治療Clostridium difficile感染的 fidaxomycin (DIFICID)

DIFICID is a macrolide antibacterial drug indicated in adults ≥18 years
of age for treatment of Clostridium difficile-associated diarrhea.

To reduce the
development of drug-resistant bacteria and maintain the effectiveness of
DIFICID and other antibacterial drugs, DIFICID should be used only to treat
infections that are proven or strongly suspected to be caused by Clostridium
difficile.

 

About C. difficile-associated Diarrhea (CDAD)

C. difficile is a
spore-forming, gram-positive anaerobe¹

• C. difficile produces two toxins, A and B, which
  activate the release of cytokines from monocytes²

• Toxins A and B lead to inflammation, intestinal
  epithelial cell damage, fluid secretion, and diarrhea, as well as other
  symptoms³

Transmission of C.
difficile⁴

• The primary mode of transmission is person-to-person
  spread through the fecal-oral route


• Environmental contamination also plays an important
  role (eg, commodes, bedpans, thermometers, etc)

Pathogenesis of C.
difficile^3,5

• C. difficile-ingested spores are able to survive the
  acidic stomach


• Spores reach the small intestine and germinate to
  vegetative form


• If intestinal microflora is disrupted, C. difficile can
  proliferate

• Toxigenic strains of C. difficile may produce clinical
  disease

C. difficile: a persistent pathogen

• C. difficile spores can be stable for months and
  cultured from hospital surfaces (eg, railings, bedpans, walls, floors,
  sinks, etc)⁴




• Spores are resistant to antibacterial soaps,
  alcohol-based hand sanitizers, and conventional disinfectants⁴




• The vegetative form of C. difficile can survive in the
  environment on moist surfaces for up to 6 hours⁵




• Vegetative form is susceptible to gastric acid,
  antibacterial soaps, and alcohol-based hand sanitizers⁶




• Formation of spores and the inadequacy of standard
  methods of disinfection (not killed by conventional detergents or
  solvents) lead to persistence in the environment and the spread of
  infection⁴

• Disinfection requires bleach or other strong oxidizers
  (eg, peroxide), extreme heat (greater than the boiling point of water), or
  long contact times⁷




• CDC recommends meticulous cleaning followed by use of
  hypochlorite-based germicides for desinfection of surfaces in
  patient-care areas⁷

Appr

Approximately 700,000 new cases per year in the United States^5,6

·        
CDI accounts for
significant rates of morbidity and mortality that increase with patient age,
with a mortality rate as high as 14% in elderly patients⁷

·        
According to the CDC,
CDI rates increased 200% for hospitalized patients aged ≥65 years from 1996 to
2009⁸

·        
C.
difficile has surpassed
methicillin-resistant Staphylococcus aureus (MRSA) as the leading cause
of healthcare-acquired infections in community hospitals⁹

·        
C.
difficile is the most common
cause of infectious diarrhea in healthcare settings¹⁰

·        
CDAD is the most
common symptom of CDI¹⁰

Efficacy of DIFICID

DIFICID has primary
activity against species of clostridia, including C. difficile in vitro¹

• Bactericidal against C. difficile in vitro¹


• Minimal inhibitory concentration (MIC₉₀) =
  0.25 μg/mL^2,3




• MIC range: 0.03-0.25 μg/mL¹

• Inhibits bacterial RNA polymerase¹


• Demonstrates no cross-resistance with other classes of
  antibacterial drugs in vitro¹


• Demonstrates a post-antibiotic effect versus C.
  difficile of 6-10 hours in vitro¹

DIFICID ACTS LOCALLY IN
THE

GASTROINTESTINAL TRACT¹

 

DIFICID is mainly
confined to the GI tract¹

• Acts locally in the gastrointestinal tract against C.
  difficile


• Plasma concentrations were minimal, in the ng/mL range
  (ranging from 2-179 ng/mL within the T_max window [1-5 hours])


• Fecal concentrations in samples collected within 24 hrs
  of the last dose ranged from 639-2710 μg/g

 

Safety and
Dosing of DIFICID

Important Safety Information

·        
DIFICID should not be
used for systemic infections

·        
Only use DIFICID for
infection proven or strongly suspected to be caused by C. difficile.
Prescribing DIFICID in the absence of a proven or strongly suspected C.
difficile infection is unlikely to provide benefit to the patient and
increases the risk of the development of drug-resistant bacteria

