Avelox

Generic Name: Moxifloxacin Hydrochloride
Class: Quinolones
VA Class: AM900
Chemical Name: (4aS - cis) - 1 - Cyclopropyl - 6 - fluoro - 1,4 - dihydro - 8 - methoxy - 7 - (octahydro - 6H - pyrrolol[3,4 - b]pyridin - 6 - yl) - 4 - oxo - 3 - quinolinecarboxylic acid monohydrochloride
Molecular Formula: C₂₁H₂₄FN₃O₄
CAS Number: 186826-86-8

• 
  

  Fluoroquinolones, including moxifloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.^{1 98 99} This risk is further increased in older adults (usually those >60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.^{1 98 99} (See Tendinopathy and Tendon Rupture under Cautions.)

  
  

REMS:

FDA approved a REMS for moxifloxacin to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antibacterial; 8-methoxy fluoroquinolone.^{1 2}

Uses for Avelox

Respiratory Tract Infections

Treatment of acute bacterial sinusitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.¹

Treatment of acute bacterial exacerbations of chronic bronchitis caused by susceptible S. pneumoniae, H. influenzae, H. parainfluenzae, Klebsiella pneumoniae, Staphylococcus aureus, or M. catarrhalis.¹

Treatment of community-acquired pneumonia (CAP) caused by susceptible S. pneumoniae (including multidrug-resistant strains), S. aureus (oxacillin-susceptible [methicillin-susceptible] strains), K. pneumoniae, H. influenzae, M. catarrhalis, Mycoplasma pneumoniae, or Chlamydophila pneumoniae (formerly Chlamydia pneumoniae).^{1 17 53}

Select regimen for empiric treatment of CAP based on most likely pathogens and local susceptibility patterns; after pathogen is identified, modify to provide more specific therapy (pathogen-directed therapy).¹⁷ Do not use a fluoroquinolone alone for empiric treatment of CAP in patients requiring treatment in an intensive care unit (ICU).¹⁷

For empiric outpatient treatment of CAP in previously healthy adults without risk factors for drug-resistant S. pneumoniae (DRSP), IDSA and ATS recommend monotherapy with a macrolide (azithromycin, clarithromycin, erythromycin) or, alternatively, doxycycline.¹⁷ If risk factors for DRSP are present (e.g., chronic heart, lung, liver, or renal disease, diabetes mellitus, alcoholism, malignancy, asplenia, immunosuppression, history of anti-infective treatment within the last 3 months), IDSA and ATS recommend monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam active against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide or doxycycline.¹⁷

For empiric inpatient treatment of CAP in non-ICU patients, IDSA and ATS recommend adults receive monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.¹⁷ For empiric inpatient treatment of CAP in ICU patients when Pseudomonas and oxacillin-resistant (methicillin-resistant) Staphylococcus aureus are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or a fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin).¹⁷

Treatment of nosocomial pneumonia†, including hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.⁵¹ Local susceptibility data should be used when selecting the empiric regimen.^{50 51}

Skin and Skin Structure Infections

Treatment of uncomplicated skin and skin structure infections (abscesses, furuncles, cellulitis, impetigo) caused by susceptible S. aureus (oxacillin-susceptible [methicillin-susceptible] strains) or S. pyogenes (group A β-hemolytic streptococci).^{1 13 43}

Treatment of complicated skin and skin structure infections caused by susceptible S. aureus (oxacillin-susceptible strains), Escherichia coli, K. pneumoniae, or Enterobacter cloacae.^{1 43 44}

Intra-abdominal Infections

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.^{1 39 40}

Anthrax

Alternative for postexposure prophylaxis following suspected or confirmed exposure to aerosolized anthrax spores (inhalational anthrax)† when oral ciprofloxacin and oral doxycycline are unavailable.¹⁴

Alternative for treatment of inhalational anthrax† 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).¹⁴ A multiple-drug parenteral regimen (ciprofloxacin or doxycycline and 1 or 2 other anti-infectives predicted to be effective) is preferred for initial treatment of inhalational anthrax that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.^{14 16 37}

