FDA Approves New Indication for INVANZ(R) (ertapenem) for the Treatment of Moderate to Severe Complicated Foot Infection in Diabetic Patients without Osteomyelitis

Merck & Co., Inc. announced today that the U.S. Food andDrug Administration (FDA) has approved INVANZ(R) (ertapenem), aonce-daily injectable antibiotic, for the treatment of moderate tosevere complicated foot infection due to indicated pathogens indiabetic patients without osteomyelitis. The approval was based on theresults of the SIDESTEP study, the largest prospective, randomized anddouble-blind clinical trial ever conducted in diabetic patients withmoderate to severe complicated foot infection. Foot infectionscommonly occur in patients with diabetes and are known to be difficultto treat.

"Currently there are limited data available for helping cliniciansdecide on the most appropriate treatment for foot infections indiabetic patients," said Murray A. Abramson, M.D., M.P.H., medicaldirector, Clinical Development, Infectious Diseases and Oncology atMerck and Co., Inc, Horsham Pennsylvania. "The study supporting thisnew indication for INVANZ provides physicians with another provenoption in the treatment of diabetic foot infections."

INVANZ is indicated for the treatment of moderate to severecomplicated skin and skin structure infections including diabetic footinfections without osteomyelitis due to Staphylococcus aureus(methicillin susceptible isolates only), Streptococcus agalactiae,Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae,Proteus mirabilis, Bacteroides fragilis, Peptostreptococcus species,Porphyromonas asaccharolytica, or Prevotella bivia. INVANZ has notbeen studied in diabetic foot infections with concomitantosteomyelitis.

Appropriate specimens for bacteriological examination should beobtained in order to isolate and identify the causative organisms andto determine their susceptibility to ertapenem. Therapy with INVANZmay be initiated empirically before results of these tests are known;once results become available, antimicrobial therapy should beadjusted accordingly.

To reduce the development of drug-resistant bacteria and maintainthe effectiveness of INVANZ and other antibacterial drugs, INVANZshould be used only to treat or prevent infections that are proven orstrongly suspected to be caused by susceptible bacteria. When cultureand susceptibility information are available, they should beconsidered in selecting or modifying antibacterial therapy. In theabsence of such data, local epidemiology and susceptibility patternsmay contribute to the empiric selection of therapy.

INVANZ is contraindicated in patients with known hypersensitivityto any component of this product or to other drugs in the same classor in patients who have demonstrated anaphylactic reactions tobeta-lactams. Due to the use of lidocaine HCl as a diluent, INVANZadministered intramuscularly is contraindicated in patients with knownhypersensitivity to local anesthetics of the amide type. Serious andoccasionally fatal hypersensitivity (anaphylactic) reactions have beenreported in patients receiving therapy with beta-lactams.

New indication based on the SIDESTEP study, the largest trialconducted to date in diabetic patients with moderate to severecomplicated foot infections without osteomyelitis

The SIDESTEP study, a randomized, double-blind, multi-center trialconducted in adult patients, was designed to determine if INVANZ wasat least as clinically effective as piperacillin/tazobactam in thetreatment of foot infection in patients with diabetes. Patients withosteomyelitis (bone infection usually caused by bacteria) were notstudied in this patient population.

In the SIDESTEP study, 586 patients were randomized into twotreatment groups to receive intravenously either INVANZ 1 g once daily(n=295) or piperacillin/tazobactam 3.375 g every six hours (n=291) fora minimum of five days with the option to switch to oralamoxicillin/clavulanate for a total of five to 28 days of treatment(parenteral and oral). Patients were evaluated by their clinicalresponse between treatment groups at the 10-day post therapy follow upvisit. All patients were eligible to receive appropriate adjunctivetreatment methods, such as debridement, as is typically required inthe treatment of diabetic foot infections, and most patients receivedthese treatments. Investigators had the option to add open-labelvancomycin if enterococci or methicillin-resistant Staphylococcusaureus (MRSA) were among the pathogens isolated or if patients had ahistory of MRSA infection and additional therapy was indicated in theopinion of the investigator. Of those patients that were described asevaluable (INVANZ n=204; and piperacillin/tazobactam n=202), 75.0percent of the patients taking INVANZ had a favorable clinicalresponse compared to 70.8 percent of the patients takingpiperacillin/tazobactam (CI=95%). Rates of favorable microbiologicalresponses and adverse events were also similar between the twotreatment groups. In this study, the adverse experiences for INVANZwere similar to those found in other clinical trials for INVANZ.

During clinical trials, the most common side effects in adultsrelated to treatment with INVANZ were diarrhea (5.5%), infused veincomplication (3.7%), nausea (3.1%), headache (2.2%), vaginitis infemales (2.1%), phlebitis/thrombophlebitis (1.3%), and vomiting(1.1%).

Pseudomembranous colitis has been reported with nearly allantibacterial agents, including INVANZ, and may range in severity frommild to life threatening.

About INVANZ

INVANZ, a carbapenem related to the class of antibiotics known asbeta-lactams, is generally given to adults as a 1-gram dose, once aday, by intravenous infusion or intramuscular injection. Dosageadjustment of INVANZ is required in diabetic patients with reducedrenal function (see prescribing information). INVANZ is also indicatedfor the treatment of adults and pediatric patients over three monthsof age for the following moderate to severe infections caused bysusceptible isolates of the designated pathogens:

-- Complicated intra-abdominal infections: Due to Escherichia coli, Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus species, Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis.

-- Complicated skin and skin structure infections including diabetic foot infections without osteomyelitis: Due to Staphylococcus aureus (methicillin susceptible isolates only), Streptococcus agalactiae, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Bacteroides fragilis, Peptostreptococcus species, Porphyromonas asaccharolytica, or Prevotella bivia.

-- Community-acquired pneumonia: Due to Streptococcus pneumoniae (penicillin susceptible isolates only) including cases with concurrent bacteremia, Haemophilus influenzae (beta-lactamase negative isolates only), or Moraxella catarrhalis.

-- Complicated urinary tract infections, including pyelonephritis (kidney infections): Due to Escherichia coli, including cases with concurrent bacteremia, or Klebsiella pneumoniae.

-- And acute pelvic infections, including postpartum endomyometritis, septic abortion and post-surgical gynecologic infections: Due to Streptococcus agalactiae, Escherichia coli, Bacteroides fragilis, Porphyromonas asaccharolytica, Peptostreptococcus species, or Prevotella bivia.

