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Fluoroquinolones (Systemic)

This monograph includes information on the following:

1) Ciprofloxacin
2) Enoxacin 
3) Gatifloxacin 
4) Levofloxacin
5) Lomefloxacin 
6) Moxifloxacin 
7) Norfloxacin
8) Ofloxacin
9) Sparfloxacin 

VA CLASSIFICATION
Primary: AM402

Commonly used brand name(s): Avelox6; Avelox I.V.6; Cipro1; Cipro I.V.1; Floxin8; Floxin I.V.8; Levaquin4; Maxaquin5; Noroxin7; Penetrex2; Tequin3; Zagam9.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Antibacterial (systemic)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

General considerations
Fluoroquinolones are broad-spectrum anti-infectives, active against a wide range of aerobic gram-positive and gram-negative organisms. They are active in vitro against most Enterobacteriaceae, including Citrobacter diversus , Citrobacter freundii , and Citrobacter koseri ; Enterobacter aerogenes and Enterobacter cloacae ; Escherichia coli ; Klebsiella oxytoca , Klebsiella ozaenae , and Klebsiella pneumoniae ; Morganella morganii ; Proteus mirabilis and Proteus vulgaris ; Providencia alcalifaciens , Providencia rettgeri , and Providencia stuartii ; Salmonella enteritidis and Salmonella typhi ; Shigella boydii , Shigella dysenteriae , Shigella flexneri , and Shigella sonnei ; Vibrio cholerae , Vibrio parahaemolyticus , and Vibrio vulnificus ; and Yersinia enterocolitica {52}0. All of the fluoroquinolones also have good in vitro activity against penicillin-resistant strains of Neisseria gonorrhoeae , beta-lactamase–producing strains of Haemophilus influenzae and Moraxella (Branhamella) catarrhalis , and some gram-negative bacilli that are resistant to other antimicrobial agents {52}9. Ciprofloxacin is the most active fluoroquinolone against Pseudomonas aeruginosa , although longitudinal studies have reported progressively decreasing susceptibility in Europe, North America, and South America {52}8. It is not generally effective against most strains of Burkholderia (Pseudomonas) cepacia or some strains of Strenotrophomonas (Xanthomonas) maltophilia {52}7. Ofloxacin's potency against P. aeruginosa is similar to that of norfloxacin, and greater than that of enoxacin or lomefloxacin {52}6 {52}5 {52}4.

Fluoroquinolones also have good in vitro activity against Staphylococcus saprophyticus , Staphylococcus epidermidis , and Staphylococcus aureus , including some methicillin-resistant (MRSA) strains {52}3 {52}2 {52}1 {52}0. However, most methicillin-resistant strains also are resistant to fluoroquinolones {52}9. Any bacteria that are resistant to one fluoroquinolone also may be resistant to another {52}8 {52}7. Streptococci, including Streptococcus pneumoniae , Streptococcus pyogenes , and Enterococcus faecalis , are all moderately susceptible to ofloxacin and ciprofloxacin in vitro {52}6 {52}5 {52}4 {52}3 {52}2. Sparfloxacin is more active in vitro against S. pneumoniae than is ciprofloxacin, and levofloxacin appears to be equal to or slightly more active than ciprofloxacin in this regard {52}1 . Resistant strains of streptococci are often seen. The MIC 90 values for these species, especially E. faecalis , are often equal to or greater than the susceptible breakpoint for ciprofloxacin and ofloxacin {52}0. Therapeutic failures have been reported in patients taking ciprofloxacin for the treatment of pneumococcal pneumonia {52}9 {52}8. However, levofloxacin is highly effective against S. pneumoniae isolates, including penicillin-susceptible isolates and those with intermediate or high-level resistance to penicillin. Gatifloxacin and moxifloxacin are both effective in vitro against penicillin-resistant strains of S. pneumoniae.{52}7{52}6

Ciprofloxacin and ofloxacin have been found to have good in vitro activity against Chlamydia trachomatis , Mycoplasma hominis , Mycoplasma pneumoniae , and Legionella pneumophila {52}5 {52}4 {52}3 {52}2 {52}1. These two fluoroquinolones have moderate activity in vitro against Mycobacterium tuberculosis , but neither antimicrobial is indicated for tuberculosis {52}0 {52}9 {52}8. The susceptibility of Mycobacterium avium-intracellulare , however, is only fair to poor, and inhibition requires significantly higher drug concentrations {52}7 {52}6 {52}5 {52}4.

Ciprofloxacin has been found to be active against Bacillus anthracisboth in vitro and by use of serum levels as a surrogate marker.
{52}3{52}2
The emergence of bacterial resistance to fluoroquinolones, and of cross-resistance within this class of antimicrobial agents, has become a significant clinical concern. Decreased susceptibility among Enterobacteriaceae, including E. coli , K. pneumoniae , and Salmonella , has been reported worldwide {52}1 {52}0 {96}. Strains of N. gonorrhoeae with low-level resistance to fluoroquinolones have been isolated {87} {88} {97}; strains with high-level resistance to ciprofloxacin have been documented, and treatment failures have been reported {47}. Fluoroquinolone resistance also has been documented for H. influenzae in patients with recurrent respiratory tract infections {79} {89}, and for S. epidermidis in several cases of nosocomial infections {90} {91} {117} {118}. Use of fluoroquinolones in poultry may be at least partially responsible for the emergence of fluoroquinolone resistance in Salmonella and Campylobacter {82} {83}. Mechanisms underlying fluoroquinolone resistance may include plasmid transfer, chromosomal mutations in DNA gyrase ( gyrA) or topoisomerase IV ( parC), and/or antibiotic efflux {80} {81} {94}. Extensive and continuous use of fluoroquinolones, and antimicrobials in general, encourages the multiplication and spread of resistant bacterial strains; therefore, the World Health Organization recommends that prescribing practices for antimicrobial agents should be modified to reflect this growing concern {15}.

Accepted

Anthrax, inhalational (treatment)1—Ciprofloxacin is indicated to reduce the incidence or progression of the disease following exposure to aerosolized Bacillus anthracis {159}{160}

Bone and joint infections (treatment)—Ciprofloxacin {04} {63} is indicated in the treatment of bone and joint infections caused by susceptible organisms.

Bronchitis, bacterial exacerbations (treatment)— Ciprofloxacin {04} {63}, gatifloxacin{157}, moxifloxacin, {155} levofloxacin {17}{158}, lomefloxacin1 {03}, ofloxacin {66} {98}, and sparfloxacin1 {52} are indicated in the treatment of bacterial exacerbations of chronic bronchitis caused by susceptible organisms.

Cervicitis, nongonococcal (treatment) or
Urethritis, nongonococcal (treatment)— Ofloxacin {66} {98} is indicated in the treatment of nongonococcal cervicitis or urethritis caused by C. trachomatis .

Diarrhea, infectious (treatment)—Ciprofloxacin {04} {63} is indicated in the treatment of infectious diarrhea caused by enterotoxigenic strains of Campylobacter jejuni , E. coli , S. boydii , S. dysenteriae , S. flexneri , or S. sonnei . Although ciprofloxacin is approved for the treatment of diarrhea caused by Campylobacter , use of fluoroquinolones is not generally recommended due to the high frequency with which single-step mutations occur in Campylobacter , which result in fluoroquinolone resistance {35} {139} {140} {151}.
—[Norfloxacin is indicated in the treatment of acute diarrheal disease in patients with enterotoxigenic E. coli or Shigella infection, and in patients with severe enteritis {35} {148} {149} . Norfloxacin is also effective in the treatment of symptoms due to Salmonella infection; however, treatment with norfloxacin appears to delay bacterial elimination {35} {36} {150}. (Evidence rating: I)]1

Gonorrhea, endocervical and urethral (treatment)—Ciprofloxacin {04} {63}, enoxacin1 {16}, gatifloxacin {157} , norfloxacin {09} {64}, and ofloxacin {66} {98} are indicated in the treatment of endocervical and urethral infections caused by N. gonorrhoeae . Ofloxacin {66} {98} is indicated also for mixed infections of the cervix or urethra caused by C. trachomatis and N. gonorrhoeae . Gatifloxacin is indicated for acute, uncomplicated rectal infection in women due to N. gonorrhoeae.{157}

Intra-abdominal infections (treatment)—Ciprofloxacin {04} {63}, in combination with metronidazole, is indicated in the treatment of complicated intra-abdominal infections caused by Bacteroides fragilis , E. coli , K. pneumoniae , P. mirabilis , or P. aeruginosa .

Lower respiratory tract infections (treatment)— Ciprofloxacin {04}and levofloxacin {158} is indicated in the treatment of lower respiratory tract infections caused by susceptible organisms.

Neutropenia, febrile, empiric therapy (treatment) 1—Parenteral ciprofloxacin {05}, in combination with piperacillin, is indicated for empiric therapy in patients with febrile neutropenia.

Pelvic inflammatory disease (treatment)—Ofloxacin {66} {98} is indicated in the treatment of pelvic inflammatory disease, including severe infection, caused by C. trachomatis and/or N. gonorrhoeae .
—If anaerobic microorganisms are suspected of contributing to the infection, appropriate therapy for anaerobic pathogens should also be administered {98}.

Pneumonia, community-acquired (treatment)— gatifloxacin{157}, moxifloxacin{155} levofloxacin,{17}{158} ofloxacin {66} {98}, and sparfloxacin1 {52} are indicated in the treatment of community-acquired pneumonia caused by susceptible organisms.
—Caution should be used in treating streptococcal and pneumococcal pneumonia with fluoroquinolones. Although they have been effective in limited trials, treatment failures have been reported; fluoroquinolones should not be considered the drugs of first choice in the treatment of presumed or confirmed pneumococcal pneumonia. {55}

Pneumonia, nosocomial (treatment)—Parenteral ciprofloxacin {05} {63} is indicated in the treatment of nosocomial pneumonia.
—Caution should be used in treating streptococcal and pneumococcal pneumonia with fluoroquinolones. Although they have been effective in limited trials, treatment failures have been reported; fluoroquinolones should not be considered the drugs of first choice in the treatment of presumed or confirmed pneumococcal pneumonia. {55}

Prostatitis, bacterial (treatment)—Ciprofloxacin {04} {63}, norfloxacin 1 {09}, and ofloxacin {66} {98} are indicated in the treatment of bacterial prostatitis caused by susceptible organisms.

Pyelonephritis (treatment)—Gatifloxacin{157} and levofloxacin{17}{158} are indicated in the treatment of pyelonephritis caused by susceptible E. coli .

Sinusitis, acute (treatment)—Ciprofloxacin {04}1gatifloxacin{157}, moxifloxacin{155}, and levofloxacin {17}{158} are indicated in the treatment of acute sinusitis caused by H. influenzae , M. catarrhalis , or S. pneumoniae .

Skin and soft tissue infections (treatment)—Ciprofloxacin {04}{63}, levofloxacin {17}{158}, moxifloxacin {164} and ofloxacin {66} {98} are indicated in the treatment of skin and soft tissue infections caused by susceptible organisms.

Typhoid fever (treatment)—Oral ciprofloxacin {04} {63} is indicated in the treatment of typhoid fever caused by susceptible strains of S. typhi .

Urinary tract infections, bacterial (prophylaxis) 1—Lomefloxacin {03} is indicated preoperatively for the prophylaxis of urinary tract infections in patients undergoing transurethral surgical procedures.

Urinary tract infections, bacterial (treatment)— Ciprofloxacin {04} {63}, enoxacin1 {16}, gatifloxacin{157}levofloxacin {17}{158}, lomefloxacin 1 {03}, norfloxacin {09} {64}, and ofloxacin {66} {98} are indicated in the treatment of complicated and uncomplicated urinary tract infections, including cystitis, caused by susceptible organisms.

[Chancroid (treatment)]1—Ciprofloxacin is indicated in the treatment of chancroid caused by Haemophilus ducreyi {33} {34}.

[Cystic fibrosis, pulmonary exacerbations (treatment)]1—Ciprofloxacin, alone or in combination with other antibacterial agents, is indicated in patients with cystic fibrosis for the treatment of pulmonary exacerbations caused by susceptible P. aeruginosa {23} {28} {29} {65}.
—Although studies have shown that ciprofloxacin decreases the number of viable P. aeruginosa organisms during treatment {29} {152}, the number of organisms returns to pretreatment levels within days of ciprofloxacin discontinuation {152}. Some clinical studies report that treatment with ciprofloxacin for 14 to 21 days results in low to moderate levels of resistance {29} {152}; others report no change in ciprofloxacin susceptibility over the same period of treatment {23}.

[Meningococcal carriers (treatment)]—Oral ciprofloxacin {63} is indicated in the treatment of asymptomatic carriers of Neisseria meningitidis for the elimination of meningococci from the nasopharynx.

[Septicemia, bacterial (treatment)]—Parenteral ciprofloxacin {63} is indicated in the treatment of septicemia caused by E. coli or S. typhi .

—Not all species or strains of a particular organism may be susceptible to a particular fluoroquinolone.

Unaccepted
Fluoroquinolones have not been shown to be effective in the treatment of syphilis and have poor activity against most anaerobic bacteria (including Bacteroides fragilis and Clostridium difficile ). {04} {16} {49} {98} {102} {115}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Table 1. Pharmacology/Pharmacokinetics {03} {04} {08} {17} {27} {30} {47} {59} {60} {63} {68} {69} {70} {73} {85} {98} {99} {100} {101} {103} {104} {105} {107} {108} {109} {110} {111} {112} {130} {132} {142} {143} {144} {146}{155}{157}



Drug  Bioavailability (%)   Half-life (hr)   Time to peak serum concentration (hr)  Peak serum concentration after dose   Peak urine concentration after dose  
Normal renal function  Impaired renal function  mcg/mL  Dose (mg)  mcg/mL  Dose (mg)  
Ciprofloxacin                 
Oral  70–80 *  4   6–8  1–2  1.2–1.4   250  > 200  250 
          2.4–4.3  500     
          3.4–4.3  750     
          5.4  1000     
IV    5–6    End of infusion  2.1  200  > 200  200 
          4.6  400  > 400  400 
Enoxacin                  
Oral  90  3–6  9–10  1–3  0.9  200     
          400     
Gatifloxacin                 
Oral  96      1–2  200     
    7.1  11.2–30.7    3.8  400     
IV    12.3    End of infusion  2.4  200     
    13.9      4.6  400     
Levofloxacin                  
Oral  99  4–8  6–28  1–2   5.7  500     
IV          6.4  500     
Lomefloxacin                 
Oral  95–98    21–45  1.5  0.8  100  > 300  400 
          1.4  200     
          3–5.2  400     
Moxifloxacin                 
Oral  90  12    1–3  4.5  400     
IV    14.8    End of infusion  4.2–4.6   400     
Norfloxacin                 
Oral  30–70 *  3–4  6–9  1–2   1.4–1.6  400  98–200  400 
          2.5  800     
Ofloxacin    4.7–7 #  15–60 **           
Oral  95–100      1–2  1.5–2.6  200     
          4.6–5  400     
IV        End of infusion  2.3–2.7  200     
          5.5–7.2  400      
Sparfloxacin                 
Oral  92  16–30    3–6  1.3  400     
          1.1  200     
* Absorption delayed in presence of food, although overall absorption not substantially affected.
 Half-life of ciprofloxacin slightly prolonged in elderly patients (approximately 6 hours).
# Half-life of ofloxacin slightly prolonged in elderly patients (approximately 6 to 8.5 hours).
**  Half-life of ofloxacin also prolonged in patients who have cirrhosis with ascites (approximately 7.3 to 19.5 hours).


