Y36-002-592 **DUPLEX**^®^

Package Insert *DRUG DELIVERY SYSTEM*

**Cefepime for Injection**

**For Intravenous Use Only** Rx only

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

**DESCRIPTION**

Cefepime hydrochloride is a semi-synthetic, broad spectrum,
cephalosporin antibiotic for parenteral administration. The chemical
name is
1-\[\[6*R*,7*R*)-7-\[2-(2-amino-4-thiazolyl)glyoxylamido\]-2-carboxy-8-oxo-5-thia-1-azabicyclo\[4.2.0\]oct-2-en-3-yl\]methyl\]-1-methlypyrrolidinium
chloride, 7^2^-(*Z*)-(*O*-methyloxime), monohydrochloride, monohydrate,
which corresponds to the following structural formula:

![](media/image1.wmf)

Cefepime hydrochloride is a white to pale yellow powder. Cefepime
hydrochloride contains the equivalent of not less that 825 mcg and not
more than 911 mcg of cefepime (C~19~H~24~N~6~O~5~S~2~) per mg,
calculated on an anhydrous basis. It is highly soluble in water.

Cefepime for Injection in the Duplex dual chamber container is supplied
for intravenous administration in strengths equivalent to 1 g and 2 g of
cefepime (See **DOSAGE AND ADMINISTRATION**.) Cefepime for Injection is
supplied as a sterile, nonpyrogenic, single use packaged combination of
cefepime hydrochloride with L-arginine (drug chamber) and Dextrose
Injection (diluent chamber).

Cefepime for Injection contains the equivalent of not less than 90
percent and not more than 115 percent of the labeled amount of cefepime
(C~19~H~24~N~6~O~5~S~2~). The L-arginine, at an approximate
concentration of 725 mg/g of cefepime, is added to control the pH of the
reconstituted solution at 4.0 to 6.0.

After removing the peelable foil strip, activating the seals, and
thoroughly mixing, the reconstituted drug product is intended for single
intravenous use. Each 50 mL contains cefepime hydrochloride equivalent
to either 1 gram or 2 grams of cefepime. Reconstituted solutions of
Cefepime for Injection range in color from colorless to amber.

The DUPLEX Container is Latex-free, PVC-free, and DEHP-free.

The DUPLEX dual chamber container is made from a specially formulated
material. The product (diluent and drug) contact layer is a mixture of
thermoplastic rubber and a polypropylene ethylene copolymer that
contains no plasticizers. The safety of the container system is
supported by USP biological evaluation procedures.

**CLINICAL PHARMACOLOGY**

**Pharmacokinetics**

The average plasma concentrations of cefepime observed in healthy adult
male volunteers (n=9) at various times following single 30-minute
infusions (IV) of cefepime 500 mg, 1 g, and 2 g are summarized in
Table 1. Elimination of cefepime is principally via renal excretion with
an average (±SD) half-life of 2 (±0.3) hours and total body clearance of
120 (±8) mL/min in healthy volunteers. Cefepime pharmacokinetics are

linear over the range 250 mg to 2 g. There is no evidence of
accumulation in healthy adult male volunteers (n=7) receiving clinically
relevant doses for a period of 9 days.

**Absorption**

The average plasma concentrations of cefepime and its derived
pharmacokinetic parameters after intravenous administration are
portrayed in Table 1.

**Table 1: Average Plasma Concentrations in mcg/mL of Cefepime and
Derived Pharmacokinetic Parameters (±SD), Intravenous Administration**

  --------------------- ----------------- ----------------- ---------------
                        **Cefepime**                        

  **Parameter**         **500 mg IV**     **1 g IV**        **2 g IV**

  0.5 h                 38.2              78.7              163.1

  1.0 h                 21.6              44.5              85.8

  2.0 h                 11.6              24.3              44.8

  4.0 h                 5.0               10.5              19.2

  8.0 h                 1.4               2.4               3.9

  12.0 h                0.2               0.6               1.1

  Cmax, mcg/mL          39.1 (3.5)        81.7 (5.1)        163.9 (25.3)

  AUC, h•mcg/mL         70.8 (6.7)        148.5 (15.1)      284.8 (30.6)

  Number of subjects    9                 9                 9
  (male)                                                    
  --------------------- ----------------- ----------------- ---------------

**Distribution**

The average steady-state volume of distribution of cefepime is 18 (±2)
L. The serum protein binding of cefepime is approximately 20% and is
independent of its concentration in serum.

Cefepime is excreted in human milk. A nursing infant consuming
approximately 1000 mL of human milk per day would receive approximately
0.5 mg of cefepime per day. (See **PRECAUTIONS: Nursing Mothers**.)

Concentrations of cefepime achieved in specific tissues and body fluids
are listed in Table 2.

**Table 2: Average Concentrations of Cefepime in Specific Body Fluids
(mcg/mL) or Tissues (mcg/g)**

  --------------- ---------------- ------------ -------------------- -----------------
  **Tissue or     **Dose/Route**   **\# of      **Average Time of    **Average
  Fluid**                          Patients**   Sample Post-Dose     Concentration**
                                                (h)**                

  Blister Fluid   2 g IV           6            1.5                  81.4 mcg/mL

  Bronchial       2 g IV           20           4.8                  24.1 mcg/g
  Mucosa                                                             

  Sputum          2 g IV           5            4.0                  7.4 mcg/mL

  Urine           500 mg IV        8            0-4                  292 mcg/mL

                  1 g IV           12           0-4                  926 mcg/mL

                  2 g IV           12           0-4                  3120 mcg/mL

  Bile            2 g IV           26           9.4                  17.8 mcg/mL

  Peritoneal      2 g IV           19           4.4                  18.3 mcg/mL
  Fluid                                                              

  Appendix        2 g IV           31           5.7                  5.2 mcg/g

  Gallbladder     2 g IV           38           8.9                  11.9 mcg/g

  Prostate        2 g IV           5            1.0                  31.5 mcg/g
  --------------- ---------------- ------------ -------------------- -----------------

Data suggest that cefepime does cross the inflamed blood-brain barrier.
**The clinical relevance of these data are uncertain at this time.**

**Metabolism and Excretion**

Cefepime is metabolized to N-methylpyrrolidine (NMP) which is rapidly
converted to the N-oxide (NMP-N-oxide). Urinary recovery of unchanged
cefepime accounts for approximately 85% of the administered dose. Less
than 1% of the administered dose is recovered from urine as NMP, 6.8% as
NMP-N-oxide, and 2.5% as an epimer of cefepime. Because renal excretion
is a significant pathway of elimination, patients with renal dysfunction
and patients undergoing hemodialysis require dosage adjustment. (See
**DOSAGE AND ADMINISTRATION**.)

