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Update on New Fluoroquinolones
Boxed Warning & Increasing
Fluoroquinolone Resistance
JENNIFER DOAN, PHARM. D
PHARMACY RESIDENT, UNITY HEALTH
SEPTEMBER 30, 2016
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Learning Objectives
 Recognize potential fluoroquinolone toxicities that may
occur with systemic fluoroquinolone use
 Discuss the efficacy of systemic fluoroquinolone use for the
following indications:
 Acute bacterial sinusitis
 Acute bacterial exacerbation of chronic bronchitis
 Uncomplicated urinary tract infections
 Understand increasing resistance with fluoroquinolone use
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Fluoroquinolones
 Mechanism of Action: Inhibition of DNA replication by binding to
topoisomerase II (DNA gyrase) and topoisomerase IV
 FDA-Approved Indications
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Community-acquired pneumonia
Nosocomial pneumonia
Chronic bronchitis (acute bacterial exacerbation)
Acute bacterial rhinosinusitis
Prostatitis
Urinary tract infection (uncomplicated or complicated)
Acute pyelonephritis
Skin or skin structure infections (uncomplicated or complicated)
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Potential Adverse Effects
 Photosensitivity
 Hypersensitivity
 QT prolongation
 Peripheral neuropathy
 Tendinitis or tendon rupture
 CNS effects
 Myasthenia gravis exacerbation
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Photosensitivity & Hypersensitivity
 Photosensitivity/Phototoxicity: Moderate to severe
photosensitivity/phototoxicity reactions, the latter of which
may manifest as exaggerated sunburn reactions involving
areas exposed to light, can be associated with the use of
fluoroquinolones after sun or UV light exposure
 Hypersensitivity: Serious and potentially fatal anaphylactic
reactions may occur in patients who receive fluoroquinolone
therapy
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QT-Interval Prolongation
 Fluoroquinolones may lead to prolonged QT intervals due to
inhibition of potassium channels
 Prolonged QTc interval >500 milliseconds is associated with an
increased risk for Torsades de Pointes, a life-threatening cardiac
arrhythmia
 Although QT prolongation is not common, caution should be
warranted with fluoroquinolone use when being administered
with other agents that cause QT prolongation
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Peripheral Neuropathy
 Peripheral neuropathy: Nerve
disorder that occurs in the arms or legs
 Symptoms: Pain, tingling, numbness,
weakness
 These reactions may occur at any
time during treatment and may persist
for months to years after the agent is
discontinued
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Tendinitis or Tendon Rupture
 Symptoms: Pain, swelling, inflammation of a
tendon or tendon rupture
 The risk of developing tendinitis or tendon
rupture is further increased in:
 Patients who are older than 60 years old
 Patients who are taking corticosteroid drugs
 Patients who are kidney, heart, and lung
transplant recipients
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CNS Effects
 Fluoroquinolones have potential for CNS adverse effects such
as:
 Depression, suicidal thoughts
 Hallucinations
 Confusion
 Anxiety
 Mild headache
 Drowsiness or insomnia
 Seizures – rare but may still occur (especially in patients with a
lower seizure threshold)
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Myasthenia Gravis
Myasthenia gravis is a disease characterized by
skeletal muscle weakness and may involve
symptoms such as:
 Drooping eyelid, blurred or double vision
 Slurred speech, difficulty chewing/swallowing
 Weakness in arms/legs
 Case reports revealed that fluoroquinolone
exposure may lead to life-threatening
myasthenia gravis exacerbations in patients with
underlying disease
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November 2015
 Antimicrobial Drugs Advisory
Committee and Drug Safety and Risk
Management Advisory Committee
met to discuss the efficacy and safety
of fluoroquinolone use in cases of
acute bacterial sinusitis, acute
bacterial exacerbation of chronic
bronchitis, and uncomplicated urinary
tract infection
 The suggestion of stronger warnings
for systemic fluoroquinolones was
discussed
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Literature Review Before FDA-Approval
 Acute Bacterial Exacerbation of Chronic Bronchitis: The FDA reviewed 15
placebo-controlled trials and found that only six of the trials revealed statistically
significant results
 Fluoroquinolone use may be considered in patients who have moderate-tosevere acute bacterial exacerbation of chronic bronchitis
 Acute Bacterial Sinusitis: The FDA reviewed 20 published placebo-controlled
trials and found that only six of the trials revealed statistically significant results
 Lack of clinical criteria to differentiate between bacterial and viral acute
rhinosinusitis has led to inappropriate antibacterial therapy
 Uncomplicated Urinary Tract Infection: The FDA reviewed 5 prospective,
randomized, controlled trials for patients in an outpatient setting
 A good proportion of patients who received placebo treatment still achieved
microbiological eradication
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New Fluoroquinolone Boxed Warning
Fluoroquinolones should be reserved for use in
patients who have no other treatment options for
acute bacterial sinusitis, acute bacterial
exacerbation of chronic bronchitis, and
uncomplicated urinary tract infections
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Excessive Fluoroquinolone Use Consequences
 Excessive use of fluoroquinolone agents had led to widespread
resistance among bacterial pathogens
 Resistance develops by either mutation or acquisition of novel
genetic information
 Fluoroquinolone resistance has been demonstrated in urinary
infections, respiratory infections, gastrointestinal tract infections,
skin and soft-tissue and bone and joint infections, sexually
transmitted diseases, and ulcers
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Common Organisms with Potential for Resistance
Burkholderia cepacia
Mycoplasma pneumoniae
Campylobacter jejuni
Neisseria gonorrhoeae
Chlamydia trachomatis
Pseudomonas aeruginosa
Enterococcus faecium
Staphylococcus aureus
Escherichia coli
Streptococcus pneumoniae
Klebsiella pneumoniae
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Antibiogram Chart
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Preserving Fluoroquinolone Efficacy
 Develop an evidence-based approach to antimicrobial
selection
 Assess the appropriateness of drug utilization by reviewing
the activity of these agents and the patient’s disease state
 Ensure that patients who are candidates for fluoroquinolone
use, are provided an indicated dose for an appropriate duration
of time
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Question
The new FDA boxed warning opposes the use of fluoroquinolones in all cases of ABS, ACBECB,
and uUTI due to the disabling and potentially permanent adverse effects that are associated
with systemic fluoroquinolone use.
A. True
B. False
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