Table 2. Pharmacology/Pharmacokinetics * {01} {03} {04} {07} {16} {17} {47} {59} {60} {61} {62} {63} {68} {69} {70} {73} {76} {77} {92} {93} {98} {99} {100} {102} {103} {104} {105} {107} {109} {114} {120} {130} {136} {138} {142} {144} {146}{155}



Drug   Protein binding (%)  Renal excretion
(% unchanged/hrs) 
Metabolism (%)  Biliary excretion (%)  Vol D (liter/kg)  Removal by dialysis 
HD (%)  PD (%) 
Ciprofloxacin  20–40     20    <10  < 10 
Oral    40–50/24    20–35       
IV    50–70/24    15       
Enoxacin  40   40–60/48  20  18  1.6  < 5   
Gatifloxacin  20  70/48  <1  1.5–2  14  11§  
Levofloxacin  24–38   79–87/48      1.09–1.26  12  12 
Lomefloxacin  10  60–80/48  10  1.8–2.5   < 3  < 3 
Moxifloxacin  50   20  55  25   1.7–2.7     
Norfloxacin  10–15  26–40/24–48  20  28–30  3.2  < 10   
Ofloxacin  20–25  70–90/36   4–8  0.9–1.8  10–30  2–10 
Sparfloxacin  45  50/24      3.9     
* Abbreviations: Vol D = volume of distribution; HD = hemodialysis; PD = peritoneal dialysis; NS = not significant.
 Approximately 14% of enoxacin is bound to plasma proteins in patients with impaired renal function.
 Recovered over 4 hours
§ Recovered over 8 days


Physicochemical characteristics:
Molecular weight—
    Ciprofloxacin: 331.35 {18}
    Ciprofloxacin hydrochloride: 385.82 {18}
    Enoxacin: 320.33 {18}
    Gatifloxacin: 402.42{157}
    Levofloxacin: 370.38 {18}
    Lomefloxacin: 351.36 {18}
    Lomefloxacin hydrochloride: 387.82 {18}
    Moxifloxacin: 437.9{155}
    Norfloxacin: 319.34 {18}
    Ofloxacin: 361.38 {18}
    Sparfloxacin: 392.41 {18}

Mechanism of action/Effect:

Bactericidal; fluoroquinolones act intracellularly by inhibiting topoisomerase II (DNA gyrase) and/or topoisomerase IV. Topoisomerases are essential bacterial enzymes that are critical catalysts in the duplication, transcription, and repair of bacterial DNA. {155}{157}

Distribution:

Fluoroquinolones are widely distributed to most body fluids and tissues; high concentrations are attained in the kidneys, gallbladder, liver, lungs, gynecologic tissue, prostatic tissue, phagocytic cells, urine, sputum, and bile {03} {09} {16} {27} {101} {102} {105}{155}{157}. Ciprofloxacin is also distributed to skin, fat, muscle, bone, and cartilage {04}. The skin, fascia, and subcutaneous fat concentrations of ofloxacin are less than 50% of those found in the serum {101} {102}.

Ciprofloxacin and ofloxacin have been found to penetrate into the cerebrospinal fluid (CSF). CSF concentrations of ciprofloxacin reach 10% of the peak serum concentration with noninflamed meninges, and 30 to 50% with inflamed meninges{27}. Ofloxacin penetrates into the CSF in both the presence and the absence of meningeal inflammation (range, 14 to 60%). The CSF distribution pattern of these agents has resulted in their bactericidal CSF titers ranging from inadequate to high, depending on the microorganism and its sensitivity to these antibiotics {98} {106}.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients allergic to one fluoroquinolone or other chemically related quinolone derivatives (e.g., cinoxacin, nalidixic acid) may be allergic to other fluoroquinolones also {03} {04} {09} {16} {98}{155}{157}.

Carcinogenicity/Tumorigenicity

Ciprofloxacin—Long-term carcinogenicity studies (up to 2 years) in rats and mice with oral ciprofloxacin have shown no evidence that ciprofloxacin had any carcinogenic or tumorigenic effects {04}.

Enoxacin—Long-term studies to determine the carcinogenic potential of enoxacin in animals have not been conducted {16} .

Gatifloxacin—Gatifloxacin given at doses up to 81 mg/kg/day in male and 90 mg/kg/day in female B6C3F1 mice (0.13 and 0.18 times the maximum recommended human dose (MRHD) based upon on daily systemic exposure) for 18 months showed no increases in neoplasms. In a 2–year study in Fischer 344 rats at a high dose of 100 mg/kg/day (approximately 0.74 times MRHD based upon daily systemic exposure), gatifloxacin significantly increased the incidence of large granular lymphocytes leukemia in males. {157}

Levofloxacin—In a long-term study in rats, levofloxacin did not show carcinogenic or tumorigenic potential after daily dietary administration for 2 years. The highest dose was two times the recommended human dose based on body surface area, or 10 times the recommended human dose based on body weight. {17}

Lomefloxacin—One study lasting up to 52 weeks showed that 92% of hairless (Skh-1) mice that were exposed to UVA light for 3.5 hours, five times every two weeks, and that had received lomefloxacin concurrently developed skin tumors within 16 weeks. These tumors were well-differentiated squamous cell carcinomas of the skin that were nonmetastatic and endophytic in character. Two thirds of these squamous cell carcinomas contained large keratinous inclusion masses and were thought to arise from the vestigial hair follicles in these hairless animals. In this study, mice treated with lomefloxacin alone did not develop skin or systemic tumors. The clinical significance of these findings to humans is not known. {03}

Moxifloxacin—Long-term studies to determine the carcinogenic potential of moxifloxacin in animals has not been performed.{155}

Norfloxacin—Studies lasting up to 96 weeks in rats given doses of eight to nine times the usual human dose have shown that norfloxacin causes no increase in neoplastic changes, compared with controls {09}.

Ofloxacin—Long-term studies to determine the carcinogenic potential of ofloxacin in animals have not been conducted.{98}

Sparfloxacin—Sparfloxacin was not carcinogenic in mice or rats administered 3.5 or 6.2 times, respectively, the maximum recommended human dose (MRHD) (400 mg per day), on a mg per square meter of body surface area (mg/m 2) basis, for 104 weeks. These doses correspond to plasma concentrations approximately equal to (in mice) and 2.2 times greater than (in rats) maximum human plasma concentrations. {52}

Mutagenicity

CiprofloxacinIn vitro mutagenicity studies have shown both positive and negative results. Negative results were obtained in the Salmonella microsome test, Escherichia coli DNA repair test, Chinese hamster V79 cell HGPRT test, Syrian hamster embryo cell transformation assay, Saccharomyces cerevisiae point mutation assay, and the S. cerevisiae mitotic crossover and gene conversion assay. Positive results were obtained in the mouse lymphoma cell forward mutation assay and the rat hepatocyte DNA repair assay. Although positive results were obtained in two of eight in vitro studies, negative results were obtained in the in vivo rat hepatocyte DNA repair assay, micronucleus test in mice, and the dominant lethal test in mice. {04}

Enoxacin—Enoxacin did not induce point mutations in bacterial cells or mitotic gene conversion in yeast cells, with or without metabolic activation. Enoxacin did not induce sister chromatid exchanges or structural chromosomal aberrations in mammalian cells in vitro , with or without metabolic activation. Also, it did not induce chromosomal aberrations in mice. There was a minimal, dose-related, statistically significant increase in micronuclei at high doses of enoxacin in mice; however, the significance of these findings, in the absence of effects in other test systems, is not established. {16}

Gatifloxacin—Gatifloxacin was not mutagenic in several strains of bacteria used in the Ames test; however, it was mutagenic to Salmonella strain TA102. Gatifloxacin was negative in in vivo oral and intravenous micronucleus tests in mice, oral cytogenetics test in rats, and oral DNA repair test in rats. Gatifloxacin was positive in in vitro gene-mutation assays in Chinese hamster V-79 cells and in vivo cytogenetics assays in Chinese hamster CHL/IU cells.{157}

Levofloxacin—Levofloxacin was not mutagenic in the Ames test, CHO/HGPRT forward mutation assay, mouse micronucleus test, mouse dominant lethal assay, rat unscheduled DNA repair test, or the mouse sister chromatid exchange assay. It was positive in the in vitro chromosomal aberration (CHL cell line) and sister chromatid exchange (CHL/IU cell line) assays. {17}

Lomefloxacin—One in vitro mutagenicity test (CHO/HGPRT assay) was weakly positive at concentrations of 226 mcg per mL (mcg/mL) and higher, and negative at concentrations of less than 226 mcg/mL. Mutagenicity tests were negative in two other in vitro tests (chromosomal aberrations in Chinese hamster ovary cells and in human lymphocytes). Two in vivo mouse micronucleus mutagenicity tests were also negative. {03}

Moxifloxacin—Moxifloxacin was not mutagenic in the Ames Salmonella reversion assay and the CHO/HGPRT mammalian cell gene mutation assay. Moxifloxacin was clastogenic in the V79 chromosome aberration assay, but it did not induce unscheduled DNA synthesis in cultured rat hepatocytes. In vivo micronucleus test or dominant lethal test in mice did not show genotoxicity.{155}

Norfloxacin—Studies in mice have shown that norfloxacin causes no mutagenic effects in the dominant lethal test. Studies in hamsters and rats given doses of 30 to 60 times the usual human dose have shown that norfloxacin causes no chromosomal aberrations. The Ames test, studies in Chinese hamster fibroblasts, and the V79 mammalian cell assay have shown that norfloxacin causes no mutagenic activity in vitro . {09}

Ofloxacin—Ofloxacin was not found to be mutagenic in the Ames test, in in vitro and in vivo cytogenetic assays, in sister chromatid exchange (Chinese hamster and human cell lines) assays, in the unscheduled DNA repair test using human fibroblasts, in the mouse micronucleus assay, or in dominant lethal assays. However, ofloxacin was mutagenic in the unscheduled DNA repair test using rat hepatocytes and in the mouse lymphoma assay. {98}

Sparfloxacin—Although sparfloxacin was not mutagenic in Salmonella typhimurium TA98, TA100, TA1535, or TA1537, in E. coli strain WP2 uvrA, or in Chinese hamster lung cells, it was mutagenic in S. typhimurium TA102, and it induced DNA repair in E. coli . Sparfloxacin induced chromosomal aberrations in Chinese hamster lung cells in vitro at cytotoxic concentrations; however, no increase in chromosomal aberrations or micronuclei in bone marrow cells was observed after sparfloxacin was administered orally to mice. {52}

Pregnancy/Reproduction
Fertility—

Ciprofloxacin

Adequate and well-controlled studies in humans have not been done. Studies in rats and mice given doses of up to six times the usual daily human dose have not shown that ciprofloxacin causes adverse effects on fertility. {04}



Enoxacin

No consistent effects on fertility and reproductive parameters were noted in female rats given oral doses of up to 1000 mg per kg of body weight (mg/kg) of enoxacin. Decreased spermatogenesis and subsequent impaired fertility were noted in male rats given oral doses of 1000 mg/kg. {16}



Gatifloxacin

Gatifloxacin did not adversely affect fertility or reproduction in rats at oral doses up to 200 mg/kg/day (approximately equivalent to the maximum human recommended dose (MHRD) based on systemic exposure).{157}



Levofloxacin

Levofloxacin had no effect on the fertility or reproductive performance of male or female rats at oral doses of up to 360 mg/kg (2124 mg/m 2) per day (corresponding to 18 and 3 times the MRHD based on body weight and body surface area, respectively), or at parenteral doses of up to 100 mg/kg (590 mg/m 2) per day (corresponding to 5 and 1 times the MRHD based on body weight and body surface area, respectively). {17}



Lomefloxacin

The fertility of male and female rats was not affected when lomefloxacin was administered at oral doses of up to eight times the recommended human dose on a mg/m 2 basis, or 34 times the recommended human dose on a mg/kg basis. {03}



Moxifloxacin

Moxifloxacin had not effect on fertility in male and female rats at oral doses up to 500 mg/kg/day (approximately 12 times the MRHD based on body surface area (mg/m2). At 500 mg/kg, it had slight effects on sperm morphology (head-tail separation) in male rats and on the estrous cycle in female rats.{155}



Norfloxacin

Studies in male and female mice given oral doses of up to 30 times the usual human dose have not shown that norfloxacin causes adverse effects on fertility. {09}



Sparfloxacin

Sparfloxacin had no effect on the fertility or reproductive performance of male or female rats at oral doses of up to 15.4 times the MRHD (400 mg) on a mg/m 2 basis. {52}


Pregnancy—

For all fluoroquinolones

Adequate and well-controlled studies in humans have not been done. However, since fluoroquinolones have been shown to cause arthropathy in immature animals of a variety of species, their use is not recommended during pregnancy.



Ciprofloxacin

Ciprofloxacin crosses the placenta {119}.

Studies in rats and mice given doses of up to six times the usual daily human dose have not shown that ciprofloxacin causes adverse effects on the fetus. Studies in rabbits given oral doses of 30 and 100 mg/kg have shown that ciprofloxacin causes gastrointestinal disturbances, resulting in maternal weight loss and an increased incidence of abortion. However, these studies have not shown that ciprofloxacin is teratogenic at either dose. Studies using intravenous doses of up to 20 mg/kg have not shown that ciprofloxacin causes maternal toxicity, embryotoxicity, or teratogenic effects. {04}

FDA Pregnancy Category C {04}.



Enoxacin

Rats and mice given oral enoxacin have shown no evidence of teratogenic potential. Intravenous infusion of enoxacin into pregnant rabbits at doses of 10 to 50 mg/kg caused dose-related maternal toxicity (venous irritation, weight loss, and reduced food intake). At 50 mg/kg, there were increased incidences of postimplantation loss and stunted growth of fetuses. The incidence of fetal malformations also was significantly increased at this dose in the presence of overt maternal and fetal toxicity. {16}

FDA Pregnancy Category C {16}.



Gatifloxacin

Gatifloxacin was not teratogenic in rats or rabbits at oral doses up to 150 and 50 mg/kg, respectively (0.7 and 0.9 times the maximum human recommended dose (MHRD) based on systemic exposure). However, skeletal malformations were observed in rats at an oral dose of 200 mg/kg/day or intravenous dose of 60 mg/kg/day during organogenesis. Fetotoxicity was seen in rat fetuses at oral doses ³ 150 mg/kg or intravenous doses ³ 30 mg/kg daily during organogenesis, and in rats during late pregnancy and throughout lactation at oral doses of 200 mg/kg.{157}

FDA Pregnancy Category C



Levofloxacin

Levofloxacin was not teratogenic in rats at oral doses of up to 810 mg/kg (4779 mg/m 2) per day (corresponding to 82 and 14 times the MRHD based on body weight and body surface area, respectively), or at parenteral doses of up to 160 mg/kg (944 mg/m 2) per day (corresponding to 16 and 2.7 times the MRHD based on body weight and body surface area, respectively). Doses equivalent to 81 and 26 times the MRHD of levofloxacin (based on body weight and body surface area, respectively) caused decreased fetal body weight and increased fetal mortality in rats when administered orally at doses of 810 mg/kg (8910 mg/m 2) per day. No teratogenicity was observed when rabbits were given oral doses of up to 50 mg/kg (550 mg/m 2) per day (corresponding to 5 and 1.6 times the MRHD based on body weight and body surface area, respectively), or parenteral doses of up to 25 mg/kg (275 mg/m 2) per day (corresponding to 2.5 and 0.8 times the MRHD based on body weight and body surface area, respectively). {17}

FDA Pregnancy Category C {17}.



Lomefloxacin

Reproduction studies done in rats given oral doses of up to 34 times the recommended human dose on a mg/kg basis reported no harm to the fetus. An increased incidence of fetal loss in monkeys has been observed at approximately 6 to 12 times the recommended human dose on a mg/kg basis. No teratogenicity has been observed in rats or monkeys at doses of up to 16 times the recommended human dose. In rabbits, maternal toxicity and associated fetal toxicity, decreased placental weight, and variations of the coccygeal vertebrae occurred at doses two times the recommended human dose on a mg/m 2 basis. {03}

FDA Pregnancy Category C {03}.



