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moxifloxacin hcl 400 mg tablet generic avelox

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Uses

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Moxifloxacin is used orally or IV for the treatment of respiratory tract infections (acute sinusitis, acute exacerbations of chronic bronchitis, community-acquired pneumonia), complicated intra-abdominal infections, and uncomplicated and complicated skin and skin structure infections caused by susceptible bacteria.

Moxifloxacin also is used as an alternative for the treatment of endocarditis, certain GI infections, and mycobacterial infections. In addition, the drug is recommended as an alternative for postexposure prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores (inhalational anthrax) or the treatment of inhalational anthrax and for the treatment or prophylaxis of plague.

Respiratory Tract Infections

Acute Sinusitis

Moxifloxacin is used for the treatment of acute bacterial sinusitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.

Moxifloxacin should be used for the treatment of acute bacterial sinusitis only when there are no other treatment options.Because systemic fluoroquinolones, including moxifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient(see Cautions)and because acute bacterial sinusitis may be self-limiting in some patients,the risks of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with acute sinusitis.

Clinical Experience

In a controlled, double-blind study in 457 patients with acute bacterial sinusitis, the clinical success rate (cure plus improvement) at the test-of-cure visit 7-21 days after treatment was 90% in those who received moxifloxacin (400 mg once daily for 10 days) and 89% in those who received cefuroxime axetil (250 mg twice daily for 10 days). In a noncomparative study, the clinical success and eradication/presumed eradication rate at 21-37 days after moxifloxacin treatment (400 mg once daily for 7 days) was 97, 83, or 80% for infections caused by S. pneumoniae, M. catarrhalis, or H. influenzae, respectively.

Acute Exacerbations of Chronic Bronchitis

Moxifloxacin is used for the treatment of acute bacterial exacerbations of chronic bronchitis caused by susceptible S. pneumoniae, H. influenzae, H. parainfluenzae, Klebsiella pneumoniae, Staphylococcus aureus (methicillin-susceptible [oxacillin-susceptible] strains), or M. catarrhalis.

Moxifloxacin should be used for the treatment of acute bacterial exacerbations of chronic bronchitis only when there are no other treatment options.Because systemic fluoroquinolones, including moxifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient (see Cautions)and because acute bacterial exacerbations of chronic bronchitis may be self-limiting in some patients,the risks of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with these infections.

Clinical Experience

In a randomized, double-blind, controlled trial in 629 patients with acute bacterial exacerbations of chronic bronchitis, the clinical success rate 7-17 days after treatment was 89% in those who received moxifloxacin (400 mg once daily for 5 days) and also was 89% in those who received clarithromycin (500 mg twice daily for 10 days). The microbiologic eradication rate (eradication plus presumed eradication) in those who received moxifloxacin was 100% for S. pneumoniae, 89% for H. influenzae, 100% for H. parainfluenzae, 85% for M. catarrhalis, 94% for S. aureus, and 85% for K. pneumoniae.

Community-acquired Pneumonia

Moxifloxacin is used for the treatment of community-acquired pneumonia (CAP) caused by susceptible S. pneumoniae (including multidrug-resistant strains [MDRSP]), S. aureus (methicillin-susceptible [oxacillin-susceptible] strains), K. pneumoniae, H. influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae), or M. catarrhalis.

Initial treatment of CAP generally involves use of an empiric anti-infective regimen based on the most likely pathogens and local susceptibility patterns; treatment may then be changed (if possible) to provide a more specific regimen (pathogen-directed therapy) based on results of in vitro culture and susceptibility testing. The most appropriate empiric regimen varies depending on the severity of illness at the time of presentation, whether outpatient treatment or hospitalization in or out of an intensive care unit (ICU) is indicated, and the presence or absence of cardiopulmonary disease and other modifying factors that increase the risk of certain pathogens (e.g., methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus], penicillin-resistant S. pneumoniae, MDRSP, enteric gram-negative bacilli, Ps. aeruginosa).

For additional information on management of CAP, the current clinical practice guidelines from the Infectious Diseases Society of America (IDSA) available at http://www.idsociety.org should be consulted.

Clinical Experience

In randomized studies in patients with clinically and radiologically documented CAP, the rate of clinical success with a sequential regimen of IV moxifloxacin followed by oral moxifloxacin (400 mg daily for 7-14 days) was similar to that achieved with 7-14 days of therapy with similar regimens using other fluoroquinolones (levofloxacin) or a regimen of ceftriaxone with or without erythromycin. In a randomized study in CAP patients 65 years of age or older (mean age 77.9 years), the clinical cure rate at the test-of-cure visit (5-21 days after end of treatment) was 92.9% in those who received moxifloxacin and 87.9% in those who received levofloxacin; the bacteriologic success rate was 81% in those who received moxifloxacin and 75% in those who received levofloxacin.

Data on efficacy of moxifloxacin for the treatment of CAP caused by S. pneumoniae in adults have been obtained from various clinical studies. In these studies, moxifloxacin resulted in clinical cure in about 95% of patients with CAP caused by S. pneumoniae. In those patients with documented infections caused by penicillin-resistant S. pneumoniae (penicillin MICs of 2 mcg/mL or greater), the bacteriologic cure rate was 100%. In 37 patients with CAP caused by multidrug-resistant strains, the clinical cure rate with moxifloxacin was 95%. Moxifloxacin has been effective for the treatment of infections caused by S. pneumoniae resistant to penicillin, second generation cephalosporins (e.g., cefuroxime), macrolides, tetracyclines, and/or co-trimoxazole.

Nosocomial Pneumonia

Moxifloxacin is used in the treatment of nosocomial pneumonia, including hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.

Local susceptibility data should be used when selecting initial empiric regimens for the treatment of nosocomial pneumonia, including hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. For empiric treatment of hospital-acquired bacterial pneumonia in patients with risk factors for multidrug-resistant bacteria, the American Thoracic Society (ATS) and IDSA recommend use of anti-infectives that have a broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria. An anti-infective active against MRSA (e.g., vancomycin, linezolid) should be included in the initial empiric regimen in hospitals where MRSA is common or if there are other factors that increase the risk for these strains.

For additional information on management of nosocomial pneumonia, the current clinical practice guidelines from IDSA available at http://www.idsociety.org should be consulted.

Skin and Skin Structure Infections

Moxifloxacin is used for the treatment of uncomplicated skin and skin structure infections caused by susceptible S. aureus (methicillin-susceptible [oxacillin-susceptible] strains) or Streptococcus pyogenes (group A β-hemolytic streptococci) and for the treatment of complicated skin and skin structure infections caused by susceptible S. aureus (methicillin-susceptible [oxacillin-susceptible] strains), Escherichia coli, K. pneumoniae, or Enterobacter cloacae.