**Special Populations**

*Pediatric patients*: Cefepime pharmacokinetics have been evaluated in
pediatric patients from 2 months to 11 years of age following single and
multiple doses on q8h (n=29) and q12h (n=13) schedules. Following a
single IV dose, total body clearance and the steady-state volume of
distribution averaged 3.3 (±1) mL/min/kg and 0.3 (±0.1) L/kg,
respectively. The urinary recovery of unchanged cefepime was 60.4
(±30.4) percent of the administered dose, and the average renal
clearance was 2 (±1.1) mL/min/kg. There were no significant effects of
age or gender (25 male vs. 17 female) on total body clearance or volume
of distribution, corrected for body weight. No accumulation was seen
when cefepime was given at 50 mg/kg q12h (n=13), while Cmax, AUC, and t½
were increased about 15% at steady state after 50 mg/kg q8h. The
exposure to cefepime following a 50 mg/kg IV dose in a pediatric patient
is comparable to that in an adult treated with a 2 g IV dose.

*Geriatric patients*: Cefepime pharmacokinetics have been investigated
in elderly (65 years of age and older) men (n=12) and women (n=12) whose
mean (SD) creatinine clearance was 74 (±15) mL/min. There appeared to be
a decrease in cefepime total body clearance as a function of creatinine
clearance. Therefore, dosage administration of cefepime in the elderly
should be adjusted as appropriate if the patient's creatinine clearance
is 60 mL/min or less. (See **DOSAGE AND ADMINISTRATION**).

*Renal insufficiency*: Cefepime pharmacokinetics have been investigated
in patients with various degrees of renal insufficiency (n=30). The
average half-life in patients requiring hemodialysis was 13.5 (±2.7)
hours and in patients requiring continuous peritoneal dialysis was 19
(±2) hours. Cefepime total body clearance decreased proportionally with
creatinine clearance in patients with abnormal renal function, which
serves as the basis for dosage adjustment recommendations in this group
of patients. (See **DOSAGE AND ADMINISTRATION**.)

*Hepatic insufficiency*: The pharmacokinetics of cefepime were unaltered
in patients with impaired hepatic function who received a single 1 g
dose (n=11).

**Microbiology**

Cefepime is a bactericidal agent that acts by inhibition of bacterial
cell wall synthesis. Cefepime has a broad spectrum of *in vitro*
activity that encompasses a wide range of gram-positive and
gram-negative bacteria. Cefepime has a low affinity for
chromosomally-encoded beta-lactamases. Cefepime is highly resistant to
hydrolysis by most beta-lactamases and exhibits rapid penetration into
gram-negative bacterial cells. Within bacterial cells, the molecular
targets of cefepime are the penicillin binding proteins (PBP).

Cefepime has been shown to be active against most strains of the
following microorganisms, both *in vitro* and in clinical infections as
described in the **INDICATIONS AND USAGE** section.

Aerobic Gram-Negative Microorganisms:

*Enterobacter*

*Escherichia coli*

*Klebsiella pneumoniae*

*Proteus mirabilis*

*Pseudomonas aeruginosa*

Aerobic Gram-Positive Microorganisms:

*Staphylococcus aureus* (methicillin-susceptible strains only)

*Streptococcus pneumoniae*

*Streptococcus pyogenes* (Lancefield's Group A streptococci)

Viridans group streptococci

The following *in vitro* data are available, **[but their clinical
significance is unknown]{.underline}**. Cefepime has been shown to have
*in vitro* activity against most strains of the following
microorganisms; however, the safety and effectiveness of cefepime in
treating clinical

infections due to the microorganisms have not been established in
adequate and well-controlled trials.

Aerobic Gram-Positive Microorganisms:

*Staphylococcus epidermidis* (methicillin-susceptible strains only)

*Staphylococcus saprophyticus*

*Streptococcus agalactiae* (Lancefield's Group B streptococci)

NOTE: Most strains of enterococci, e.g., *Enterococcus faecalis*, and
methicillin-resistant staphylococci are resistant to cefepime.

Aerobic Gram-Negative Microorganisms:

*Acinetobacter calcoaceticus* subsp. *lwoffi*

*Citrobacter diversus*

*Citrobacter freundii*

*Enterobacter agglomerans*

*Haemophilus infuenzae* (including beta-lactamase producing strains)

*Hafnia alvei*

*Klebsiella oxytoca*

*Moraxella catarrhalis* (including beta-lactamase producing strains)

*Morganella morganii*

*Proteus vulgaris*

*Providencia rettgeri*

*Providencia stuartii*

*Serratia marcescens*

NOTE: Cefepime is inactive against many strains of *Stenotrophomonas*
(formerly *Xanthomonas maltophilia* and *Pseudomonas maltophilia*).

Anaerobic Microorganisms:

NOTE: Cefepime is inactive against most strains of *Clostridium
difficile*.

**Susceptibility Tests**

**Dilution Techniques**

Quantitative methods are used to determine antimicrobial minimum
inhibitory concentrations (MICs). These MICs provide estimates of the
susceptibility of bacteria to antimicrobial compounds. The MICs should
be determined using a standardized procedure. Standardized procedures
are based on a dilution method^1^ (broth or agar) or equivalent with
standardized inoculum concentrations and standardized concentrations of
cefepime powder. The MIC values should be interpreted according to the
following criteria:

Table 3

  ---------------------------- --------------------- ---------------- --------------------
                               **MIC (mcg/mL)**                       

  **Microorganism**            **Susceptible (S)**   **Intermediate   **Resistant (R)**
                                                     (I)**            

  Microorganisms other than    [\<]{.underline}8     16               [\>]{.underline}32
  *Haemophilus spp.\** and                                            
  *S. pneumoniae\**                                                   

  *Haemophilus spp.\**         [\<]{.underline}2     --\*             --\*

  *Streptococcus pneumoniae\** [\<]{.underline}0.5   1                [\>]{.underline}2
  ---------------------------- --------------------- ---------------- --------------------

\*NOTE: Isolates from these species should be tested for susceptibility
using specialized dilution testing methods.^1^ Also, strains of
*Haemophilus spp*. with MICs greater than 2 mcg/mL should be considered
equivocal and should be further evaluated.