Moxifloxacin

Moxifloxacin was not teratogenic in pregnant rats during organogenesis at oral doses up to 500 mg/kg/day (0.24 times the MRHD based on systemic exposure). Fetotoxicity such as decreased fetal body weights and slightly delayed fetal skeletal development were observed. There was also an increase in the incidence of rib and vertebral malformations. There was no evidence of teratogenicity when pregnant Cynomolgus monkeys were given oral doses up to 100 mg/kg/day (2.5 times the MRHD based on systemic exposure). There was an increase in incidence of smaller fetuses. At dose of 500 mg/kg/day in rats, slight increase in duration of pregnancy and prenatal loss, reduced pup birth weight, decreased neonatal survival, and treatment-related maternal mortality were observed.{155}


FDA Pregnancy Category C




Norfloxacin

The human umbilical cord serum concentration ranges from undetectable to 0.5 mg per mL (mg/mL) and the amniotic fluid concentration ranges from undetectable to 0.92 mg/mL following the administration of a single 200-mg dose of norfloxacin {64}.

Studies in monkeys given doses of 10 times the MRHD (800 mg daily) have shown that norfloxacin causes embryonic loss. Peak plasma concentrations were two to three times those seen in humans. Studies in cynomolgus monkeys given doses of 150 mg/kg per day or more have shown that norfloxacin is embryocidal and causes slight maternal toxicity (vomiting and anorexia) as well. However, studies in rats, rabbits, mice, and monkeys given doses of 6 to 50 times the usual human dose have not shown that norfloxacin is teratogenic.

FDA Pregnancy Category C {09}.



Ofloxacin

Ofloxacin crosses the placenta. In one small study, umbilical cord serum concentrations reached 80 to 90% of maternal serum concentrations after mothers received 200-mg doses. Ofloxacin was also detected in the amniotic fluid from more than 50% of the mothers {102}. Another small study found that ofloxacin concentrated in the amniotic fluid, reaching up to 35 to 257% of the simultaneous maternal serum concentration {119}.

Studies in rats and rabbits given doses of up to 810 and 160 mg/kg per day, respectively, have not shown ofloxacin to be teratogenic. Studies in rats given doses of up to 360 mg/kg per day showed no adverse effect on late fetal development, labor, delivery, lactation, neonatal viability, or growth of the newborn. Doses equivalent to 50 and 10 times the MRHD were fetotoxic in rats (decreased fetal body weight) and rabbits (increased fetal mortality), respectively. Rats given 810 mg/kg per day, greater than 10 times the MRHD, were reported to produce offspring with minor skeletal variations. {98}

FDA Pregnancy Category C {98}.



Sparfloxacin

Reproduction studies performed in rats, rabbits, and monkeys at oral doses of 6.2, 4.4, and 2.6 times the MRHD (on a mg/m 2 basis), respectively, did not show evidence of teratogenic effects. At these doses, sparfloxacin produced clear evidence of maternal toxicity in rabbits and in monkeys, and slight evidence of maternal toxicity in rats. When administered to pregnant rats at clearly defined maternally toxic doses, sparfloxacin induced a dose-dependent increase in the incidence of ventricular septal defects in fetuses. Among the three species tested, this effect was specific to the rat. {52}

FDA Pregnancy Category C {52}.


Breast-feeding

Ciprofloxacin, ofloxacin, and sparfloxacin are known to be distributed into human breast milk {04} {52} {98}. The concentration of ofloxacin in breast milk is similar to that found in plasma {98} {102}. One small study found that ofloxacin was highly concentrated in breast milk, reaching 98% of the simultaneous maternal serum level within 2 hours of administration {119}. It is not known whether enoxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, or norfloxacin is distributed into breast milk. However, based on data for ofloxacin, it is expected that levofloxacin is distributed into breast milk {17}{155}{157}. Norfloxacin was not detected in breast milk following its administration in low (200-mg) doses to nursing mothers. However, other quinolone derivatives are distributed into human breast milk {03} {09} {16}. Therefore, if an alternative antibiotic cannot be prescribed and a fluoroquinolone must be administered, breast-feeding is not recommended {98} {119}.

In immature animals, fluoroquinolones have been shown to cause permanent lesions of the cartilage of weight-bearing joints, as well as other signs of arthropathy. {98} {119} Moxifloxacin is distributed in the breast milk of lactating rats.{164}

Pediatrics


For all fluoroquinolones:

With the exception of ciprofloxacin when used post-exposure for inhalational anthrax,{159}{160} fluoroquinolones currently are not recommended for use in infants and children. Patients younger than 18 years of age usually have not been included in clinical trials because fluoroquinolones caused lameness in immature dogs due to permanent lesions of the cartilage of weight-bearing joints. Fluoroquinolones and other related quinolones have been reported to cause arthropathy in immature animals of various species; the effects vary with animal species and with quinolone dose and develop within days to weeks of the start of quinolone treatment. The mechanism by which quinolones produce this cartilage damage is unknown. {03} {04} {09} {16} {22} {98}{155}{157}

Fluoroquinolones have been used in neonates, infants, and children with serious infections that have not responded to other therapeutic regimens, or infections caused by multiple organisms resistant to other antibiotics {20} {21} {22}. More than 2500 pediatric patients to date, most of whom have cystic fibrosis, a disease that has a significant background prevalence of arthralgia and arthritis {38}, are reported to have undergone treatment with ciprofloxacin {21} {22} {54} {56} {57} {62}. The reported rate of musculoskeletal adverse events following ciprofloxacin administration in clinical trials was similar to that seen with placebo {22} {23} {28} {29} {65}, and only 1 to 2% of these events were considered to be possibly or probably due to ciprofloxacin. Arthropathy was reversible in almost all of these patients without additional treatment or fluoroquinolone discontinuation. Additional studies in pediatric patients with multidrug-resistant typhoid fever also documented no evidence of acute or subclinical joint toxicity or of diminished height velocity over a 2-year follow-up period {153}. Furthermore, postmortem examination of knee cartilage was normal in two juvenile patients who received oral ciprofloxacin for 9 to 10 months (and subsequently died secondary to complications of cystic fibrosis) {53}. There are case reports that document the reversibility of arthropathy only after discontinuation of ciprofloxacin {45} {46}. However, there has not been one report of irreversible damage to cartilage in a pediatric patient treated with fluoroquinolones {154}.

In 1993, the International Society of Chemotherapy commission developed guidelines for use of fluoroquinolones in the pediatric population based on a review of international experience. The commission does not promote the use of fluoroquinolones in children; when effective and nonrestricted alternative therapies are available for infections in pediatric patients, these therapies should be used. However, the commission also stated that critical and cautious use of fluoroquinolone antibiotics in pediatric patients suffering from specific infections complicated by pathologic or special conditions is justified by experimental and clinical data when alternative safe therapy is not available. The recommendations conclude that the risks and benefits of fluoroquinolone use should be assessed and a determination made on an individual basis for each compassionate use. {54}




Adolescents


For all fluoroquinolones

With the exception of ciprofloxacin when used post-exposure for inhalational anthrax,{159}{160} fluoroquinolones currently are not recommended for use in adolescents. Patients younger than 18 years of age usually have not been included in clinical trials because fluoroquinolones caused lameness in immature dogs due to permanent lesions of the cartilage of weight-bearing joints. One clinical report of 1219 adolescent patients (74 of whom had cystic fibrosis) who received ciprofloxacin at least once did not reveal any cases of newly diagnosed acute arthritis or joint toxicity that were likely to have been caused by the medication {61}. In general, arthralgias have been reported primarily in adolescent females who received fluoroquinolones; these arthralgias were not severe, were transient, and disappeared with either a dosage reduction or discontinuation of the medication {154}.

See also Pediatrics .



Geriatrics



For all fluoroquinolones:

Studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of fluoroquinolones in the elderly. However, tendinitis or tendon rupture, central nervous system (CNS) effects (e.g., hallucinations), and other side effects may occur more frequently in the elderly. Elderly patients also are more likely to have an age-related decrease in renal function, which may require an adjustment of dosage in patients receiving any of these medications. {08} {30} {61} {64} {67}{155}{157}

In geriatric intravenous moxifloxacin trials in community acquired pneumonia, the following ECG abnormalities were reported: ST-T wave changes, QT prolongation, ventricular tachycardia, atrial flutter, atrial fibrillation, supraventricular tachycardia, ventricular extrasystoles, and arrhythmia. None of these abnormalities was associated with a fatal outcome and a majority of these patients completed a full-course of therapy. {164}


Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Alkalizers, urinary, such as:
Carbonic anhydrase inhibitors
Citrates
Sodium bicarbonate    (urinary alkalizers may reduce the solubility of ciprofloxacin or norfloxacin in the urine; patients should be observed for signs of crystalluria and nephrotoxicity, although the incidence is rare {12} {13} {14} {86})


» Aminophylline or
» Oxtriphylline or
» Theophylline    (concurrent use of aminophylline, oxtriphylline, or theophylline with ciprofloxacin or enoxacin significantly reduces the hepatic metabolism and clearance of theophylline, probably by competitive inhibition at its binding sites within the cytochrome P450 enzyme system; this may result in a prolonged theophylline elimination half-life, increased serum concentration, and increased risk of theophylline-related toxicity; enoxacin has the greatest effect on theophylline clearance and it is recommended that the dose of theophylline be decreased by 50% during concurrent use; ciprofloxacin may also increase the risk of toxicity, especially in patients with theophylline concentrations at the upper end of the therapeutic range; serum theophylline concentrations should be monitored and dosage adjustments may be required; norfloxacin and ofloxacin have a minor effect on theophylline clearance; one study with ofloxacin found an increase of approximately 10% in the theophylline serum concentration; however, other studies have found that ofloxacin has a negligible effect on theophylline metabolism; theophylline dosage adjustment is usually not necessary in patients receiving norfloxacin or ofloxacin; theophylline clearance has not been found to be significantly altered by gatifloxacin, levofloxacin, lomefloxacin, or moxifloxacin {03} {04} {16} {17} {71} {98} {127} {128} {129} {135} {147}{155}{157})


» Amiodarone or
» Antidepressants, tricyclic or
» Astemizole or
» Bepredil or
» Cisapride or
» Disopyramide or
» Erythromycin or
» Pentamidine or
» Phenothiazines or
» Procainamide or
» Quinidine or
» Sotalol or
» Terfenadine or
» Other medications reported to prolong the QTc interval     (concurrent use of sparfloxacin with amiodarone and disopyramide has resulted in torsades de pointes; concurrent use of sparfloxacin with any medication reported to prolong the QTc interval or to produce torsades de pointes is contraindicated {52}; concurrent use of gatifloxacin, levofloxacin {163} and moxifloxacin with class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents should be avoided.{155}{157})


» Antacids, aluminum, calcium, and/or magnesium-containing or
» Ferrous sulfate or
Laxatives, magnesium-containing or
» Sucralfate or
Zinc    (antacids, ferrous sulfate, zinc, or sucralfate may reduce the absorption of fluoroquinolones by chelation, resulting in lower serum and urine concentrations; therefore, concurrent use is not recommended; because the bioavailability of enoxacin is decreased the most by concurrent administration of these medications, it is recommended that enoxacin be taken at least 2 hours before or 8 hours after taking any of these medications; ciprofloxacin should be taken at least 2 hours before or 6 hours after taking any of these medications; gatifloxacin should be taken 4 hours before taking iron, magnesium-containing antacids, and zinc; lomefloxacin should be taken at least 2 hours before or 4 hours after taking any of these medications; levofloxacin, norfloxacin, or ofloxacin should be taken at least 2 hours before or 2 hours after taking any of these medications; moxifloxacin should be taken at least 4 hours before and 8 hours after taking any of these medications; and sparfloxacin should be taken at least 4 hours before or 4 hours after taking any of these medications {03} {04} {09} {16} {17} {51} {98} {102} {147}{155}{157})


Anticonvulsants, hydantoin, especially:
» Phenytoin    (concurrent administration of ciprofloxacin with phenytoin has resulted in a 34 to 80% decrease in the plasma concentration of phenytoin; caution should be used when administering quinolones, especially ciprofloxacin, to patients stabilized on phenytoin; careful monitoring of phenytoin dosage after discontinuation of quinolones is highly recommended {04} {122} {123} {124})


Antidiabetic agents, sulfonylurea, especially:
Glyburide or
Insulin    (concurrent use of ciprofloxacin, or levofloxacin with glyburide or other antidiabetic agents has, on rare occasions, resulted in hypoglycemia; also, hyperglycemia and hypoglycemia have been reported in patients taking quinolone antibiotics and antidiabetic agents concurrently; since the mechanism is not understood, similar effects with other sulfonylurea antidiabetic agents may be expected when these medications are used with fluoroquinolones; careful monitoring of blood glucose concentrations is recommended when these medications are used concurrently; concurrent administration of moxifloxacin and glyburide did not result in clinically significant interaction {04} {17} {98}{155}{157})


Anti-inflammatory drugs, nonsteroidal (NSAIDs)    (fluoroquinolones, particularly enoxacin and norfloxacin, are competitive inhibitors of gamma-aminobutyric acid receptor binding, and some NSAIDs have been shown to enhance this effect; seizures have been reported in patients taking enoxacin and fenbufen concurrently; concurrent administration of NSAIDs with quinolone antibiotics may increase the risks of CNS stimulation and convulsions {16} {48} {58} {147}{155})


Bismuth    (the bioavailability of enoxacin is decreased by approximately 25% when bismuth subsalicylate is administered concurrently or within 60 minutes of enoxacin administration; concurrent administration of these medications is not recommended {16})


» Caffeine or
Theobromine    (concurrent use of caffeine with enoxacin has been found to decrease the hepatic metabolism of caffeine, resulting in a dose-related increase in the half-life of caffeine of up to five times normal; ciprofloxacin and, to a lesser extent, norfloxacin also reduce the hepatic metabolism and clearance of caffeine, increasing its half-life and the risk of caffeine-related CNS stimulation; lomefloxacin and ofloxacin do not produce any significant change in caffeine metabolism {03} {04} {16} {29} {98})


Cyclosporine    (concurrent use with ciprofloxacin or norfloxacin has been reported to elevate serum creatinine and serum cyclosporine concentrations; other studies have not found ciprofloxacin, enoxacin, or levofloxacin to alter the pharmacokinetics of cyclosporine; cyclosporine concentrations should be monitored when used concurrently with fluoroquinolones, and dosage adjustments may be required {03} {04} {09} {17} {39})


» Didanosine    (concurrent use of didanosine with ciprofloxacin, norfloxacin, or ofloxacin has been shown to reduce the absorption of these fluoroquinolones due to chelation of the fluoroquinolone by the aluminum and magnesium buffers in didanosine; didanosine should not be administered concurrently with any fluoroquinolone; also, didanosine should not be taken within within 2 hours before or 2 hours after taking norfloxacin or ofloxacin; gatifloxacin should be taken 4 hours before didanosine; moxifloxacin should be taken at least 4 hours before and 8 hours after taking didanosine {09} {75} {98}{155}{157})


Digoxin    (enoxacin may raise serum digoxin concentrations in some patients; digoxin serum concentrations should be monitored; gatifloxacin and moxifloxacin did not have any clinically significant interaction with digoxin {16}{155}{157})


Probenecid    (concurrent use of probenecid decreases the renal tubular secretion of fluoroquinolones, resulting in decreased urinary excretion of the fluoroquinolone, prolonged elimination half-life, and increased risk of toxicity; this interaction is more significant with gatifloxacin and ofloxacin, which is excreted largely unchanged in the urine, and of less clinical significance with fluoroquinolones that have larger nonrenal elimination, such as ciprofloxacin and enoxacin; moxifloxacin did not have any clinically significant interaction with probenecid {03} {04} {147}{155}{157})