Seizures and other central nervous system (CNS) adverseexperiences have been reported during treatment with INVANZ. Duringclinical investigations in adult patients treated with INVANZ (1 gonce a day), seizures, irrespective of drug relationship, occurred in0.5% of patients during study therapy plus 14-day follow-up period.These experiences have occurred most commonly in patients with CNSdisorders (e.g., brain lesions or history of seizures) and/orcompromised renal function. Close adherence to the recommended dosageregimen is urged, especially in patients with known factors thatpredispose to convulsive activity.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceuticalcompany dedicated to putting patients first. Established in 1891,Merck discovers, develops, manufactures and markets vaccines andmedicines in more than 20 therapeutic categories. The company devotesextensive efforts to increase access to medicines through far-reachingprograms that not only donate Merck medicines but help deliver them tothe people who need them. Merck also published unbiased healthinformation as a not-for-profit service. For more information, visitwww.merck.com.

Forward-Looking Statement

This press release contains "forward-looking statements" as thatterm is defined in the Private Securities Litigation Reform Act of1995. These statements involve risks and uncertainties, which maycause results to differ materially from those set forth in thestatements. The forward-looking statements may include statementsregarding product development, product potential or financialperformance. No forward-looking statement can be guaranteed, andactual results may differ materially from those projected. Merckundertakes no obligation to publicly update any forward-lookingstatement, whether as a result of new information, future events, orotherwise. Forward-looking statements in this press release should beevaluated together with the many uncertainties that affect Merck'sbusiness, particularly those mentioned in the cautionary statements inItem 1 of Merck's Form 10-K for the year ended Dec. 31, 2004, and inits periodic reports on Form 10-Q and Form 8-K, which the companyincorporates by reference.

Full prescribing information for INVANZ is attached.

INVANZ is a registered trademark of Merck & Co., Inc. All otherbrands are trademarks of their respective owners and are nottrademarks of Merck & Co., Inc.
INVANZ(R) 9671406
(ERTAPENEM FOR INJECTION)

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

For Intravenous or Intramuscular Use

DESCRIPTION

INVANZ**(C) (Ertapenem for Injection) is a sterile, synthetic,
parenteral, 1-(beta) methyl-carbapenem that is structurally related to
beta-lactam antibiotics.
Chemically, INVANZ is described as
(4R-(3(3S*,5S*),4(alpha),5(beta),6(beta)(R*)))-3-((5-(((3-carboxypheny
l)amino)carbonyl)-3-pyrrolidinyl)thio)-6-(1-hydroxyethyl)-4-methyl-7-o
xo-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylic
acid monosodium salt. Its molecular weight is 497.50. The empirical
formula is C22H24N3O7SNa, and its structural formula is:

(GRAPHIC OMITTED)

Ertapenem sodium is a white to off-white hygroscopic, weakly
crystalline powder. It is soluble in water and 0.9% sodium chloride
solution, practically insoluble in ethanol, and insoluble in isopropyl
acetate and tetrahydrofuran.
INVANZ is supplied as sterile lyophilized powder for intravenous
infusion after reconstitution with appropriate diluent (see DOSAGE AND
ADMINISTRATION, PREPARATION OF SOLUTION) and transfer to 50 mL 0.9%
Sodium Chloride Injection or for intramuscular injection following
reconstitution with 1% lidocaine hydrochloride. Each vial contains
1.046 grams ertapenem sodium, equivalent to 1 gram ertapenem. The
sodium content is approximately 137 mg (approximately 6.0 mEq).
Each vial of INVANZ contains the following inactive ingredients:
175 mg sodium bicarbonate and sodium hydroxide to adjust pH to 7.5.

CLINICAL PHARMACOLOGY

Pharmacokinetics

Average plasma concentrations (mcg/mL) of ertapenem following a
single 30-minute infusion of a 1 g intravenous (IV) dose and
administration of a single 1 g intramuscular (IM) dose in healthy
young adults are presented in Table 1.


Table 1
Plasma Concentrations of Ertapenem in Adults After Single Dose
Administration
--------------------------------------------------------------------
Average Plasma Concentrations (mcg/mL)
Dose/Route 0.5 1 hr 2 hr 4 hr 6 hr 8 hr 12 hr 18 hr 24 hr
hr
--------------------------------------------------------------------
1 g IV* 155 115 83 48 31 20 9 3 1
1 g IM 33 53 67 57 40 27 13 4 2

*Infused at a constant rate over 30 minutes
--------------------------------------------------------------------

The area under the plasma concentration-time curve (AUC) of
ertapenem in adults increased less-than dose-proportional based on
total ertapenem concentrations over the 0.5 to 2 g dose range, whereas
the AUC increased greater-than dose proportional based on unbound
ertapenem concentrations. Ertapenem exhibits non-linear
pharmacokinetics due to concentration-dependent plasma protein binding
at the proposed therapeutic dose. (See CLINICAL PHARMACOLOGY,
Distribution.)
There is no accumulation of ertapenem following multiple IV or IM
1 g daily doses in healthy adults.
Average plasma concentrations (mcg/mL) of ertapenem in pediatric
patients are presented in Table 2.


Table 2
Plasma Concentrations of Ertapenem in Pediatric Patients After Single
IV* Dose Administration
----------------------------------------------------------------------
Age Group Dose Average Plasma Concentrations (mcg/mL)
----------------------------------------------------------------------
0.5 hr 1 hr 2 hr 4 hr 6 hr 8 hr 12 hr 24 hr
----------------------------------------------------------------------
3 to 23 15
months mg/kg+
20
mg/kg+ 103.8 57.3 43.6 23.7 13.5 8.2 2.5 -
40 126.8 87.6 58.7 28.4 - 12.0 3.4 0.4
mg/kg++ 199.1 144.1 95.7 58.0 - 20.2 7.7 0.6
----------------------------------------------------------------------
2 to 12
years 15
mg/kg+
20
mg/kg+ 113.2 63.9 42.1 21.9 12.8 7.6 3.0 -
40 147.6 97.6 63.2 34.5 - 12.3 4.9 0.5
mg/kg++ 241.7 152.7 96.3 55.6 - 18.8 7.2 0.6
----------------------------------------------------------------------
13 to 17 20
years mg/kg+
1 gss. 170.4 98.3 67.8 40.4 - 16.0 7.0 1.1
40 155.9 110.9 74.8 - 24.0 - 6.2 -
mg/kg++ 255.0 188.7 127.9 76.2 - 31.0 15.3 2.1
----------------------------------------------------------------------
* Infused at a constant rate over 30 minutes
+ up to a maximum dose of 1 g/day
++ up to a maximum dose of 2 g/day
ss. Based on three patients receiving 1 g ertapenem who volunteered
for pharmacokinetic assessment in one of the two safety and efficacy
studies
----------------------------------------------------------------------

Absorption

Ertapenem, reconstituted with 1% lidocaine HCl injection, USP (in
saline without epinephrine), is almost completely absorbed following
intramuscular (IM) administration at the recommended dose of 1 g. The
mean bioavailability is approximately 90%. Following 1 g daily IM
administration, mean peak plasma concentrations (Cmax) are achieved in
approximately 2.3 hours (Tmax).