Endocarditis

Alternative for treatment of native or prosthetic valve endocarditis† caused by fastidious gram-negative bacilli known as the HACEK group (Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Haemophilus aphrophilus, H. influenzae, H. parainfluenzae, H. paraphrophilus, Kingella denitrificans, K. kingae).³⁵ AHA and IDSA recommend ceftriaxone or ampicillin-sulbactam as drugs of choice,³⁵ but a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) may be considered when β-lactam anti-infectives cannot be used.³⁵ Consultation with an infectious disease specialist is recommended.³⁵

Meningitis and CNS Infections

Alternative for 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).⁴⁷

Safety and efficacy not established for CNS infections.⁴⁷ Limited data from animal studies indicate moxifloxacin has been effective for treatment of experimental meningitis caused by S. pneumoniae or E. coli.^{48 49} Fluoroquinolones (ciprofloxacin, moxifloxacin) should be considered for 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.⁴⁷

Tuberculosis

Alternative for use in multiple-drug regimens for treatment of active tuberculosis†.²²

CDC, ATS, and IDSA state that use of fluoroquinolones can be considered in patients with relapse, treatment failure, or Mycobacterium tuberculosis resistant to isoniazid and/or rifampin or when first-line drugs cannot be tolerated.²² There have been recent reports of extensively drug-resistant tuberculosis (XDR tuberculosis).^{63 64} XDR tuberculosis is caused by M. tuberculosis resistant to rifampin and isoniazid (multiple-drug resistant strains) that also are resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial (capreomycin, kanamycin, amikacin).^{63 64}

Although there is clinical experience with several fluoroquinolones in the treatment of tuberculosis (e.g., ciprofloxacin, levofloxacin, moxifloxacin, ofloxacin),^{22 61 65 85} levofloxacin and moxifloxacin are the fluoroquinolones recommended by CDC, ATS, and IDSA and levofloxacin may be preferred on the basis of cumulative experience.²²

The most recent CDC, ATS, and IDSA recommendations for treatment of tuberculosis should be consulted for more specific information.²²

Other Mycobacterial Infections

Treatment of M. kansasii† infections in conjunction with other antimycobacterials.⁹⁷ ATS and IDSA recommend a multiple-drug regimen of isoniazid, rifampin, and ethambutol for treatment of pulmonary or disseminated infections caused by M. kansasii.⁹⁷ 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.⁹⁷

Role of fluoroquinolones in treatment of M. avium complex† (MAC) infections has not been established.⁹⁷ Moxifloxacin may be preferred if a fluoroquinolone is used in conjunction with other antimycobacterial anti-infectives for the treatment of MAC infections, but many strains are resistant in vitro.⁹⁷ Treatment of MAC infections is complicated and should be directed by clinicians familiar with mycobacterial diseases; consultation with a specialist is particularly important when the patient cannot tolerate first-line drugs or when the infection has not responded to prior therapy or is caused by macrolide-resistant MAC.⁹⁷

Avelox Dosage and Administration

Administration

Administer orally or by slow IV infusion.¹ Do not give IM, sub-Q, intrathecally, or intraperitoneally.¹

If IV route is used initially, switch to oral route when clinically indicated.¹

Patients receiving oral or IV moxifloxacin should be well hydrated and should be instructed to drink fluids liberally.¹

Oral Administration

Administer orally without regard to meals.¹ (See Pharmacokinetics.)

IV Infusion

Premixed injection for IV infusion containing 400 mg of moxifloxacin in 0.8% sodium chloride injection may be used without further dilution.¹

Premixed injection for IV infusion does not contain preservatives; discard any unused portions.¹

Additives or other drugs should not be infused simultaneously through the same IV line.¹

For solution and drug compatibility information, see Compatibility under Stability.

Rate of Administration

Administer by IV infusion over 1 hour.¹ Avoid rapid IV infusion.¹

Dosage

Available as moxifloxacin hydrochloride; dosage expressed in terms of moxifloxacin.¹

Dosage of oral and IV moxifloxacin is identical.¹ Dosage adjustment not needed when switching from IV to oral administration, or vice versa.¹

Adults

Respiratory Tract Infections

Acute Bacterial Sinusitis

Oral or IV

400 mg once daily for 10 days.¹

Acute Bacterial Exacerbations of Chronic Bronchitis

Oral or IV

400 mg once daily for 5 days.¹

Community-acquired Pneumonia (CAP)

Oral or IV

400 mg once daily for 7–14 days.¹ IDSA and ATS state that CAP should be treated for a minimum of 5 days and patients should be afebrile for 48–72 hours before discontinuing anti-infective therapy.¹⁷