A report of "Susceptible" indicates that the pathogen is likely to be
inhibited if the antimicrobial compound in the blood reaches the
concentrations usually achievable. A report of "Intermediate" indicates
that the result should be considered equivocal, and, if the
microorganism is not fully susceptible to alternative, clinically
feasible drugs, the test should be repeated. This category implies
possible clinical applicability in body sites where the drug is
physiologically concentrated or in situations where high dosage of drug
can be used. This category also provides a buffer zone which prevents
small uncontrolled technical factors from causing major discrepancies in
interpretation. A

report of "Resistant" indicates that the pathogen is not likely to be
inhibited if the

antimicrobial compound in the blood reaches the concentrations usually
achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of
laboratory control microorganisms to control the technical aspects of
the laboratory procedures. Laboratory control microorganisms are
specific strains of microbiological assay organisms with intrinsic
biological properties relating to resistance mechanisms and their
genetic expression within bacteria; the specific strains are not
clinically significant in their current microbiological status. Standard
cefepime powder should provide the following MIC values (Table 4) when
tested against the designated quality control strains:

**Table 4**

  ----------------------- ----------------------- -----------------------
  **Microorganism**       **ATCC**                **MIC (mcg/mL)**

  *Escherichia coli*      25922                   0.016-0.12

  *Staphylococcus aureus* 29213                   1-4

  *Pseudomonas            27853                   1-4
  aeruginosa*                                     

  *Haemophilus            49247                   0.5-2
  influenzae*                                     

  *Streptococcus          49619                   0.06-0.25
  pneumoniae*                                     
  ----------------------- ----------------------- -----------------------

**Diffusion Techniques**

Quantitative methods that require measurement of zone diameters also
provide reproducible estimates of the susceptibility of bacteria to
antimicrobial compounds. One such standardized procedure^2^ requires the
use of standardized inoculum concentrations. This procedure uses paper
disks impregnated with 30 mcg of cefepime to test the susceptibility of
microorganisms of cefepime. Interpretation is identical to that stated
above for results using dilution techniques.

Reports from the laboratory providing results of the standard
single-disk susceptibility test with a 30-mcg cefepime disk should be
interpreted according to the following criteria:

Table 5

  ------------------- -------------------- ----------------- --------------------
                      **Zone Diameter                        
                      (mm)**                                 

  **Microorganism**   **Susceptible (S)**  **Intermediate    **Resistant (R)**
                                           (I)**             

  Microorganisms      [\>]{.underline}18   15-17             [\<]{.underline}14
  other than                                                 
  *Haemophilus*                                              
  spp.\* and *S.                                             
  pneumoniae*\*                                              

  *Haemophilus*       [\>]{.underline}26   --\*              --\*
  spp.\*                                                     
  ------------------- -------------------- ----------------- --------------------

\* NOTE: Isolates from these species should be tested for susceptibility
using specialized diffusion testing methods^2^. Isolates of
*Haemophilus* spp. with zones smaller than 26 mm should be considered
equivocal and should be further evaluated. Isolates of *S. pneumoniae*
should be tested against a 1 mcg oxacillin disk; isolates with oxacillin
zone sizes larger than or equal to 20 mm may be considered susceptible
to cefepime.

As with standardized dilution techniques, diffusion methods require the
use of laboratory control microorganisms to control the technical
aspects of the laboratory procedures. Laboratory control microorganisms
are specific strains of microbiological assay organisms with intrinsic
biological properties relating to resistance mechanisms and their
genetic expression within bacteria; the specific strains are not
clinically significant in their current microbiological status. For the
diffusion technique, the 30 mcg cefepime disk should provide the
following zone diameters in these laboratory test quality control
strains (Table 6):

Table 6

  ----------------------- ----------------------- -----------------------
  **Microorganism**       **ATCC**                **Zone Size Range
                                                  (mm)**

  *Escherichia coli*      25922                   29-35

  *Staphylococcus aureus* 25923                   23-29

  *Pseudomonas            27853                   24-30
  aeruginosa*                                     

  *Haemophilus            49247                   25-31
  influenzae*                                     
  ----------------------- ----------------------- -----------------------

**INDICATIONS AND USAGE**

Cefepime for Injection is indicated in the treatment of the following
infections caused by susceptible strains of the designated
microorganisms (see also **PRECAUTIONS: Pediatric Use** and **DOSAGE AND
ADMINISTRATION**):

> **Pneumonia** (moderate to severe) caused by *Streptococcus
> pneumoniae*, including cases associated with concurrent bacteremia.
> *Pseudomonas* *aeruginosa*, *Klebsiella pneumoniae*, or *Enterobacter*
> species.
>
> **Empiric Therapy for Febrile Neutropenic Patients**. Cefepime as
> monotherapy is indicated for empiric treatment of febrile neutropenic
> patients. In patients at high risk for severe infection (including
> patients with a history of recent bone marrow transplantation, with
> hypotension at presentation, with an underlying hematologic
> malignancy, or with severe or prolonged neutropenia), antimicrobial
> monotherapy may not be appropriate. Insufficient data exist to support
> the efficacy of cefepime monotherapy in such patients. (See **CLINICAL
> STUDIES**.)
>
> **Uncomplicated and Complicated Urinary Tract Infections (including
> pyelonephritis)** caused by *Escherichia coli* or *Klebsiella
> pneumoniae*, when the infection is severe, or caused by *Escherichia
> coli*, *Klebsiella pneumoniae*, or *Proteus mirabilis*, when the
> infection is mild to moderate, including cases associated with
> concurrent bacteremia with these microorganisms.
>
> **Uncomplicated Skin and Skin Structure Infections** caused by
> *Staphylococcus aureus* (methicillin-susceptible strains only) or
> *Streptococcus pyogenes*.
>
> **Complicated Intra-abdominal Infections** (used in combination with
> metronidazole) caused by *Escherichia coli*, viridans group
> streptococci, *Pseudomonas aeruginosa*, *Klebsiella pneumoniae*,
> *Enterobacter* species, or *Bacteroides fragilis*. (See **CLINICAL
> STUDIES**.)