Distribution

Ertapenem is highly bound to human plasma proteins, primarily
albumin. In healthy young adults, the protein binding of ertapenem
decreases as plasma concentrations increase, from approximately 95%
bound at an approximate plasma concentration of less than 100
micrograms (mcg)/mL to approximately 85% bound at an approximate
plasma concentration of 300 mcg/mL. The apparent volume of
distribution at steady state (Vss) of ertapenem in adults is
approximately 0.12 liter/kg, approximately 0.2 liter/kg in pediatric
patients 3 months to 12 years of age and approximately 0.16 liter/kg
in pediatric patients 13 to 17 years of age. The concentrations of
ertapenem achieved in suction-induced skin blister fluid at each
sampling point on the third day of 1 g once daily IV doses are
presented in Table 3. The ratio of AUC0-24 in skin blister
fluid/AUC0-24 in plasma is 0.61.

Table 3
Concentrations (mcg/mL) of Ertapenem in Adult
Skin Blister Fluid at each Sampling Point on
the Third Day of 1-g Once Daily IV Doses
------------------------------------------------
0.5 hr 1 hr 2 hr 4 hr 8 hr 12 hr 24 hr
------------------------------------------------
7 12 17 24 24 21 8

The concentration of ertapenem in breast milk from 5 lactating
women with pelvic infections (5 to 14 days postpartum) was measured at
random time points daily for 5 consecutive days following the last 1 g
dose of intravenous therapy (3-10 days of therapy). The concentration
of ertapenem in breast milk within 24 hours of the last dose of
therapy in all 5 women ranged from less than 0.13 (lower limit of
quantitation) to 0.38 mcg/mL; peak concentrations were not assessed.
By day 5 after discontinuation of therapy, the level of ertapenem was
undetectable in the breast milk of 4 women and below the lower limit
of quantitation (less than 0.13 mcg/mL) in 1 woman.

Metabolism

In healthy young adults, after infusion of 1 g IV radiolabeled
ertapenem, the plasma radioactivity consists predominantly (94%) of
ertapenem. The major metabolite of ertapenem is the inactive
ring-opened derivative formed by hydrolysis of the beta-lactam ring.
In vitro studies in human liver microsomes indicate that ertapenem
does not inhibit metabolism mediated by any of the following
cytochrome p450 (CYP) isoforms: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. (See
DRUG INTERACTIONS.)
In vitro studies indicate that ertapenem does not inhibit
P-glycoprotein-mediated transport of digoxin or vinblastine and that
ertapenem is not a substrate for P-glycoprotein-mediated transport.
(See PRECAUTIONS, Drug Interactions.)

Elimination

Ertapenem is eliminated primarily by the kidneys. The mean plasma
half-life in healthy young adults is approximately 4 hours and the
plasma clearance is approximately 1.8 L/hour. The mean plasma
half-life in pediatric patients 13 to 17 years of age is approximately
4 hours and approximately 2.5 hours in pediatric patients 3 months to
12 years of age.
Following the administration of 1 g IV radiolabeled ertapenem to
healthy young adults, approximately 80% is recovered in urine and 10%
in feces. Of the 80% recovered in urine, approximately 38% is excreted
as unchanged drug and approximately 37% as the ring-opened metabolite.
In healthy young adults given a 1 g IV dose, the mean percentage
of the administered dose excreted in urine was 17.4% during 0-2 hours
postdose, 5.4% during 4-6 hours postdose, and 2.4% during 12-24 hours
postdose.

Special Populations

Renal Insufficiency

Total and unbound fractions of ertapenem pharmacokinetics were
investigated in 26 adult subjects (31 to 80 years of age) with varying
degrees of renal impairment. Following a single 1 g IV dose of
ertapenem, the unbound AUC increased 1.5-fold and 2.3-fold in subjects
with mild renal insufficiency (CLCR 60-90 mL/min/1.73 m2) and moderate
renal insufficiency (CLCR 31-59 mL/min/1.73 m2), respectively,
compared with healthy young subjects (25 to 45 years of age). No
dosage adjustment is necessary in patients with CLCR (greater than or
equal to)31 mL/min/1.73 m2. The unbound AUC increased 4.4-fold and
7.6-fold in subjects with advanced renal insufficiency (CLCR 5-30
mL/min/1.73 m2) and end-stage renal insufficiency (CLCR less than 10
mL/min/1.73 m2), respectively, compared with healthy young subjects.
The effects of renal insufficiency on AUC of total drug were of
smaller magnitude. The recommended dose of ertapenem in adult patients
with CLCR (less than or equal to)30 mL/min/1.73 m2 is 0.5 grams every
24 hours. Following a single 1 g IV dose given immediately prior to a
4 hour hemodialysis session in 5 adult patients with end-stage renal
insufficiency, approximately 30% of the dose was recovered in the
dialysate. A supplementary dose of 150 mg is recommended if ertapenem
is administered within 6 hours prior to hemodialysis. (See DOSAGE AND
ADMINISTRATION.) There are no data in pediatric patients with renal
insufficiency.

Hepatic Insufficiency

The pharmacokinetics of ertapenem in patients with hepatic
insufficiency have not been established. However, ertapenem does not
appear to undergo hepatic metabolism based on in vitro studies and
approximately 10% of an administered dose is recovered in the feces.
(See PRECAUTIONS and DOSAGE AND ADMINISTRATION.)

