moxifloxacin

University of Maryland Medical Center. 07 May 2007.

Pronunciation

(moxs i FLOKS a sin)

U.S. Brand Names

Avelox�; Avelox� I.V.; Vigamox�

Synonyms

Moxifloxacin Hydrochloride

Generic Available

Canadian Brand Names

Avelox�

Use

Treatment of mild-to-moderate community-acquired pneumonia, including multidrug-resistant Streptococcus pneumoniae (MDRSP); acute bacterial exacerbation of chronic bronchitis; acute bacterial sinusitis; uncomplicated skin infections; bacterial conjunctivitis (ophthalmic formulation)

Pregnancy Risk Factor

Pregnancy Implications

Reports of arthropathy (observed in immature animals and reported rarely in humans) have limited the use of fluoroquinolones during pregnancy. Teratogenic effects were not observed with moxifloxacin in animal studies; however, delayed skeletal development and smaller fetuses were observed in some species. There are no adequate and well-controlled studies in pregnant women. Based on limited data, quinolones are not expected to be a major human teratogen. Although quinolone antibiotics should not be used as first-line agents during pregnancy, when considering treatment for life-threatening infection and/or prolonged duration of therapy, the potential risk to the fetus must be balanced against the severity of the potential illness.

Lactation

Excretion in breast milk unknown/not recommended

Contraindications

Hypersensitivity to moxifloxacin, other quinolone antibiotics, or any component of the formulation

Warnings/Precautions

Use with caution in patients with significant bradycardia or acute myocardial ischemia. Moxifloxacin causes a concentration-dependent QT prolongation. Do not exceed recommended dose or infusion rate. Coadministration of moxifloxacin with other drugs that also prolong the QT interval or induce bradycardia should be avoided. Use with caution in individuals at risk of seizures (CNS disorders or concurrent therapy with medications which may lower seizure threshold). Discontinue in patients who experience significant CNS adverse effects (dizziness, hallucinations, suicidal ideation or actions). Not recommended in patients with moderate to severe hepatic insufficiency. Use with caution in diabetes; glucose regulation may be altered. Tendon inflammation and/or rupture have been reported with quinolone antibiotics. Risk may be increased with concurrent corticosteroids, particularly in the elderly. Discontinue at first signs or symptoms of tendon pain.

Severe hypersensitivity reactions, including anaphylaxis, have occurred with quinolone therapy. If an allergic reaction occurs (itching, urticaria, dyspnea or facial edema, loss of consciousness, tingling, cardiovascular collapse) discontinue drug immediately. Prolonged use may result in superinfection; pseudomembranous colitis may occur and should be considered in all patients who present with diarrhea. Quinolones may exacerbate myasthenia gravis, use with caution (rare, potentially life-threatening weakness of respiratory muscles may occur). Peripheral neuropathy may rarely occur.

Ophthalmic: Eye drops should not be injected subconjunctivally or introduced directly into the anterior chamber of the eye. Contact lenses should not be worn during therapy.

Adverse Reactions

Systemic:

3% to 10%:

Central nervous system: Dizziness (3%)

Gastrointestinal: Nausea (7%), diarrhea (6%)

0.1% to 3%:

Cardiovascular: Chest pain, hypertension, palpitation, peripheral edema, QT prolongation, tachycardia

Central nervous system: Anxiety, chills, confusion, headache, insomnia, nervousness, pain, somnolence, tremor, vertigo

Dermatologic: Dry skin, pruritus, rash (maculopapular, purpuric, pustular)

Endocrine & metabolic: Serum chloride increased (≥2%), serum ionized calcium increased (≥2%), serum glucose decreased (≥2%)

Gastrointestinal: Abdominal pain, amylase increased, amylase decreased (≥2%), anorexia, constipation, dry mouth, dyspepsia, flatulence, glossitis, lactic dehydrogenase increased, stomatitis, taste perversion, vomiting

Hematologic: Eosinophilia, leukopenia, prothrombin time prolonged, increased INR, thrombocythemia, thrombocytopenia

Increased serum levels of the following (≥2%): MCH, neutrophils, WBC

Decreased serum levels of the following (≥2%): Basophils, eosinophils, hemoglobin, RBC, neutrophils

Hepatic: Bilirubin decreased (≥2%), cholestatic jaundice, GGTP increased, liver function test abnormal

Local: Injection site reaction

Neuromuscular & skeletal: Arthralgia, back pain, leg pain, myalgia, paresthesia, malaise, weakness