Skin and Skin Structure Infections

Uncomplicated Infections

Oral or IV

400 mg once daily for 7 days.¹

Complicated Infections

Oral or IV

400 mg once daily for 7–21 days.¹

Intra-abdominal Infections

Complicated Infections

IV, then Oral

Initiate therapy with 400 mg IV once daily.¹ When appropriate, switch to oral moxifloxacin 400 mg once daily and continue to complete 5–14 days of therapy.¹

Anthrax†

Postexposure Prophylaxis Following Exposure in the Context of Biologic Warfare or Bioterrorism†

Oral

400 mg once daily¹⁴ for ≥60 days.^{14 15 37 45 46}

Optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear, but prolonged postexposure prophylaxis usually required.^{14 37 38} A duration of 60 days may be adequate for a low-dose exposure, but a duration >4 months may be necessary to reduce the risk following a high-dose exposure.³⁸ CDC, US Working Group on Civilian Biodefense, and US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommend that postexposure prophylaxis in unvaccinated individuals be continued for ≥60 days following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures).^{14 15 37 45} The USPHS Advisory Committee on Immunization Practices (ACIP) and USAMRIID recommend that individuals who are partially or fully vaccinated against anthrax receive postexposure prophylaxis for ≥30 days; if given in conjunction with anthrax vaccine, continue prophylaxis for at least 7–14 days after the third vaccine dose.^{37 46}

Treatment of Inhalational Anthrax†

Oral or IV

400 mg once daily¹⁴ for ≥60 days.^{14 16 37}

Initial parenteral regimen preferred; use oral regimen 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).^{14 16 37} Continue for total duration of ≥60 days if inhalational anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.^{14 16 37}

Mycobacterial Infections†

Active Tuberculosis†

Oral or IV

400 mg once daily.²² Must be used in conjunction with other antituberculosis agents.²²

Multiple-drug regimen usually given for 12–18 months when rifampin-resistant M. tuberculosis are involved; for 18–24 months when isoniazid- and rifampin-resistant strains are involved; or for 24 months when the strain is resistant to isoniazid, rifampin, ethambutol, and/or pyrazinamide.²²

Prescribing Limits

Adults

Do not exceed usual dosage or duration of therapy.¹

Special Populations

Hepatic Impairment

Dosage adjustments not required in adults with mild or moderate hepatic impairment (Child-Pugh class A or B).¹ Pharmacokinetics not evaluated in those with severe hepatic impairment (Child-Pugh class C).¹

Renal Impairment

Dosage adjustments not required in adults with renal impairment, including those on hemodialysis or CAPD.¹

Geriatric Patients

Routine dosage adjustment based solely on age not necessary.¹ Select dosage with caution because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Cautions for Avelox

Contraindications

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  Known hypersensitivity to moxifloxacin, other quinolones, or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Tendinopathy and Tendon Rupture

Fluoroquinolones, including moxifloxacin, are associated with increased risk of tendinitis and tendon rupture in all age groups.^{1 98 99} This risk is further increased in older adults (usually those >60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.^{1 98 99} (See Geriatric Use under Cautions.)

Other factors that may independently increase risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.^{1 98 99} Tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any of these risk factors.¹

Fluoroquinolone-associated tendinitis and tendon rupture most frequently involve the Achilles tendon and may require surgical repair.¹ Tendinitis and tendon rupture in the rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites also reported.¹

Tendon rupture can occur during or following fluoroquinolone therapy and has been reported up to several months after completion of therapy.¹

Discontinue if pain, swelling, inflammation, or rupture of a tendon occurs.^{1 98 99} Advise patients to rest and refrain from exercise and contact a clinician at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon or weakness or inability to use a joint).^{1 98 99} (See Advice to Patients.)

Prolongation of QT Interval

Prolonged QT interval leading to ventricular arrhythmias, including torsades de pointes, reported with some fluoroquinolones, including moxifloxacin.^{1 55}

Do not exceed usual recommended dosage or IV infusion rate since this may increase risk of prolonged QT interval.¹

Avoid use in patients with a history of prolonged QT interval, in those with uncorrected electrolyte disorders (e.g., hypokalemia), and in those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.¹ (See Drugs that Prolong QT Interval under Interactions.)