Gender

The effect of gender on the pharmacokinetics of ertapenem was
evaluated in healthy male (n=8) and healthy female (n=8) subjects. The
differences observed could be attributed to body size when body weight
was taken into consideration. No dose adjustment is recommended based
on gender.

Geriatric Patients

The impact of age on the pharmacokinetics of ertapenem was
evaluated in healthy male (n=7) and healthy female (n=7) subjects
(greater than or equal to )65 years of age. The total and unbound AUC
increased 37% and 67%, respectively, in elderly adults relative to
young adults. These changes were attributed to age-related changes in
creatinine clearance. No dosage adjustment is necessary for elderly
patients with normal (for their age) renal function.

Pediatric Patients

Plasma concentrations of ertapenem are comparable in pediatric
patients 13 to 17 years of age and adults following a 1 g once daily
IV dose.
Following the 20 mg/kg dose (up to a maximum dose of 1 g), the
pharmacokinetic parameter values in patients 13 to 17 years of age
(N=6) were generally comparable to those in healthy young adults.
Plasma concentrations at the midpoint of the dosing interval
following a single 15 mg/kg IV dose of ertapenem in patients 3 months
to 12 years of age are comparable to plasma concentrations at the
midpoint of the dosing interval following a 1 g once daily IV dose in
adults (see Pharmacokinetics). The plasma clearance (mL/min/kg) of
ertapenem in patients 3 months to 12 years of age is approximately
2-fold higher as compared to that in adults. At the 15 mg/kg dose, the
AUC value (doubled to model a twice daily dosing regimen, i.e., 30
mg/kg/day exposure) in patients 3 months to 12 years of age was
comparable to the AUC value in young healthy adults receiving a 1 g IV
dose of ertapenem.

Microbiology

Ertapenem has in vitro activity against gram-positive and
gram-negative aerobic and anaerobic bacteria. The bactericidal
activity of ertapenem results from the inhibition of cell wall
synthesis and is mediated through ertapenem binding to penicillin
binding proteins (PBPs). In Escherichia coli, it has strong affinity
toward PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3.
Ertapenem is stable against hydrolysis by a variety of
beta-lactamases, including penicillinases, and cephalosporinases and
extended spectrum beta-lactamases. Ertapenem is hydrolyzed by
metallo-beta-lactamases.
Ertapenem has been shown to be active against most isolates of the
following microorganisms in vitro and in clinical infections. (See
INDICATIONS AND USAGE):

Aerobic and facultative gram-positive microorganisms:

Staphylococcus aureus (methicillin susceptible isolates only)

Streptococcus agalactiae

Streptococcus pneumoniae (penicillin susceptible isolates only)

Streptococcus pyogenes

Note: Methicillin-resistant staphylococci and Enterococcus spp.
are resistant to ertapenem.

Aerobic and facultative gram-negative microorganisms:

Escherichia coli

Haemophilus influenzae (Beta-lactamase negative isolates only)

Klebsiella pneumoniae

Moraxella catarrhalis

Proteus mirabilis

Anaerobic microorganisms:

Bacteroides fragilis

Bacteroides distasonis

Bacteroides ovatus

Bacteroides thetaiotaomicron

Bacteroides uniformis

Clostridium clostridioforme

Eubacterium lentum

Peptostreptococcus species

Porphyromonas asaccharolytica

Prevotella bivia

The following in vitro data are available, but their clinical
significance is unknown.
At least 90% of the following microorganisms exhibit an in vitro
minimum inhibitory concentration (MIC) less than or equal to the
susceptible breakpoint for ertapenem; however, the safety and
effectiveness of ertapenem in treating clinical infections due to
these microorganisms have not been established in adequate and
well-controlled clinical studies:

Aerobic and facultative gram-positive microorganisms:

Staphylococcus epidermidis (methicillin susceptible isolates only)

Streptococcus pneumoniae (penicillin-intermediate isolates only)

Aerobic and facultative gram-negative microorganisms:

Citrobacter freundii

Citrobacter koseri

Enterobacter aerogenes

Enterobacter cloacae

Haemophilus influenzae (Beta-lactamase positive isolates)

Haemophilus parainfluenzae

Klebsiella oxytoca (excluding ESBL producing isolates)

Morganella morganii

Proteus vulgaris

Providencia rettgeri

Providencia stuartii

Serratia marcescens

Anaerobic microorganisms:

Bacteroides vulgatus

Clostridium perfringens

Fusobacterium spp.

Susceptibility Tests Methods:

When available, the results of in vitro susceptibility tests
should be provided to the physician as periodic reports which describe
the susceptibility profile of nosocomial and community-acquired
pathogens. These reports should aid the physician in selecting the
most effective antimicrobial.

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 broth dilution method1,2 or equivalent with
standardized inoculum concentrations and standardized concentrations
of ertapenem powder. The MIC values should be interpreted according to
criteria provided in Table 4.

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(2,3)
requires the use of standardized inoculum concentrations. This
procedure uses paper disks impregnated with 10-(mu)g ertapenem to test
the susceptibility of microorganisms to ertapenem. The disk diffusion
interpretive criteria should be interpreted according to criteria
provided in Table 4.

Anaerobic Techniques:

For anaerobic bacteria, the susceptibility to ertapenem as MICs
can be determined by standardized test methods(4). The MIC values
obtained should be interpreted according to criteria provided in Table
4.

Registered trademark of MERCK & CO., Inc.

COPYRIGHT 2001, 2003, 2004 MERCK & CO., Inc.