To reduce the development of drug-resistant bacteria and maintain the
effectiveness of Cefepime for Injection and other antibacterial drugs,
Cefepime for Injection should be used only to treat or prevent
infections that are proven or strongly suspected to be caused by
susceptible bacteria. When culture and susceptibility information are
available, they should be considered in selecting or modifying
antibacterial therapy. In the absence of such data, local epidemiology
and susceptibility patterns may contribute to the empiric selection of
therapy.

**CLINICAL STUDIES**

**Febrile Neutropenic Patients**

The safety and efficacy of empiric cefepime monotherapy of febrile
neutropenic patients have been assessed in two multicenter, randomized
trials, comparing cefepime monotherapy (at a dose of 2 g IV q8h) to
ceftazidime monotherapy (at a dose of 2 g IV q8h). These studies
comprised 317 evaluable patients. Table 7 describes the characteristics
of the evaluable patient population.

**Table 7: Demographics of Evaluable Patients (First Episodes Only)**

  -------------------------------- ------------------ -------------------
                                   **Cefepime**       **Ceftazidime**

  **Total**                        **164**            **153**

  Median age (yr)                  56 (range, 18-82)  55 (range, 16-84)

  Male                             86 (52%)           85 (56%)

  Female                           78 (48%)           68 (44%)

  Leukemia                         65 (40%)           52 (34%)

  Other hematologic malignancies   43 (26%)           36 (24%)

  Solid tumor                      54 (33%)           56 (37%)

  Median ANC nadir (cells/mcL)     20 (range, 0-500)  20 (range, 0-500)

  Median duration of neutropenia   6 (range, 0-39)    6 (range, 0-32)
  (days)                                              

  Indwelling venous catheter       97 (59%)           86 (56%)

  Prophylactic antibiotics         62 (38%)           64 (42%)

  Bone marrow graft                9 (5%)             7 (5%)

  SBP \<90 mm Hg at entry          7 (4%)             2 (1%)
  -------------------------------- ------------------ -------------------

ANC = absolute neutrophil count; SBP = systolic blood pressure

Table 8 describes the clinical response rates observed. For all outcome
measures, cefepime was therapeutically equivalent to ceftazidime.

**Table 8: Pooled Response Rates for Empiric Therapy of Febrile
Neutropenic Patients**

+-----------------------------------------------+----------+----------+
|                                               | **%      |          |
|                                               | Re       |          |
|                                               | sponse** |          |
+-----------------------------------------------+----------+----------+
| **Outcome Measures**                          | **Ce     | **Cefta  |
|                                               | fepime** | zidime** |
|                                               |          |          |
|                                               | **(      | **(n =   |
|                                               | n=164)** | 153)**   |
+-----------------------------------------------+----------+----------+
| **Primary episode resolved with no treatment  | **51**   | **55**   |
| modification, no new febrile episodes or      |          |          |
| infection, and oral antibiotics allowed for   |          |          |
| completion of treatment**                     |          |          |
+-----------------------------------------------+----------+----------+
| **Primary episode resolved with no treatment  | **34**   | **39**   |
| modification, no new febrile episodes or      |          |          |
| infection\                                    |          |          |
| and no post-treatment oral antibiotics**      |          |          |
+-----------------------------------------------+----------+----------+
| Survival, any treatment modification allowed  | 93       | 97       |
+-----------------------------------------------+----------+----------+
| Primary episode resolved with no treatment    | 62       | 67       |
| modification and oral antibiotics allowed for |          |          |
| completion of treatment                       |          |          |
+-----------------------------------------------+----------+----------+
| Primary episode resolved with no treatment    | 46       | 51       |
| modification and no post-treatment oral       |          |          |
| antibiotics                                   |          |          |
+-----------------------------------------------+----------+----------+

Insufficient data exist to support the efficacy of cefepime monotherapy
in patients at high risk for severe infection (including patients with a
history of recent bone marrow transplantation, with hypotension at
presentation, with an underlying hematologic malignancy, or with severe
or prolonged neutropenia). No data are available in patients with septic
shock.

**Complicated Intra-abdominal Infections**

Patients hospitalized with complicated intra-abdominal infections
participated in a randomized, double-blind, multicenter trial comparing
the combination of cefepime (2 g q12h) plus intravenous metronidazole
(500 mg q6h) versus imipenem/cilastatin (500 mg q6h) for a maximum
duration of 14 days of therapy. The study was designed to demonstrate
equivalence of the two therapies. The primary analyses were conducted on
the protocol-valid population, which consisted of those with a
surgically confirmed complicated infection, at least one pathogen
isolated pretreatment, at least 5 days of treatment, and a 4-6 week
follow-up assessment for cured patients. Subjects in the
imipenem/cilastatin arm had higher APACHE II scores at baseline. The
treatment groups were otherwise generally comparable with regard to
their pretreatment characteristics. The overall clinical cure rate among
the protocol-valid patients was 81% (51 cured/63 evaluable patients) in
the cefepime plus metronidazole group and 66% (62/94) in the
imipenem/cilastatin group. The observed differences in efficacy may have
been due to a greater proportion of patients with high APACHE II scores
in the imipenem/cilastatin group.

**CONTRAINDICATIONS**

Cefepime for Injection is contraindicated in patients who have shown
immediate hypersensitivity reactions to cefepime or the cephalosporin
class of antibiotics, penicillins or other beta-lactam antibiotics.

Solutions containing dextrose may be contraindicated in patients with
hypersensitivity to corn products.