» Warfarin    (concurrent use of warfarin with ciprofloxacin or norfloxacin has been reported to increase the anticoagulant effect of warfarin, increasing the chance of bleeding; other studies have not found fluoroquinolones to alter the prothrombin time [PT] significantly; enoxacin decreases the clearance of R-warfarin, the less active isomer of racemic warfarin, but not the active S-isomer; changes in clotting time have not been observed when enoxacin, gatifloxacin, levofloxacin, or moxifloxacin is administered concurrently with warfarin; however, it is recommended that the PT of patients receiving warfarin and fluoroquinolones concurrently be monitored carefully {02} {03} {04} {09} {16} {17} {126}{155})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Mycobacterium tuberculosis culture    (sparfloxacin may produce a false-negative culture result for M. tuberculosis by suppressing mycobacterial growth {52})

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) and
Alkaline phosphatase and
Amylase and
Aspartate aminotransferase (AST [SGOT]) and
Lactate dehydrogenase (LDH)    (serum values may be increased {03} {04} {16} {58} {98}{155})


Electrocardiogram    (moxifloxacin may prolong QT interval {164})


Prothrombin time {163}    (International Normalized Ratio (INR) values may be increased with levofloxacin {163})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Previous allergic reaction or hypersensitivity to fluoroquinolones or other chemically related quinolone derivatives {04} {98}
» Photosensitivity, history of    (moderate to severe phototoxic reactions have occurred in patients exposed to direct or indirect sunlight or to artificial ultraviolet light during or following sparfloxacin treatment; these reactions also have occurred in patients exposed to shaded or diffuse light, including exposure through glass or during cloudy weather; sparfloxacin is contraindicated in patients with a history of photosensitivity or those whose lifestyle or employment will not permit compliance with the required safety precautions {52})

    (moderate to severe phototoxic reactions also have occurred in patients exposed to direct sunlight during or following treatment with enoxacin, levofloxacin, norfloxacin, or ofloxacin; treatment with these fluoroquinolones should be discontinued if phototoxic reactions occur {09} {16} {17} {98})

    (gatifloxacin and moxifloxacin does not show phototoxicity when compared to placebo, however patients should avoid exposure to excessive sunlight or artificial ultraviolet light (e.g. tanning beds){155}{157})


» QTc-interval prolongation    (prolongation of the QTc interval has been observed in healthy volunteers receiving sparfloxacin or moxifloxacin; sparfloxacin is contraindicatedand moxifloxacin is not recommended in patients with known QTc-interval prolongation {52}{164})


» Tendinitis or tendon rupture, history of    (fluoroquinolones have been reported to cause tendinitis or tendon rupture during or after treatment; enoxacin is contraindicated in patients with a history of tendinitis or tendon rupture; other fluoroquinolones are not recommended for patients with these problems {19}{155}{157})


Risk-benefit should be considered when the following medical problems exist
» Bradycardia, significant{163}    (levofloxacin may cause cardiac arrhythmias and prolongation of the QT interval in the presence of significant bradycardia; moxifloxacin should be used with caution{164}{163})


CNS disorders, including:
» Cerebral arteriosclerosis or
» Epilepsy or
» Other factors that predispose to seizures    (fluoroquinolones may cause CNS stimulation or toxicity; convulsions may occur within 3 to 4 days after the start of fluoroquinolone treatment and usually resolve with discontinuation of the fluoroquinolone; fluoroquinolones should be used with caution in patients with confirmed or suspected CNS disorders {67} {84}{155}{157})


Diabetes mellitus    (levofloxacin has been reported to cause hyperglycemia and hypoglycemia, usually in diabetic patients who are taking oral hypoglycemic agents or insulin; diabetic patients should be monitored carefully {17})


Hepatic function impairment    (patients with severe hepatic function impairment, such as cirrhosis with ascites, may have decreased clearance of ofloxacin, resulting in an increase in peak serum concentration and elimination half-life; patients with both hepatic and renal function impairment may require a reduction in the dosage of ciprofloxacin; cirrhosis has not been found to decrease the nonrenal clearance of lomefloxacin {03} {04} {98} {105})


» Hypokalemia, uncorrected    (gatifloxacin , levofloxacin {163}and moxifloxacin may worsen QT prolongation in patients with uncorrected hypokalemia resulting in ventricular arrhythmias)

{155}
Myocardial ischemia, acute    (moxifloxacin should be used with caution{164})


» Proarrhythmias    (gatifloxacin, moxifloxacin, and sparfloxacin is not recommended for use in patients with ongoing proarrhythmias or cardiovascular conditions predisposing the patient to proarrhythmic conditions, including atrial fibrillation, congestive heart failure, hypokalemia, myocardial infarction, and significant bradycardia {52}{155}{157})


» Renal function impairment    (in general, fluoroquinolones primarily are excreted renally; it is recommended that patients with impaired renal function be administered reduced doses of fluoroquinolones {03} {04} {16} {98}{157})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Digoxin toxicity signs and symptoms    (gatifloxacin may increase digoxin serum concentrations, which should be determined in patients who showed signs of digoxin toxicity{157})


» Electrocardiogram (ECG)    (patients who are being treated concurrently with sparfloxacin or moxifloxacin and medications known to produce an increase in the QTc interval and/or torsades de pointes should receive appropriate cardiac monitoring {52}{164})


Prothrombin time (PT)    (the PT of patients concurrently receiving fluoroquinolones and warfarin should be monitored closely )

{155}


Side/Adverse Effects

Note: The relative insolubility of ciprofloxacin and norfloxacin at an alkaline pH has resulted in crystalluria, usually when the urinary pH exceeds 7. Because normal urinary pH is acidic, approximately 5 to 6, crystalluria is very unlikely to occur unless the patient's urine has become alkalinized. {09} {12} {27} {86}
Seizures have been reported very rarely with ciprofloxacin therapy; however, the patients who did have seizures either had a previous seizure history, were alcoholic, or were taking ciprofloxacin concurrently with theophylline. {24} {27}
Prolongation of the QTc interval was observed in healthy volunteers receiving sparfloxacin and in some moxifloxacin patients.{52}{155} The magnitude of QT prolongation may increase with increasing concentrations of moxifloxacin or increasing rates of intravenous infusion of moxifloxacin. QT prolongation may lead to an increased risk for ventricular arrhythmias including torsade de pointes.{164}
Phototoxic reactions have occurred in patients exposed to direct or indirect sunlight, or to artificial ultraviolet light, during or following sparfloxacin treatment; these reactions also have occurred in patients exposed to shaded or diffuse light, including exposure through glass or during cloudy weather. Phototoxic reactions have occurred with and without the use of sunscreens or sunblocks and have occurred after a single dose of sparfloxacin. Patients should avoid exposure to direct or indirect sunlight or artificial UV light during treatment and for 5 days following sparfloxacin treatment. Patients should discontinue sparfloxacin at the first sign or symptom of phototoxicity. Sparfloxacin is contraindicated in patients with a history of photosensitivity or those whose lifestyle or employment will not permit compliance with the required safety precautions. Patients who experience sparfloxacin-induced photosensitivity or phototoxicity should be treated within 2 weeks of the onset of symptoms to prevent development of lichenoid tissue reaction. {52} {67} {145}
Achilles tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones {25}{72}. The ruptures occurred 2 to 42 days after the start of therapy. Concomitant use of corticosteroids with fluoroquinolones may increase the risk of tendon disorders or ruptures {67}. These injuries may require surgical repair or result in prolonged disability. It is recommended that fluoroquinolone treatment be discontinued at the first sign of tendon pain or inflammation, and that patients refrain from exercising until the diagnosis of tendinitis has been excluded {03} {04} {09} {16} {98} {72}.{155} {157}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
QTc-interval prolongation {52}{164}(irregular or slow heart rate; recurrent fainting)—for sparfloxacin and less frequent for moxifloxacin{164}

Incidence less frequent
    
Chest pain{164}
    
hypertension{164} (blurred vision; dizziness; nervousness; headache; pounding in the ears; slow or fast heartbeat )
    
peripheral edema{164} (bloating or swelling of face, arms, hands, lower legs, or feet; rapid weight gain; tingling of hands or feet; unusual weight gain or loss)
    
phototoxicity {52}(blisters; sensation of skin burning; skin itching, rash, or redness; swelling )—more frequent for lomefloxacin and sparfloxacin

Incidence rare

Note: Frequency of incidence with moxifloxacin varies between ³ 0.1% and £ 3%

    
Amnesia{164} (loss of memory; problems with memory)
    
aphasia{164} ( problems with speech or speaking)
    
Arthralgia {155}{164}( joint pain)
    
asthenia{164} (lack or loss of strength)
    
asthma{164} (cough; difficulty breathing; noisy breathing; shortness of breath; tightness in chest; wheezing)
    
atrial fibrillation{164} (fast or irregular heartbeat; dizziness; fainting)
    
CNS stimulation {67}{121}{155}(acute psychosis; agitation; confusion; hallucinations; tremors)
    
cardiovascular reactions such as palpitation {164}(fast or irregular heartbeat), vasodilation {164}(dizziness; faintness; feeling of warmth or heat; flushing or redness of skin especially on face and neck; headache; light-headedness ; sweating; weakness), or tachycardia ( fainting; fast, pounding, or irregular heartbeat or pulse ){155}{157}{164}
    
convulsions{164} (seizures)
    
depersonalization{164} (feeling of unreality; sense of detachment from self or body.)
    
dysphagia{164} (difficulty swallowing)
    
dyspnea{164} (shortness of breath; difficult or labored breathing; tightness in chest; wheezing)
    
electrocardiogram (ECG), abnormal{164}
    
eosinophilia{164}
leukopenia{164} (black, tarry stools; chest pain; chills; cough; fever; painful or difficult urination; shortness of breath; sore throat; sores, ulcers, or white spots on lips or in mouth)
    
face edema{164} (swelling or puffiness of face)
    
glossitis{164} (redness, swelling, or soreness of tongue)
    
hematuria {157}(blood in the urine)
    
hepatotoxicity {19}{67}{40}{155}(dark or amber urine; loss of appetite; pale stools; stomach pain; unusual tiredness or weakness ; yellow eyes or skin)
    
hyperglycemia{164} (abdominal pain; blurred vision; dry mouth; fatigue; flushed, dry skin; fruit-like breath odor; increased hunger; increased thirst; increased urination; nausea; sweating; troubled breathing; unexplained weight loss; vomiting)
    
hyperlipidemia{164} (large amount of fat in the blood)
    
hypertonia{164} (excessive muscle tone; muscle tension or tightness; muscle stiffness )
    
hyperuricemia{164} (joint pain, stiffness, or swelling; lower back, side, or stomach pain; swelling of feet or lower legs)
    
hypesthesia{164} (burning, crawling, itching, numbness, prickling, "pins and needles" , or tingling feelings)
    
injection site reaction{164} (bleeding; blistering; burning; coldness; discoloration of skin; feeling of pressure; hives; infection; inflammation; itching; lumps; numbness; pain; rash; redness; scarring; soreness; stinging; swelling; tenderness; tingling; ulceration; warmth)
    
hypersensitivity reactions {67}{125}{155}( skin rash, itching, or redness; shortness of breath; swelling of face or neck; vasculitis)
    
hypotension{164} (blurred vision; confusion; dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly; sweating; unusual tiredness or weakness)
    
incoordination{164}
    
interstitial nephritis {41}{42}{43}{44}{67}(bloody or cloudy urine; fever; skin rash; swelling of feet or lower legs)
    
jaundice{164} (chills; clay-colored stools; dark urine; dizziness; fever; headache; itching; loss of appetite; nausea; abdominal or stomach pain; area rash; unpleasant breath odor; unusual tiredness or weakness; vomiting of blood; yellow eyes or skin)
    
maculopapular rash{164} (rash with flat lesions or small raised lesions on the skin)
    
phlebitis {05}{132}( pain at site of injection)—for intravenous ciprofloxacin and ofloxacin; occurred in 5% of patients receiving intravenous gatifloxacin{157}
    
pseudomembranous colitis ( abdominal or stomach cramps and pain, severe; abdominal tenderness; diarrhea, watery and severe, which may also be bloody; fever)
    
Stevens-Johnson Syndrome {163}(blistering, itching, loosening, peeling, or redness of skin; diarrhea, )
    
stomatitis {164}(swelling or inflammation of the mouth)
    
superventricular tachycardia{164}
{164}
vertricular tachycardia{164} (fainting; fast, pounding, or irregular heartbeat or pulse; palpitations )
    
thrombocythemia{164} (pain, warmth, or burning in fingers, toes and legs; headache; dizziness; problems with vision or hearing)
    
tendinitis or tendon rupture {25}{72}(pain in calves, radiating to heels; swelling of calves or lower legs)
    
urticaria{164} (hives or welts; itching; redness of skin; skin rash)

Incidence not determined and indicating the need for medical attention
—Observed during clinical practice; estimates of frequency cannot be determined    
Abnormal electroencephalogram{04} (abnormal brain waves)—with levofloxacin
    
allergic pneumonitis{04} (difficult breathing)— with levofloxacin
    
anaphylactic reaction{164} (cough; difficulty swallowing; dizziness fast heartbeat; hives; itching; puffiness or swelling of the eyelids or around the eyes, face, lips or tongue; shortness of )—with moxifloxacin
    
anaphylactic shock{04}{164} (sharp drop in blood pressure; hives )— with levofloxacin and moxifloxacin
    
encephalopathy{04} ( blurred vision; coma; confusion; dizziness )—with levofloxacin
    
eosinophilia{04} (black, tarry stools; sore throat; swollen glands; unusual bleeding or bruising)—with levofloxacin
    
erythema multiforme{04} (blistering, peeling, loosening of skin; itching; joint or muscle pain )—with levofloxacin
    
hemolytic anemia{04} ( bleeding gums; dark urine; fatigue; general body swelling )—with levofloxacin
    
increased international normalized ratio/prothrombin time{04} (increased bleeding time)—with levofloxacin
    
multi-system organ failure{04} (failure of the heart, lungs, kidneys and/or liver)—with levofloxacin
    
pseudomembranous colitis{164} (abdominal or stomach cramps; pain; bloating; abdominal tenderness; diarrhea, watery and severe, which may also be bloody; fever; increased thirst; nausea or vomiting; unusual tiredness or weakness; unusual weight loss)— with moxifloxacin
    
torsades de pointes{04} {163}(fast heartbeat; prolonged QT interval)—with levofloxacin
    
tendon rupture{164} (bone pain; lower back or side pain; painful, swollen joints)—with moxifloxacin



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
CNS toxicity (dizziness or lightheadedness; headache; nervousness; drowsiness; insomnia)
    
gastrointestinal reactions {01}{61}{155}{157}{164}(abdominal or stomach pain or discomfort, mild; diarrhea, mild; nausea or vomiting)
    
vaginitis {52}{157}{164}( vaginal pain and discharge)—most frequent for sparfloxacin and less frequent for moxifloxacin