All rights reserved

Table 4
Susceptibility Interpretive Criteria for Ertapenem
----------------------------------------------------------------------
Pathogen Minimum Inhibitory Disk Diffusion(a)
Concentrations(a) Zone Diameter (mm)
MIC ((mu)g/mL)
----------------------------------------------------------------------
S I R S I R
----------------------------------------------------------------------
Enterobacteriaceae (less (greater (greater (less
and than=)2.0 than=)8.0 than=)19 than=)15
Staphylococcus spp. 4.0 16-18
----------------------------------------------------------------------
Haemophilus spp. (less (greater
than=)0.5 - - than=)19 - -
----------------------------------------------------------------------
Streptococcus (less (greater
pneumoniae (b,c) than=)1.0 - - than=)19 - -
----------------------------------------------------------------------
Streptococcus spp. (less (greater
other than than=)1.0 than=)19
Streptococcus
pneumoniae( d,e) - - - -
----------------------------------------------------------------------
Anaerobes (less (greater
than=)4.08.0 than=)16.0 - - -
----------------------------------------------------------------------
(a) The current absence of data in resistant isolates precludes
defining any results other than "Susceptible". Isolates yielding MIC
results suggestive of a "Nonsusceptible" category should be
submitted to a reference laboratory for further testing.
(b) Streptococcus pneumoniae that are susceptible to penicillin
(penicillin MIC (less than =)0.06 (mu)g/mL) can be considered
susceptible to ertapenem. Testing of ertapenem against penicillin-
intermediate or penicillin-resistant isolates is not recommended
since reliable interpretive criteria for ertapenem are not
available.
(c) Streptococcus pneumoniae that are susceptible to penicillin (1-
(mu)g oxacillin disk zone diameter (greater than =)20 mm), can be
considered susceptible to ertapenem. Isolates with 1-(mu)g oxacillin
zone diameter (less than =)19 mm should be tested against ertapenem
using an MIC method.
(d) Streptococcus spp. other than Streptococcus pneumoniae that are
susceptible to penicillin (MIC (less than =)0.12 (mu)g/mL) can be
considered susceptible to ertapenem. Testing of ertapenem against
penicillin-intermediate or penicillin-resistant isolates is not
recommended since reliable interpretive criteria for ertapenem are
not available.
(e) Streptococcus spp. other than Streptococcus pneumoniae that are
susceptible to penicillin (10-units penicillin disk zone diameter
(greater than =)24 mm), can be considered susceptible to ertapenem.
Isolates with 10-units penicillin disk zone diameter less than 24 mm
should be tested against ertapenem using an MIC method. Penicillin
disk diffusion interpretive criteria are not available for viridans
group streptococci and they should not be tested against ertapenem.
----------------------------------------------------------------------

Note: Staphylococcus spp. can be considered susceptible to
ertapenem if the penicillin MIC is (less than or equal to)0.12
(mu)g/mL. If the penicillin MIC is greater than 0.12 (mu)g/mL, then
test oxacillin. Staphylococcus aureus can be considered susceptible to
ertapenem if the oxacillin MIC is (less than or equal to)2.0 (mu)g/mL
and resistant to ertapenem if the oxacillin MIC is (greater than or
equal to)4.0 (mu)g/mL. Coagulase negative staphylococci can be
considered susceptible to ertapenem if the oxacillin MIC is (less than
or equal to)0.25 (mu)g/mL and resistant to ertapenem if the oxacillin
MIC (greater than or equal to )0.5 (mu)g/mL. Staphylococcus spp. can
be considered susceptible to ertapenem if the penicillin (10 U disk)
zone is (greater than or equal to )29 mm. If the penicillin zone is
(less than or equal to)28 mm, then test oxacillin by disk diffusion (1
(mu)g disk). Staphylococcus aureus can be considered susceptible to
ertapenem if the oxacillin (1 (mu)g disk) zone is (greater than or
equal to)13 mm and resistant to ertapenem if the oxacillin zone is
(less than or equal to)10 mm. Coagulase negative staphylococci can be
considered susceptible to ertapenem if the oxacillin zone is (greater
than or equal to)18 mm and resistant to ertapenem if the oxacillin (1
(mu)g disk) zone is (less than or equal to)17 mm. A report of
"Susceptible" indicates that the pathogen is likely to be inhibited if
the antimicrobial compound in 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.

Quality Control

Standardized susceptibility test procedures require the use of
laboratory control microorganisms to control the technical aspects of
the laboratory procedures(1,2,3,4). Quality control microorganisms are
specific strains of organisms with intrinsic biological properties. QC
strains are very stable strains which will give a standard and
repeatable susceptibility pattern. The specific strains used for
microbiological quality control are not clinically significant.
Standard ertapenem powder should provide the following range of values
noted in Table 5.
Table 5
Acceptable Quality Control Ranges for Ertapenem
----------------------------------------------------------------------
Microorganism Minimum Disk
Inhibitory Diffusion
Concentrations Zone
MIC Range Diameter
((mu)g/mL) (mm)
----------------------------------------------------------------------
Escherichia coli ATCC 25922 0.004-0.016 29-36
----------------------------------------------------------------------
Haemophilus influenzae ATCC 49766 0.016-0.06 27-33
----------------------------------------------------------------------
Staphylococcus aureus ATCC 29213 0.06-0.25 -
----------------------------------------------------------------------
Staphylococcus aureus ATCC 25923 - 24-31
----------------------------------------------------------------------
Streptococcus pneumoniae ATCC 49619 0.03-0.25 28-35
----------------------------------------------------------------------
Bacteroides fragilis ATCC 25285 0.06-0.5(f)
0.06-0.25(g) -
----------------------------------------------------------------------
Bacteroides thetaiotaomicron ATCC 29741 0.5-2.0(f)
0.25-1.0(g) -
----------------------------------------------------------------------
Eubacterium lentum ATCC 43055 0.5-4.0(f)
0.5-2.0(g) -
----------------------------------------------------------------------
(f) Quality control ranges for broth microdilution testing
(g) Quality control ranges for agar microdilution testing
----------------------------------------------------------------------


INDICATIONS AND USAGE

INVANZ is indicated for the treatment of patients with the
following moderate to severe infections caused by susceptible isolates
of the designated microorganisms. (See DOSAGE AND ADMINISTRATION):
Complicated Intra-abdominal Infections due to Escherichia coli,
Clostridium clostridioforme, Eubacterium lentum, Peptostreptococcus
species, Bacteroides fragilis, Bacteroides distasonis, Bacteroides
ovatus, Bacteroides thetaiotaomicron, or Bacteroides uniformis.
Complicated Skin and Skin Structure Infections, including diabetic
foot infections without osteomyelitis due to Staphylococcus aureus
(methicillin susceptible isolates only), Streptococcus agalactiae,
Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae,
Proteus mirabilis, Bacteroides fragilis, Peptostreptococcus species,
Porphyromonas asaccharolytica, or Prevotella bivia. INVANZ has not
been studied in diabetic foot infections with concomitant
osteomyelitis (see CLINICAL STUDIES).
Community Acquired Pneumonia due to Streptococcus pneumoniae
(penicillin susceptible isolates only) including cases with concurrent
bacteremia, Haemophilus influenzae (beta-lactamase negative isolates
only), or Moraxella catarrhalis.
Complicated Urinary Tract Infections including pyelonephritis due
to Escherichia coli, including cases with concurrent bacteremia, or
Klebsiella pneumoniae.
Acute Pelvic Infections including postpartum endomyometritis,
septic abortion and post surgical gynecologic infections due to
Streptococcus agalactiae, Escherichia coli, Bacteroides fragilis,
Porphyromonas asaccharolytica, Peptostreptococcus species, or
Prevotella bivia.
Appropriate specimens for bacteriological examination should be
obtained in order to isolate and identify the causative organisms and
to determine their susceptibility to ertapenem. Therapy with INVANZ
(ertapenem) may be initiated empirically before results of these tests
are known; once results become available, antimicrobial therapy should
be adjusted accordingly.
To reduce the development of drug-resistant bacteria and maintain
the effectiveness of INVANZ and other antibacterial drugs, INVANZ
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.