Use with caution in patients receiving drugs that prolong QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants) and in those with ongoing proarrhythmic conditions, such as clinically important bradycardia or AMI.¹

Musculoskeletal Effects

Fluoroquinolones, including moxifloxacin, cause arthropathy and osteochondrosis in immature animals of various species.^{1 88 89 90 91 92 93 94 95 96} Permanent lesions in cartilage reported in moxifloxacin studies in immature dogs.¹ Relevance of these adverse effects in immature animals to use in humans unknown.^{1 93 94 95 97} Safety and efficacy not established in children and adolescents <18 years of age (see Pediatric Use under Cautions) or in pregnant or lactating women (see Pregnancy and see Lactation under Cautions).¹

CNS Effects

Seizures, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or acts have been reported in patients receiving quinolones, and may occur after the first dose.¹

Use with caution 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.¹

If CNS effects occur, discontinue moxifloxacin and institute appropriate measures.¹

Peripheral Neuropathy

Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness reported with fluoroquinolones.¹

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.¹ Institute appropriate therapy if superinfection occurs.¹

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.^{1 70 71 72 73 74} C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including moxifloxacin, and may range in severity from mild diarrhea to fatal colitis.^{1 70 71 72 73 74 76 80 81} Outbreaks of severe CDAD caused by fluoroquinolone-resistant C. difficile have been reported with increasing frequency over the past several years.^{75 76 77 78 80} Hyper toxin-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.¹

Consider CDAD if diarrhea develops and manage accordingly.^{1 70 71 72 73 74 79} 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.^{1 70 71 72 73 74}

If CDAD is suspected or confirmed, moxifloxacin may need to be discontinued.^{1 70 71 72 73 74} Some mild cases of CDAD may respond to discontinuance alone.^{70 71 72 73 74} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, anti-infective therapy active against C. difficile(e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.^{1 70 71 72 73 74}

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions reported in patients receiving fluoroquinolones, including moxifloxacin.¹ Although generally reported after multiple doses, these reactions may occur with first dose.¹

Some reactions have been accompanied by cardiovascular collapse, loss of consciousness, tingling, edema (pharyngeal or facial), dyspnea, urticaria, or pruritus.¹

In addition, other possible severe and potentially fatal reactions (may be hypersensitivity reactions or of unknown etiology) have been reported, most frequently after multiple doses.¹ These include fever, rash or other 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.¹

Discontinue moxifloxacin at first appearance of rash, jaundice, or any other sign of hypersensitivity.^{1 23} Institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).¹

Photosensitivity Reactions

Moderate to severe photosensitivity/phototoxicity reactions reported with fluoroquinolones, including moxifloxacin.¹

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).¹

Relative potential of the various fluoroquinolones to cause photosensitivity/phototoxicity unclear.¹ Factors that contribute to susceptibility to this adverse effect during fluoroquinolone therapy include patient's skin pigmentation, frequency and duration of exposure to sun and UV light, use of protective clothing and sunscreen, concomitant use of other drugs, and dosage and duration of fluoroquinolone therapy.¹

Avoid unnecessary or excessive exposure to sunlight or artificial UV light (tanning beds, UVA/UVB treatment) while receiving moxifloxacin.¹ If patient needs to be outdoors, they should wear loose-fitting clothing that protects skin from sun exposure and use other sun protection measures (sunscreen).¹

Discontinue moxifloxacin if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.¹

General Precautions

Selection and Use of Anti-infectives

When prescribing a fluoroquinolone, consider potential benefits and risks for the individual patient.^{98 99} Most patients tolerate the drugs, but serious adverse reactions (e.g., CNS effects, QT prolongation, C. difficile-associated diarrhea and colitis, damage to liver, kidneys, or bone marrow, alterations in glucose homeostatis) may occur rarely.^{98 99}

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.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk in rats; may be distributed into human milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established in children or adolescents <18 years of age.¹ Like other quinolones, moxifloxacin causes arthropathy in juvenile animals.¹ (See Musculoskeletal Effects under Cautions.)