For additional information on management of skin and skin structure infections, the current clinical practice guidelines from IDSA available at http://www.idsociety.org should be consulted.

Clinical Experience

Moxifloxacin has been effective for the treatment of uncomplicated abscesses, furuncles, cellulitis, impetigo, and other skin infections. In a randomized double-blind study, moxifloxacin (400 mg once daily for 7 days) was as effective as cephalexin (500 mg 3 times daily for 7 days) in the treatment of uncomplicated skin and skin structure infections caused by susceptible bacteria; clinical success (resolution or improvement) occurred in 89 or 91% of those receiving moxifloxacin or cephalexin, respectively (intent-to-treat analysis).

In 2 randomized, comparator-controlled studies in adults with complicated skin and skin structure infections, the clinical success rate in those receiving a sequential regimen of IV moxifloxacin followed by oral moxifloxacin (400 mg once daily for 7-14 days) was similar to that in those who received a sequential IV then oral regimen of a fixed-combination preparation containing a β-lactam antibiotic and a β-lactamase inhibitor (77-81% for moxifloxacin versus 82-85% for the comparator agent). When data were stratified by the causative agent, the clinical success rate in patients who received moxifloxacin was about 82% in those with infections caused by S. aureus infections (methicillin-susceptible [oxacillin-susceptible] strains), E. coli, or E. cloacae and 92% in those with infections caused by K. pneumoniae.

Intra-abdominal Infections

Moxifloxacin is used for the treatment of complicated intra-abdominal infections, including polymicrobial infections such as abscess caused by susceptible Bacteroides fragilis, B. thetaiotaomicron, Clostridium perfringens, Enterococcus faecalis, E. coli, Proteus mirabilis, S. anginosus, S. constellatus, or Peptostreptococcus.

For initial empiric treatment of mild to moderate community-acquired, extrabiliary, complicated intra-abdominal infections in adults (e.g., perforated or abscessed appendicitis), IDSA recommends either monotherapy with cefoxitin, ertapenem, moxifloxacin, tigecycline, or the fixed combination of ticarcillin and clavulanic acid, or a combination regimen that includes either a cephalosporin (cefazolin, ceftriaxone, cefotaxime, cefuroxime) or fluoroquinolone (ciprofloxacin, levofloxacin) in conjunction with metronidazole. IDSA states that use of moxifloxacin should be avoided in patients who received a quinolone within the past 3 months and are likely to harbor B. fragilis since such strains are likely to be resistant to the drug.

For additional information on management of intra-abdominal infections, the current clinical practice guidelines from IDSA available at http://www.idsociety.org should be consulted.

Clinical Experience

Safety and efficacy of moxifloxacin monotherapy for the treatment of surgically confirmed complicated intra-abdominal infections (including peritonitis, abscess, appendicitis with perforation, bowel perforation) were established in 2 randomized, active-controlled studies in adults. In one double-blind study, patients were randomized to receive a sequential regimen of IV moxifloxacin followed by oral moxifloxacin (400 mg once daily for 5-14 days) or a sequential regimen of the IV fixed-combination preparation of piperacillin and tazobactam followed by the oral fixed-combination preparation of amoxicillin and clavulanate potassium. At the test-of-cure visit (day 25-50 after initiation of study), the clinical cure rate in the efficacy-valid population was 80% in those who received moxifloxacin and 78% in those who received the comparator regimen. The bacteriologic success rate (eradication or presumed eradication) at the test-of-cure visit was 78% in those who received moxifloxacin (83% of those with hospital-acquired or 77% of those with community-acquired infections) and 77% in those who received the comparator regimen (55% of those with hospital-acquired or 82% of those with community-acquired infections). Similar results were obtained in an open-label study in which patients were randomized to receive 400 mg of moxifloxacin daily for 5-14 days or a sequential regimen of IV ceftriaxone in conjunction with IV metronidazole followed by the oral fixed-combination preparation of amoxicillin and clavulanate potassium. In this open-label study, the clinical success rate at the test-of-cure visit (day 25-50 after initiation of study) was 81% in those who received moxifloxacin and 82% in those who received the comparator regimen.

Endocarditis

Moxifloxacin is used as an alternative for treatment of endocarditis (native or prosthetic valve or other prosthetic material) caused by fastidious gram-negative bacilli known as the HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens, Kingella).

The American Heart Association (AHA) and IDSA recommend ceftriaxone (or other third or fourth generation cephalosporin) for the treatment of endocarditis caused by the HACEK group, but state that a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) may be considered in patients who cannot tolerate cephalosporins. Because only limited data are available regarding use of fluoroquinolones for the treatment of HACEK endocarditis, an infectious disease specialist should be consulted when treating such infections in patients who cannot tolerate cephalosporins.

GI Infections

Salmonella Gastroenteritis

Moxifloxacin is used as an alternative for the treatment of Salmonella gastroenteritis (with or without bacteremia).

Anti-infective therapy generally is not indicated in otherwise healthy individuals with uncomplicated (noninvasive) gastroenteritis caused by Salmonella since such therapy may prolong the duration of fecal excretion of the organism and there is no evidence that it shortens the duration of the disease; however, the US Centers for Disease Control and Prevention (CDC), American Academy of Pediatrics (AAP), IDSA, and others recommend anti-infective therapy in individuals with severe Salmonella gastroenteritis and in those who are at increased risk of invasive disease. These individuals include infants younger than 3-6 months of age; individuals older than 50 years of age; individuals with hemoglobinopathies, severe atherosclerosis or valvular heart disease, prostheses, uremia, chronic GI disease, or severe colitis; and individuals who are immunocompromised because of malignancy, immunosuppressive therapy, human immunodeficiency virus (HIV) infection, or other immunosuppressive illness.

Because HIV-infected individuals with Salmonella gastroenteritis are at high risk for bacteremia, CDC, National Institutes of Health (NIH), and IDSA recommend that such patients receive anti-infective treatment to prevent extraintestinal spread of the infection. These experts state that the initial drug of choice for the treatment of salmonella gastroenteritis (with or without bacteremia) in HIV-infected adults is ciprofloxacin; other fluoroquinolones (levofloxacin, moxifloxacin) also are likely to be effective in these patients, but clinical data are limited. Depending on results of in vitro susceptibility testing of the causative organism, alternatives for treatment of Salmonella gastroenteritis in HIV-infected adults are co-trimoxazole or third generation cephalosporins (ceftriaxone, cefotaxime).

Shigella Infections

Moxifloxacin is used for the treatment of shigellosis caused by susceptible Shigella.

