Approved Drug Label (PDF)
4
Contraindications
4.1 Hypersensitivity to Cefepime or the Cephalosporin Class of Antibacterials, Penicillins, or Other Beta-lactam Antibacterials
Subsection title
revised; Additions and/or revisions underlined:
Cefepime
for Injection and Dextrose Injection is contraindicated in patients who have shown
immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibacterial
drugs, penicillins or other beta-lactam antibacterials.
5
Warnings and Precautions
5.1 Hypersensitivity Reactions
Additions and/or
revisions underlined:
Before therapy with Cefepime for Injection and
Dextrose Injection is instituted, careful inquiry should be made to determine
whether the patient has had previous immediate hypersensitivity reactions to
cefepime, cephalosporins, penicillins, or other drugs. Exercise caution if this
product is to be given to penicillin-sensitive patients because
cross-hypersensitivity among beta-lactam antibacterials has been clearly
documented and may occur in up to 10% of patients with a history of penicillin
allergy. If an allergic reaction to Cefepime for Injection and Dextrose
Injection occurs, discontinue the drug and institute appropriate supportive
measures.
5.2 Neurotoxicity
Additions and/or
revisions underlined:
Serious adverse reactions have been reported
including life-threatening or fatal occurrences of the following:
encephalopathy (disturbance of consciousness including confusion,
hallucinations, stupor, and coma), aphasia, myoclonus, seizures, and nonconvulsive
status epilepticus [see Adverse Reactions
(6.2)]. Most cases occurred in patients with renal impairment who did not
receive appropriate dosage adjustment. However, some cases of neurotoxicity
occurred in patients receiving a dosage adjustment appropriate for their degree
of renal impairment.
In the majority of cases, symptoms of neurotoxicity
were reversible and resolved after discontinuation of cefepime and/or after
hemodialysis. If neurotoxicity associated with cefepime therapy occurs, discontinue
cefepime and institute appropriate supportive measures.
5.3 Clostridioides difficile-Associated Diarrhea
Subsection title
revised; Additions and/or revisions underlined:
Clostridioides difficile-associated diarrhea (CDAD) has been
reported with use of nearly all antibacterial agents, including cefepime, and
may range in severity from mild diarrhea to fatal colitis. Treatment with
antibacterial agents alters the normal flora of the colon leading to overgrowth
of C. difficile.
C. difficile produces toxins A
and B, which contribute to the development of CDAD. Hypertoxin- producing
strains of C. difficile cause
increased morbidity and mortality, as these infections can be refractory to
antimicrobial therapy and may require colectomy. CDAD must be considered in all
patients who present with diarrhea following antibacterial drug use.
Careful medical history is necessary since CDAD has been reported to occur over
two months after the administration of antibacterial agents.
If
CDAD is suspected or confirmed, ongoing antibacterial use not directed
against C. difficile may need to be
discontinued. Appropriate fluid and electrolyte management, protein
supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation should be instituted as clinically
indicated.
5.5 Drug/Laboratory Test Interactions
Additions and/or
revisions underlined:
Urinary
Glucose
The
administration of cefepime may result in a false-positive reaction with glucose
in the urine
when
using glucose tests based on Benedict’s copper reduction reaction that
determine the amount of reducing substances like glucose in the urine. It
is recommended that glucose tests based on enzymatic glucose oxidase be used.
Coombs’
Test
Positive
direct Coombs' tests have been reported during treatment with cefepime. In patients
who develop hemolytic anemia, discontinue the drug and institute appropriate
therapy. Positive Coombs' test may be observed in newborns whose mothers
have received cephalosporin antibacterial drugs before parturition.
…
6
Adverse Reactions
Additions and/or
revisions underlined:
The following adverse reactions are discussed in
other sections of the labeling:
Hypersensitivity reactions [see
Warnings and Precautions (5.1)]
Neurotoxicity [see Warnings and Precautions
(5.2)]
Clostridioides difficile-associated diarrhea [see Warnings
and Precautions (5.3)]
6.1 Clinical Trials Experience
Extensive changes;
please refer to label
6.2 Postmarketing Experience
Additions and/or
revisions underlined:
The
following adverse reactions have been reported during postapproval use of
cefepime. Because these reactions are reported voluntarily from a population of
uncertain size, it is not always possible to readily estimate their frequency
or establish a causal relationship to drug exposure.
In
addition to the adverse reactions reported during the North American clinical
trials with cefepime, the following adverse reactions have been reported during
worldwide postmarketing experience.
Encephalopathy
(disturbance of consciousness including confusion, hallucinations, stupor, and
coma), aphasia, myoclonus, seizures, and nonconvulsive status epilepticus have
been reported [see Warnings and
Precautions (5.2)].
Anaphylaxis
(including anaphylactic shock, transient leukopenia, neutropenia,
agranulocytosis and thrombocytopenia) has been reported.