AAP states use of fluoroquinolones may be justified in children <18 years of age in special circumstances after careful assessment of the risks and benefits for the individual patient and after these benefits and risks have been explained to the parents or caregivers.³⁶

Geriatric Use

No overall differences in safety or efficacy relative to younger adults.¹

Risk of severe tendon disorders, including tendon rupture, is increased in older adults (usually those >60 years of age).^{1 98 99} This risk is further increased in those receiving concomitant corticosteroids.^{1 98 99} (See Tendinopathy and Tendon Rupture under Cautions.) Use caution in geriatric adults, especially those receiving concomitant corticosteroids.¹

Risk of QT interval prolongation may be increased in geriatric patients.¹ (See Prolongation of QT Interval under Cautions.)

Hepatic Impairment

Dosage adjustments not required in adults with mild or moderate hepatic impairment (Child Pugh class A or B).¹ Pharmacokinetics not studied in those with severe hepatic impairment (Child-Pugh class C).¹

Renal Impairment

Dosage adjustment is not required in adults with renal impairment.¹

Common Adverse Effects

GI effects (nausea, diarrhea), dizziness.¹

Interactions for Avelox

Not metabolized by CYP isoenzymes and does not inhibit CYP3A4, 2D6, 2C9, 2C19, or 1A2.¹ Pharmacokinetic interactions with drugs metabolized by CYP isoenzymes unlikely.¹

Drugs That Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT interval prolongation).¹ Avoid use in patients receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.¹ Use with caution in patients receiving drugs that prolong QT interval (e.g., cisapride [commercially available under a limited-access protocol only], erythromycin, antipsychotic agents, tricyclic antidepressants).¹ (See Prolongation of QT Interval under Cautions.)

Specific Drugs

Drug	Interaction	Comments
Antacids (aluminum- or magnesium-containing)	Decreased absorption of moxifloxacin1	Administer moxifloxacin at least 4 hours before or 8 hours after such antacids1
Anticoagulants, oral (warfarin)	No evidence of pharmacokinetic interaction;1 11 some quinolones enhance anticoagulant effects of warfarin1 29	Monitor PT, INR, or other suitable coagulation tests1
Antifungal agents, azoles (itraconazole)	Pharmacokinetic interactions unlikely1
Atenolol	Pharmacokinetic interactions unlikely1
Calcium supplements	No clinically important pharmacokinetic interactions 1
Corticosteroids	Increased risk of tendinitis or tendon rupture, especially in patients >60 years of age1 98 99
Didanosine	Decreased absorption of moxifloxacin with buffered didanosine preparations1	Administer moxifloxacin at least 4 hours before or 8 hours after buffered didanosine (pediatric oral solution admixed with antacid)1
Digoxin	Transient increase in digoxin concentrations; no clinically important effect on pharmacokinetics of either drug1	Dosage adjustment of moxifloxacin or digoxin not necessary1
Glyburide	No clinically important interactions1
Hormonal contraceptives	No clinically important effect on pharmacokinetics of ethinyl estradiol/levonorgestrel oral contraceptives1
Iron preparations	Decreased absorption of moxifloxacin1 82	Administer moxifloxacin at least 4 hours before or 8 hours after iron preparations1
Morphine	Pharmacokinetic interactions unlikely1
Multivitamins and dietary supplements	Decreased absorption of moxifloxacin1	Administer moxifloxacin at least 4 hours before or 8 hours after multivitamins or dietary supplements containing iron or zinc1
NSAIAs	Possible increased risk of CNS stimulation, seizures;1 animal studies using other fluoroquinolones suggest risk varies depending on the specific NSAIA86
Probenecid	Pharmacokinetic interactions unlikely1
Ranitidine	Pharmacokinetic interactions unlikely1
Sucralfate	Decreased absorption of moxifloxacin1	Administer moxifloxacin at least 4 hours before or 8 hours after sucralfate1
Theophylline	Pharmacokinetic interaction unlikely1

Avelox Pharmacokinetics

Absorption

Bioavailability

86–92%.^{1 4 5}

Peak plasma concentrations attained within 0.5–4 hours; steady-state attained after at least 3 days.^{1 6}

Food

Administration of a 400-mg tablet with a high-fat breakfast (2 eggs fried in butter, 2 strips bacon, 2 slices buttered toast, hash brown potatoes, 240 mL whole milk) decreased peak plasma concentrations and AUC by 12 and 3%, respectively; not considered clinically important.^{1 83}