Infections caused by Sh. sonnei usually are self-limited (48-72 hours), and mild cases may not require treatment with anti-infectives. However, because there is some evidence that anti-infectives may shorten the duration of diarrhea and the period of fecal excretion of Shigella, anti-infective treatment generally is recommended in addition to fluid and electrolyte replacement in patients with severe shigellosis, dysentery, or underlying immunosuppression. An empiric treatment regimen can be used initially, but in vitro susceptibility testing of clinical isolates is indicated since resistance is common. A fluoroquinolone (preferably ciprofloxacin or, alternatively, levofloxacin or moxifloxacin) generally has been recommended for the treatment of shigellosis. However, fluoroquinolone-resistant Shigella have been reported in the US, especially in international travelers, the homeless, and men who have sex with men (MSM). Depending on in vitro susceptibility, alternatives to fluoroquinolones for the treatment of shigellosis include co-trimoxazole or azithromycin (not recommended in those with bacteremia); ceftriaxone or azithromycin are considered drugs of choice for the treatment of shigellosis when the susceptibility of the isolate is unknown or when ampicillin- or co-trimoxazole-resistant strains are involved.

Anthrax

Oral moxifloxacin is considered an alternative for postexposure prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores (inhalational anthrax) and for treatment of inhalational anthrax.

CDC, US Public Health Service Advisory Committee on Immunization Practices (ACIP), US Working Group on Civilian Biodefense, and US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommend oral ciprofloxacin and oral doxycycline as the initial drugs of choice for postexposure prophylaxis following exposure to aerosolized anthrax spores, including exposures that occur in the context of biologic warfare or bioterrorism. Some of these experts (e.g., ACIP, US Working Group on Civilian Biodefense) state that levofloxacin or other oral fluoroquinolones (moxifloxacin, ofloxacin) are alternatives for postexposure prophylaxis when ciprofloxacin or doxycycline cannot be used.

US Working Group on Civilian Biodefense and USAMRIID also suggest that oral levofloxacin or other oral fluoroquinolones (moxifloxacin, ofloxacin) can be considered alternatives for the treatment of inhalational anthrax when a parenteral regimen is not available. Although CDC and these experts recommend that treatment of inhalational anthrax be initiated with a multiple-drug parenteral regimen that includes ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective, use of these parenteral regimens may not be possible if large numbers of individuals require treatment in a mass casualty setting and it may be necessary to use an oral regimen. In vitro data suggest that other fluoroquinolones would be as effective as and could be substituted for ciprofloxacin for treatment of inhalational anthrax.

For additional information on postexposure prophylaxis or treatment of anthrax, see Uses: Anthrax in Ciprofloxacin 8:12.18.

Meningitis and CNS Infections

Moxifloxacin is recommended as an alternative for the treatment of meningitis caused by susceptible gram-positive bacteria (e.g., S. pneumoniae) or gram-negative bacteria (e.g., Neisseria meningitidis, H. influenzae, E. coli).

The safety and efficacy of moxifloxacin for the treatment of CNS infections have not been established. Limited data from animal studies indicate that moxifloxacin is distributed into CSF to some extent and has been effective for the treatment of experimental meningitis caused by S. pneumoniae or E. coli. Some experts state that fluoroquinolones (e.g., ciprofloxacin, moxifloxacin) should be considered for the treatment of meningitis only when the infection is caused by multidrug-resistant gram-negative bacilli or when the usually recommended anti-infectives cannot be used or have been ineffective.

Mycobacterial Infections

Treatment of Active Tuberculosis

Moxifloxacin is used in multiple-drug regimens for the treatment of active tuberculosis caused by Mycobacterium tuberculosis.

Although the potential role of fluoroquinolones and the optimal length of therapy have not been fully defined, ATS, CDC, IDSA, and others state that use of fluoroquinolones as alternative (second-line) agents can be considered for the treatment of active tuberculosis in patients intolerant of certain first-line agents and in those with relapse, treatment failure, or M. tuberculosis resistant to certain first-line agents. If a fluoroquinolone is used in multiple-drug regimens for the treatment of active tuberculosis, ATS, CDC, IDSA, and others recommend levofloxacin or moxifloxacin.

Although levofloxacin (or moxifloxacin) has been used instead of ethambutol during the intensive phase of treatment in adults who could not receive ethambutol and has been used instead of isoniazid throughout the course of treatment in adults who could not receive isoniazid, ATS, CDC, and IDSA state that there is no evidence that levofloxacin (or moxifloxacin) can be used to replace a rifamycin or pyrazinamide while maintaining a 6-month treatment regimen.

The fact that there are reports of fluoroquinolone-resistant M. tuberculosis and increasing reports of extensively drug-resistant tuberculosis (XDR tuberculosis) should be considered. XDR tuberculosis is caused by strains of M. tuberculosis that are resistant to rifampin and isoniazid (multiple-drug resistant strains) and also are resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial (capreomycin, kanamycin, amikacin).

The most recent ATS, CDC, and IDSA recommendations for treatment of tuberculosis should be consulted for more specific information.

Other Mycobacterial Infections

Moxifloxacin is used in the treatment of M. kansasii infections in conjunction with other antimycobacterials. ATS and IDSA recommend a multiple-drug regimen of isoniazid, rifampin, and ethambutol for treatment of pulmonary or disseminated infections caused by M. kansasii. If rifampin-resistant M. kansasii are involved, ATS and IDSA recommend a 3-drug regimen based on results of in vitro susceptibility testing, including clarithromycin (or azithromycin), moxifloxacin, ethambutol, sulfamethoxazole, or streptomycin.

Moxifloxacin has been used in multiple-drug regimens for the treatment of M. avium complex (MAC) infections. ATS and IDSA state that the role of fluoroquinolones in the treatment of MAC infections has not been established. If a fluoroquinolone is included in a treatment regimen (e.g., for macrolide-resistant MAC infections), moxifloxacin or levofloxacin may be preferred, although many strains are resistant in vitro.

The most recent ATS, CDC, and IDSA recommendations for treatment of other mycobacterial infections should be consulted for more specific information.

Nongonococcal Urethritis

Moxifloxacin is considered as an alternative agent for the treatment of nongonococcal urethritis (NGU). NGU can be caused by various organisms (e.g., Chlamydia, M. genitalium, Trichomonas vaginalis, Ureaplasma, enteric bacteria) and is treated presumptively at the time of diagnosis. CDC states that a single dose of oral azithromycin or a 7-day regimen of oral doxycycline are the recommended regimens for the treatment of NGU; a 7-day regimen of oral erythromycin base or ethylsuccinate or a 7-day regimen of oral levofloxacin or ofloxacin are alternative regimens.