CONTRAINDICATIONS

INVANZ is contraindicated in patients with known hypersensitivity
to any component of this product or to other drugs in the same class
or in patients who have demonstrated anaphylactic reactions to
beta-lactams.
Due to the use of lidocaine HCl as a diluent, INVANZ administered
intramuscularly is contraindicated in patients with a known
hypersensitivity to local anesthetics of the amide type. (Refer to the
prescribing information for lidocaine HCl.)

WARNINGS

SERIOUS AND OCCASIONALLY FATAL HYPERSENSITIVITY (ANAPHYLACTIC)
REACTIONS HAVE BEEN REPORTED IN PATIENTS RECEIVING THERAPY WITH
BETA-LACTAMS. THESE REACTIONS ARE MORE LIKELY TO OCCUR IN INDIVIDUALS
WITH A HISTORY OF SENSITIVITY TO MULTIPLE ALLERGENS. THERE HAVE BEEN
REPORTS OF INDIVIDUALS WITH A HISTORY OF PENICILLIN HYPERSENSITIVITY
WHO HAVE EXPERIENCED SEVERE HYPERSENSITIVITY REACTIONS WHEN TREATED
WITH ANOTHER BETA-LACTAM. BEFORE INITIATING THERAPY WITH INVANZ,
CAREFUL INQUIRY SHOULD BE MADE CONCERNING PREVIOUS HYPERSENSITIVITY
REACTIONS TO PENICILLINS, CEPHALOSPORINS, OTHER BETA-LACTAMS AND OTHER
ALLERGENS. IF AN ALLERGIC REACTION TO INVANZ OCCURS, DISCONTINUE THE
DRUG IMMEDIATELY. SERIOUS ANAPHYLACTIC REACTIONS REQUIRE IMMEDIATE
EMERGENCY TREATMENT WITH EPINEPHRINE, OXYGEN, INTRAVENOUS STEROIDS,
AND AIRWAY MANAGEMENT, INCLUDING INTUBATION. OTHER THERAPY MAY ALSO BE
ADMINISTERED AS INDICATED.
Seizures and other CNS adverse experiences have been reported
during treatment with INVANZ. (See PRECAUTIONS and ADVERSE REACTIONS.)
Pseudomembranous colitis has been reported with nearly all
antibacterial agents, including ertapenem, 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 pseudomembranous colitis has been
established, therapeutic measures should be initiated. Mild cases of
pseudomembranous 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.
Lidocaine HCl is the diluent for intramuscular administration of
INVANZ. Refer to the prescribing information for lidocaine HCl.

PRECAUTIONS

General

During clinical investigations in adult patients treated with
INVANZ (1 g once a day), seizures, irrespective of drug relationship,
occurred in 0.5% of patients during study therapy plus 14-day
follow-up period. (See ADVERSE REACTIONS.) These experiences have
occurred most commonly in patients with CNS disorders (e.g., brain
lesions or history of seizures) and/or compromised renal function.
Close adherence to the recommended dosage regimen is urged, especially
in patients with known factors that predispose to convulsive activity.
Anticonvulsant therapy should be continued in patients with known
seizure disorders. If focal tremors, myoclonus, or seizures occur,
patients should be evaluated neurologically, placed on anticonvulsant
therapy if not already instituted, and the dosage of INVANZ
re-examined to determine whether it should be decreased or the
antibiotic discontinued. Dosage adjustment of INVANZ is recommended in
patients with reduced renal function. (See DOSAGE AND ADMINISTRATION.)
As with other antibiotics, prolonged use of INVANZ may result in
overgrowth of non-susceptible organisms. Repeated evaluation of the
patient's condition is essential. If superinfection occurs during
therapy, appropriate measures should be taken.
Prescribing INVANZ in the absence of a 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.
Caution should be taken when administering INVANZ intramuscularly
to avoid inadvertent injection into a blood vessel. (See DOSAGE AND
ADMINISTRATION.)
Lidocaine HCl is the diluent for intramuscular administration of
INVANZ. Refer to the prescribing information for lidocaine HCl for
additional precautions.

Information for patients

Patients should be counseled that antibacterial drugs including
INVANZ should only be used to treat bacterial infections. They do not
treat viral infections (e.g., the common cold). When INVANZ 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 INVANZ or other antibacterial drugs in the future.

Laboratory Tests

While INVANZ possesses toxicity similar to the beta-lactam group
of antibiotics, periodic assessment of organ system function,
including renal, hepatic, and hematopoietic, is advisable during
prolonged therapy.

Drug Interactions

When ertapenem is co-administered with probenecid (500 mg p.o.
every 6 hours), probenecid competes for active tubular secretion and
reduces the renal clearance of ertapenem. Based on total ertapenem
concentrations, probenecid increased the AUC by 25% and reduced the
plasma and renal clearances by 20% and 35%, respectively. The
half-life increased from 4.0 to 4.8 hours. Because of the small effect
on half-life, the coadministration with probenecid to extend the
half-life of ertapenem is not recommended.
In vitro studies indicate that ertapenem does not inhibit
P-glycoprotein-mediated transport of digoxin or vinblastine and that
ertapenem is not a substrate for P-glycoprotein-mediated transport. In
vitro studies in human liver microsomes indicate that ertapenem does
not inhibit metabolism mediated by any of the following six cytochrome
p450 (CYP) isoforms: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. Drug
interactions caused by inhibition of P-glycoprotein-mediated drug
clearance or CYP-mediated drug clearance with the listed isoforms are
unlikely. (See CLINICAL PHARMACOLOGY, Distribution and Metabolism.)
Other than with probenecid, no specific clinical drug interaction
studies have been conducted.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies in animals have been performed to evaluate
the carcinogenic potential of ertapenem.
Ertapenem was neither mutagenic nor genotoxic in the following in
vitro assays: alkaline elution/rat hepatocyte assay, chromosomal
aberration assay in Chinese hamster ovary cells, and TK6 human
lymphoblastoid cell mutagenesis assay; and in the in vivo mouse
micronucleus assay.
In mice and rats, IV doses of up to 700 mg/kg/day (for mice,
approximately 3 times the recommended human dose of 1 g based on body
surface area and for rats, approximately 1.2 times the human exposure
at the recommended dose of 1 g based on plasma AUCs) resulted in no
effects on mating performance, fecundity, fertility, or embryonic
survival.