Incidence less frequent or rare
    
Abdominal pain{164}
    
allergic reaction{164} (cough; difficulty swallowing; dizziness; fast heartbeat; hives; itching; puffiness or swelling of the eyelids or around the eyes, face, lips or tongue; shortness of breath )
    
amblyopia{164} ( blurred vision; change in vision; impaired vision)
    
anorexia{164} (loss of appetite; weight loss)
    
anxiety{164} (fear; nervousness)
    
arthritis{164} (pain, swelling, or redness in joints; muscle pain or stiffness; difficulty in moving)
    
back pain {157}
    
change in sense of taste {01}{67}{155}
    
constipation{164}
    
depression{164}
    
dizziness{164}
    
dream, abnormal {157}{164}—especially with gatifloxacin and rare with moxifloxacin
    
dry mouth{164}
    
dyspepsia{164} (acid or sour stomach; belching; heartburn; indigestion; stomach discomfort upset or pain)
    
dysuria {157}(difficulty in urination )
    
emotional lability{164} (crying; depersonalization; dysphoria; euphoria; mental depression; paranoia; quick to react or overreact emotionally; rapidly changing moods )
    
flatulence{164} ( bloated full feeling; excess air or gas in stomach or intestines; passing gas)
    
gastritis{164} (burning feeling in chest or stomach; tenderness in stomach area; stomach upset; indigestion)
    
headache {155}—more frequent for sparfloxacin
    
insomnia{164} (sleeplessness; trouble sleeping; unable to sleep)
    
leg pain{164}
    
malaise{164} ( general feeling of discomfort or illness; unusual tiredness or weakness)
    
moniliasis, oral {155}(sore mouth or tongue; white patches in mouth and/or on tongue)
    
moniliasis, vaginal {155}(vaginal yeast infection )
    
myalgia {155}(muscle pain)
    
nervousness{164}
    
pain{164}
    
paresthesia{164} (burning, crawling, itching, numbness, prickling, "pins and needles" , or tingling feelings)
    
parosmia{164} ( change in sense of smell)
    
pelvic pain{164}
    
photosensitivity (increased sensitivity of skin to sunlight)
    
pruritus{164} (itching skin)
    
purpuric rash{164} (pinpoint red or purple spots on skin)
    
pustular rash{164} (spots on skin resembling a blister or pimple)
    
sleep disorder{164} (difficulty in sleeping)
    
somnolence{164} (sleepiness or unusual drowsiness)
    
speech disorders{164} (difficulty in speaking)
    
sweating{164}
    
taste {164}
    
taste loss or perversion{164} (change in taste; bad, unusual or unpleasant (after) taste)
    
thinking, abnormal{164}
    
tinnitus{164} (continuing ringing or buzzing or other unexplained noise in ears; hearing loss)
    
tongue discoloration{164}
    
vertigo{164} ( dizziness or lightheadedness; feeling of constant movement of self or surroundings; sensation of spinning)
    
vision, abnormal {157}
    
vomiting{164}

Note: Some patients note a reduced incidence of nausea and taste perversion if the dose is administered in the evening {67}.
Photosensitivity reactions generally appear within a few days of the start of fluoroquinolone treatment but can occur up to 3 weeks after its discontinuation. The reactions usually subside within 1 month of discontinuation. {67}




Those indicating possible phototoxicity, pseudomembranous colitis, or tendinitis or tendon rupture and the need for medical attention if they occur after medication is discontinued
    
Abdominal or stomach cramps and pain, severe
abdominal tenderness
blisters
diarrhea, watery and severe, which may also be bloody
fever
pain in calves, radiating to heels
sensation of skin burning
skin rash, itching, or redness
swelling of calves or lower legs





Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing ).

Treatment of overdose
Since there is no specific antidote for overdose of fluoroquinolone antibiotics, treatment should be symptomatic and supportive and may include the following {04} {58} {98}{155}{157}:

To decrease absorption—Induction of emesis or use of gastric lavage to empty the stomach; activated charcoal may be used with moxifloxacin.{164}

Specific treatment—Patients with sparfloxacin overdose should avoid sun exposure for 5 days.

Monitoring—Electrocardiogram (ECG) monitoring for at least 24 hours after gatifloxacin, moxifloxacin, and sparfloxacin overdose is recommended, due to the possibility of prolongation of the QTc interval and other cardiac complications, including arrhythmias.

To enhance elimination—Gatifloxacin is not efficiently removed from the body by hemodialysis (about 14% recovered over 4 hours) or by chronic ambulatory peritoneal dialysis (about 11% recovered over 8 days).

Supportive care—Maintenance of adequate hydration. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Fluoroquinolones (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Allergies to fluoroquinolones or other quinolone derivatives

Pregnancy—Fluoroquinolones are not recommended for use during pregnancy because they have been shown to cause arthropathy in immature animals





Breast-feeding—Not recommended since fluoroquinolones have been shown to cause arthropathy in immature animals





Use in children— With the exception of ciprofloxacin for post-exposure inhalational anthrax, use of fluoroquinolones is not recommended in infants and children since these medications have been shown to cause arthropathy in immature animals




Use in adolescents—
With the exception of ciprofloxacin for post-exposure inhalational anthrax, use of fluoroquinolones is not recommended in adolescents since these medications have been shown to cause arthropathy in immature animals




Contraindicated medications
Amiodarone, astemizole, bepridil, cisapride, disopyramide, erythromycin, pentamidine, phenothiazines, procainamide, quinidine, sotalol, terfenadine, tricyclic antidepressants, or other medications reported to prolong the QTc interval (for sparfloxacin, moxifloxacin, and levofloxacin)
Other medications, especially aluminum, calcium, and/or magnesium-containing antacids, aminophylline, caffeine-containing products, didanosine, ferrous sulfate, oxtriphylline, phenytoin, sucralfate, theophylline, or warfarin

Gatifloxacin and moxifloxacin did not have any clinical significant drug interaction with theophylline or warfarin.
Other medical problems, especially allergy to quinolones; cerebral arteriosclerosis, bradycardia, epilepsy, or other factors that predispose to seizures; hepatic function failure; history of photosensitivity; history of tendinitis or tendon rupture; proarrhythmias; QTc-interval prolongation; renal function impairment, and uncorrected hypokalemia

Proper use of this medication
» Not giving to infants, children, adolescents, or pregnant women; fluoroquinolones have been shown to cause arthropathy in immature animals

» Taking with full glass (240 mL) of water; maintaining adequate fluid intake

» For enoxacin or norfloxacin—Taking on an empty stomach (1 hour before or 2 hours after a meal)

» For ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, ofloxacin, or sparfloxacin—Taking with meals or on an empty stomach; sparfloxacin may also be taken with milk or caffeine-containing products; gatifloxacin may be taken with milk or calcium-containing antacids and supplements; ciprofloxacin should NOT be taken with dairy products or calcium-fortified juices alone, but may be taken with a meal that contains these products

» Compliance with full course of therapy

» Importance of not missing doses and taking at evenly spaced times

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Checking with physician if no improvement of symptoms within a few days

» Avoiding concurrent use of antacids or sucralfate and fluoroquinolones; taking antacids or sucralfate at least 6 hours before or 2 hours after administration of ciprofloxacin; 4 hours after administration of gatifloxacin; 2 hours before or 2 hours after administration of levofloxacin, norfloxacin, or ofloxacin; 4 hours before or 2 hours after administration of lomefloxacin; 4 hours before or 4 hours after administration of sparfloxacin; 4 hours before or 8 hours after administration of moxifloxacin, and 8 hours before or 2 hours after administration of enoxacin

» Avoid concurrent use of Class IA and Class III antiarrhythmic agents with levofloxacin.

» Avoiding taking caffeine-containing products (e.g., coffee, tea, chocolate, certain carbonated beverages) during treatment with enoxacin

Possible phototoxicity reactions (e.g., blistering or burning sensation of skin)
» Avoiding exposure to direct or indirect sunlight and to artificial ultraviolet light (e.g., sunlamps) during treatment and for 5 days after treatment

» Discontinuing medication at the first sign or symptom of phototoxicity, such as blistering; itching, rash, or redness of skin; sensation of skin burning; or swelling

» If phototoxicity has occurred, avoiding further sunlight and artificial light until the phototoxicity reaction has been resolved, or for 5 days, whichever is longer
» Possible photosensitivity reactions; discontinuing medicine at the first sign of skin rash or other allergic reaction; checking with physician to determine if further treatment is needed

» Caution if dizziness, lightheadedness, or drowsiness occurs

» Discontinuing medicine and notifying physician if pain, inflammation, or rupture of a tendon is experienced; resting and refraining from exercise until the diagnosis of tendinitis or tendon rupture has been excluded

» Discontinuing medicine and notifying physician if a diabetic patient has a hypoglycemic episode while being treated with a fluoroquinolone and insulin or an oral hypoglycemic agent


Side/adverse effects
Signs of potential side effects, especially abnormal electrocardiogram (ECG), amnesia, aphasia, arthralgia, asthenia, asthma, atrial fibrillation, CNS stimulation, cardiovascular reactions such as palpitation, vasodilation, and tachycardia, chest pain, convulsions, depersonalization, dysphagia, dyspnea, face edema, glossitis, hematuria, hepatotoxicity, hypesthesia, hyperglycemia, hyperlipidemia, hypersensitivity reactions, hypertension, hypertonia, hyperuricemia, hypotension, injection site reaction, interstitial nephritis, jaundice, leukopenia, maculopapular rash, peripheral edema, phlebitis, phototoxicity, QTc-interval prolongation, Stevens-Johnson syndrome, stomatitis, superventricular tachycardia, thrombocythemia, ventricular tachycardia, tendinitis, or urticaria.

Signs of potential side effects observed during clinical practice, especially abnormal electroencephalogram (EEG), allergic pneumonitis, anaphylactic reaction, anaphylactic shock, encephalopathy, eosinophilia, erythema multiforme, hemolytic anemia, increased international normalized ration/prothrombin time, multi-system organ failure, pseudomembranous colitis, or torsade de pointes, or tendon rupture.


General Dosing Information
Due to the risk of increase in magnitude of QT prolongation, the recommended dose of gatifloxacin, levofloxacin {163} and moxifloxacin should not be exceeded. This is especially important in patients with risk factors such as significant bradycardia, acute myocardial ischemia, uncorrected hypoglycemia, and in patients receiving drugs that prolong QT interval.{155}{157}

Patients with impaired renal function may require a reduction in dosage based on creatinine clearance. Creatinine clearance (in mL per minute) may be calculated as follows:

• Adult males—Creatinine clearance = [(140 - age) × (ideal body weight in kg)]/[72 × serum creatinine (in milligrams per dL)]


• Adult females—Creatinine clearance = [(140 - age) × (ideal body weight in kg)]/[72 × serum creatinine (in milligrams per dL)] × 0.85


Creatinine clearance may also be calculated in SI units (as mL per second) as follows:

• Adult males—Creatinine clearance = [(140 - age) × (ideal body weight in kg)]/[50 × serum creatinine (in micromoles per L)]


• Adult females—Creatinine clearance = [(140 - age) × (ideal body weight in kg)]/[50 × serum creatinine (in micromoles per L)] × 0.85


Patients whose therapy is started with gatifloxacin or moxifloxacin injection may be switched to tablets without dosage adjustment.{157}{164}

For inhalational anthrax (post exposure) treatment: 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. Total duration of ciprofloxacin administration (I.V. or oral) is 60 days.{159}{160}

For treatment of adverse effects


For antibiotic-associated pseudomembranous colitis (AAPMC):
   • Some patients may develop antibiotic-associated pseudomembranous colitis (AAPMC), caused by Clostridium difficile toxin, during or after administration of a fluoroquinolone. Mild cases may respond to discontinuation of the medication alone. Moderate to severe cases may require fluid, electrolyte, and protein replacement.
   • In cases not responding to the above measures or in more severe cases, oral doses of an antibacterial medication effective against C. difficile should be administered.
   • In addition, AAPMC may result in severe watery diarrhea, which may occur during therapy or up to several weeks after therapy is discontinued. If diarrhea occurs, administration of antiperistaltic antidiarrheals (e.g., diphenoxylate and atropine combination, loperamide, opiates) is not recommended since they may delay the removal of toxins from the colon, thereby prolonging and/or worsening the condition.


CIPROFLOXACIN

Summary of Differences
Indications: Also indicated to reduce the incidence or progression of inhalational anthrax following exposure to aerosolized Bacillus anthracis.

Pharmacology/pharmacokinetics: Distribution—

• Penetrates CSF


• Distributed to skin, fat, muscle, bone, cartilage


• Crosses placenta


Precautions: Drug interactions—

• Interacts with aminophylline, oxtriphylline, and theophylline; phenytoin; urinary alkalizers; warfarin


Side/adverse effects: Phlebitis (parenteral dosage form only)


Additional Dosing Information

Diet/Nutrition
The presence of food in the stomach may delay the rate of absorption of oral ciprofloxacin; however, the overall absorption is not affected. Therefore, ciprofloxacin may be taken with meals or on an empty stomach. Ciprofloxacin should NOT be taken with dairy products or calcium-fortified juices alone; however, ciprofloxacin may be taken with a meal that contains these products {165} Ciprofloxacin should be taken with a full glass (240 mL) of water.

Crystalluria has been reported, especially in patients with alkaline urine (pH 7 or above). Therefore, alkalinization of the urine should be avoided. Although crystalluria has been reported only rarely in humans, fluid intake should be sufficient to maintain urine output of at least 1200 to 1500 mL per day in adults.

Bioequivalence information
The oral suspension and tablet dosage forms of ciprofloxacin are bioequivalent.

Parenteral dosage forms only
Parenteral ciprofloxacin should be administered by intravenous infusion over a period of at least 60 minutes to minimize patient discomfort and reduce the risk of venous irritation.


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

The dosing and strengths of the dosage forms available are expressed in terms of ciprofloxacin base.

CIPROFLOXACIN FOR ORAL SUSPENSION

Usual adult dose
Anthrax, inhalational (treatment) 1
Oral, 500 mg (base) every 12 hours for 60 days.{159}

Bone and joint infections
Mild or moderate: Oral, 500 mg (base) every twelve hours for at least four to six weeks {04}.

Severe or complicated: Oral, 750 mg (base) every twelve hours for at least four to six weeks {04}.

Diarrhea, infectious
Mild to severe: Oral, 500 mg (base) every twelve hours for five to seven days {04}.

Gonorrhea, endocervical and urethral
Oral, 250 mg (base) as a single dose {04}.

Intra-abdominal infections
Oral, 500 mg (base) every twelve hours for seven to fourteen days, in combination with oral metronidazole {04}.

Lower respiratory tract infections
Mild to moderate: Oral, 500 mg (base) every twelve hours for seven to fourteen days {04}.

Severe or complicated: Oral, 750 mg (base) every twelve hours for seven to fourteen days {04}.

[Meningococcal carriers ]
Oral, 750 mg (base) as a single dose {63}.

Prostatitis, chronic
Mild or moderate: Oral, 500 mg (base) every twelve hours for twenty-eight days {04}.

Sinusitis, mild or moderate 1 or
Typhoid fever
Oral, 500 mg (base) every twelve hours for ten days {04}.

Skin and soft tissue infections
Mild or moderate: Oral, 500 mg (base) every twelve hours for seven to fourteen days {04}.

Severe or complicated: Oral, 750 mg (base) every twelve hours for seven to fourteen days {04}.

Urinary tract infections
Acute uncomplicated: Oral, 100 mg (base) every twelve hours for three days {04}.

Mild or moderate: Oral, 250 mg (base) every twelve hours for seven to fourteen days {04}.

Severe or complicated: Oral, 500 mg (base) every twelve hours for seven to fourteen days {04}.


Note: Adults with impaired renal function may require a reduction in dose as follows {04}:

Creatinine clearance
(mL/min)/(mL/sec) 
Dose (base) 
> 50/0.83  See Usual adult dose
30–50/0.5–0.83  250–500 mg every 12 hours 
5–29/0.08–0.48  250–500 mg every 18 hours 
Hemodialysis or
Peritoneal dialysis patients 
250–500 mg every 24 hours
after dialysis 
In patients with severe infection and severe renal function impairment, a unit dose of 750 mg may be administered at the intervals noted above; however, these patients should be monitored carefully and serum concentrations of ciprofloxacin should be measured periodically {04}.