CDC states that men with persistent or recurrent NGU who were not compliant with the treatment regimen or were reexposed to untreated sexual partner(s) can be retreated with the initial regimen. In other patients, symptoms alone (without documentation of signs or laboratory evidence of urethral inflammation) are not a sufficient basis for retreatment and an objective diagnosis of persistent or recurrent NGU should be made before considering additional treatment. Because there is some evidence that M. genitalium is the most frequent cause of persistent or recurrent NGU, CDC states that those initially treated with doxycycline should receive retreatment with a single dose of oral azithromycin and those initially treated with azithromycin should receive retreatment with a 7-day regimen of oral moxifloxacin. However, if the patient with persistent or recurrent urethritis has sex with women and is in an area where T. vaginalis is prevalent, CDC recommends presumptive retreatment with a single 2-g dose of oral metronidazole or tinidazole and referral of their partner(s) for evaluation and appropriate treatment.

NGU may facilitate transmission of HIV and men diagnosed with NGU should be tested for HIV. Individuals with HIV infection should receive the same treatment regimens recommended for other individuals with NGU.

Any individual who had sexual contact with a patient with NGU within the preceding 60 days should be referred for evaluation, testing, and presumptive treatment with a regimen effective against Chlamydia. To minimize transmission and avoid reinfection, men treated for NGU should abstain from sexual intercourse until they and their sexual partner(s) have been adequately treated.

Plague

Moxifloxacin is used for the treatment of plague, including pneumonic and septicemic plague, caused by susceptible Yersinia pestis and for prophylaxis of plague. Based on results of in vitro and animal testing, fluoroquinolones (e.g., ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin) are recommended as alternatives for the treatment of plague and for postexposure prophylaxis following a high risk exposure to Y. pestis, including exposure in the context of biologic warfare or bioterrorism.

Efficacy of moxifloxacin for treatment or prophylaxis of plague has not been evaluated in clinical trials in humans for ethical and feasibility reasons. The drug is labeled by the FDA for this indication based on an efficacy study in animals that demonstrated a survival benefit and supportive animal and human pharmacokinetic data. In a randomized, blinded, placebo-controlled study, African green monkeys were exposed to an inhaled dose of Y. pestis (mean dose of 100 LD50 [range 92-127 LD50]) and then randomized to receive a 10-day regimen of moxifloxacin or placebo initiated after fever developed and was sustained for at least 4 hours. All study monkeys were febrile and bacteremic with Y. pestis prior to initiation of study treatment. In vitro testing indicated that the Y. pestis strain (CO92 strain) used in this study had a moxifloxacin MIC of 0.06 mcg/mL. Pharmacokinetic data indicated that mean plasma concentrations of moxifloxacin attained in the study monkeys (4.4 mcg/mL) were similar to mean peak plasma concentrations attained in adults receiving 400 mg of moxifloxacin IV (3.9 mcg/mL). Study results indicated that all monkeys in the moxifloxacin treatment group survived for the 30-day period after treatment (10 out of 10), but all monkeys in the placebo group succumbed to the disease within 83-139 hours (10 out of 10).

For the treatment of plague, IM streptomycin (or IM or IV gentamicin) historically has been considered the regimen of choice. Alternatives recommended for the treatment of plague when aminoglycosides are not used include IV doxycycline (or IV tetracycline), IV chloramphenicol (a drug of choice for plague meningitis), an IV fluoroquinolone (ciprofloxacin [a drug of choice for plague meningitis], levofloxacin, moxifloxacin), or co-trimoxazole (may be less effective than other alternatives). Anti-infective regimens recommended for treatment of naturally occurring or endemic bubonic, septicemic, or pneumonic plague also are recommended for treatment of plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism. Some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that treatment of plague in the context of biologic warfare or bioterrorism be initiated with a parenteral anti-infective regimen. However, an oral regimen of doxycycline (or tetracycline) or a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin) may be substituted when the patient's condition improves or when a parenteral regimen is unavailable (e.g., when there are supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting); oral chloramphenicol is considered an alternative in these situations.

In the context of biologic warfare or bioterrorism, some experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that asymptomatic individuals with exposure to plague aerosol or asymptomatic individuals with household, hospital, or other close contact (within about 2 m) with an individual who has pneumonic plague receive an oral anti-infective regimen for postexposure prophylaxis; however, any exposed individual who develops a temperature of 38.5°C or higher or new cough should promptly receive a parenteral anti-infective for treatment of the disease. If postexposure prophylaxis is indicated, these experts recommend a regimen of oral doxycycline (or tetracycline) or an oral fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin); oral chloramphenicol is considered an alternative.

For additional information on use of fluoroquinolones for treatment or prophylaxis of plague,

Ophthalmic Infections

For use of moxifloxacin in the topical treatment of ophthalmic infections caused by susceptible organisms,

Dosage and Administration

Administration

Moxifloxacin hydrochloride is administered orally or by IV infusion. The drug should not be given IM, subcutaneously, intrathecally, or intraperitoneally.

IV administration of moxifloxacin is indicated in patients who do not tolerate or are unable to take the drug orally and in other patients in whom the IV route offers a clinical advantage.

Patients receiving oral or IV moxifloxacin should be well hydrated and instructed to drink fluids liberally.

Oral Administration

Moxifloxacin tablets may be given without regard to meals.

Administration of a 400-mg moxifloxacin tablet with a high-fat breakfast or with yogurt does not have a clinically important effect on absorption of the drug.

Moxifloxacin should be administered orally at least 4 hours before or 8 hours after antacids containing magnesium or aluminum, metal cations (e.g., iron), sucralfate, multivitamins or dietary supplements containing iron or zinc, or buffered didanosine (pediatric oral solution admixed with antacid). These drugs may substantially interfere with absorption of moxifloxacin, resulting in systemic concentrations considerably lower than desired.(See Drug Interactions.)

IV Infusion

Commercially available injection for IV infusion containing 400 mg of moxifloxacin in 0.8% sodium chloride injection in single-use flexible containers may be used without further dilution.

Moxifloxacin should not be admixed with other drugs or infused simultaneously through the same tubing with other drugs. If the same IV line or a Y-type line is used for sequential infusion of other drugs or if the piggyback method of administration is used, the tubing should be flushed before and after infusion of moxifloxacin using an IV solution compatible with both moxifloxacin and the other drug(s).

Moxifloxacin IV solutions should be inspected visually for particulate matter prior to administration; the premixed solution should appear yellow.

Because commercially available moxifloxacin premixed injection for IV infusion contains no preservatives, any unused portions of the solution should be discarded.

Rate of Administration

Moxifloxacin solutions should be administered by IV infusion over 1 hour.

Rapid IV infusion of the drug should be avoided.

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Dosage of moxifloxacin hydrochloride is expressed in terms of moxifloxacin.

Dosage of oral and IV moxifloxacin is identical.

