Moxifloxacin (Systemic)

Moxifloxacin is a DNA gyrase inhibitor, and also inhibits topoisomerase IV. DNA gyrase (topoisomerase II) is an essential bacterial enzyme that maintains the superhelical structure of DNA. DNA gyrase is required for DNA replication and transcription, DNA repair, recombination, and transposition; inhibition is bactericidal.

Absorption

Well absorbed; not affected by high-fat meal or yogurt

Distribution

Vd: 1.7 to 2.7 L/kg; tissue concentrations often exceed plasma concentrations in respiratory tissues, alveolar macrophages, abdominal tissues/fluids, uterine tissue (endometrium, myometrium), and sinus tissues

Metabolism

Hepatic (~52% of dose) via glucuronide (~14%) and sulfate (~38%) conjugation

Excretion

Urine (as unchanged drug [20%] and glucuronide conjugates); feces (as unchanged drug [25%] and sulfate conjugates)

Half-Life Elimination

Single dose: Oral: 12-16 hours; IV: 8-15 hours

Protein Binding

~30% to 50%

Treatment of mild to moderate community-acquired pneumonia, including multidrug-resistant Streptococcus pneumoniae (MDRSP); acute bacterial exacerbation of chronic bronchitis; acute bacterial sinusitis; complicated and uncomplicated skin and skin structure infections; complicated intra-abdominal infections; prophylaxis and treatment of plague, including pneumonic and septicemic plague, due to Yersinia pestis.

Limitations of use: Because fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions (eg, tendinitis and tendon rupture, peripheral neuropathy, CNS effects), reserve moxifloxacin for use in patients who have no alternative treatment options for acute exacerbation of chronic bronchitis or acute sinusitis.

Anthrax

Based on the Centers for Disease Control and Prevention (CDC) Expert Panel Meetings on Prevention and Treatment of Anthrax in Adults, moxifloxacin is as an effective and recommended agent for the treatment of cutaneous anthrax and an alternative agent for postexposure prophylaxis and treatment of systemic anthrax (with or without possible/confirmed meningitis).

Bacterial meningitis

Based on the Infectious Diseases Society of America (IDSA) guidelines for the management of bacterial meningitis, moxifloxacin is an effective and recommended alternative agent for the treatment of penicillin-resistant Streptococcus pneumoniae meningitis.

Bite wounds (animal/human)

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), moxifloxacin is an effective and recommended alternative option for treatment of bite wounds, particularly in patients with a human bite wound who are hypersensitive to beta-lactams.

Diabetic foot infections

Based on the Infectious Diseases Society of America (IDSA) guidelines for diagnosis and treatment of diabetic foot infections, moxifloxacin is an effective and recommended treatment option for moderate to severe diabetic foot infections.

Mycoplasma genitalium

Noncontrolled trials support the use of moxifloxacin as alternative treatment in patients with persistent detection of Mycoplasma genitalium who have not responded to or are intolerant of azithromycin.

Centers for Disease Control and Prevention (CDC) guidelines for treatment of sexually transmitted diseases (STDs) state that moxifloxacin is the preferred second-line agent for urethritis, cervicitis, or pelvic inflammatory disease (PID) in patients resistant to azithromycin and/or with persistent detection of M. genitalium.

Nocardiosis

Data from a limited number of patients studied suggest that moxifloxacin, with or without other antimicrobials, may be beneficial for the treatment of infections caused by susceptible Nocardia spp. [Fihman 2006], [Kandasamy 2008], [Tripodi 2011]. Additional data may be necessary to further define the role of moxifloxacin in this condition.

Pelvic inflammatory disease

Based on the Centers for Disease Control and Prevention (CDC) sexually transmitted diseases treatment guidelines, moxifloxacin may be considered as alternative treatment in patients allergic to cephalosporins with pelvic inflammatory disease. The CDC recommends use as an alternative therapy only if standard parenteral cephalosporin therapy is not feasible and community prevalence of quinolone-resistant gonococcal organisms is low. Culture sensitivity must be confirmed.

Surgical prophylaxis

Based on the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Surgical Infection Society (SIS), and the Society of Healthcare Epidemiology of America (SHEA) guidelines for antimicrobial prophylaxis in surgery, moxifloxacin (systemic) may be administered (in combination with either clindamycin or vancomycin) as an alternative regimen in patients with beta-lactam allergy.

Tuberculosis (second-line therapy)

Based on the American Thoracic Society, Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) Treatment of Tuberculosis guidelines, moxifloxacin (systemic) given for second-line therapy of tuberculosis is effective and recommended in the management of this condition.

Additional Off-Label Uses

Community-acquired pneumonia (CAP) (mild-to-moderate), including multidrug-resistant Streptococcus pneumoniae (MDRSP) in adolescents with skeletal maturity

Acute bacterial rhinosinusitis: Oral, IV: 400 mg every 24 hours for 10 days (manufacturer’s labeling) or 5 to 7 days (Chow 2012). Note: Recommended in patients with beta-lactam allergy; may also be used if initial therapy fails, in areas with high endemic rates of penicillin nonsusceptible S. pneumoniae, those with severe infections, age >65 years, recent hospitalization, antibiotic use within the past month, or who are immunocompromised.