**WARNINGS**

**BEFORE THERAPY WITH CEFEPIME FOR 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. IF THIS PRODUCT IS TO BE GIVEN TO
PENICILLIN-SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE
CROSS-HYPERSENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS 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
OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS
MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER EMERGENCY MEASURES
INCLUDING OXYGEN, CORTICOSTEROIDS, INTRAVENOUS FLUIDS, INTRAVENOUS
ANTIHISTAMINES, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS CLINICALLY
INDICATED.**

In patients with impaired renal function (creatinine clearance
[\<]{.underline}60 mL/min), the dose of Cefepime for Injection should be
adjusted to compensate for the slower rate of renal elimination. Because
high and prolonged serum antibiotic concentrations can occur from usual
dosages in patients with renal insufficiency or other conditions that
may compromise renal function, the maintenance dosage should be reduced
when cefepime is administered to such patients. Continued dosage should
be determined by degree of renal impairment, severity of infection, and
susceptibility of the causative organisms. (See specific recommendations
for dosing adjustment in **DOSAGE AND ADMINISTRATION**.) During post
marketing surveillance, serious adverse events have been reported
including life-threatening or fatal occurrences of the following:
encephalopathy (disturbance of consciousness including confusion,
hallucinations, stupor, and coma), myoclonus, and seizures (see
**ADVERSE REACTIONS: Postmarketing Experience**). Most cases occurred in
patients with renal impairment who received doses of cefepime that
exceeded the recommended dosage schedules. However, some cases of
encephalopathy occurred in patients receiving a dosage adjustment for
their renal function. In the majority of cases, symptoms of
neurotoxicity were reversible and resolved after discontinuation of
cefepime and/or after hemodialysis.

**Pseudomembraneous colitis has been reported with nearly all
antibacterial agents, including Cefepime, and may range in severity from
mild to life-threatening. Therefore, it is important to consider this
diagnosis in patients who present with diarrhea subsequent to the
administration of antibacterial agents.**

Treatment with antibacterial agents alters the normal flora of the colon
and may permit overgrowth of clostridia. Studies indicate that a toxin
produced by *Clostridium difficile* is a primary cause of
"antibiotic-associated colitis".

After the diagnosis of pseudomembraneous colitis has been established,
therapeutic measures should be initiated. Mild cases of
pseudomembraneous colitis usually respond to drug discontinuation alone.
In moderate-to-severe cases, consideration should be given to management
with fluids and electrolytes, protein supplementation, and treatment
with an antibacterial drug clinically effective against *Clostridium
difficile* colitis.

**PRECAUTIONS**

**General**

Prescribing Cefepime for Injection in the absence of proven or strongly
suspected bacterial infection or a prophylactic indication is unlikely
to provide benefit to the patient and increases the risk of the
development of drug-resistant bacteria.

As with other antimicrobials, prolonged use of Cefepime for Injection
may result in overgrowth of nonsusceptible microorganisms. Repeated
evaluation of the patient's condition is essential. Should
superinfection occur during therapy, appropriate measures should be
taken.

Many cephalosporins, including cefepime, have been associated with a
fall in prothrombin activity. Those at risk include patients with renal
or hepatic impairment, or poor nutritional state, as well as patients
receiving a protracted course of antimicrobial therapy. Prothrombin time
should be monitored in patients at risk, and exogenous vitamin K
administered as indicated.

Positive direct Coombs' tests have been reported during treatment with
cefepime. In hematologic studies or in transfusion cross-matching
procedures when antiglobulin tests are performed on the minor side or in
Coombs' testing of newborns whose mothers have received cephalosporin
antibiotics before parturition, it should be recognized that a positive
Coombs' test may be due to the drug.

Cefepime for Injection should be prescribed with caution in individuals
with a history of gastrointestinal disease, particularly colitis.

Arginine has been shown to alter glucose metabolism and elevate serum
potassium transiently when administered at 33 times the amount provided
by the maximum recommended human dose of cefepime. The effect of lower
doses is not presently known.

As with other dextrose-containing solutions, Cefepime for Injection
should be prescribed with caution in patients with overt or known
subclinical diabetes mellitus or carbohydrate intolerance for any
reason.

If administration is controlled by a pumping device, care must be taken
to discontinue pumping action before the container runs dry or air
embolism may result.

Use only if solution is clear and container and seals are intact.

**Information for Patients**

Patients should be counseled that antibacterial drugs including Cefepime
for Injection should only be used to treat bacterial infections. They do
not treat viral infections (e.g., the common cold). When Cefepime for
Injection is prescribed to treat a bacterial infection, patients should
be told that although it is common to feel better early in the course of
therapy, the medication should be taken exactly as directed. Skipping
doses or not completing the full course of therapy may (1) decrease the
effectiveness of the immediate treatment and (2) increase the likelihood
that bacteria will develop resistance and will not be treatable by
Cefepime for Injection or other antibacterial drugs in the future.

**Drug Interactions**

Renal function should be monitored carefully if high doses of
aminoglycosides are to be administered with Cefepime for Injection
because of the increased potential of nephrotoxicity and ototoxicity of
aminoglycoside antibiotics. Nephrotoxicity has been reported following
concomitant administration of other cephalosporins with potent diuretics
such as furosemide.

**Drug/Laboratory Test Interactions**

The administration of cefepime may result in a false-positive reaction
for glucose in the urine when using Clinitest^®^ tablets. It is
recommended that glucose tests based on enzymatic glucose oxidase
reactions (such as Clinistix^®^) be used.

**Carcinogenesis, Mutagenesis, and Impairment of Fertility**

No long-term animal carcinogenicity studies have been conducted with
cefepime. A battery of *in vivo* and *in vitro* genetic toxicity tests,
including the Ames Salmonella reverse mutation assay, CHO/HGPRT
mammalian cell forward gene mutation assay, chromosomal aberration and
sister chromatid exchange assays in human lymphocytes, CHO fibroblast
clastogenesis assay, and cytogenetic and micronucleus assays in mice
were conducted. The overall conclusion of these tests indicated no
definitive evidence of genotoxic potential. No untoward effects on
fertility or reproduction have been observed in rats, mice, and rabbits
when cefepime is administered subcutaneously at 1 to 4 times the
recommended maximum human dose calculated on a mg/m^2^ basis.

**Usage in Pregnancy -- Teratogenic effects -- Pregnancy Category B**

Cefepime was not teratogenic or embryocidal when administered during the
period of organogenesis to rats at doses up to 1000 mg/kg/day (4 times
the recommended maximum human dose calculated on a mg/m^2^ basis) or to
mice at doses up to 1200 mg/kg (2 times the recommended maximum human
dose calculated on a mg/m^2^ basis) or to rabbits at a dose level of 100
mg/kg (approximately equal to the recommended maximum human dose
calculated on a mg/m^2^ basis).

There are, however, no adequate and well-controlled studies of cefepime
use in pregnant women. Because animal reproduction studies are not
always predictive of human response, this drug should be used during
pregnancy only if clearly needed.

**Nursing Mothers**

Cefepime is excreted in human breast milk in very low concentrations
(0.5 mcg/mL). Caution should be exercised when cefepime is administered
to a nursing woman.

