (20 mL, 40 mL, 120 mL)
Microcapsules for oral suspension (Cipro®): 250 mg/5 mL (100 mL); 500 mg/5 mL (100 mL)
Tablet [film coated]: 250 mg, 500 mg, 750 mg
Cipro®: 100 mg, 250 mg, 500 mg, 750 mg

Tablet, extended release [film coated] (Cipro® XR): 500 mg [equivalent to ciprofloxacin hydrochloride 287.5 mg and ciprofloxacin base 212.6 mg]; 1000 mg [equivalent to ciprofloxacin hydrochloride 574.9 mg and ciprofloxacin base 425.2 mg]

Gatifloxacin (Tequin ®)  top of page icon

Dosing: 400 mg po/IV qd
Renal Dosing:
[CRCL >40]: No changes.
[<40 ]: 400mg x 1, then 200mg qd.
Hemodialysis: 400 mg x 1, then 200mg qd. (On dialysis days, schedule dose after dialysis.).
PD: 400 mg x 1, then 200mg qd

Levofloxacin  (Levaquin ®) top of page icon

Mechanism of Action
Levofloxacin is the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The antibacterial activity of ofloxacin resides primarily in the L-isomer. The mechanism of action of levofloxacin and other fluoroquinolone antimicrobials involves inhibition of bacterial topoisomerase IV and DNA gyrase (both of which are type II topoisomerases), enzymes required for DNA replication, transcription, repair and recombination.

Dosing (Adults):
Oral, I.V.:
Note: Sequential therapy (intravenous to oral) may be instituted based on prescriber's discretion.
Chronic bronchitis (acute bacterial exacerbation): 500 mg every 24 hours for at least 7 days

 Inhalational anthrax: 500 mg every 24 hours for 60 days, beginning as soon as possible after exposure
Maxillary sinusitis (acute): 500 mg every 24 hours for 10-14 days

Pneumonia:
Community-acquired: 500 mg every 24 hours for 7-14 days or 750 mg every 24 hours for 5 days (efficacy of 5-day regimen for MDRSP not established)
Nosocomial: 750 mg every 24 hours for 7-14 days

Prostatitis (chronic bacterial): 500 mg every 24 hours for 28 days

Skin infections:
Uncomplicated: 500 mg every 24 hours for 7-10 days
Complicated: 750 mg every 24 hours for 7-14 days

Urinary tract infections:
Uncomplicated: 250 mg once daily for 3 days
Complicated, including acute pyelonephritis: 250 mg every 24 hours for 10 days

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Renal Dosing:
[CRCL >50] No change.
[20-49]: 500 x 1, then 250mg q24h. Complicated skin/structure: 750 mg x 1, then 750mg q48h.
[10-19]: 500mg x 1, 250mg q48h. Complicated skin/structure: 750 mg x 1, then 500mg q48h.
[<10] same as above.
Hemodialysis or PD: 500mg x 1, 250mg q48h. Complicated skin/structure: 750 mg x 1, then 500mg q48h. On dialysis days, schedule dose after dialysis.

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SUPPLIED:
Infusion [premixed in D5W] (Levaquin®): 250 mg (50 mL); 500 mg (100 mL); 750 mg (150 mL)
Injection, solution [preservative free] (Levaquin®): 25 mg/mL (20 mL, 30 mL)
Solution, oral (Levaquin®): 25 mg/mL (480 mL) [contains benzyl alcohol]
Tablet (Levaquin®): 250 mg, 500 mg, 750 mg
Levaquin® Leva-Pak: 750 mg (5s)

Moxifloxacin  (Avelox ®) top of page icon

Overview:
Moxifloxacin has in vitro activity against a wide range of Gram-positive and Gram-negative microorganisms. The bactericidal action of moxifloxacin results from inhibition of the topoisomerase II (DNA gyrase) and topoisomerase IV required for bacterial DNA replication, transcription, repair, and recombination. It appears that the C8-methoxy moiety contributes to enhanced activity and lower selection of resistant mutants of Gram-positive bacteria compared to the C8-H moiety. The presence of the bulky bicycloamine substituent at the C-7 position prevents active efflux, associated with the NorA or pmrA genes seen in certain Gram-positive bacteria.

The mechanism of action for quinolones, including moxifloxacin, is different from that of macrolides, beta-lactams, aminoglycosides, or tetracyclines; therefore, microorganisms resistant to these classes of drugs may be susceptible to moxifloxacin and other quinolones. There is no known cross-resistance between moxifloxacin and other classes of antimicrobials.

INDICATIONS AND USAGE
AVELOX Tablets and I.V. are indicated for the treatment of adults (greater than or equal 18 years of age) with infections caused by susceptible strains of the designated microorganisms in the conditions listed below.