When IV moxifloxacin is used initially, therapy may be changed to oral moxifloxacin (when appropriate) using the same dosage to complete therapy. The timing of the change from IV to oral therapy should be individualized, taking into account the clinical status of the patient.

Respiratory Tract Infections

Acute Sinusitis

If moxifloxacin is used for the treatment of acute bacterial sinusitis, the usual adult dosage is 400 mg once daily for 10 days. (See Acute Sinusitis under Uses: Respiratory Tract Infections.)

Acute Exacerbations of Chronic Bronchitis

If moxifloxacin is used for the treatment of acute bacterial exacerbations of chronic bronchitis, the usual adult dosage is 400 mg once daily for 5 days.(See Acute Exacerbations of Chronic Bronchitis under Uses: Respiratory Tract Infections.)

Community-acquired Pneumonia

For the treatment of community-acquired pneumonia (CAP), the usual adult dosage of moxifloxacin is 400 mg once daily for 7-14 days.

Skin and Skin Structure Infections

For the treatment of uncomplicated skin and skin structure infections, the usual adult dosage of moxifloxacin is 400 mg once daily for 7 days.

For the treatment of complicated skin and skin structure infections, the usual adult dosage of moxifloxacin is 400 mg once daily for 7-21 days.

Intra-abdominal Infections

For the treatment of complicated intra-abdominal infections, the usual adult dosage of moxifloxacin is 400 mg once daily. The drug should be administered IV initially, but therapy may be changed to oral administration when clinically appropriate.

The manufacturer recommends a total duration of therapy of 5-14 days for the treatment of complicated intra-abdominal infections. The Infectious Diseases Society of America (IDSA) states that the usual duration of treatment for these infections is 4-7 day; a longer duration of treatment has not been associated with improved outcome and is not recommended unless adequate source control is difficult to achieve.

GI Infections

Salmonella Gastroenteritis

For the treatment of Salmonella gastroenteritis (with or without bacteremia) in adults with human immunodeficiency virus (HIV) infection, the recommended dosage of oral or IV moxifloxacin is 400 mg once daily.

The recommended duration of treatment in HIV-infected patients is 7-14 days in those with CD4 T-cell counts of 200 cells/mm or greater (14 days or longer if the patient is bacteremic or the infection is complicated) or 2-6 weeks in those with CD4 T-cell counts less than 200 cells/mm.

The role of long-term treatment (secondary prophylaxis) in those with recurrent bacteremia is not well established and the benefits must be weighed against the risks of long-term anti-infective exposure.

Shigella Infections

For the treatment of Shigella infections in HIV-infected adults, the recommended dosage of oral or IV moxifloxacin is 400 mg once daily.

The recommended duration of treatment in HIV-infected patients is 7-10 days for gastroenteritis or at least 14 days for bacteremic infections. Recurrent infections, especially in those with CD4 T-cell counts less than 200 cells/mm, may require up to 6 weeks of treatment.

Anthrax

Postexposure Prophylaxis of Anthrax

If oral moxifloxacin is used as an alternative for postexposure prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores (inhalational anthrax), US Working Group on Civilian Biodefense suggests that adults can receive a dosage of 400 mg once daily.

Anti-infective prophylaxis should be initiated as soon as possible following suspected or confirmed exposure to aerosolized anthrax. If subsequent epidemiologic and laboratory test data indicate that individuals started on prophylaxis were not exposed, the anti-infective regimen should be discontinued.

Because of possible persistence of spores in lung tissue following an aerosol exposure, US Centers for Disease Control and Prevention (CDC), US Public Health Service Advisory Committee on Immunization Practices (ACIP), US Working Group on Civilian Biodefense, and US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommend that anti-infective postexposure prophylaxis in unvaccinated individuals be continued for at least 60 days following a confirmed exposure.

If anthrax vaccine is used in conjunction with anti-infective prophylaxis for postexposure prophylaxis in exposed individuals, ACIP and USAMRIID recommend that the anti-infective prophylaxis regimen be continued until 14 days after the third dose of the vaccine series (even if this results in more than 60 days of anti-infective prophylaxis).

In fully or partially vaccinated laboratory workers or other individuals who work in occupations that result in repeated exposure to aerosolized B. anthracis spores, ACIP recommends that anti-infective postexposure prophylaxis be given for at least 30 days in conjunction with any remaining indicated doses of anthrax vaccine if there has been any type of disruption of personal protective equipment (PPE). Following an occupational exposure to B. anthracis spores in previously unvaccinated workers, ACIP recommends that anti-infective postexposure prophylaxis be given for 60 days in conjunction with postexposure vaccination; the anti-infective prophylaxis regimen should be continued until 14 days after the third vaccine dose (even if this results in more than 60 days of anti-infective prophylaxis).

Treatment of Anthrax

If oral moxifloxacin is used as an alternative for the treatment of inhalational anthrax when a parenteral regimen is not available (see Uses: Anthrax), US Working Group on Civilian Biodefense suggests that adults can receive a dosage of 400 mg once daily for at least 60 days.

An initial parenteral regimen is preferred for the treatment of inhalational anthrax; an oral regimen should be used for initial treatment only when a parenteral regimen is not available (e.g., supply or logistic problems because large numbers of individuals require treatment in a mass casualty setting). Because of the possible persistence of anthrax spores in lung tissue following an aerosol exposure, the total duration of anti-infective therapy of inhalational anthrax that occurs as the result of exposure to B. anthracis in the context of biologic warfare or bioterrorism should be at least 60 days.

Mycobacterial Infections

Treatment of Active Tuberculosis

If moxifloxacin is used as an alternative (second-line) agent in multiple-drug regimens for the treatment of active tuberculosis, the American Thoracic Society (ATS), CDC, and IDSA recommend that adults receive 400 mg once daily. These experts state that data are insufficient to support intermittent regimens of moxifloxacin for the treatment of tuberculosis.

Other Mycobacterial Infections

If oral moxifloxacin is used as an alternative in multiple-drug regimens for the treatment of disseminated infections caused by Mycobacterium avium complex (MAC) in HIV-infected adults, CDC, National Institutes of Health (NIH), and IDSA recommend a dosage of 400 mg once daily.

Nongonococcal Urethritis

If oral moxifloxacin is used as an alternative for the treatment of persistent or recurrent nongonococcal urethritis (NGU) in patients initially treated with azithromycin (see Uses: Nongonococcal Urethritis), CDC recommends a dosage of 400 mg once daily for 7 days.

Plague

If moxifloxacin is used for the treatment or prophylaxis of plague caused by Yersinia pestis in adults, the manufacturer recommends a dosage of 400 mg once daily for 10-14 days. The drug should be initiated as soon as possible after suspected or known exposure to Y. pestis.