**Labor and Delivery**

Cefepime has not been studied for use during labor and delivery.
Treatment should only be given if clearly indicated.

**Pediatric Use**

The safety and effectiveness of cefepime 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 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**).

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 in pediatric patients under 2 months of age
or 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.

**Geriatric Use**

Of the more than 6400 adults treated with cefepime in clinical studies,
35% were 65 years or older while 16% were 75 years or older. When
geriatric patients received the usual recommended adult dose, clinical
efficacy and safety were comparable to clinical efficacy and safety in
nongeriatric adult patients.

Serious adverse events have occurred in geriatric patients with renal
insufficiency given unadjusted doses of cefepime, including
life-threatening or fatal occurrences of the following: encephalopathy,
myoclonus, and seizures. (See **WARNINGS** and **ADVERSE REACTIONS**.)

This drug is known to be substantially excreted by the kidney, and the
risk of toxic reactions to this drug may be grater to patients with
impaired renal function. Because elderly patients are more likely to
have decreased renal function, care should be taken in dose selection,
and renal function should be monitored. (See **CLINICAL PHARMACOLOGY:
Special Populations**, **WARNINGS**, and **DOSAGE AND ADMINISTRATION**.)

**ADVERSE REACTIONS**

**Clinical Trials**

In clinical trials using multiple doses of cefepime, 4137 patients were
treated with the recommended dosages of cefepime (500 mg to 2 g IV
q12h). There were no deaths or permanent disabilities thought related to
drug toxicity. Sixty-four (1.5%) patients discontinued medication due to
adverse events thought by the investigators to be possibly, probably, or
almost certainly related to drug toxicity. Thirty-three (51%) of these
64 patients who discontinued therapy did so because of rash. The
percentage of cefepime-treated patients who discontinued study drug
because of drug-related adverse events was very similar at daily doses
of 500 mg, 1 g, and 2 g q12h (0.8%, 1.1%, and 2%, respectively).
However, the incidence of discontinuation due to rash increased with the
higher recommended doses.

The following adverse events were thought to be probably related to
cefepime during evaluation of the drug in clinical trials conducted in
North America (n=3125 cefepime-treated patients).

**Table 9: Adverse Clinical Reactions**

**Cefepime Multiple-Dose Dosing Regimens**

**Clinical Trials -- North America**

  ----------------------------------- -----------------------------------
  INCIDENCE EQUAL TO OR GREATER THAN  Local reactions (3%), including
  1%                                  phlebitis (1.3%), pain and/or
                                      inflammation (0.6%)\*; rash (1.1%)

  INCIDENCE LESS THAN 1% BUT GREATER  Colitis (including pseudomembranous
  THAN 0.1%                           colitis), diarrhea, fever,
                                      headache, nausea, oral moniliasis,
                                      pruritus, urticaria, vaginitis,
                                      vomiting
  ----------------------------------- -----------------------------------

\* Local reactions, irrespective of relationship to cefepime in those
patients who received intravenous infusion (n=3048).

At the higher dose of 2 g q8h, the incidence of probably-related adverse
events was higher among the 795 patients who received this dose of
cefepime. They consisted of rash (4%), diarrhea (3%), nausea (2%),
vomiting (1%), pruritus (1%), fever (1%), and headache (1%).

The following adverse laboratory changes, irrespective of relationship
to therapy with cefepime, were seen during clinical trials conducted in
North America.

**Table 10: Adverse Laboratory Changes**

**Cefepime Multiple-Dose Dosing Regimens**

**Clinical Trials -- North America**

  ----------------------------------- -----------------------------------
  INCIDENCE EQUAL TO OR GREATER THAN  Positive Coombs' test (without
  1%                                  hemolysis) (16.2%); decreased
                                      phosphorus (2.8%); increased
                                      ALT/SGPT (2.8%), AST/SGOT (2.4%),
                                      eosinophils (1.7%); abnormal PTT
                                      (1.6%), PT (1.4%)

  INCIDENCE LESS THAN 1% BUT GREATER  Increased alkaline phosphatase,
  THAN 0.1%                           BUN, calcium, creatinine,
                                      phosphorus, potassium, total
                                      bilirubin; decreased calcium\*,
                                      hematocrit, neutrophils, platelets,
                                      WBC
  ----------------------------------- -----------------------------------

\* Hypocalcemia was more common among elderly patients. Clinical
consequences from changes in either calcium or phosphorus were not
reported.

A similar safety profile was seen in clinical trials of pediatric
patients (see **PRECAUTIONS: Pediatric Use**).

**Postmarketing Experience**

In addition to the events reported during North American clinical trials
with cefepime, the following adverse experiences have been reported
during worldwide postmarketing experience.

> As with some other drugs in this class, encephalopathy (disturbance of
> consciousness including confusion, hallucinations, stupor, and coma),
> myoclonus, and seizures have been reported. Although most cases
> occurred in patients with renal impairment who received doses of
> cefepime that exceeded the recommended dosage schedules, some cases of
> encephalopathy occurred in patients receiving a dosage adjustment for
> their renal function. (See also **WARNINGS**.) If seizures associated
> with drug therapy occur, the drug should be discontinued.
> Anticonvulsant therapy can be given if clinically indicated.
> Precautions should be taken to adjust daily dosage in patients with
> renal insufficiency or other conditions that may compromise renal
> function to reduce antibiotic concentrations that can lead or
> contribute to these and other serious adverse events, including renal
> failure.

As with other cephalosporins, anaphylaxis including anaphylactic shock,
transient leukopenia, neutropenia, agranulocytosis and thrombocytopenia
have been reported.

**Cephalosporin-class Adverse Reactions**

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 antibiotics:

Stevens-Johnson syndrome, erythematic multiforme, toxic epidermal
necrolysis, renal dysfunction, toxic nephropathy, aplastic anemia,
hemolytic anemia, hemorrhage, hepatic dysfunction including cholestasis,
and pancytopenia.

**OVERDOSAGE**

Patients who receive an overdose should be carefully observed and given
supportive treatment. In the presence of renal insufficiency,
hemodialysis, not peritoneal dialysis, is recommended to aid in the
removal of cefepime from the body. Accidental overdosing has occurred
when large doses were given to patients with impaired renal function.
Symptoms of overdose include encephalopathy (disturbance of
consciousness including confusion, hallucinations, stupor, and coma),
myoclonus, seizures, and neuromuscular excitability. (See **WARNINGS**,
**ADVERSE REACTIONS**, and **DOSAGE** **AND ADMINISTRATION**.)