Acute Bacterial Sinusitis caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.

Acute Bacterial Exacerbation of Chronic Bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus, or Moraxella catarrhalis.

Community Acquired Pneumonia caused by Streptococcus pneumoniae (including multi-drug resistant strains*), Haemophilus influenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae, or Chlamydia pneumoniae.

* MDRSP, Multi-drug resistant Streptococcus pneumoniae includes isolates previously known as PRSP (Penicillin-resistant S. pneumoniae), and are strains resistant to two or more of the following antibiotics: penicillin (MIC greater than or equal 2 µg/mL), 2nd generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, and trimethoprim/sulfamethoxazole.

Uncomplicated Skin and Skin Structure Infections caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogenes.

Complicated Intra-Abdominal Infections including polymicrobial infections such as abscess caused by Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron, or Peptostreptococcus species.

Complicated Skin and Skin Structure Infections caused by methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Enterobacter cloacae (See Clinical Studies).

Dosing (Adults):  400 mg orally or IV q24h.

Acute bacterial sinusitis: Oral, I.V.: 400 mg every 24 hours for 10 days.
Chronic bronchitis, acute bacterial exacerbation: Oral, I.V.: 400 mg every 24 hours for 5 days. Note: Avelox® ABC Pack™ (Avelox® Bronchitis Course) contains five tablets of 400 mg each.
Intra-abdominal infections, complicated: Oral, I.V.: 400 mg every 24 hours for 5-14 days (initiate with I.V.).
Legionella(unlabeled use): Oral, I.V.: 400 mg every 24 hours for 10-21 days.
Pneumonia, community-acquired (including MDRSP): Oral, I.V.: 400 mg every 24 hours for 7-14 days.
Skin and skin structure infections: Oral, I.V.:
Complicated: 400 mg every 24 hours for 7-21 days
Uncomplicated: 400 mg every 24 hours for 7 days


Renal Dosing: No adjustment necessary. Hemo: No specific guidelines available.

Supplied: Tablet: 400mg. Avelox® ABC Pack: contains 5 unit dose 400mg tablets. IV (premixed): 400mg/250 ml NS. Ophthalmic soln ( Vigamox ®): 0.5% (3 ml).

"RESPIRATORY QUINOLONE"
Similar to other new-generation fluoroquinolones, such as grepafloxacin, levofloxacin, and trovafloxacin, moxifloxacin exhibits improved activity against pneumococci (S. pneumoniae) and other clinically relevant respiratory pathogens (eg, Haemophilus influenzae, Chlamydia, Mycoplasma), suggesting that it has a role in the treatment of ambulatory community-acquired pneumonia, sinusitis, and acute exacerbations of chronic bronchitis, particularly in older patients with underlying disease and those with resistance to other agents. Until direct comparative data are available, selection of one of these drugs over the other will be guided by mainly by cost. The overall in vitro activity of moxifloxacin is similar to that of trovafloxacin (Woodcock et al, 1997); (Barman et al, 1999). Compared to ciprofloxacin, moxifloxacin is more active against gram-positive organisms and anaerobes, but less active against the Enterobacteriaceae and Pseudomonas spp. Dave's Note: Not indicated for tx of UTI.

Norfloxacin (Noroxin ®) top of page icon

Oral: Adults:
Urinary tract infections: 400 mg twice daily for 3-21 days depending on severity of infection or organism sensitivity; maximum: 800 mg/day

Uncomplicated gonorrhea: 800 mg as a single dose (CDC recommends as an alternative regimen to ciprofloxacin or ofloxacin)

Prostatitis: 400 mg every 12 hours for 4 weeks

Dosing interval in renal impairment: Clcr 10-30 mL/minute: Urinary tract infections: Administer 400 mg every 24 hours

Supplied
Tablet: 400 mg

Ofloxacin (Floxin ®) top of page icon

 Dosing (Adults):  200-400 mg po or IV q12h.

Renal Dosing:
[> 50 ml/min]: no changes.
[20-50]: 200-400mg q24h.
[<20]: 100-200mg q24h (1/2 of usual dose q24h.).
Hemodialysis: Manufacturer states: For CRCL <20 ml/min give 50% of usual dose q24h. No specific info for hemodialysis.

Disclaimer

Listed dosages are for - Adult patients ONLY. PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER. GlobalRPH does not directly or indirectly practice medicine or provide medical services and therefore assumes no liability whatsoever of any kind for the information and data accessed through the Service or for any diagnosis or treatment made in reliance thereon.

David F. McAuley, Pharm.D., R.Ph.  GlobalRPh Inc.
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