Anthrax (off-label use) (CDC [Hendricks 2014]):

Inhalational (postexposure prophylaxis): Oral: 400 mg every 24 hours for 60 days

Cutaneous (without systemic involvement): Oral: 400 mg every 24 hours for 7 to 10 days for naturally acquired infection; 60 days for bioterrorism-related cases

Systemic (including meningitis), treatment: IV: 400 mg every 24 hours; use in combination with a protein synthesis inhibitor (eg, clindamycin, linezolid); if meningitis is suspected or cannot be ruled out, use in combination with another bactericidal antimicrobial (eg, beta-lactam) and a protein synthesis inhibitor (eg, clindamycin, linezolid). Duration of therapy is 2 weeks or until clinically stable when meningitis has been excluded; ≥2 to 3 weeks for possible/confirmed meningitis. Patients exposed to aerosolized spores require prophylaxis to complete an antimicrobial course of 60 days from illness onset.

Bacterial meningitis (off-label use): IV: 400 mg every 24 hours for 10 to 14 days (IDSA [Tunkel 2004])

Bite wounds (animal/human) (off-label use): Oral, IV: Note: Recommended as an alternative therapy for human bite wound in patients hypersensitive to beta-lactams: 400 mg once daily (IDSA [Stevens 2014])

Chronic bronchitis, acute bacterial exacerbation: Oral, IV: 400 mg every 24 hours for 5 days

Community-acquired pneumonia (CAP) (including MDRSP): Oral, IV:

Manufacturer’s labeling: 400 mg every 24 hours for 7 to 14 days

Alternate dosing: 400 mg every 24 hours for 5 days (IDSA [Mandell 2007])

Diabetic foot infection (off-label use): Oral, IV: 400 mg once daily (Vick-Fragoso 2009)

Intra-abdominal infections, complicated: Oral, IV: 400 mg every 24 hours for 5 to 14 days (initiate with IV); Note: 2010 IDSA guidelines recommend a treatment duration of 4 to 7 days (provided source controlled) for community-acquired, mild to moderate IAI

Mycoplasma genitalium (off-label use): Oral: 400 mg every 24 hours for 7, 10, or 14 days (Bissessor 2015; CDC [Workowski 2015])

Nocardiosis (off-label use): Oral, IV: 400 mg once daily; may be used in combination with other antimicrobials (Fihman 2006; Kandasamy 2008; Tripodi 2011). Additional data may be necessary to further define the role of moxifloxacin in this condition.

Pelvic inflammatory disease (in patients allergic to cephalosporins) (off-label use): Oral: 400 mg every 24 hours for 14 days. Note: The CDC recommends use as an alternative therapy only if standard parenteral cephalosporin therapy is not feasible and community prevalence of quinolone-resistant gonococcal organisms is low. Culture sensitivity must be confirmed (CDC [Workowski 2015])

Plague: Oral, IV: 400 mg every 24 hours for 10 to 14 days

Skin and skin structure infections: Oral, IV:

Complicated: 400 mg every 24 hours for 7 to 21 days

Uncomplicated: 400 mg every 24 hours for 7 days

Surgical (perioperative) prophylaxis (off-label use): IV: 400 mg within 120 minutes prior to surgical incision (Bratzler 2013).

Tuberculosis, drug-resistant tuberculosis, or intolerance to first-line agents (off-label use): Oral: 400 mg every 24 hours (CDC 2003)

Refer to adult dosing.

Community-acquired pneumonia (CAP) due to atypical pathogens (M. pneumoniae, Chlamydophila [also known as Chlamydia] pneumoniae, C. trachomatis), mild infection or step-down therapy in adolescents with skeletal maturity, (alternative to azithromycin) (IDSA/PIDS 2011) (off-label use): Adolescents: Oral: 400 mg once daily

Surgical (perioperative) prophylaxis (off-label use): Children ≥1 year and Adolescents: IV: 10 mg/kg within 120 minutes prior to surgical incision (maximum dose: 400 mg) (Bratzler 2013)

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Avoid high humidity. Do not refrigerate infusion solution; discard unused portion.

Some quinolones may produce a false-positive urine screening result for opioids using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opioid screens by more specific methods should be considered.

Concerns related to adverse effects:

• Altered cardiac conduction: Fluoroquinolones may prolong QTc interval; avoid use in patients with known QTc prolongation, ventricular arrhythmias including torsades de pointes, proarrhythmic conditions (eg, clinically significant bradycardia, acute myocardial ischemia), uncorrected hypokalemia, hypomagnesemia, or concurrent administration of other medications known to prolong the QT interval (including Class Ia and Class III antiarrhythmics, cisapride, erythromycin, antipsychotics, and tricyclic antidepressants).