**DOSAGE AND ADMINISTRATION**

The recommended adult and pediatric dosages and routes of administration
are outlined in the following table. Cefepime for Injection should be
administered intravenously over approximately 30 minutes.

**Table 11: Recommended Dosage Schedule for Cefepime for Injection in
Patients with CrCL \>60 mL/min**

  ------------------------------------------ ---------- --------------- -------------
  **Site and Type of Infection**             **Dose**   **Frequency**   **Duration\
                                                                        (days)**

  **Adults**                                                            

  **Moderate to Severe** Pneumonia due to    1-2 g IV   q12h            10
  *S. pneumoniae*\*, *P. aeruginosa*, *K.                               
  pneumoniae*, or *Enterobacter* species                                

  Empiric therapy for febrile neutropenic    2 g IV     q8h             7\*\*
  patients (See **INDICATIONS AND USAGE**                               
  and **CLINICAL STUDIES**.)                                            

  **Mild to Moderate** Uncomplicated or      0.5-1 g IV q12h            7-10
  Complicated Urinary Tract Infections,                                 
  including pyelonephritis, due to *E.                                  
  coli*, *K. pneumoniae*, or *P.                                        
  mirabilis*\*                                                          

  **Severe** Uncomplicated or Complicated    2 g IV     q12h            10
  Urinary Tract Infections, including                                   
  pyelonephritis, due to *E. coli* or                                   
  *K. pneumoniae*\*                                                     

  **Moderate to Severe** Uncomplicated Skin  2 g IV     q12h            10
  and Skin Structure Infections due to *S.                              
  aureus* or *S. pyogenes*                                              

  **Complicated Intra-abdominal Infections** 2 g IV     q12h            7-10
  (used in combination with metronidazole)                              
  caused by *E. coli*, viridans group                                   
  streptococci, *P. aeruginosa*, *K.                                    
  pneumoniae*, *Enterobacter* species, or                               
  *B. fragilis* (See **CLINICAL**                                       
  **STUDIES**.)                                                         

  **Pediatric Patients (2 months up to 16                               
  years)**\                                                             
  The maximum dose for pediatric patients                               
  should not exceed the recommended adult                               
  dose. The usual recommended dosage in                                 
  pediatric patients up to 40 kg in weight                              
  for uncomplicated and complicated urinary                             
  tract infections (including                                           
  pyelonephritis), uncomplicated skin and                               
  skin structure infections, and pneumonia                              
  is 50 mg/kg/dose, administered q12h (50                               
  mg/kg/dose, q8h for febrile neutropenic                               
  patients), for durations as given above.                              
  ------------------------------------------ ---------- --------------- -------------

\* including cases associated with concurrent bacteremia

\*\* or until resolution of neutropenia. In patients whose fever
resolves but who remain neutropenic for more than 7 days, the need for
continued antimicrobial therapy should be re-evaluated frequently.

**Impaired Hepatic Function**

No adjustment is necessary for patients with impaired hepatic function.

**Impaired Renal Function**

In patients with impaired renal function (creatinine clearance
[\<]{.underline}60 mL/min), the dose of Cefepime for Injection should be
adjusted to compensate for the slower rate of renal elimination. The
recommended initial dose of Cefepime for Injection should be the same as
in patients with normal renal function except in patients undergoing
hemodialysis. The recommended doses of Cefepime for Injection in
patients with renal insufficiency are presented in Table 12.

When only serum creatinine is available, the following formula
(Cockcroft and Gault equation)^3^ may be used to estimate creatinine
clearance. The serum creatinine should represent a steady state of renal
function:

Males: Creatinine Clearance (mL/min) = Weight (kg) x (140-age)

72 x serum creatinine (mg/dL)

Females: 0.85 x above value

**Table 12: Recommended Dosing Schedule for Cefepime for Injection in
Adult Patients (Normal Renal Function, Renal Insufficiency, and
Hemodialysis)**

  ---------------- --------------- -------------- -------------- --------------
  **Creatinine     **Recommended                                 
  Clearance        Maintenance                                   
  (mL/min)**       Schedule**                                    

  \>60 Normal      500 mg q12h     1 g q12h       2 g q12h       2 g q8h
  recommended                                                    
  dosing schedule                                                

  30-60            500 mg q24h     1 g q24h       2 g q24h       2 g q12h

  11-29            500 mg q24h     500 mg q24h    1 g q24h       2 g q24h

  \<11             250 mg q24h     250 mg q24h    500 mg q24h    1 g q24h

  CAPD             500 mg q48h     1 g q48h       2 g q48h       2 g q48h

  Hemodialysis\*   1 g on day 1,                                 1 g q24h
                   then 500 mg                                   
                   q24h thereafter                               

  \* On                                                          
  hemodialysis                                                   
  days, cefepime                                                 
  should be                                                      
  administered                                                   
  following                                                      
  hemodialysis.                                                  
  Whenever                                                       
  possible,                                                      
  cefepime should                                                
  be administered                                                
  at the same time                                               
  each day.                                                      
  ---------------- --------------- -------------- -------------- --------------

In patients undergoing continuous ambulatory peritoneal dialysis,
Cefepime for Injection may be administered at normally recommended doses
at a dosage interval of every 48 hours (see Table 12).

In patients undergoing hemodialysis, approximately 68% of the total
amount of cefepime present in the body at the start of dialysis will be
removed during a 3-hour dialysis period. The dosage of Cefepime for
Injection for hemodialysis patients is 1 g on Day 1 followed by 500 mg
q24h for the treatment of all infections except febrile neutropenia,
which is 1 g q24h. Cefepime for Injection should be administered at the
same time each day and following the completion of hemodialysis on
hemodialysis days (see Table 12).

Data in pediatric patients with impaired renal function are not
available; however, since cefepime pharmacokinetics are similar in
adults and pediatric patients (see **CLINICAL PHARMACOLOGY**), changes
in the dosing regimen proportional to those in adults (see Tables 11 and
12) are recommended for pediatric patients.

**Administration:**

This reconstituted solution is for intravenous use only.