Usual adult prescribing limits
1.5 grams (base) daily {07}.

Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals {04}. However, ciprofloxacin has been given to pediatric patients, as indicated below, when alternative therapy could not be used. Based on pharmacokinetic studies, dosing for patients with cystic fibrosis should be higher and at more frequent intervals than for patients without cystic fibrosis {154} {156}. Dosing for cystic fibrosis patients also should be decreased as body weight increases {32}.
Anthrax, inhalational (treatment) 1
Oral, 15 mg per kg of body weight per dose (base), not to exceed 500 mg per dose, every 12 hours for 60 days.{159}

[Cystic fibrosis, pulmonary exacerbations]1
For children 14 to 28 kg of body weight: Oral, 28 to 20 mg (base) per kg of body weight every twelve hours, up to 2 grams per day {32}.

For children 28 to 42 kg of body weight: Oral, 20 to 15 mg (base) per kg of body weight every twelve hours, up to 2 grams per day {31} {32} {134}.

[For other infections]1
Oral, 10 to 15 mg (base) per kg of body weight twice a day, up to 1.5 grams per day {31}.


Usual geriatric dose
See Usual adult dose .

Strength(s) usually available
U.S.—


250 mg (base) per 5 mL (5%) (Rx) [Cipro (sucrose)]{04}


500 mg (base) per 5 mL (10%) (Rx) [Cipro (sucrose)]{04}

Canada—
Not commercially available.

Packaging and storage:
Prior to reconstitution, store below 25 °C (77 °F). Protect from freezing.

After reconstitution, store below 30 °C (86 °F). Protect from freezing.

Preparation of dosage form:
To prepare the oral suspension, the small bottle containing the microcapsules should be emptied into the large bottle containing the diluent. Water should not be added to the suspension . The large bottle should be closed and shaken vigorously for about 15 seconds.

Stability:
The suspension is stable for 14 days when stored in a refrigerator or at room temperature (below 30 °C [86 °F]).

Auxiliary labeling:
   • Shake well before use.
   • Take with a full glass of water.
   • May cause dizziness or lightheadedness.
   • Continue medicine for full time of treatment.
   • Avoid too much sun or use of sunlamp.
   • Take ciprofloxacin at least 2 hours before or 6 hours after antacids containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc, or didanosine (Videx®) chewable/buffered tablets or the pediatric powder for oral solution. {165}


CIPROFLOXACIN TABLETS USP

Usual adult dose
See Ciprofloxacin for Oral Suspension .

Usual adult prescribing limits
See Ciprofloxacin for Oral Suspension .

Usual pediatric dose
See Ciprofloxacin for Oral Suspension .

Usual geriatric dose
See Ciprofloxacin for Oral Suspension .

Strength(s) usually available
U.S.—


100 mg (base) (Rx) [Cipro]{04}


250 mg (base) (Rx) [Cipro]{04}


500 mg (base) (Rx) [Cipro]{04}


750 mg (base) (Rx) [Cipro]{04}

Canada—


100 mg (base) (Rx) [Cipro]{63}


250 mg (base) (Rx) [Cipro]{63}


500 mg (base) (Rx) [Cipro]{63}


750 mg (base) (Rx) [Cipro]{63}

Packaging and storage:
Store below 30 °C (86 °F) in a well-closed container.

Auxiliary labeling:
   • Take with a full glass of water.
   • May cause dizziness or lightheadedness.
   • Continue medicine for full time of treatment.
   • Avoid too much sun or use of sunlamp.
   • Take ciprofloxacin at least 2 hours before or 6 hours after antacids containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc, or didanosine (Videx®) chewable/buffered tablets or the pediatric powder for oral solution. {165}



Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

CIPROFLOXACIN INJECTION USP

Usual adult dose
Anthrax, inhalational (treatment) 1
Intravenous, 400 mg every 12 hours. Total duration of administration is 60 days.{160}

Bone and joint infections; or
Lower respiratory tract infections; or
Skin and soft tissue infections
Mild or moderate: Intravenous infusion, 400 mg every twelve hours {05}.

Severe or complicated: Intravenous infusion, 400 mg every eight hours {05}.

Intra-abdominal infections
Intravenous infusion, 400 mg every twelve hours, in combination with parenteral metronidazole {05}.

Neutropenia, febrile, empiric therapy1
Severe: Intravenous infusion, 400 mg every eight hours, in combination with piperacillin 50 mg per kg of body weight every four hours (up to 24 grams per day), for seven to fourteen days {05}.

Pneumonia, nosocomial
Mild to severe: Intravenous infusion, 400 mg every eight hours {05}.

Prostatitis, chronic or
Sinusitis, mild to moderate1
Intravenous infusion, 400 mg every twelve hours {05}.

[Septicemia]
Intravenous infusion, 400 mg every twelve hours {63}.

Urinary tract infections
Mild or moderate: Intravenous infusion, 200 mg every twelve hours {05}.

Severe or complicated: Intravenous infusion, 400 mg every twelve hours {05}.


Note: Adults with impaired renal function may require a reduction in dose as follows {05}:

Creatinine clearance
(mL/min)/(mL/sec) 
Dose (base) 
³ 30/0.5  See Usual adult dose
5–29/0.08–0.48   200–400 mg every 18 to 24 hours 



Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals {05}. However, ciprofloxacin has been given to pediatric patients, as indicated below, when alternative therapy could not be used. Based on pharmacokinetic studies, dosing for patients with cystic fibrosis should be higher and at more frequent intervals than for patients without cystic fibrosis {154} {156}. Dosing for cystic fibrosis patients also should be decreased as body weight increases {32}.
Anthrax, inhalational (treatment) 1
Intravenous, 10 mg per kg of body weight per dose, not to exceed 400 mg per dose, administered every 12 hours. Total duration of administration is 60 days.{160}

[Cystic fibrosis, pulmonary exacerbations]1
Intravenous infusion, 10 to 15 mg per kg every eight hours, up to 1.2 grams per day {31} {32}.

[For other infections]1
Neonates: Intravenous infusion, 3.5 to 20 mg per kg of body weight every twelve hours {20} {31}.
Infants and children: Intravenous infusion, 7.5 to 10 mg per kg of body weight every twelve hours, up to 800 mg per day {31}.


Usual geriatric dose
See Usual adult dose .

Strength(s) usually available
U.S.—


200 mg per 20 mL (Rx) [Cipro I.V. (in sterile water for injection; requires dilution prior to administration)]{05}


200 mg per 100 mL (Rx) [Cipro I.V. (in 5% dextrose injection; premixed)]{05}


400 mg per 40 mL (Rx) [Cipro I.V. (in sterile water for injection; requires dilution prior to administration)]{05}


400 mg per 200 mL (Rx) [Cipro I.V. (in 5% dextrose injection; premixed)]{05}


1200 mg per 120 mL (Rx) [Cipro I.V. (in sterile water for injection; requires dilution prior to administration)]{05}

Canada—


200 mg per 20 mL (Rx) [Cipro I.V. (in sterile water for injection; requires dilution prior to administration)]{63}


400 mg per 40 mL (Rx) [Cipro I.V. (in sterile water for injection; requires dilution prior to administration)]{63}

Packaging and storage:
Store in a cool place (between 8 and 15 °C [46 and 59 °F]) or at controlled room temperature (between 20 and 25 °C [68 and 77 °F]), unless otherwise specified by manufacturer. Protect from light and freezing.

Preparation of dosage form:
To prepare a solution for intravenous infusion, the concentrate in sterile water for injection should be withdrawn aseptically from the vial and diluted to a final concentration of 1 to 2 mg per mL with a suitable intravenous solution (see manufacturer's package insert). Solutions that come from the manufacturer in 5% dextrose injection should not be diluted prior to intravenous infusion. The resulting solution should be infused over a period of at least 60 minutes by direct infusion or through a Y-type intravenous infusion set. It is recommended that administration of any other solutions be discontinued during infusion of ciprofloxacin. {05}

Stability:
When diluted with appropriate intravenous fluids (see manufacturer's package insert) to concentrations from 0.5 to 2 mg per mL, solutions retain their potency for up to 14 days when refrigerated or stored at room temperature {05}.

Incompatibilities:
Ciprofloxacin is incompatible with aminophylline, amoxicillin, cefepime, clindamycin, dexamethasone, floxacillin, furosemide, heparin, and phenytoin {48}.

If ciprofloxacin is to be given concurrently with another medication, each medication should be administered separately according to the recommended dosage and route of administration for each medication. {05}


ENOXACIN

Summary of Differences
Precautions:

• Drug interactions—

• Enoxacin has the greatest effect in decreasing the clearance of caffeine and theophylline, increasing the risk of toxicity for these medications.


• Interacts also with bismuth and digoxin



• Medical considerations—Contraindicated in patients with tendinitis



Additional Dosing Information

Diet/Nutrition
The effect of food on the absorption of enoxacin tablets has not been studied; it is recommended that enoxacin be taken at least 1 hour before or 2 hours after a meal; however, decreased gastric acidity has been shown to decrease the bioavailability of enoxacin {137}.

Caffeine-containing products (e.g., coffee, tea, chocolate, certain carbonated beverages) should be avoided during treatment with enoxacin.


Oral Dosage Forms

ENOXACIN TABLETS

Usual adult dose
Gonorrhea
Oral, 400 mg as a single dose {16}.

Urinary tract infections, endocervical and urethral
Complicated: Oral, 400 mg every twelve hours for fourteen days {16}.

Uncomplicated: Oral, 200 mg every twelve hours for seven days {16}.


Note: Adults with impaired renal function may require a reduction in dose as follows {16}:

Creatinine clearance
(mL/min)/(mL/sec) 
Dose 
> 30/0.5  See Usual adult dose
£ 30/0.5  50% of the recommended dose every 12 hours 



Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals {16}.

Usual geriatric dose
See Usual adult dose .

Strength(s) usually available
U.S.—


200 mg (Rx) [Penetrex]{16}


400 mg (Rx) [Penetrex]{16}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight container {16}.

Auxiliary labeling:
   • Take with a full glass of water.
   • May cause dizziness, lightheadedness, or drowsiness.
   • Continue medicine for full time of treatment.


GATIFLOXACIN

Summary of Differences
Pharmacology/pharmacokinetic: Longer half-life; may be dosed once a day; does not inhibit cytochrome P450 isoenzymes and is not an enzyme inducer.

Precautions: Drug interactions—does not significantly interact with cimetidine, digoxin, glyburide, midazolam, theophylline, and warfarin.

Side effects—does not show phototoxicity when compared with placebo and had a lower potential for producing delayed photosensitivity skin reactions than ciprofloxacin or lomefloxacin.


Additional Dosing Information

Bioequivalence information
Dosage adjustment is not necessary when switching treatment of gatifloxacin from injection to tablets.

Diet/Nutrition
Gatifloxacin may be taken with or without food.

Antacids with aluminum and magnesium, vitamins containing iron or zinc, and sucralfate should not be taken within 4 hours after taking gatifloxacin.

For parenteral dosage forms only
Gatifloxacin injection should be administered only by slow intravenous infusion over a period of 60 minutes


Oral Dosage Form

GATIFLOXACIN TABLETS

Usual adult dose
Bronchitis, bacterial exacerbations
Oral, 400 mg every 24 hours for 7 to 10 days.{157}

Gonorrhea, endocervical and rectal in women; and urethral in men
Oral, 400 mg single dose.{157}

Pneumonia, community-acquired
Oral, 400 mg every 24 hours for 7 to 14 days.{157}

Pyelonephritis
Oral, 400 mg every 24 hours for 7 to 10 days.{157}

Sinusitis, acute
Oral, 400 mg every 24 hours for 10 days.{157}

Urinary tract infections, bacterial , uncomplicated
Oral, 400 mg single dose; or 200 mg every 24 hours for 3 days.{157}

Urinary tract infections, bacterial, complicated
Oral, 400 mg every 24 hours for 7 to 10 days.{157}


Note: Adults with renal function impairment, creatinine clearance < 40 mL/min including patients on hemodialysis and on chronic ambulatory peritoneal dialysis, may require a reduction in dose as follows:{157}

Creatinine clearance   Initial dose  Subsequent dose* 
³ 40 mL/min  400 mg  400 mg every day 
< 40 mL/min  400 mg  200 mg every day 
Hemodialysis  400 mg  200 mg every day 
Continuous peritoneal dialysis   400 mg  200 mg every day  
* Start of subsequent dose on Day 2 of dosing
 



Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals.{157}

Usual geriatric dose
See Usual adult dose

Strength(s) usually available
U.S.—


200 mg (Rx) [Tequin (methylcellulose) (polysorbate 80)]{157}


400 mg [Tequin ( methylcellulose) (polysorbate 80)]

Canada—
Not commercially available.

Packaging and storage:
Store at 25 °C (77 °F); excursion permitted to between 15 and 30 °C (59 and 86 °F).

Auxiliary labeling:
   • May cause dizziness, drowsiness, or lightheadedness.
   • Avoid too much sun exposure or use of sunlamp.
   • Continue medicine for full time of treatment.



Parenteral Dosage Forms

GATIFLOXACIN INTRAVENOUS SOLUTION — PREMIX BAGS

Usual adult dose
Bronchitis, bacterial exacerbations
Intravenous infusion, 400 mg every 24 hours for 7 to 10 days.{157}

Gonorrhea, endocervical and rectal in women; and urethral in men
Intravenous infusion, 400 mg single dose.{157}

Pneumonia, community-acquired
Intravenous infusion, 400 mg every 24 hours for 7 to 14 days.{157}

Pyelonephritis
Intravenous infusion, 400 mg every 24 hours for 7 to 10 days.{157}

Sinusitis, acute
Intravenous infusion, 400 mg every 24 hours for 10 days.{157}

Urinary tract infections, bacterial , uncomplicated
Intravenous infusion, 400 mg single dose; or 200 mg every 24 hours for 3 days.{157}

Urinary tract infections, bacterial, complicated
Intravenous infusion, 400 mg every 24 hours for 7 to 10 days.{157}


Note: Adults with renal function impairment, creatinine clearance < 40 mL/min including patients on hemodialysis and on chronic ambulatory peritoneal dialysis, may require a reduction in dose as follows:{157}

Creatinine clearance   Initial dose  Subsequent dose* 
³ 40 mL/min  400 mg  400 mg every day 
< 40 mL/min  400 mg  200 mg every day 
Hemodialysis  400 mg  200 mg every day 
Continuous peritoneal dialysis   400 mg  200 mg every day  
* Start of subsequent dose on Day 2 of dosing
 



Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals.{157}

Usual geriatric dose
See Usual adult dose

Strength(s) usually available
U.S.—


200 mg per 100 ml (Rx) [Tequin (in 5% dextrose)]


400 mg per 200 ml (Rx) [Tequin (in 5% dextrose)]

Canada—
Not commercially available.

Packaging and storage:
Store at 25 °C (77 °F); excursion permitted to between 15 and 30 °C (59 and 86 °F). Do not freeze.