• Glucose regulation: Fluoroquinolones have been associated with the development of serious, and sometimes fatal, hypoglycemia. These events have occurred most often in elderly patients with diabetes, but have also been reported in patients without a prior history of diabetes. Prompt identification and treatment of hypoglycemia is essential. Individual quinolones may differ in their potential to cause this effect. It was most evident with gatifloxacin (no longer marketed as s systemic formulation). Hyperglycemia has also been associated with the use of fluoroquinolones. Patients should be monitored closely for signs/symptoms of disordered glucose regulation.

• Hepatotoxicity: Fulminant hepatitis potentially leading to liver failure (including fatalities) has been reported with use; patients should be advised to discontinue treatment and promptly report signs/ symptoms of hepatitis (eg, abdominal pain, jaundice, dark urine, pale stools).

• Hypersensitivity reactions: Severe hypersensitivity reactions, including anaphylaxis, have occurred with quinolone therapy. The spectrum of these reactions can vary widely; reactions may present as typical allergic symptoms (eg, itching, urticaria, rash, edema) after a single dose, or may manifest as severe idiosyncratic dermatologic (eg, Stevens-Johnson, toxic epidermal necrolysis), vascular (eg, vasculitis), pulmonary (eg, pneumonitis), renal (eg, nephritis), hepatic (eg, hepatic failure or necrosis), and/or hematologic (eg, anemia, cytopenias) events, usually after multiple doses. Prompt discontinuation of drug should occur if skin rash or other symptoms arise.

• Photosensitivity: Avoid excessive sunlight and take precautions to limit exposure (eg, loose fitting clothing, sunscreen); may rarely cause moderate to severe phototoxicity reactions. Discontinue use if phototoxicity occurs.

• Serious adverse reactions: [US Boxed Warning]: Fluoroquinolones are associated with disabling and potentially irreversible serious adverse reactions that may occur together, including tendinitis and tendon rupture, peripheral neuropathy, and CNS effects. Discontinue moxifloxacin immediately and avoid use of fluoroquinolones in patients who experience any of these serious adverse reactions. Patients of any age or without pre-existing risk factors have experienced these reactions; may occur within hours to weeks after initiation.

- CNS effects: Fluoroquinolones have been associated with an increased risk of CNS effects including seizures, increased intracranial pressure (including pseudotumor cerebri), and toxic psychosis; may also cause nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or actions. May occur following the first dose; discontinue immediately and avoid further use of fluoroquinolones in patients who experience these reactions. Use with caution in patients with known or suspected CNS disorder, or risk factors that may predispose to seizures or lower the seizure threshold.

- Peripheral neuropathy: Fluoroquinolones have been associated with an increased risk of peripheral neuropathy; may occur soon after initiation of therapy and may be irreversible; discontinue if symptoms of sensory or sensorimotor neuropathy occur. Avoid use in patients who have previously experienced peripheral neuropathy.

- Tendinitis/tendon rupture: Fluoroquinolones have been associated with an increased risk of tendonitis and tendon rupture in all ages; risk may be increased with concurrent corticosteroids, solid organ transplant recipients, and in patients >60 years of age, but has also occurred in patients without these risk factors. Rupture of the Achilles tendon has been reported most frequently; but other tendon sites (eg, rotator cuff, biceps, hand) have also been reported. Inflammation and rupture may occur bilaterally. Cases have been reported within hours or days of initiation, and up to several months after discontinuation of therapy. Strenuous physical activity, renal failure, and previous tendon disorders may be independent risk factor for tendon rupture. Discontinue at first sign of tendon pain, swelling, inflammation or rupture. Avoid use in patients with a history of tendon disorders or who have experienced tendinitis or tendon rupture.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with significant bradycardia or acute myocardial ischemia.

• Diabetes: Use with caution in patients with diabetes mellitus; glucose regulation may be altered.

• Hepatic impairment: Use with caution in patients with mild, moderate, or severe hepatic impairment or liver cirrhosis; may increase the risk of QT prolongation.

• Myasthenia gravis: [US Boxed Warning]: May exacerbate muscle weakness related to myasthenia gravis; avoid use in patients with known history of myasthenia gravis. Cases of severe exacerbations, including the need for ventilatory support, and deaths have been reported.

• Renal impairment: Use with caution in patients with renal failure; may increase risk of tendon rupture.

• Rheumatoid arthritis: Use with caution in patients with rheumatoid arthritis; may increase risk of tendon rupture.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Adverse effects (eg, tendon rupture, QT changes) may be increased in elderly patients.

• G6PD deficiency: Hemolytic reactions may (rarely) occur with quinolone use in patients with latent or actual G6PD deficiency.

• Pediatric: Efficacy of systemically administered moxifloxacin (oral, intravenous) have not been established in pediatric patients.

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: Reserve use of moxifloxacin for treatment of acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis for patients who have no alternative treatment options because of the risk of disabling and potentially serious adverse reactions (eg, tendinitis and tendon rupture, peripheral neuropathy, CNS effects).