Pregnancy: Teratogenic Effects

Pregnancy Category B: In mice and rats given IV doses of up to 700
mg/kg/day (for mice, approximately 3 times the recommended human dose
of 1 g based on body surface area and for rats, approximately 1.2
times the human exposure at the recommended dose of 1 g based on
plasma AUCs), there was no evidence of developmental toxicity as
assessed by external, visceral, and skeletal examination of the
fetuses. However, in mice given 700 mg/kg/day, slight decreases in
average fetal weights and an associated decrease in the average number
of ossified sacrocaudal vertebrae were observed. Ertapenem crosses the
placental barrier in rats.
There are, however, no adequate and well-controlled studies 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

Ertapenem is excreted in human breast milk. (See CLINICAL
PHARMACOLOGY, Distribution.) Caution should be exercised when INVANZ
is administered to a nursing woman. INVANZ should be administered to
nursing mothers only when the expected benefit outweighs the risk.

Labor and delivery

INVANZ has not been studied for use during labor and delivery.

Pediatric Use

Safety and effectiveness of INVANZ in pediatric patients 3 months
to 17 years of age are supported by evidence from adequate and
well-controlled studies in adults, pharmacokinetic data in pediatric
patients, and additional data from comparator-controlled studies in
pediatric patients 3 months to 17 years of age with the following
infections (see INDICATIONS AND USAGE and CLINICAL STUDIES):

-- Complicated Intra-abdominal Infections

-- Complicated Skin and Skin Structure Infections

-- Community Acquired Pneumonia

-- Complicated Urinary Tract Infections

-- Acute Pelvic Infections

INVANZ is not recommended in infants under 3 months of age as no
data are available.
INVANZ is not recommended in the treatment of meningitis in the
pediatric population due to lack of sufficient CSF penetration.

Geriatric Use

Of the 1,835 patients in Phase IIb/III studies treated with
INVANZ, approximately 26 percent were 65 and over, while approximately
12 percent were 75 and over. No overall differences in safety or
effectiveness were observed between these patients and younger
patients. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients, but
greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney, and
the risk of toxic reactions to this drug may be greater in patients
with impaired renal function. Because elderly patients are more likely
to have decreased renal function, care should be taken in dose
selection, and it may be useful to monitor renal function. (See DOSAGE
AND ADMINISTRATION.)

Hepatic Insufficiency

The pharmacokinetics of ertapenem in patients with hepatic
insufficiency have not been established. Of the total number of
patients in clinical studies, 37 patients receiving ertapenem 1 g
daily and 36 patients receiving comparator drugs were considered to
have Child-Pugh Class A, B, or C liver impairment. The incidence of
adverse experiences in patients with hepatic impairment was similar
between the ertapenem group and the comparator groups.

ANIMAL PHARMACOLOGY

In repeat-dose studies in rats, treatment-related neutropenia
occurred at every dose-level tested, including the lowest dose of 2
mg/kg (approximately 2% of the human dose on a body surface area
basis).
Studies in rabbits and Rhesus monkeys were inconclusive with
regard to the effect on neutrophil counts.

ADVERSE REACTIONS

Adults

Clinical studies enrolled 1954 patients treated with ertapenem; in
some of the clinical studies, parenteral therapy was followed by a
switch to an appropriate oral antimicrobial. (See CLINICAL STUDIES.)
Most adverse experiences reported in these clinical studies were
described as mild to moderate in severity. Ertapenem was discontinued
due to adverse experiences in 4.7% of patients. Table 6 shows the
incidence of adverse experiences reported in (greater than or equal to
)1.0% of patients in these studies. The most common drug-related
adverse experiences in patients treated with INVANZ, including those
who were switched to therapy with an oral antimicrobial, were diarrhea
(5.5%), infused vein complication (3.7%), nausea (3.1%), headache
(2.2%), vaginitis in females (2.1%), phlebitis/thrombophlebitis
(1.3%), and vomiting (1.1%).


Table 6
Incidence (%) of Adverse Experiences Reported During Study Therapy
Plus 14-Day Follow-Up in (greater than =)1.0% of Adult Patients
Treated With INVANZ in Clinical Studies
----------------------------------------------------------------------
Piperacillin/
INVANZ* Tazobactam* INVANZ+ Ceftriaxone+
1 g 3.375 g q6h 1 g daily 1 or 2 g
Adverse Events daily (N=774) (N=1152) daily
(N=802) (N=942)
----------------------------------------------------------------------
Local:
Extravasation 1.9 1.7 0.7 1.1
Infused vein complication 7.1 7.9 5.4 6.7
Phlebitis/thrombophlebitis 1.9 2.7 1.6 2.0
----------------------------------------------------------------------
Systemic:
Asthenia/fatigue 1.2 0.9 1.2 1.1
Death 2.5 1.6 1.3 1.6
Edema/swelling 3.4 2.5 2.9 3.3
Fever 5.0 6.6 2.3 3.4
Abdominal pain 3.6 4.8 4.3 3.9
Chest pain 1.5 1.4 1.0 2.5
Hypertension 1.6 1.4 0.7 1.0
Hypotension 2.0 1.4 1.0 1.2
Tachycardia 1.6 1.3 1.3 0.7
Acid regurgitation 1.6 0.9 1.1 0.6
Oral candidiasis 0.1 1.3 1.4 1.9
Constipation 4.0 5.4 3.3 3.1
Diarrhea 10.3 12.1 9.2 9.8
Dyspepsia 1.1 0.6 1.0 1.6
Nausea 8.5 8.7 6.4 7.4
Vomiting 3.7 5.3 4.0 4.0
Leg pain 1.1 0.5 0.4 0.3
Anxiety 1.4 1.3 0.8 1.2
Altered mental status++ 5.1 3.4 3.3 2.5
Dizziness 2.1 3.0 1.5 2.1
Headache 5.6 5.4 6.8 6.9
Insomnia 3.2 5.2 3.0 4.1
Cough 1.6 1.7 1.3 0.5
Dyspnea 2.6 1.8 1.0 2.4
Pharyngitis 0.7 1.4 1.1 0.6
Rales/rhonchi 1.1 1.0 0.5 1.0
Respiratory distress 1.0 0.4 0.2 0.2
Erythema 1.6 1.7 1.2 1.2
Pruritus 2.0 2.6 1.0 1.9
Rash 2.5 3.1 2.3 1.5
Vaginitis 1.4 1.0 3.3 3.7
----------------------------------------------------------------------
* Includes Phase IIb/III Complicated intra-abdominal infections,
Complicated skin and skin structure infections and Acute pelvic
infections studies
+ Includes Phase IIb/III Community acquired pneumonia and Complicated
urinary tract infections, and Phase IIa studies
++ Includes agitation, confusion, disorientation, decreased mental
acuity, changed mental status, somnolence, stupor
----------------------------------------------------------------------

