Dosing and uses of Avelox, Moxifloxacin Systemic (moxifloxacin)
Adult dosage forms and strengths
injectable solution
- 400mg/250mL
tablet
- 400mg
Acute Bacterial Sinusitis
400 mg PO/IV qDay for 5-10 days
Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for acute sinusitis
Community-Acquired Pneumonia
400 mg PO/IV qDay for 7-14 days
Acute Exacerbation of Chronic Bronchitis
Indicated for acute exacerbations of chronic bronchitis caused by bacterial infections
400 mg PO/IV qDay for 5 days
Limitations-of-use: Reserve fluoroquinolones for patients who do not have other available treatment options for acute bacterial exacerbation of chronic bronchitis
Skin & Skin Structure Infections
Uncomplicated: 400 mg PO/IV qDay for 7 days
Complicated: 400 mg PO/IV qDay for 7-21 days
Intra-abdominal Infections
Complicated: 400 mg PO/IV qDay for 5-14 days
Pneumonic & Septicemic Plague
Indicated in adults for the treatment of plague, including pneumonic and septicemic plague, caused by susceptible isolates of Yersinia pestis; it is also indicated for prophylaxis of plague in adults
400 mg PO/IV qDay x10-14 days
Begin administration as soon as possible after suspected or confirmed exposure to Yersinia pestis
Dosing Considerations
Initial IV administration may be changed to PO administration at same dosage to complete therapy, depending on patient's clinical status
Susceptible organisms
- Aeromonas hydrophila, Bacillus anthracis, Bacteroides fragilis, Bacteroides thetaiotaomicron, Campylobacter jejuni, Citrobacter diversus, Citrobacter freundii, Clostridium perfringens, Escherichia coli, Enterobacter spp, Haemophilus influenzae, Hafnia alvei, Klebsiella pneumoniae, Legionella pneumophila, Morganella morganii, Moraxella catarrhalis, Mycobacterium pneumoniae, Mycobacterium tuberculosis, Neisseria gonorrhoeae, Peptostreptococcus spp, Proteus mirabilis, Proteus vulgaris, Providencia spp, Pseudomonas aeruginosa, Salmonella typhi, Shigella spp, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus anginosus, Streptococcus constellatus, Streptococcus pneumoniae, Vibrio cholerae, Yersinia pestis
- First-line therapy: C jejuni; no unanimity on others (eg, L pneumophila, M morganii)
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Avelox, Moxifloxacin Systemic (moxifloxacin) adverse (side) effects
1-10%
Nausea (7%)
Diarrhea (6%)
Dizziness (3%)
Decreased amylase (2%)
Decreased basophils, eosinophils, hemoglobin, prothrombin time, red blood cells, neutrophils (2%)
Decreased serum glucose (2%)
Increased serum chloride (2%)
Increased serum ionized calcium (2%)
Immune hypersensitivity reaction (0.1-2%)
Prolonged QT interval (0.1-2%)
<1%
Acute renal failure
Agranulocytosis
Anaphylactoid reaction
Aplastic anemia
Extrinsic allergic alveolitis
Hemolytic anemia
Hepatic failure
Hepatic necrosis
Hepatitis
Pancytopenia
Seizure
Serum sickness due to drug
Stevens-Johnson syndrome
Tendon rupture, tendinitis
Thrombocytopenia
Torsades de pointes
Toxic epidermal necrolysis
Postmarketing Reports
Blood and lymphatic disorders: Agranulocytosis, pancytopenia
Cardiovascular disorders: Ventricular tachyarrhythmias (including in very rare cases cardiac arrest and torsade de pointes)
Ear and labyrinth disorders: Hearing impairment, including deafness (reversible in most cases)
Eye disorders: Vision loss (especially in the course of CNS reactions, transient in majority of cases)
Hepatobiliary disorders: Hepatitis, hepatic failure, jaundice, acute hepatic necrosis
Immune system disorders: Anaphylactic reactions including shock, angioedema (including laryngeal edema)
Musculoskeletal/connective tissue disorders: Tendon rupture, arthralgia, myalgia
Nervous system disorders: Exacerbation of myasthenia gravis symptoms, altered coordination, abnormal gait, muscle weakness, peripheral neuropathy, polyneuropathy
Central nervous system effects: Hallucinations, anxiety, depression, insomnia, severe headaches, and confusion
Psychiatric disorders: Psychotic reaction (very rarely culminating in self-injurious behavior, such as suicidal ideation/thoughts or suicide attempts)
Renal and urinary disorders: Renal dysfunction, interstitial nephritis
Respiratory disorders: Allergic pneumonitis
Skin and tissue disorders: Photosensitivity/phototoxicity reaction, Stevens-Johnson syndrome, Toxic epidermal necrolysis
Warnings
Black box warnings
Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together including: tendinitis and tendon rupture, peripheral neuropathy, and CNS effects
Discontinue the drug immediately and avoid use of systemic fluoroquinolones in patients who experience any of these serious adverse reactions
May exacerbate muscle weakness in patients with myasthenia gravis; fluoroquinolones should be avoided in patients with known history of myasthenia gravis
Serious adverse effects and limitations-of-use
- Both oral and injectable fluroquinolones are associated with disabling side effects involving tendons, muscles, joints, nerves and the central nervous system