Special Populations

Dosage adjustments of moxifloxacin are not necessary in adults with mild, moderate, or severe hepatic insufficiency (Child-Pugh class A, B, or C). However, moxifloxacin should be used with caution in patients with hepatic impairment.(See Hepatic Impairment under Warning/Precautions: Specific Populations, in Cautions.)

Dosage adjustments of moxifloxacin are not necessary in adults with renal impairment, including those on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

Dosage adjustments of moxifloxacin based solely on age are not necessary in geriatric patients 65 years of age and older.

Cautions

Contraindications

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Moxifloxacin is contraindicated in patients with a history of hypersensitivity to moxifloxacin or other quinolones.

Warnings/Precautions

Warnings

Disabling and Potentially Irreversible Serious Adverse Reactions

Systemic fluoroquinolones, including moxifloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient. These serious reactions may occur within hours to weeks after a systemic fluoroquinolone is initiated and have occurred in all age groups and in patients without preexisting risk factors for such adverse reactions.

Moxifloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reactions.

Systemic fluoroquinolones, including moxifloxacin, should be avoided in patients who have experienced any of the serious adverse reactions associated with fluoroquinolones.

Tendinitis and Tendon Rupture

Systemic fluoroquinolones, including moxifloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.

The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in older adults (usually those older than 60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.(See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any risk factors for such adverse effects.

Fluoroquinolone-associated tendinitis and tendon rupture most frequently involve the Achilles tendon and have also been reported in the rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites. Tendinitis or tendon rupture can occur within hours or days after moxifloxacin is initiated or as long as several months after completion of therapy and can occur bilaterally.

Moxifloxacin should be discontinued immediately if pain, swelling, inflammation, or rupture of a tendon occurs.(See Advice to Patients.)

Systemic fluoroquinolones, including moxifloxacin, should be avoided in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture.

Peripheral Neuropathy

Systemic fluoroquinolones, including moxifloxacin, have been associated with an increased risk of peripheral neuropathy.

Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness has been reported in patients receiving systemic fluoroquinolones, including moxifloxacin. Symptoms may occur soon after initiation of moxifloxacin and, in some patients, may be irreversible.

Moxifloxacin should be discontinued immediately if symptoms of peripheral neuropathy (e.g., pain, burning, tingling, numbness, and/or weakness) occur or if there are other alterations in sensations (e.g., light touch, pain, temperature, position sense, vibratory sensation).(See Advice to Patients.)

Systemic fluoroquinolones, including moxifloxacin, should be avoided in patients who have experienced peripheral neuropathy.

CNS Effects

Systemic fluoroquinolones, including moxifloxacin, have been associated with an increased risk of CNS effects.

Convulsions, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis have been reported in patients receiving fluoroquinolones. Fluoroquinolones may also cause CNS stimulation, which may lead to nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or acts. These CNS effects may occur after the first dose.

If CNS effects occur, moxifloxacin should be discontinued immediately and appropriate measures initiated.(See Advice to Patients.)

Moxifloxacin should be used in patients with known or suspected CNS disorders (e.g., severe cerebral arteriosclerosis, epilepsy) or other risk factors that predispose to seizures or lower seizure threshold only if potential benefits of the drug outweigh risks.

Systemic fluoroquinolones, including moxifloxacin, should be avoided in patients who have experienced CNS effects associated with fluoroquinolones.

Exacerbation of Myasthenia Gravis

Fluoroquinolones, including moxifloxacin, have neuromuscular blocking activity and may exacerbate muscle weakness in individuals with myasthenia gravis. Use of fluoroquinolones in myasthenia gravis patients has resulted in requirements for ventilatory support and in death.

Moxifloxacin should be avoided in patients with a known history of myasthenia gravis. Patients should be advised to immediately contact a clinician if they have any symptoms of muscle weakness, including respiratory difficulties.(See Advice to Patients.)

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving fluoroquinolones, including moxifloxacin. Although generally reported after multiple doses, these reactions may occur with first dose.

Some hypersensitivity reactions have been accompanied by cardiovascular collapse, loss of consciousness, tingling, edema (pharyngeal or facial), dyspnea, urticaria, or pruritus.

Other serious and sometimes fatal adverse reactions that have been reported with fluoroquinolones, including moxifloxacin, and that may or may not be related to hypersensitivity reactions include one or more of the following: fever, rash or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome); vasculitis, arthralgia, myalgia, serum sickness; allergic pneumonitis; interstitial nephritis, acute renal insufficiency or failure; hepatitis, jaundice, acute hepatic necrosis or failure; anemia (including hemolytic and aplastic), thrombocytopenia (including thrombotic thrombocytopenic purpura), leukopenia, agranulocytosis, pancytopenia, and/or other hematologic effects.

Moxifloxacin should be discontinued immediately at the first appearance of rash, jaundice, or any other sign of hypersensitivity. Appropriate therapy should be initiated as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).(See Advice to Patients.)

Photosensitivity Reactions

Moderate to severe photosensitivity/phototoxicity reactions have been reported with fluoroquinolones, including moxifloxacin.

Phototoxicity may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) on areas exposed to sun or artificial ultraviolet (UV) light (usually the face, neck, extensor surfaces of forearms, dorsa of hands).

As with other fluoroquinolones, patients should be advised to avoid unnecessary or excessive exposure to sunlight or artificial UV light (e.g., tanning beds, UVA/UVB treatment) while receiving moxifloxacin. If a patient needs to be outdoors, they should wear loose-fitting clothing that protects skin from sun exposure and use other sun protection measures (sunscreen).

Moxifloxacin should be discontinued if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.

Other Warnings/Precautions

Hepatotoxicity

Severe hepatotoxicity, including acute hepatitis, has occurred in patients receiving moxifloxacin and sometimes resulted in death.

Prolongation of QT Interval

Prolonged QT interval leading to ventricular arrhythmias, including torsades de pointes, has been reported with some fluoroquinolones, including moxifloxacin.

Following an oral dose of 400 mg of moxifloxacin, the mean change in QT interval corrected for rate (QTc) from baseline was 6 msec. When moxifloxacin was given IV in a dosage of 400 mg once daily by IV infusion over 1 hour, the mean change in QTc from baseline was 10 msec on day 1 and 7 msec on day 3.

The recommended moxifloxacin dosage and IV infusion rate should not be exceeded since this may increase the risk of QT interval prolongation.

Moxifloxacin should be avoided in patients with known prolongation of the QT interval, ventricular arrhythmias (including torsades de pointes), any ongoing proarrhythmic conditions (including clinically important bradycardia and acute myocardial ischemia), or uncorrected hypokalemia or hypomagnesemia.