Stability:
Gatifloxacin injection contains no preservative or bacteriostatic agent. Because of this, the premix bags are for single use only; any unused portion remaining in the bag should be discarded.{157}

Incompatibilities:
Because there are only limited data on the compatibility of other substances with gatifloxacin injection, additives or other medications should not be added to gatifloxacin injection or infused simultaneously through the same intravenous line.{157}

This product should be inspected visually for any particulate matter before administration. Samples with visible particles should be discarded.{157}


GATIFLOXACIN INTRAVENOUS SOLUTION — SINGLE-USE VIALS

Usual adult dose
Bronchitis, bacterial exacerbations
Intravenous infusion, 400 mg every 24 hours for 7 to 10 days.{157}

Gonorrhea, endocervical and rectal in women; and urethral in men
Intravenous infusion, 400 mg single dose.{157}

Pneumonia, community-acquired
Intravenous infusion, 400 mg every 24 hours for 7 to 14 days.{157}

Pyelonephritis
Intravenous infusion, 400 mg every 24 hours for 7 to 10 days.{157}

Sinusitis, acute
Intravenous infusion, 400 mg every 24 hours for 10 days.{157}

Urinary tract infections, bacterial , uncomplicated
Intravenous infusion, 400 mg single dose; or 200 mg every 24 hours for 3 days.{157}

Urinary tract infections, bacterial, complicated
Intravenous infusion, 400 mg every 24 hours for 7 to 10 days.{157}


Note: Adults with renal function impairment, creatinine clearance < 40 mL/min including patients on hemodialysis and on chronic ambulatory peritoneal dialysis, may require a reduction in dose as follows:{157}

Creatinine clearance   Initial dose  Subsequent dose* 
³ 40 mL/min  400 mg  400 mg every day 
< 40 mL/min  400 mg  200 mg every day 
Hemodialysis  400 mg  200 mg every day 
Continuous peritoneal dialysis   400 mg  200 mg every day  
* Start of subsequent dose on Day 2 of dosing
 



Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals.{157}

Usual geriatric dose
See Usual adult dose

Strength(s) usually available
U.S.—


200 mg per 20 ml (requires dilution prior to administration) (Rx) [Tequin]


400 mg per 40 ml (requires dilution prior to administration) (Rx) [Tequin]

Packaging and storage:
Store at 25 °C (77 °F); excursion permitted to between 15 and 30 °C (59 and 86 °F).

Preparation of dosage form:
To prepare a 200–mg dose for intravenous injection, withdraw 20 mL of gatifloxacin from the vial and dilute with a compatible intravenous solution (see manufacturer's labeling instruction) to a final concentration of 2 mg/mL or a final volume of 100 mL. To prepare a 400–mg dose for intravenous injection, withdraw 40 mL of gatifloxacin from the vial and dilute with a compatible intravenous solution (see manufacturer's labeling instruction) to a final concentration of 2 mg/mL or a final volume of 200 mL.{157}

Stability:
When diluted in a compatible intravenous solution to a concentration of 2 mg/mL, gatifloxacin is stable for 14 days when stored between 20 and 26 °C (68 and 77 °F) or under refrigeration between 2 and 8 °C (36 and 46 °F). Diluted solution that are frozen and stored between –25 and –10 °C (–13 to 14 °F) are stable for 6 months. Frozen solution may be thawed at controlled room temperature. Thawed solution are stable for 14 days when stored between 20 and 25 °C (68 and 77 °F) or when stored under refrigeration between 2 and 8 °C (36 and 46 °F). Solutions should not be refrozen.{157}

Gatifloxacin injection contains no preservative or bacteriostatic agent. Because of this, the vials are for single use only; any unused portion remaining in the vial should be discarded.{157}

Incompatibilities:
Because there are only limited data on the compatibility of other substances with gatifloxacin injection, additives or other medications should not be added to gatifloxacin injection or infused simultaneously through the same intravenous line.{157}

This product should be inspected visually for any particulate matter before administration. Samples with visible particles should be discarded.{157}


LEVOFLOXACIN

Summary of Differences
Precautions: Medical considerations—Diabetes mellitus


Additional Dosing Information

Bioequivalence information
Oral and parenteral dosage forms of levofloxacin are bioequivalent on a mg-per-mg basis; therefore, oral and parenteral routes of administration are considered to be interchangeable.

Diet/Nutrition
Levofloxacin may be taken with or without food.

Antacids, vitamins containing iron or zinc, or sucralfate should not be taken within 2 hours before or 2 hours after taking levofloxacin.

For parenteral dosage forms only
Levofloxacin should be administered only by slow intravenous infusion over a period of not less than 60 minutes and up to 90 minutes, depending on the dose to avoid hypotension that may result from rapid intravenous injection.{161}


Oral Dosage Forms

LEVOFLOXACIN TABLETS

Usual adult dose
Bronchitis, bacterial exacerbations
Oral, 500 mg every twenty-four hours for seven days {17}.

Pneumonia, community-acquired
Oral, 500 mg every twenty-four hours for seven to fourteen days {17}.

Note: Canadian manufacturer recommends 10 to 14 days for severe infections.{162}


Pyelonephritis or
Urinary tract infections, complicated
Oral, 250 mg every twenty-four hours for ten days {17}.

Sinusitis, acute maxillary
Oral, 500 mg every twenty-four hours for ten to fourteen days {17}.

Skin and soft tissue infections, complicated, treatment
Oral, 750 mg every twenty-four hours for seven to fourteen days.{17}


Note: Canadian manufacturer recommends 500 mg every twelve hours for seven to fourteen days.{162}

Skin and soft tissue infections, uncomplicated
Oral, 500 mg every twenty-four hours for seven to ten days {17}.


Note: Adults with renal function impairment may require a reduction in dose as follows {17}:

Creatinine clearance
(mL/min)/(mL/sec) 
Initial dose (base)  Subsequent dose (base) 
For complicated urinary tract infections or acute pyelonephritis: 
³ 20/0.33  250 mg  250 mg every 24 hours 
10–19/0.16–0.32  250 mg  250 mg every 48 hours 
For all other indications: 
50–80/0.83–1.33  500 mg  500 mg every 24 hours 
20–49/0.33–0.82  500 mg  250 mg every 24 hours 
10–19/0.16–0.32  500 mg  250 mg every 48 hours 
Hemodialysis patients or CAPD patients  500 mg  250 mg every 48 hours 



Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals {17}.

Strength(s) usually available
U.S.—


250 mg (Rx) [Levaquin (synthetic red iron oxide)]{17}{161}


500 mg (Rx) [Levaquin ( microcrystalline cellulose) (magnesium stearate ) (titanium dioxide) (synthetic red iron oxide) (synthetic yellow iron oxide)]{17}{161}


750 mg (Rx) [Levaquin (hydroxypropyl methylcellulose ) (crospovidone) (magnesium stearate) (polyethylene glycol) ( titanium dioxide) (polysorbate 80)]{161}

Canada—


250 mg (Rx) [Levaquin]{17}


500 mg (Rx) [Levaquin]{17}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F).

Auxiliary labeling:
   • Take with a full glass of water.
   • May cause dizziness, drowsiness, or lightheadedness.
   • Avoid too much sun exposure or use of sunlamp.
   • Continue medicine for full time of treatment.



Parenteral Dosage Forms

LEVOFLOXACIN FOR INJECTION

Usual adult dose
Bronchitis, bacterial exacerbations
Intravenous infusion, 500 mg every twenty-four hours for seven to fourteen days {17}.

Pneumonia, community-acquired
Intravenous infusion, 500 mg every twenty-four hours for seven to fourteen days {17}.

Pyelonephritis or
Urinary tract infections, complicated
Intravenous infusion, 250 mg every twenty-four hours for ten days {17}.

Sinusitis, acute maxillary
Intravenous infusion, 500 mg every twenty-four hours for ten to fourteen days {17}.

Skin and soft tissue infections
Intravenous infusion, 500 mg every twenty-four hours for seven to ten days {17}.


Note: Adults with renal function impairment may require a reduction in dose as follows {17}:

Creatinine clearance
(mL/min)/(mL/sec) 
Initial dose (base)  Subsequent dose (base) 
For complicated urinary tract infections or acute pyelonephritis: 
³ 20/0.33  250 mg  250 mg every 24 hours 
10–19/0.16–0.32  250 mg  250 mg every 48 hours 
For all other indications: 
50–80/0.83–1.33  500 mg  500 mg every 24 hours 
20–49/0.33–0.82  500 mg  250 mg every 24 hours 
10–19/0.16–0.32  500 mg  250 mg every 48 hours 
Hemodialysis patients or CAPD patients  500 mg  250 mg every 48 hours 



Usual pediatric dose
Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals {17}.

Strength(s) usually available
U.S.—


500 mg per 20 mL (requires dilution prior to administration) (Rx) [Levaquin]{17}

Canada—


500 mg per 20 mL (requires dilution prior to administration) (Rx) [Levaquin]{17}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F). Protect from light.

Preparation of dosage form:
Levofloxacin concentrate must be further diluted with compatible intravenous fluids prior to intravenous administration. The concentration of the resulting diluted solution must be 5 mg/mL prior to administration. {162}

To prepare a 250-mg dose for intravenous infusion, withdraw 10 mL of levofloxacin for injection from the vial and dilute with 40 mL of a compatible intravenous solution (see manufacturer's labeling instructions), for a total volume of 50 mL. To prepare a 500-mg dose, withdraw 20 mL of levofloxacin for injection from the vial and dilute with 80 mL of a compatible intravenous solution (see manufacturer's labeling instructions), for a total volume of 100 mL.

To prepare a 750-mg dose for intravenous infusion, withdraw 30 mL of levofloxacin concentrate for injection from the vial and dilute with 120 mL of a compatible intravenous solution, for a total volume of 150 mL. {162}



Stability:
When diluted to a concentration of 5 mg per mL, levofloxacin for injection is stable for 72 hours when stored at or below 25 °C (77 °F) and for 14 days when refrigerated (5 °C [41 °F]) in plastic intravenous containers. Diluted solutions that are frozen in glass bottles or plastic containers are stable for 6 months when stored at –20 °C (–4 °F). Frozen solutions should be thawed at room temperature or in a refrigerator. They should not be thawed in a microwave or by water-bath immersion. Thawed solutions should not be refrozen. {17}

Levofloxacin for injection contains no preservative or bacteriostatic agent. Because of this, the vials are for single use only; any unused portion remaining in the vial should be discarded. {17}

Incompatibilities:
Because there is only limited data on the compatibility of other substances with levofloxacin for injection, additives or other medications should not be added to levofloxacin for injection in the single-use vials or infused simultaneously through the same intravenous line. {17}

This product should be inspected visually for any particulate matter before administration. Samples with visible particles should be discarded. {17}


LEVOFLOXACIN INJECTION

Usual adult dose
See Levofloxacin for Injection .

Usual pediatric dose
See Levofloxacin for Injection .

Strength(s) usually available
U.S.—


250 mg per 50 mL (in dextrose solution) (Rx) [Levaquin (5% Dextrose )]{17}


500 mg per 100 mL (in dextrose solution) (Rx) [Levaquin (5% Dextrose )]{17}{161}


750 mg per 150 mL (Rx) [Levaquin (5% Dextrose )]{161}

Canada—


250 mg per 50 mL (in dextrose solution) (Rx) [Levaquin (5% Dextrose )]{162}


500 mg per 100 mL (in dextrose solution) (Rx) [Levaquin (5% Dextrose )]{158}{162}

Packaging and storage:
Store at or below 25 °C (77 °F); however, brief exposure at up to 40 °C (104 °F) does not adversely affect the product. Protect from excessive heat, freezing, and light.

Stability:
Levofloxacin injection in flexible containers is for single use only; any unused portion should be discarded. {17}

Incompatibilities:
Because there are only limited data on the compatibility of other substances with levofloxacin injection, additives or other medications should not be added to levofloxacin injection in flexible containers or infused simultaneously through the same intravenous line. {17}

This product should be inspected visually for any particulate matter before administration. Samples with visible particles should be discarded. {17}

Levofloxacin pre-mix injection flexible containers are for single use only; any unused portion should be discarded. Do not use levofloxacin flexible containers in series connections.{162}


LOMEFLOXACIN

Summary of Differences
Pharmacology/pharmacokinetics: Longer half-life; may be dosed once a day.

Precautions: Drug interactions—Does not significantly interfere with the clearance of caffeine and theophylline.


Additional Dosing Information

Diet/Nutrition
When lomefloxacin was administered with food, the extent of absorption was only slightly decreased. Lomefloxacin may be taken with or without food.


Oral Dosage Forms

Note: The dosing and strength of the dosage form available are expressed in terms of lomefloxacin base.

LOMEFLOXACIN TABLETS

Usual adult dose
Bronchitis, bacterial exacerbations1
Oral, 400 mg (base) once a day for ten days {03}.

Urinary tract infections, prophylaxis1
Transrectal biopsy patients: Oral, 400 mg (base) as a single dose one to six hours prior to the start of surgery {03}.

Transurethral surgical patients: Oral, 400 mg (base) as a single dose two to six hours prior to the start of surgery {03}.

Urinary tract infections, treatment1
Complicated: Oral, 400 mg (base) once a day for fourteen days {03}.

Uncomplicated, due to Escherichia coli : Oral, 400 mg (base) once a day for three days {03}.

Uncomplicated, due to Klebsiella pneumoniae , Proteus mirabilis , or Staphylococcus saprophyticus : Oral, 400 mg (base) once a day for ten days {03}.


Note: Adults with impaired renal function may require a reduction in dose as follows {03}:

Creatinine clearance
(mL/min)/(mL/sec) 
Dose (base) 
> 40/0.67  See Usual adult dose
£ 40/0.67 or
Hemodialysis  
400 mg for first dose,
then 200 mg once a day 



Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, and adolescents since fluoroquinolones cause arthropathy in immature animals {03}.

Usual geriatric dose
See Usual adult dose .

Strength(s) usually available
U.S.—


400 mg (base) (Rx) [Maxaquin (scored) ( lactose)]{03}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight container {03}.

Auxiliary labeling:
   • Take with a full glass of water.
   • May cause dizziness, lightheadedness, or drowsiness.
   • Continue medicine for full time of treatment.


MOXIFLOXACIN

Summary of Differences
Pharmacology/pharmacokinetic: Longer half-life; may be dosed once a day.

Precautions: Drug interactions—does not significantly interact with digoxin, glyburide, probenecid, ranitidine, theophylline, and warfarin.

Side effects: Prolongs QT interval in some patients; does not show phototoxicity when compared with placebo.


Additional Dosing Information

Diet/Nutrition
Food does not significantly affect the absorption. May be taken with or without food.


Oral Dosage Forms

MOXIFLOXACIN TABLETS

Usual adult dose
Bronchitis, bacterial exacerbations
Oral, 400 mg once a day for 5 days.

Pneumonia, community-acquired
Oral, 400 mg once a day for 7 to 14 days.{164}

Sinusitis, acute
Oral, 400 mg once a day for 10 days.

Skin and soft tissue infections (treatment)
Oral, 400 mg once a day for 7 days {164}


Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, and adolescents since moxifloxacin causes arthropathy in immature animals.

Usual geriatric dose
See Usual adult dose.

Strength(s) usually available
U.S.—


400 mg (base) (Rx) [Avelox]{155}

Canada—
Not commercially available.

Packaging and storage:
Store at 25 °C (77 °F); excursion permitted between 15 and 30 °C (59 and 86 °F). Avoid high humidity.

Auxiliary labeling:
   • Take moxifloxacin at least 4 hours before or 8 hours after antacids containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc, or didanosine (Videx®) chewable/buffered tablets or the pediatric powder for oral solution. {164}
   • Take with a full glass of water.
   • May cause dizziness, lightheadedness, or drowsiness.
   • Continue medicine for full time of treatment.
   • Avoid too much sun or use of sunlamp.



Parenteral Dosage Forms

MOXIFLOXACIN INJECTION

Usual adult dose
Bronchitis, bacterial exacerbations
Intravenous, 400 mg once a day for 5 days.{164}

Pneumonia, community-acquired
Intravenous, 400 mg once a day for 7 to 14 days.{164}

Sinusitis, acute
Intravenous, 400 mg once a day for 10 days.{164}

Skin and soft tissue infections (treatment)
Intravenous, 400 mg once a day for 7 days {164}


Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, and adolescents since moxifloxacin causes arthropathy in immature animals.

Usual geriatric dose
See Usual adult dose.