·        
The most common
adverse reactions are nausea (11%), vomiting (7%), abdominal pain (6%),
gastrointestinal hemorrhage (4%), anemia (2%), and neutropenia (2%)

For more information,
please visit www.DIFICID.com

Mechanism of Action of DIFICID

DIFICID is the first bactericidal therapy in more than 25 years
that targets C. difficile¹

DIFICID has primary
activity against species of clostridia, including C. difficile, in vitro¹

·        
Bactericidal against C.
difficile in vitro¹

·        
Acts locally in the
gastrointestinal tract against C. difficile¹

·        
Demonstrates no
cross-resistance with other classes of antibacterial drugs in vitro¹

·        
Inhibits bacterial RNA
polymerase¹

DIFICID
acts locally in the gastrointestinal tract¹

 

Next article

Efficacy of
DIFICID

Important Safety Information

·        
DIFICID should not be
used for systemic infections

·        
Only use DIFICID for
infection proven or strongly suspected to be caused by C. difficile.
Prescribing DIFICID in the absence of a proven or strongly suspected C.
difficile infection is unlikely to provide benefit to the patient and
increases the risk of the development of drug-resistant bacteria

·        
The most common
adverse reactions are nausea (11%), vomiting (7%), abdominal pain (6%),
gastrointestinal hemorrhage (4%), anemia (2%), and neutropenia (2%)

Indications and Usage

·        
DIFICID is a macrolide
antibacterial drug indicated in adults ≥18 years of age for treatment of Clostridium
difficile-associated diarrhea

·        
To reduce the
development of drug-resistant bacteria and maintain the effectiveness of
DIFICID and other antibacterial drugs, DIFICID should be used only to treat
infections that are proven or strongly suspected to be caused by Clostridium
difficile

For more information, please visit www.DIFICID.com

FULL
PRESCRIBING INFORMATION

1
INDICATIONS AND USAGE

To
reduce the development of drug-resistant bacteria and maintain the

effectiveness
of DIFICID and other antibacterial drugs, DIFICID should be

used
only to treat infections that are proven or strongly suspected to be

caused
by Clostridium
difficile.

1.1 Clostridium
difficile-Associated
Diarrhea

DIFICID
is a macrolide antibacterial drug indicated in adults (³18 years of age)

for
treatment of Clostridium
difficile-associated
diarrhea (CDAD).

2
DOSAGE AND ADMINISTRATION

The
recommended dose is one 200 mg DIFICID tablet orally twice daily for

10 days
with or without food.

3
DOSAGE FORMS AND STRENGTHS

200 mg
white to off-white film-coated, oblong tablets; each tablet is debossed

with ²FDX² on one
side and ²200² on the
other side.

4
CONTRAINDICATIONS

None.

5
WARNINGS AND PRECAUTIONS

5.1 Not
for Systemic Infections

Since
there is minimal systemic absorption of fidaxomicin, DIFICID is not

effective
for treatment of systemic infections.

5.2
Development of Drug Resistant Bacteria

Prescribing
DIFICID in the absence of a proven or strongly suspected C.
difficile

infection
is unlikely to provide benefit to the patient and increases the
risk of the development of drug resistant bacteria.

6
ADVERSE REACTIONS

6.1
Clinical Trials Experience

Because
clinical trials are conducted under widely varying conditions, adverse

event
rates observed in the clinical trials of a drug cannot be directly compared

to
rates in the clinical trials of any other drug and may not reflect the rates

observed
in practice.

The
safety of DIFICID 200 mg tablets taken twice a day for 10 days was

evaluated
in 564 patients with CDAD in two active-comparator controlled trials

with
86.7% of patients receiving a full course of treatment.

Thirty-three
patients receiving DIFICID (5.9%) withdrew from trials as a result

of
adverse reactions (AR). The types of AR resulting in withdrawal from the

study
varied considerably. Vomiting was the primary adverse reaction leading

to
discontinuation of dosing; this occurred at an incidence of 0.5% in both the

fidaxomicin
and vancomycin patients in Phase 3 studies.