Moxifloxacin also should be avoided in patients receiving class IA (e.g., quinidine, procainamide) or III (e.g., amiodarone, sotalol) antiarrhythmic agents or other drugs that prolong the QT interval (e.g., cisapride [commercially available under a limited-access protocol only], erythromycin, antipsychotic agents, tricyclic antidepressants).(See Drug Interactions: Drugs that Prolong QT Interval.)

In addition, moxifloxacin should be used with caution in patients with mild, moderate, or severe liver cirrhosis since metabolic disturbances associated with hepatic insufficiency may lead to QT prolongation.(See Hepatic Impairment under Warnings/Precautions: Specific Populations, in Cautions.)

The risk of prolonged QT interval may be increased in geriatric patients.(See Geriatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

Musculoskeletal Effects

Fluoroquinolones, including moxifloxacin, cause arthropathy and osteochondrosis in immature animals of various species. The relevance of these adverse effects in immature animals to use in humans is unknown. Safety and efficacy of moxifloxacin have not been established in children younger than 18 years of age.(See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.)

Hypoglycemia or Hyperglycemia

Alterations in blood glucose concentrations, including hypoglycemia and hyperglycemia, have been reported with fluoroquinolones, including moxifloxacin. Blood glucose disturbances usually have occurred in elderly patients with diabetes mellitus receiving an oral antidiabetic agent (e.g., sulfonylurea agent) or insulin.

Blood glucose concentrations should be carefully monitored in diabetic patients receiving antidiabetic agents and moxifloxacin concomitantly. If a hypoglycemic reaction occurs, moxifloxacin should be discontinued and appropriate therapy initiated immediately.

Superinfection/Clostridium difficile-associated Diarrhea

Use of moxifloxacin may result in emergence and overgrowth of nonsusceptible bacteria or fungi. Appropriate therapy should be initiated if superinfection occurs.

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) have been reported in patients receiving fluoroquinolones, including moxifloxacin, and may range in severity from mild diarrhea to fatal colitis.C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Outbreaks of severe CDAD caused by fluoroquinolone-resistant C. difficile have been reported with increasing frequency over the past several years.

CDAD should be considered in the differential diagnosis of patients who develop diarrhea during or after anti-infective therapy. Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.

If CDAD is suspected or confirmed, anti-infective therapy not directed against C. difficile should be discontinued whenever possible. Patients should be managed with appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.

Selection and Use of Anti-infectives

Moxifloxacin should be used for the treatment of acute sinusitis or acute bacterial exacerbations of chronic bronchitis only when no other treatment options are available. Because moxifloxacin, like other systemic fluoroquinolones, has been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient, the risks of serious adverse reactions outweigh the benefits of moxifloxacin for patients with these infections.

To reduce development of drug-resistant bacteria and maintain effectiveness of moxifloxacin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Specific Populations

Pregnancy

Category C.

There are no adequate and well-controlled studies of moxifloxacin in pregnant women, and the drug should be used during pregnancy only if potential benefits justify potential risks to the fetus.

Reproduction studies in rats have not revealed evidence of teratogenicity at oral doses 0.24 times the maximum recommended human dose or IV doses approximately 2 times the maximum recommended human dose based on body surface area; however, decreased fetal body weights and slightly delayed fetal skeletal development (indicative of fetotoxicity) were observed with the oral doses, and maternal toxicity and marginal effects on fetal and placental weights and placenta appearance were observed with the IV doses.

Lactation

Moxifloxacin is distributed into milk in rats and may be distributed into human milk.

Because of the potential for serious adverse reactions in the infant, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.(See Musculoskeletal Effects under Warnings/Precautions: Warnings, in Cautions.)

Pediatric Use

Safety and efficacy of moxifloxacin have not been established for any indication in children or adolescents younger than 18 years of age.

Quinolones, including moxifloxacin, cause arthropathy in juvenile animals.(See Musculoskeletal Effects under Warnings/Precautions: Warnings, in Cautions.)

The American Academy of Pediatrics (AAP) states that use of systemic fluoroquinolones may be justified in children younger than 18 years of age in special circumstances when there are no safe and effective alternatives and after careful assessment of the risks and benefits for the individual patient.

Geriatric Use

Approximately 23 or 42% of patients were 65 years of age or older and 9 or 23% of patients were 75 years of age or older in clinical studies of oral or IV moxifloxacin, respectively. No overall differences in safety or efficacy were observed between geriatric individuals and younger adults.

The risk of developing severe tendon disorders, including tendon rupture, is increased in older adults (usually those older than 60 years of age). This risk is further increased in those receiving concomitant corticosteroids.(See Tendinitis and Tendon Rupture under Warnings/Precautions: Warnings, in Cautions.) Caution is advised if moxifloxacin is used in geriatric adults, especially those receiving concomitant corticosteroids.

The risk of QT interval prolongation may be increased in geriatric patients. Concomitant use of moxifloxacin and class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents and use in patients with risk factors for torsades de pointes (e.g., known QT prolongation, uncorrected hypokalemia) should be avoided.(See Prolongation of QT Interval under Warnings/Precautions: Warnings, in Cautions.)

Hepatic Impairment

Although dosage adjustments are not necessary in patients with mild, moderate, or severe hepatic insufficiency (Child-Pugh class A, B, or C), metabolic disturbances associated with hepatic insufficiency may lead to QT interval prolongation. Therefore, moxifloxacin should be used with caution in patients with any degree of hepatic impairment. ECGs should be monitored in patients with liver cirrhosis.

Renal Impairment

Pharmacokinetics of moxifloxacin are not substantially affected by mild, moderate, or severe renal impairment. Dosage adjustments are not necessary in patients with renal impairment.

Common Adverse Effects

Adverse effects occurring in 3% or more of patients receiving moxifloxacin include nausea (7%), diarrhea (6%), headache (4%), and dizziness (3%).

Drug Interactions

Drugs That Prolong QT Interval

Potential pharmacologic interaction (additive effects on QT interval prolongation). Concomitant use of moxifloxacin and class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents should be avoided. Moxifloxacin should be used with caution in patients receiving other drugs that prolong the QT interval (e.g., cisapride [currently commercially available under a limited-access protocol only], erythromycin, antipsychotic agents, tricyclic antidepressants).(See Prolongation of QT Interval under Warnings/Precautions: Warnings, in Cautions.)

Drugs Metabolized by Hepatic Microsomal Enzymes

Moxifloxacin is not metabolized by cytochrome P-450 (CYP) isoenzymes and does not inhibit CYP3A4, 2D6, 2C9, 2C19, or 1A2; pharmacokinetic interactions with drugs metabolized by CYP isoenzymes are unlikely.

Antacids

Pharmacokinetic interaction with aluminum- or magnesium-containing antacids (decreased absorption and decreased bioavailability of oral moxifloxacin).