Renal: Serum albumin increased (≥2%)

Respiratory: Dyspnea, pharyngitis, pneumonia, rhinitis, sinusitis, PO2 increased (≥2%)

Miscellaneous: Allergic reaction, infection, moniliasis, diaphoresis

<0.1%, postmarketing, and/or case reports: Abnormal dreams, agitation, amblyopia, amnesia, anaphylactic reaction, anaphylactic shock, anemia, angioedema, aphasia, arthritis, asthma, atrial fibrillation, C. difficile -positive diarrhea, cholestasis, convulsions, depersonalization, depression, dysphagia, ECG abnormalities, emotional lability, face edema, gastritis, hallucinations, hepatitis, hyperglycemia, hyperlipidemia, hypertonia, hyperuricemia, hypesthesia, hypotension, incoordination, jaundice (cholestatic), kidney function abnormalities, laryngeal edema, parosmia, pelvic pain, peripheral neuropathy, prothrombin time increased, pseudomembranous colitis, psychotic reaction, sleep disorder, speech disorder, Stevens-Johnson syndrome, supraventricular tachycardia, taste loss, tendon rupture, thinking abnormal, thromboplastin decreased, tinnitus, tongue discoloration, urticaria, ventricular tachycardia, vision abnormalities. Torsade de pointes and cardiac arrest have been reported (very rarely), usually in patients with concurrent, severe proarrhythmic conditions.

Additional reactions with ophthalmic preparation: 1% to 6%: Conjunctivitis, dry eye, ocular discomfort, ocular hyperemia, ocular pain, ocular pruritus, subconjunctival hemorrhage, tearing, visual acuity decreased

Overdosage/Toxicology

Potential symptoms of overdose may include CNS excitation, seizures, QT prolongation, and arrhythmias (including torsade de pointes). Patients should be monitored by continuous ECG in the event of an overdose. Management is supportive and symptomatic.

Drug Interactions

Corticosteroids: Concurrent use may increase the risk of tendon rupture, particularly in elderly patients (overall incidence rare).

Glyburide: Quinolones may increase the effect of glyburide; monitor

Metal cations (aluminum, calcium, iron, magnesium, and zinc) bind quinolones in the gastrointestinal tract and inhibit absorption. Concurrent administration of most antacids, oral electrolyte supplements, quinapril, sucralfate, and some didanosine formulations (chewable/buffered tablets and pediatric powder for oral suspension) should be avoided. Moxifloxacin should be administered 4 hours before or 8 hours after these agents. Calcium products do not appear to significantly affect moxifloxacin absorption.

QTc-prolonging agents: Effects may be additive with moxifloxacin. Avoid concurrent use with Class Ia and Class III antiarrhythmics, erythromycin, cisapride, antipsychotics, and cyclic antidepressants.

Warfarin: The hypoprothrombinemic effect of warfarin may be enhanced by some quinolone antibiotics; monitor INR.

Ethanol/Nutrition/Herb Interactions

Food: Absorption is not affected by administration with a high-fat meal or yogurt.

Stability

Store at 25�C (77�F). I.V.: Do not refrigerate

Compatibility

Stable in 0.9% NS, 1M sodium chloride, D5W, D10W, SWFI, LR.

Mechanism of Action

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.

Pharmacodynamics/Kinetics

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, and sinus tissues

Protein binding: 50%

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

Bioavailability: 90%

Half-life elimination: Oral: 12 hours; I.V.: 15 hours

Excretion: Approximately 45% of a dose is excreted in feces (25%) and urine (20%) as unchanged drug

Metabolites: Sulfate conjugates in feces, glucuronide conjugates in urine

Dosage

Oral, I.V.: Adults:

Acute bacterial sinusitis: 400 mg every 24 hours for 10 days

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

Note: Avelox� ABC Pack� (Avelox� Bronchitis Course) contains five tablets of 400 mg each.

Community-acquired pneumonia (including MDRSP): 400 mg every 24 hours for 7-14 days

Uncomplicated skin infections: 400 mg every 24 hours for 7 days

Elderly: No dosage adjustments are required based on age

Dosage adjustment in renal impairment: No dosage adjustment is required, including patients on hemodialysis or CAPD

Dosage adjustment in hepatic impairment: No dosage adjustment is required in mild to moderate hepatic insufficiency (Child-Pugh Class A and B). Not recommended in patients with severe hepatic insufficiency.