Administration of a 400-mg tablet with yogurt (approximately 300 mg calcium) decreases peak plasma concentration and AUC by 16 and 6%, respectively; not considered clinically important.^{1 84}

Distribution

Extent

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.¹

Distributed into CSF in rabbits.⁴⁸

Distributed into milk in rats; may be distributed into human milk.¹

Plasma Protein Binding

30–50%.^{1 6}

Elimination

Metabolism

Approximately 52% of an oral or IV dose is metabolized via glucuronide and sulfate conjugation; the metabolites are not microbiologically active.^{1 4}

Not metabolized by CYP isoenzymes.^{1 4}

Elimination Route

Eliminated in urine and by biliary excretion and metabolism.³³

Approximately 45% of an oral or IV dose excreted unchanged (20% in urine and 25% in feces).¹ A total of 96% of an oral dose is excreted as unchanged drug or metabolites.^{1 4}

Half-life

Adults with normal renal and hepatic function: Mean of 11.5–15.6 hours following single or multiple oral doses.^{1 6 33 34}

Adults with normal renal and hepatic function: Mean of 8.2–15.4 hours following single or multiple IV doses.¹

Special Populations

Pharmacokinetics in geriatric patients similar to younger adults.¹

Concentrations of sulfate and glucuronide conjugates are increased in patients with mild or moderate hepatic impairment (Child-Pugh class A or B); clinical importance of this has not been determined.¹ Pharmacokinetics have not been evaluated in those with severe hepatic impairment (Child Pugh class C).¹

Pharmacokinetics not substantially affected by mild, moderate, or severe renal impairment.¹ In patients with Cl_cr <20 mL/minute undergoing hemodialysis or CAPD, moxifloxacin concentrations are not affected but concentrations of the sulfate and glucuronide conjugates are increased; clinical importance of this has not be determined.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹ Avoid high humidity.¹

Parenteral

Injection

25°C (may be exposed to 15–30°C).¹ Do not refrigerate.¹

For single-use only, discard any unused portions.¹

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility¹

Compatible
Dextrose 5 or 10% in water
Ringer’s injection, lactated
Sodium chloride 0.9%
Sodium chloride 1 M injection

Actions and Spectrum

• 
  

  Usually bactericidal.¹

  
  


• 
  

  Like other fluoroquinolones, moxifloxacin inhibits bacterial DNA gyrase and topoisomerase IV.¹

  
  


• 
  

  Spectrum of activity includes gram-positive aerobic bacteria, some gram-negative aerobic bacteria, some anaerobic bacteria, and some other organisms (e.g., Chlamydia, Mycoplasma, Mycobacterium).^{1 23 24 28}

  
  


• 
  

  More active in vitro than some other fluoroquinolones (e.g., ciprofloxacin, levofloxacin, ofloxacin) against S. pneumoniae^{7 8 9} while generally retaining the in vitro activity of these drugs against gram-negative bacteria and etiologic agents of atypical pneumonia (e.g., C. pneumoniae, M. pneumoniae, Legionella).^{3 7 8}

  
  


• 
  

  Gram-positive aerobes: Active in vitro and in clinical infections against Enterococcus faecalis, Staphylococcus aureus (oxacillin-susceptible [methicillin-susceptible] strains only),^{1 24} S. pneumoniae (including multidrug-resistant strains),^{1 56} S. anginosus,¹ S. constellatus,^{1 24 27} and S. pyogenes (group A β-hemolytic streptococci).^{1 24} Also active in vitro against S. epidermidis (oxacillin-susceptible strains only),^{1 24} S. agalactiae (group B streptococci),^{1 24} and viridans streptococci.¹

  
  


• 
  

  Gram-negative aerobes: Active in vitro and in clinical infections against Enterobacter cloacae,¹ Escherichia coli,^{1 24} H. influenzae,^{1 24} H. parainfluenzae,¹ K. pneumoniae,¹ M. catarrhalis,¹ and Proteus mirabilis.¹ Also active in vitro against Citrobacter freundii,^{1 24} K. oxytoca,¹ and Legionella pneumophila.¹

  
  


• 
  

  Anaerobes and other organisms: Active in vitro and in clinical infections against Bacteroides fragilis, B. thetaiotaomicron, Clostridium perfringens, C. pneumoniae, Peptostreptococcus,^{1 24 41} and M. pneumoniae.¹