Oral moxifloxacin should be administered at least 4 hours before or 8 hours after antacids that contain aluminum or magnesium.

Antidiabetic Agents

Concomitant use of moxifloxacin and oral antidiabetic agents (e.g., sulfonylurea agents) or insulin has resulted in alterations in blood glucose concentrations, including hypoglycemia and hyperglycemia.

If moxifloxacin is used in patients with diabetes mellitus receiving an oral antidiabetic agent or insulin, blood glucose concentrations should be carefully monitored. If a hypoglycemic reaction occurs, moxifloxacin should be discontinued and appropriate therapy initiated immediately.

Glyburide

When moxifloxacin (40 mg once daily for 5 days) was used in patients with diabetes mellitus receiving glyburide (2.5 mg once daily beginning 2 weeks before initiation of moxifloxacin), mean peak plasma concentrations and area under the plasma concentration-time curve (AUC) of glyburide were decreased 21 and 12%, respectively. Although blood glucose concentrations were decreased slightly in patients receiving glyburide and moxifloxacin concurrently compared with glyburide alone, the manufacturer states that the pharmacokinetic interaction between the drugs was not considered clinically important and that interference by moxifloxacin on the activity of glyburide was not suggested.

Antifungal Agents

No clinically important pharmacokinetic interactions between itraconazole and moxifloxacin.

Atenolol

Moxifloxacin does not have a clinically important effect on the pharmacokinetics of atenolol.

Corticosteroids

Concomitant use of corticosteroids increases the risk of severe tendon disorders (e.g., tendinitis, tendon rupture), especially in geriatric patients older than 60 years of age.(See Tendinitis and Tendon Rupture under Warnings/Precautions: Warnings, in Cautions.)

Cyclosporine

No clinically important pharmacokinetic interactions between cyclosporine and moxifloxacin.

Didanosine

Pharmacokinetic interaction (decreased absorption of oral moxifloxacin).

Oral moxifloxacin should be given at least 4 hours before or 8 hours after buffered didanosine (pediatric oral solution admixed with antacid).

Digoxin

No clinically important pharmacokinetic interactions between digoxin and moxifloxacin. Although a transient increase in digoxin concentrations may occur, this is not considered clinically important. Dosage adjustments are not necessary for either drug.

Estrogens and Progestins

Moxifloxacin does not have a clinically important effect on the pharmacokinetics of oral contraceptives containing ethinyl estradiol and levonorgestrel.

Iron, Multivitamins, and Mineral Supplements

Pharmacokinetic interaction (decreased absorption and decreased bioavailability of oral moxifloxacin) if given concomitantly with iron preparations or multivitamins or dietary supplements containing iron or zinc. Oral moxifloxacin should be taken at least 4 hours before or 8 hours after these preparations.

Calcium dietary supplements do not have any clinically important effects on the pharmacokinetics of moxifloxacin.

Morphine

Morphine does not have a clinically important effect on the pharmacokinetics of moxifloxacin.

Nonsteroidal Anti-inflammatory Agents

Concomitant use of moxifloxacin and nonsteroidal anti-inflammatory agents (NSAIAs) may increase the risk of CNS stimulation and seizures. Animal studies using other fluoroquinolones suggest the risk varies depending on the specific NSAIA.

Probenecid

Probenecid does not have a clinically important effect on the pharmacokinetics of moxifloxacin.

Ranitidine

Ranitidine does not have a clinically important effect on the pharmacokinetics of moxifloxacin.

Sucralfate

Pharmacokinetic interaction (decreased absorption of oral moxifloxacin). Oral moxifloxacin should be taken at least 4 hours before or 8 hours after sucralfate.

Theophylline

No clinically important pharmacokinetic interactions between theophylline and moxifloxacin.

Warfarin

Although clinically important pharmacokinetic interactions have not been reported when warfarin and moxifloxacin were used concomitantly, fluoroquinolones, including moxifloxacin, have been reported to enhance the anticoagulant effects of warfarin or its derivatives. In addition, infectious disease and its accompanying inflammatory process, age, and general status of the patient also are risk factors for increased anticoagulation activity. The prothrombin time (PT), international normalized ratio (INR), or other suitable coagulation tests should be monitored in patients receiving moxifloxacin concomitantly with warfarin.

Pharmacokinetics

Absorption

Bioavailability

Moxifloxacin is well absorbed from the GI tract and absolute bioavailability is 86-92%.

Peak plasma concentrations are attained within 0.5-4 hours; steady state is attained after at least 3 days.

Food

Administration of a 400-mg moxifloxacin tablet with a high-fat breakfast or with yogurt does not have a clinically important effect on absorption of the drug.

Distribution

Extent

Moxifloxacin is widely distributed into body tissues and fluids, including saliva, nasal and bronchial secretions, sinus mucosa, skin blister fluid, subcutaneous tissue, skeletal muscle, and abdominal tissues and fluids.

Moxifloxacin is distributed into CSF in rabbits.

The drug is distributed into milk in rats and may be distributed into human milk.

Plasma Protein Binding

Moxifloxacin is 30-50% bound to plasma proteins.

Elimination

Metabolism

Approximately 52% of an oral or IV dose of moxifloxacin is metabolized via glucuronide and sulfate conjugation; the metabolites are not microbiologically active.

Moxifloxacin is not metabolized by cytochrome P-450 (CYP) isoenzymes.

Elimination Route

Moxifloxacin is eliminated in urine and by biliary excretion and metabolism.

Approximately 45% of an oral or IV dose of the drug is excreted unchanged (20% in urine and 25% in feces). A total of 96% of an oral dose is excreted as unchanged drug or metabolites.

Half-life

Adults with normal renal and hepatic function: Mean half-life of moxifloxacin is 11.5-15.6 hours following single or multiple oral doses and 8.2-15.4 hours following single or multiple IV doses.

Special Populations

Pharmacokinetics of moxifloxacin in geriatric patients are similar to that reported in younger adults.

Concentrations of the moxifloxacin sulfate and glucuronide conjugates are increased in patients with mild or moderate hepatic impairment (Child Pugh class A or B); the clinical importance of this finding has not been determined. A single-dose study indicates that plasma concentrations of moxifloxacin and its metabolites in patients with severe hepatic impairment (Child Pugh class C) are similar to those reported in patients with mild or moderate hepatic impairment.

Pharmacokinetics of moxifloxacin are not substantially affected by mild, moderate, or severe renal impairment. In patients with creatinine clearance less than 20 mL/minute undergoing hemodialysis or continuous ambulatory peritoneal dialysis (CAPD), moxifloxacin concentrations are not affected but concentrations of the sulfate and glucuronide conjugates are increased; the clinical importance of this finding has not be determined.

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