Ophthalmic: Children ≥1 year and Adults: Instill 1 drop into affected eye(s) 3 times/day for 7 days

Administration

I.V.: Infuse over 60 minutes; do not infuse by rapid or bolus intravenous infusion

Monitoring Parameters

WBC, signs of infection

Dietary Considerations

May be taken with or without food. Take 4 hours before or 8 hours after multiple vitamins, antacids, or other products containing magnesium, aluminum, iron, or zinc.

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.

I.V.: Report any redness, swelling, or pain at infusion site; any swelling of mouth, lips, tongue, or throat; chest pain or tightness; respiratory difficulty; back pain; itching; skin rash; tingling; tendon pain; dizziness; abnormal thinking; or anxiety.

Oral: Take exactly as directed with or without food. Do not take antacids 4 hours before or 8 hours after taking this medication. Do not miss a dose (take a missed dose as soon as possible, unless it is almost time for your next dose). Take entire prescription even if feeling better. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. May cause nausea, vomiting, taste perversion (small, frequent meals, good mouth care, chewing gum, or sucking hard candy may help); headache, dizziness, insomnia, anxiety (use caution when driving or engaging in tasks requiring alertness until response to drug is known). Report immediately any swelling of mouth, lips, tongue or throat; chest pain or tightness; respiratory difficulty; back pain; itching; skin rash; tingling; tendon pain; pain or numbness (loss of sensation) in extremities; confusion, dizziness, abnormal thinking, or anxiety; or insomnia. Report changes in voiding pattern; vaginal itching, burning, or discharge; vision changes or hearing; abnormal bruising or bleeding or blood in urine; or other adverse reactions.

Ophthalmic: Wash hands before instilling solution. Sit or lie down to instill. Open eye, look at ceiling, and instill prescribed amount of solution as directed. Do not touch tip of applicator or let tip of applicator touch eye. Do not wear contact lenses during therapy. Temporary stinging or blurred vision, or dry eyes may occur. Report persistent pain, burning, excessive tearing, decreased visual acuity, swelling, itching, or worsening of condition.

Anesthesia and Critical Care Concerns/Other Considerations

Moxifloxacin causes a dose-dependent QT prolongation. Coadministration of moxifloxacin with other drugs that also prolong the QT interval or induce bradycardia (eg, beta-blockers, amiodarone) should be avoided. Careful consideration should be given in the use of moxifloxacin in patients with cardiovascular disease, in those with conduction abnormalities.

Cardiovascular Considerations

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause dizziness, insomnia; may rarely produce abnormal thinking, agitation, anorexia, anxiety, asthenia, ataxia, confusion, depersonalization, depression, euphoria, hallucination, hostility, nervousness, panic attacks, paranoia, psychosis, sedation, somnolence, or stress

Mental Health: Effects on Psychiatric Treatment

Contraindicated with ziprasidone; may have potential to prolong QT interval; should avoid in patients with uncorrected hypokalemia, or concurrent administration of other medications known to prolong the QT interval (antipsychotics and tricyclic antidepressants)

Dosage Forms

Infusion [premixed in sodium chloride 0.8%] (Avelox� I.V.): 400 mg (250 mL)

Solution, ophthalmic (Vigamox�): 0.5% (3 mL)

Tablet [film coated]:

Avelox�: 400 mg

Avelox� ABC Pack [unit-dose pack]: 400 mg (5s)

References

Balfour JA and Wiseman LR, "Moxifloxacin," Drugs , 1999, 57(3):363-73.

Blondeau JM, "Expanded Activity and Utility of the New Fluoroquinolones: A Review," Clinical Therapeutics , 1999, 21(1):3-40.

"Gatifloxacin and Moxifloxacin: Two New Fluoroquinolones," The Medical Letter , 2000, Vol 42, 1072:15.

International Brand Names

Actimax� (DE); Actira� (AT, ES); Avalox� (BR, CH, DE, IE, IT); Avelon� (ZA); Avelox� (AR, AT, AU, BE, CA, CO, DK, EC, FI, GB, HR, HU, ID, IE, NZ, PL, PT, RO, SE, SG, SI, TH, TR); Bacterol� (CO); Izilox� (FR); Megaxin� (IL); Moxif� (IN); Octegra� (AR, AT, ES, IT); Proflox� (BE, ES, PT)

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is the first of its kind, requiring compliance with 53 standards of quality and accountability, verified by independent audit. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial process . A.D.A.M. is also a founding member of Hi-Ethics (www.hiethics.com) and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. � 1997-2007 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.