Parenteral drug products should be inspected visually for particulate
matter and discoloration prior to administration whenever solution and
container permit.

CAUTION: Do not use plastic containers in series connections. Such use
would result in air embolism due to residual air being drawn from the
primary container before administration of the fluid from the secondary
container is complete.

Cefepime for Injection may be administered through the tubing system by
which the patient may be receiving other intravenous solutions. However,
during infusion of the solution containing Cefepime for Injection, it is
advisable to temporarily discontinue administration of any other
solutions at the same site.

Solutions of Cefepime for Injection, like those of most beta-lactam
antibiotics, should not be added to solutions of ampicillin at
concentration greater than 40 mg/mL, and should not be added to
metronidazole, vancomycin, gentamicin, tobramycin, netilmicin sulfate or
aminophylline because of potential interaction. However, if concurrent
therapy with Cefepime for Injection is indicated, each of these
antibiotics can be administered separately.

As with other cephalosporins, the color of Cefepime for Injection
powder, as well as its solutions, tend to darken depending on storage
conditions; however, when stored as recommended, the product potency is
not adversely affected.

**Directions for Use of the DUPLEX® Drug Delivery System**

-   To avoid inadvertent activation, the DUPLEX Container should remain
    in the folded position until activation is intended.

**Patient Labeling and Drug Powder/Diluent Inspection**

-   ![](media/image2.wmf){width="1.5in" height="2.5in"}Apply
    patient-specific label on foil side of container. USE CARE\
    to avoid activation. Do not cover any portion of foil strip with\
    patient label.

-   Unlatch side tab and unfold DUPLEX Container.\
    (See Diagram 1.)

-   Visually inspect diluent chamber for particulate matter.

-   Use only if container and seals are intact.

-   To inspect the drug powder for foreign matter or discoloration,\
    peel foil strip from drug chamber. (See Diagram 2.)

-   Protect from light after removal of foil strip.

> ![](media/image3.wmf){width="1.5in"
> height="2.3201388888888888in"}**Note: If foil strip is removed,
> product must be used within\
> 7 days, but not beyond the labeled expiration date.**

-   The product should be re-folded and the side tab latched until\
    ready to activate.

**Reconstitution (Activation)**

-   Do not use directly after storage by refrigeration, allow the\
    product to equilibrate to room temperature before patient use.

-   ![](media/image4.wmf){width="1.5in"
    height="2.3756944444444446in"}Unfold the DUPLEX container and point
    the set port in a\
    downward direction. Starting at the hanger tab end, fold the DUPLEX
    Container just below the diluent meniscus trapping\
    all air above the fold. To activate, squeeze the folded diluent
    chamber until the seal between the diluent and powder opens,
    releasing diluent into the drug powder chamber.\
    (See Diagram 3.)

-   Agitate the liquid-powder mixture until the drug powder is\
    completely dissolved.

> ![](media/image5.wmf){width="1.5in"
> height="2.2958333333333334in"}**Note: Following reconstitution
> ([activation]{.underline}), product\
> must be used within 24 hours if stored at room\
> temperature or within 7 days if stored under\
> refrigeration.**

**Administration**

-   Visually inspect the reconstituted solution for particulate matter.

-   Point the set port in a downwards direction. Starting at the\
    hanger tab end, fold the DUPLEX Container just below the\
    solution meniscus trapping all air above the fold. Squeeze the\
    folded DUPLEX Container until the seal between reconstituted drug
    solution and set port opens, releasing liquid to set port.\
    (See Diagram 4.)

-   Prior to attaching the IV set, check for minute leaks by squeezing
    container firmly.\
    If leaks are found, discard container and solution as sterility may
    be impaired.

-   Using aseptic technique, remove the set port cover from the set port
    and attach sterile administration set.

-   Refer to Directions for Use accompanying the administration set.

**Precautions**

-   As with other cephalosporins, reconstituted Cefepime for Injection
    tends to darken depending on storage conditions, within the stated
    recommendations. However, product potency is not adversely affected.

-   Use only if prepared solution is clear and free from particulate
    matter.

-   Do not use in series connection.

-   Do not introduce additives into the DUPLEX Container.

-   Do not freeze.

**HOW SUPPLIED**

Cefepime for Injection in the DUPLEX® Drug Delivery System is a flexible
dual chamber container supplied in two concentrations. After
reconstitution, the concentrations are equivalent to 1 g and 2 g
cefepime. The diluent chamber contains approximately 50 mL of Dextrose
Injection. Dextrose Injection has been adjusted to 3.74% and 2.22% for
the 1 g and 2 g doses, respectively, such that the reconstituted
solution is iso-osmotic.

Cefepime for Injection is supplied sterile and nonpyrogenic in the
DUPLEX Drug Delivery System Containers packaged 24 units per case.

  ------------------------------- -------------- ---------- ---------------
  **NDC**                         **Cat. No.**   **Dose**   **Volume**

  Cefepime for Injection                                    

  0264-3193-11                    3193-11        1 g        50 mL

  Cefepime for Injection                                    

  0264-3195-11                    3195-11        2 g        50 mL
  ------------------------------- -------------- ---------- ---------------

**Storage**

Store the unactivated unit at 20-25°C (68-77°F). Excursions permitted to
15-30°C (59-86°F).

**REFERENCES**

1.  National Committee for Clinical Laboratory Standards. *Methods for
    Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow
    Aerobically* -- Third Edition. Approved Standard NCCLS Document
    M7-A3, Vol. 13, No. 25, NCCLS, Villanova, PA, December 1993.

2.  National Committee for Clinical Laboratory Standards. *Performance
    Standards for Antimicrobial Disk Susceptibility Tests* -- Fifth
    Edition. Approved NCCLS Document M2-A5, Vol. 13, No. 24, NCCLS,
    Villanova, PA, December 1993.

3.  Cockcroft DW, Gault MH. Prediction of creatinine clearance from
    serum creatinine. *Nephron*. 1976; 16:32-41.

Clinitest® and Clinistix® are registered trademarks of Bayer HealthCare
LLC.

DUPLEX is a registered trademark of B. Braun Medical Inc.

U.S. Patent Nos. D388,168, D397,789, D402,366, D407,816, 5,944,709, and
6,165,161.

Made in USA

Issued: xxxx

![](media/image6.wmf){width="3.4993055555555554in"
height="0.9458333333333333in"}