6.3 Cephalosporin-class Adverse Reactions
Additions and/or
revisions underlined:
In addition to the adverse reactions listed above
that have been observed in patients treated with cefepime, the following
adverse reactions and altered laboratory tests have been reported for
cephalosporin-class antibacterials:
Stevens-Johnson syndrome, erythema multiforme, toxic
epidermal necrolysis, renal impairment, toxic nephropathy, aplastic anemia,
hemolytic anemia, hemorrhage, hepatic impairment including cholestasis, and
pancytopenia.
7
Drug Interactions
7.1 Drug/Laboratory Test Interactions
Newly
added subsection
The
administration of Cefepime for Injection and Dextrose Injection may result in a
false-positive reaction for glucose in the urine with certain methods. It is
recommended that glucose tests based on enzymatic glucose oxidase reactions be
used.
7.2 Aminoglycosides
Additions and/or
revisions underlined:
Monitor
renal
function if aminoglycosides are to be administered with Cefepime for
Injection and Dextrose Injection because of the increased potential of
nephrotoxicity and ototoxicity of aminoglycoside antibacterials.
7.3 Diuretics
Additions and/or
revisions underlined:
Nephrotoxicity
has been reported following concomitant administration of cephalosporins with
potent diuretics such as furosemide. Monitor renal function when cefepime is
concomitantly administered with potent diuretics.
8
Use in Specific Populations
8.1 Pregnancy
PLLR
conversion
Risk
Summary
There
are no cases of cefepime exposure during pregnancy reported from postmarketing
experience or from clinical trials. Available data from published observational
studies and case reports over several decades with cephalosporin use in
pregnant women have not established drug-associated risks of major birth
defects, miscarriage or adverse maternal or fetal outcomes (see Data). Cefepime crosses the placenta.
Cefepime
was not associated with adverse developmental outcomes in rats, mice, or
rabbits when administered parenterally during organogenesis. The doses used in
these studies were 1.6 times (rats), approximately equal to (mice) and 0.3
times (rabbits) the maximum recommended human dose (see Data).
The
estimated background risk of major birth defects and miscarriage for the
indicated population is unknown. All pregnancies have a background risk of
birth defect, loss, or other adverse outcomes. In the U.S. general population,
the estimated background risk of major birth defects and miscarriage in
clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Human Data
While
available studies cannot definitively establish the absence of risk, published
data from case- control studies and case reports over several decades have not
identified an association with cephalosporin use during pregnancy and major
birth defects, miscarriage, or other adverse maternal or fetal outcomes.
Available studies have methodologic limitations, including small sample size,
retrospective data collection, and inconsistent comparator groups.
Animal Data
Cefepime
was not embryocidal and did not cause fetal malformations when administered
parenterally during the period of organogenesis to rats at doses up to 1000
mg/kg/day, to mice at doses up to 1200 mg/kg/day, or to rabbits at doses up to
100 mg/kg/day. These doses are 1.6 times (rats), approximately equal to (mice),
and 0.3 times (rabbits) the maximum recommended clinical dose based on body
surface area.
8.2 Lactation
PLLR
conversion
Risk
Summary
Cefepime
is present in human milk at low concentration (approximately 0.5 mcg/mL),
following a single intravenous dose of 1000 mg. A nursing infant consuming
approximately 1000 mL of human milk per day would receive approximately 0.5 mg
of cefepime per day (see Data). There
is no information regarding effects of cefepime on the breastfed infant or on milk
production.
The
developmental and health benefits of breastfeeding should be considered along
with the mother’s clinical need for cefepime for injection and dextrose
injection and any potential adverse effects on the breastfed child from cefepime
for injection and dextrose injection or from the underlying maternal condition.
8.4 Pediatric Use
Additions and/or
revisions underlined:
The
safety and effectiveness of Cefepime for Injection and Dextrose Injection
in the treatment of uncomplicated and complicated urinary tract infections
(including pyelonephritis), uncomplicated skin and skin structure infections,
pneumonia, and as empiric therapy for febrile neutropenic patients have been
established in the age groups 2 months up to 16 years. Use of Cefepime for
Injection and Dextrose Injection in these age groups is supported by evidence
from adequate and well-controlled studies of cefepime in adults with additional
pharmacokinetic and safety data from pediatric trials [see Clinical Pharmacology (12.3)].
Safety
and effectiveness in pediatric patients below the age of 2 months have not been
established. There are insufficient clinical data to support the use of
Cefepime for Injection and Dextrose Injection in pediatric patients for the
treatment of serious infections in the pediatric population where the suspected
or proven pathogen is Haemophilus
influenzae type b. In those patients in whom meningeal seeding from a
distant infection site or in whom meningitis is suspected or documented, an
alternate agent with demonstrated clinical efficacy in this setting should be
used.
Cefepime
for Injection and Dextrose Injection in the DUPLEX® Container should be used
only in pediatric patients who require the entire 1 or 2 gram dose and not any
fraction thereof.
8.6 Renal Impairment
Newly
added subsection
Adjust
the dose of Cefepime Injection in patients with creatinine clearance less than
or equal to
60
mL/min to compensate for the slower rate of renal elimination [see Dosage Adjustments in Patients with
Renal Impairment (2.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Extensive changes;
please refer to label
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