- These side effects can occur hours to weeks after exposure to fluoroquinolones and may potentially be permanent
- Because the risk of these serious side effects generally outweighs the benefits for patients with acute bacterial sinusitis, acute exacerbation of chronic bronchitis, and uncomplicated UTIs, that fluoroquinolones should be reserved for use in patients with these conditions who have no alternative treatment options
- For some serious bacterial infections, including anthrax, plague, and bacterial pneumonia among others, the benefits of fluoroquinolones outweigh the risks and it is appropriate for them to remain available as a therapeutic option
Contraindications
Hyersensitivity to drug or component
Cautions
In prolonged therapy, perform periodic evaluations of organ system function (eg, renal, hepatic, hematopoietic); superinfections may occur with prolonged or repeated antibiotic therapy
Phototoxicity reactions may occur; avoid excessive sunlight
Use caution in cardiovascular disease especially significant bradycardia or acute myocardial ischemia
Peripheral neuropathy: Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness reported; peripheral neuropathy may occur rapidly after initiating and may potentially become permanent
Serious, sometimes fatal hypogycemia reported including in patients without a history of hypoglycemia (common with gatifloxacin, which is no longer marketed); monitor glucose levels closely in patients with diabetes; if hypoglycemic reaction occurs, discontinue therapy and initiate appropriate therapy immediately
Fulminant hepatitis, potentially leading to liver failure reported; discontinue treatment if hepatitis symptoms occur
Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion); these reactions can occur within hours to weeks after starting therapy, including in patients of any age or without pre-existing risk factors; discontinue therapy immediately at first signs or symptoms of any serious adverse reaction; in addition, avoid use of fluoroquinolones, in patients who have experienced any serious adverse reactions associated with fluoroquinolones
Risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney, heart or lung transplants; other factors that may independently increase risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis
Avoid use in presence of drugs or conditions that prolong QT interval, uncorrected hypomagnesemia or hypokalemia
Hallucinations, convulsions, and increased intracranial pressure (including pseudotumor cerebri) and toxic psychosis reported
Acute onset of retinal detachment increased 4.5-fold with oral fluoroquinolones in a single case-controlled study - JAMA 2012;307(13):1414-1419; another study disputes these findings (relative risk, 1.29) - JAMA 2013;310(20):2184-2190
Use caution in patients with a history of diabetes, hepatic impairment, renal impairment, or rheumatoid arthrtitis
As with all fluoroquinolones, disturbances in blood glucose, including both hypoglycemia and hyperglycemia have been reported in diabetic patients; monitor blood glucose
Prescribing antibiotics in absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria
Clostridium difficile-associated diarrhea (CDAD) has been reported; if CDAD suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued; appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated
Pregnancy and lactation
Pregnancy
There are no available human data establishing a drug associated risk; however, when moxifloxacin was administered to rats during pregnancy and throughout lactation at doses associated with maternal toxicity, decreased neonatal body weights, increased incidence of skeletal variations (rib and vertebra combined), and increased fetal loss were observed
Advise pregnant women of potential risk to fetus
Lactation
Not known if moxifloxacin is present in human milk
Based on animal studies in rats, moxifloxacin may be excreted in human milk
Developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on the breastfed child from drug or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Avelox, Moxifloxacin Systemic (moxifloxacin)
Mechanism of action
Inhibits A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription
Absorption
Well absorbed; absorption is not affected by high-fat meal or yogurt
Bioavailability: 90%
Distribution
Protein bound: 50%
Vd: 1.7-2.7 L/kg; tissue concentrations often exceed plasma concentrations in respiratory tissues, alveolar macrophages, and sinus tissues
Metabolism
Metabolized in liver via glucuronide (14%) and sulfate (38%) conjugation
Elimination
Half-life: PO, 12 hr; IV, 15 hr
Excretion: Feces (25%), urine (20% as unchanged drug)
Sulfate conjugate metabolites are excreted in feces, glucuronide conjugate metabolites in urine
Administration
IV Preparation
No further dilution of infusion solution is necessary
IV Administration
Infuse over 1 hour
Do not admix with other drugs or infuse through same tubing simultaneously