Strength(s) usually available
U.S.—


400 mg (base) per 250 mL (Rx) [Avelox I.V. (in 0.8% sodium chloride) (water for injection) ( may contain hydrochloric acid (pH adjustment)) ( may contain sodium hydroxide (pH adjustment))]{164}

Canada—
Not commercially available.

Packaging and storage:
Store at 25 °C (77 °F); excursions permitted between 15 and 30 °C (59 and 86 °F).

Stability:
Since moxifloxacin premix flexible bags are for single-use only, any unused portion should be discarded. {164}

Incompatibilities:
Since only limited data are available on the compatibility of moxifloxacin intravenous injection with other intravenous substances, additives or other medications should not be added to moxifloxacin injection or infused simultaneously through the same intravenous line. See the manufacturer's package insert for a list of compatible infusion solutions.{164}

Auxiliary labeling:
   • Do not refrigerate—Product precipitates upon refrigeration. {164}
   • For intravenous infusion only. Moxifloxacin injection is not intended for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration. {164}
   • Moxifloxacin is available in ready-to-use flexible bags so no further dilution of this preparation is necessary. {164}
   • This product should be visually inspected for particulate matter prior to administration. Samples containing visible particulates should not be used.


NORFLOXACIN

Summary of Differences
Precautions: Drug interactions—Cyclosporine; warfarin


Additional Dosing Information

Diet/Nutrition
The presence of food in the stomach may slightly decrease or delay absorption of norfloxacin. Therefore, norfloxacin preferably should be taken with a full glass (240 mL) of water on an empty stomach (either 1 hour before or 2 hours after meals or milk ingestion).

In studies with volunteers, crystalluria has been reported, especially with high doses (1200 or 1600 mg) and alkaline urine (pH 7 or above). Although crystalluria has not been reported with usual adult doses (400 mg twice a day), fluid intake should be sufficient to maintain urine output of at least 1200 to 1500 mL per day in adults. {09}


Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

NORFLOXACIN TABLETS USP

Usual adult dose
[Diarrhea, infectious]1
Oral, 400 mg every eight to twelve hours for five days. {68}

Gonorrhea, endocervical and urethral
Oral, 800 mg as a single dose {09}.

Prostatitis, acute or chronic1
Oral, 400 mg every twelve hours for twenty-eight days {09}.

Urinary tract infections
Uncomplicated, due to Escherichia coli , Klebsiella pneumoniae , or Proteus mirabilis : Oral, 400 mg every twelve hours for three days {09}.

Uncomplicated, due to other indicated organisms: Oral, 400 mg every twelve hours for seven to ten days {09}.


Note: Adults with impaired renal function may require a reduction in dose as follows {09}:

Creatinine clearance
(mL/min)/(mL/sec) 
Dose 
> 30/0.5  See Usual adult dose 
£ 30/0.5  400 mg once a day 



Usual adult prescribing limits
1.2 grams per day for [infectious diarrhea]1 {68}.
800 mg per day for all other indications {09}.

Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals {09}.

Usual geriatric dose
See Usual adult dose .

Strength(s) usually available
U.S.—


400 mg (Rx) [Noroxin]{09}

Canada—


400 mg (Rx) [Noroxin]{64}

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight container {68}.

Auxiliary labeling:
   • Take with a full glass of water.
   • Take on empty stomach.
   • May cause dizziness, lightheadedness, or drowsiness.
   • Continue medicine for full time of treatment.


OFLOXACIN

Summary of Differences
Precautions:

• Pregnancy—Crosses the placenta.


• Breast-feeding—Highly concentrated in breast milk.


• Drug interactions—Ofloxacin has a minor effect on the metabolism of theophylline; probenecid prolongs elimination half-life and increases risk of toxicity.


Side/adverse effects: Phlebitis (for parenteral dosage form only).

General dosing information: Unlike intravenous ciprofloxacin, the dose of intravenous ofloxacin does not need to be changed from the oral dose.


Additional Dosing Information

Diet/Nutrition
Food has minor influence on the absorption of ofloxacin, causing only a slight decrease in the peak serum concentration and the area under the serum concentration–time curve (AUC) {102} {113}. Therefore, ofloxacin may be taken with or without food {98}.

For parenteral dosage forms only
Ofloxacin injection should be administered only by slow intravenous infusion over 60 minutes. Rapid or bolus injection may result in hypotension.


Oral Dosage Forms

OFLOXACIN TABLETS

Usual adult dose
Bronchitis, bacterial exacerbations or
Pneumonia, community-acquired or
Skin and soft tissue infections, uncomplicated
Oral, 400 mg every twelve hours for ten days {98}.

Chlamydial infections, endocervical or urethral, with or without concurrent gonorrhea
Oral, 300 mg every twelve hours for seven days {98}.

Gonorrhea, uncomplicated, endocervical and urethral
Oral, 400 mg as a single dose {98}.

Pelvic inflammatory disease, acute
Oral, 400 mg every twelve hours for ten to fourteen days {98}.

Prostatitis
Oral, 300 mg every twelve hours for six weeks {98}.

Urinary tract infections
Complicated: Oral, 200 mg every twelve hours for ten days {98}.

Cystitis, due to Escherichia coli or Klebsiella pneumoniae : Oral, 200 mg every twelve hours for three days {98}.

Cystitis, due to other indicated organisms: Oral, 200 mg every twelve hours for seven days {98}.


Note: Adults with impaired renal function may require a reduction in dose as follows {98}:

Creatinine clearance
(mL/min)/(mL/sec) 
Dose (% of Usual adult dose Dosing interval (hr) 
> 50/0.83  100  12 
20–50/0.33–0.83  100  24 
< 20/0.33   50  24 



Usual adult prescribing limits
400 mg per day for patients with severe hepatic function impairment (e.g., cirrhosis with or without ascites) {98}.

Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals {98}.

Usual geriatric dose
See Usual adult dose .

Strength(s) usually available
U.S.—


200 mg (Rx) [Floxin (lactose)]{98}


300 mg (Rx) [Floxin (lactose)]{98}


400 mg (Rx) [Floxin (lactose)]{98}

Canada—


200 mg (Rx) [Floxin (lactose)]{66}


300 mg (Rx) [Floxin (lactose)]{66}


400 mg (Rx) [Floxin (lactose)]{66}

Packaging and storage:
Store below 30 °C (86 °F). Store in a well-closed container.

Auxiliary labeling:
   • Take with a full glass of water.
   • Continue medicine for full time of treatment.
   • Do not take antacids, or zinc or iron preparations, within 2 hours of taking this medicine.



Parenteral Dosage Forms

OFLOXACIN IN DEXTROSE INJECTION

Usual adult dose
Bronchitis, bacterial exacerbations or
Pneumonia, community-acquired or
Skin and soft tissue infections, uncomplicated
Intravenous infusion, 400 mg, administered over a period of sixty minutes, every twelve hours for ten days {132}.

Chlamydial infections, endocervical or urethral, with or without concurrent gonorrhea
Intravenous infusion, 300 mg, administered over a period of sixty minutes, every twelve hours for seven days {132}.

Gonorrhea, uncomplicated
Intravenous infusion, 400 mg, administered over a period of sixty minutes, as a single dose {132}.

Pelvic inflammatory disease, acute
Intravenous infusion, 400 mg, administered over a period of sixty minutes, every twelve hours for ten to fourteen days {132}.

Prostatitis
Intravenous infusion, 300 mg, administered over a period of sixty minutes, every twelve hours for six weeks. There are no safety data presently available to support the use of parenteral ofloxacin for more than ten days. After ten days, treatment should be switched to the oral dosage form or another appropriate therapy. {132}

Urinary tract infections
Complicated: Intravenous infusion, 200 mg, administered over a period of sixty minutes, every twelve hours for ten days {132}.

Cystitis, due to Escherichia coli or Klebsiella pneumoniae : Intravenous infusion, 200 mg, administered over a period of sixty minutes, every twelve hours for three days {132}.

Cystitis, due to other indicated organisms: Intravenous infusion, 200 mg, administered over a period of sixty minutes, every twelve hours for seven days {132}.


Note: Adults with renal function impairment may require a reduction in dose as follows: {132}

Creatinine clearance
(mL/min)/(mL/sec) 
Dose (% of Usual adult dose Dosing interval (hr) 
> 50/0.83  100  12 
20–50/0.33–0.83  100  24 
< 20/0.33   50  24 



Usual adult prescribing limits
400 mg per day for patients with severe hepatic function impairment (e.g., cirrhosis with or without ascites) {132}.

Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals {132}.

Usual geriatric dose
See Usual adult dose .

Strength(s) usually available
U.S.—


200 mg per 50 mL (Rx) [Floxin I.V. (in 5% dextrose injection )]{132}


400 mg per 100 mL (Rx) [Floxin I.V. (in 5% dextrose injection )]{132}

Canada—
Not commercially available.

Packaging and storage:
Store below 30 °C (86 °F). Protect from freezing and light.

Preparation of dosage form:
Premixed ofloxacin in dextrose injection in flexible containers requires no further dilution prior to administration (see manufacturer's labeling for instructions). Since these injections contain no preservatives or bacteriostatic agent, they should be used promptly after opening; unused portions should be discarded. {132}

Do not use the flexible containers in series connections. This may result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete. {132}

Stability:
Frozen solutions should be thawed at room temperature or in a refrigerator. They should not be thawed in a microwave or by water-bath immersion. Thawed solutions should not be refrozen. {132}

Ofloxacin in dextrose injection contains no preservatives or bacteriostatic agent. It should not be used if injection is discolored or contains a precipitate. {132}

Incompatibilities:
Because only limited data are available on the compatibility of ofloxacin in dextrose injection with other intravenous substances, additives or other medications, including cefepime {50}, should not be added to the preparation or infused simultaneously through the same intravenous line {132}.


OFLOXACIN INJECTION

Usual adult dose
See Ofloxacin in Dextrose Injection.

Usual adult prescribing limits
See Ofloxacin in Dextrose Injection.

Usual pediatric dose
See Ofloxacin in Dextrose Injection .

Usual geriatric dose
See Ofloxacin in Dextrose Injection .

Strength(s) usually available
U.S.—


400 mg per 10 mL (Rx) [Floxin I.V. (in sterile water for injection; requires dilution prior to administration)]{132}

Canada—
Not commercially available.

Packaging and storage:
Store below 30 °C (86 °F). Protect from freezing and light. {132}

Preparation of dosage form:
Ofloxacin in sterile water for injection requires dilution prior to administration. To prepare a solution at a concentration of 4 mg per mL for intravenous administration, add the volume of appropriate diluent (see manufacturer's package insert) as indicated below {132}:


Dose  Volume of ofloxacin concentrate to withdraw from vial  Volume of diluent
to add 
200 mg  5 mL  45 mL 
300 mg  7.5 mL  67.5 mL 
400 mg  10 mL  90 mL 
The diluted solution should be administered only by intravenous infusion over a period of at least 60 minutes. Since these injections contain no preservatives or bacteriostatic agent, they should be used promptly after opening; unused portions should be discarded. {132}

Stability:
When diluted to a concentration between 0.4 and 4 mg/mL, ofloxacin injection is stable for 72 hours when stored at or below 24 °C (75 °F) or for 14 days when refrigerated at 5 °C (41 °F) in glass bottles or plastic intravenous containers. Solutions that are diluted and frozen are stable for 6 months when stored at -20 °C (-4 °F). Once thawed, the solution is stable for up to 14 days when refrigerated (2 to 8 °C [36 to 46 °F]). {132}

Frozen solutions should be thawed at room temperature or in a refrigerator. They should not be thawed in a microwave or by water-bath immersion. Thawed solutions should not be refrozen. {132}

Ofloxacin injection contains no preservatives or bacteriostatic agent. It should not be used if injection is discolored or contains a precipitate. {132}

Incompatibilities:
Because only limited data are available on the compatibility of ofloxacin injection with other substances, additives or other medications, including cefepime {50}, should not be added to the preparation or infused simultaneously through the same intravenous line {132}.


SPARFLOXACIN

Summary of Differences
Precautions:

• Medical considerations/Contraindications—

• QTc-interval prolongation was observed in healthy volunteers


• Contraindicated in patients with history of photosensitivity


• Not recommended for patients with ongoing proarrhythmic conditions



• Drug interactions—Medications that prolong the QTc interval are contraindicated


• Laboratory value alterations—May produce false-negative test result for Mycobacterium tuberculosis


Side/adverse effects: More frequent phototoxicity or QTc-interval prolongation; vaginitis (more frequent)


Additional Dosing Information

Diet/Nutrition
May be taken with meals or on an empty stomach.

May be taken with caffeine-containing products or milk or other dairy products.

Treatment of photosensitivity or phototoxicity
Sparfloxacin-induced photosensitivity or phototoxicity should be treated within 2 weeks of onset of symptoms to prevent lichenoid tissue reaction.


Oral Dosage Forms

SPARFLOXACIN TABLETS

Usual adult dose
Bronchitis, bacterial exacerbations or
Pneumonia, community-acquired
Oral, 400 mg on the first day, then 200 mg every twenty-four hours for a total of ten days of therapy {52}.


Note: The recommended dose for patients with renal function impairment (creatinine clearance less than 50 mL per minute) is 400 mg on the first day, then 200 mg every forty-eight hours for a total of nine days of therapy {52}.


Usual adult prescribing limits
400 mg {52}.

Usual pediatric dose
Children up to 18 years of age—Use is not recommended in infants, children, or adolescents since fluoroquinolones cause arthropathy in immature animals {52}.

Strength(s) usually available
U.S.—


200 mg (Rx) [Zagam]{52}

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F).

Auxiliary labeling:
   • Take with a full glass of water.
   • Do not take antacids or iron preparations within 4 hours of this medicine.
   • May cause dizziness or lightheadedness.
   • Avoid too much sun or use of sunlamp.
   • Continue medicine for full time of treatment.



Revised: 01/30/2003



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  1. Product Information: Avelox™ (moxifloxacin), Bayer Pharmaceutical, West Haven, CT. rev. 1/2000, reviewed 2/2000.
  1. Rubio TT, Miles MV, Lettieri JT, et al. Pharmacokinetic disposition of sequential intravenous/oral ciprofloxacin in pediatric cystic fibrosis patients with acute pulmonary exacerbation. Pediatr Infect Dis J 1997; 16(1): 112-7.
  1. Product Information: Tequin™ (gatifloxacin) tablets and intravenous solution, Bristol-Myers Squibb, Princeton, NJ. rev 12/99, reviewed 2/2000.
  1. Product Information: Levaquin, levofloxacin tablets and injection. Janssen-Ortho, Toronto, Ontario, Canada. PI revised 6/24/99, reviewed 2/2000.
  1. Product Information: Cipro®, ciprofloxacin and ciprofloxacin hydrochloride. Bayer Corporation, West Haven, CT, (PI revised 10/2000) PI reviewed 12/2000.
  1. Product Information: Cipro® I.V. , ciprofloxacin. Bayer Corporation, West Haven, CT, (PI revised 11/2000) PI reviewed 12/2000.
  1. Product Information: Levaquin, levofloxacin. Ortho-McNeil Pharmaceutical, Inc., Raritan, New Jersey, (PI Issued 09/2000) reviewed 01/2001
  1. Product Information: Levaquin, levofloxacin. Janssen-Ortho Inc., Toronto, Ontario (PI revised 6/2000) Reviewed 6/2001
  1. Product Information: Levaquin®, levofloxacin. Ortho-McNeil Pharmaceutical, Inc., Raritan, New Jersey, (PI revised 9/2001) reviewed 12/2001
  1. Product Information: Avelox® (moxifloxacin), Bayer Pharmaceutical, West Haven, CT, (PI revised 5/2002) reviewed 1/2003.
  1. Product Information: Cipro® (ciprofloxacin), Bayer Corporation, West Haven, CT, (PI revised 4/2002) reviewed 1/2003
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