In patients treated for complicated intra-abdominal infections,
death occurred in 4.7% (15/316) of patients receiving ertapenem and
2.6% (8/307) of patients receiving comparator drug. These deaths
occurred in patients with significant co-morbidity and/or severe
baseline infections. Deaths were considered unrelated to study drugs
by investigators.
In clinical studies, seizure was reported during study therapy
plus 14-day follow-up period in 0.5% of patients treated with
ertapenem, 0.3% of patients treated with piperacillin/tazobactam and
0% of patients treated with ceftriaxone. (See PRECAUTIONS.)
Additional adverse experiences that were reported with INVANZ with
an incidence greater than 0.1% within each body system are listed
below:
Body as a whole: abdominal distention, pain, chills, septicemia,
septic shock, dehydration, gout, malaise, necrosis, candidiasis,
weight loss, facial edema, injection site induration, injection site
pain, flank pain, and syncope;
Cardiovascular System: heart failure, hematoma, cardiac arrest,
bradycardia, arrhythmia, atrial fibrillation, heart murmur,
ventricular tachycardia, asystole, and subdural hemorrhage;
Digestive System: gastrointestinal hemorrhage, anorexia,
flatulence, C. difficile associated diarrhea, stomatitis, dysphagia,
hemorrhoids, ileus, cholelithiasis, duodenitis, esophagitis,
gastritis, jaundice, mouth ulcer, pancreatitis, and pyloric stenosis;
Nervous System & Psychiatric: nervousness, seizure (see WARNINGS
and PRECAUTIONS), tremor, depression, hypesthesia, spasm, paresthesia,
aggressive behavior, and vertigo;
Respiratory System: pleural effusion, hypoxemia,
bronchoconstriction, pharyngeal discomfort, epistaxis, pleuritic pain,
asthma, hemoptysis, hiccups, and voice disturbance;
Skin & Skin Appendage: sweating, dermatitis, desquamation,
flushing, and urticaria;

Special Senses: taste perversion;

Urogenital System: renal insufficiency, oliguria/anuria, vaginal
pruritus, hematuria, urinary retention, bladder dysfunction, vaginal
candidiasis, and vulvovaginitis.

Pediatric Patients

Clinical studies enrolled 384 patients treated with ertapenem; in
some of the clinical studies, parenteral therapy was followed by a
switch to an appropriate oral antimicrobial. (See CLINICAL STUDIES.)
The overall adverse experience profile in pediatric patients is
comparable to that in adult patients. Table 7 shows the incidence of
adverse experiences reported in (greater than or equal to )1.0% of
pediatric patients in clinical studies. The most common drug-related
adverse experiences in pediatric patients treated with INVANZ,
including those who were switched to therapy with an oral
antimicrobial, were diarrhea (6.5%), infusion site pain (5.5%),
infusion site erythema (2.6%), vomiting (2.1%).


Table 7
Incidence (%) of Adverse Experiences Reported During Study
Therapy Plus 14-Day Follow-Up in (greater than =)1.0% of
Pediatric Patients Treated With INVANZ in Clinical Studies
---------------------------------------------------------------
INVANZ*+ Ceftriaxone* Ticarcillin/
(N=384) (N=100) Clavulanate+
Adverse Events (N=24)
---------------------------------------------------------------
Local:
Infusion Site Erythema 3.9 3.0 8.3
Infusion Site
Induration 1.0 1.0 0.0
Infusion Site Pain 7.0 4.0 20.8
Infusion Site
Phlebitis 1.8 3.0 0.0
Infusion Site Swelling 1.8 1.0 4.2
Infusion Site Warmth 1.3 1.0 4.2
---------------------------------------------------------------
Systemic:
Abdominal Pain 4.7 3.0 4.2
Upper Abdominal Pain 1.0 2.0 0.0
Constipation 2.3 0.0 0.0
Diarrhea 11.7 17.0 4.2
Loose Stools 2.1 0.0 0.0
Nausea 1.6 0.0 0.0
Vomiting 10.2 11.0 8.3
Pyrexia 4.9 6.0 8.3
Abdominal Abscess 1.0 0.0 4.2
Herpes Simplex 1.0 1.0 4.2
Nasopharyngitis 1.6 6.0 0.0
Upper Respiratory
Tract Infection 2.3 3.0 0.0
Viral Pharyngitis 1.0 0.0 0.0
Hypothermia 1.6 1.0 0.0
Dizziness 1.6 0.0 0.0
Headache 4.4 4.0 0.0
Cough 4.4 3.0 0.0
Wheezing 1.0 0.0 0.0
Dermatitis 1.0 1.0 0.0
Pruritus 1.6 0.0 0.0
Diaper Dermatitis 4.7 4.0 0.0
Rash 2.9 2.0 8.3
---------------------------------------------------------------
* Includes Phase IIb Complicated skin and skin structure
infections, Community acquired pneumonia and Complicated
urinary tract infections studies in which patients 3 months to
12 years of age received INVANZ 15 mg/kg IV twice daily up to
a maximum of 1 g or ceftriaxone 50 mg/kg/day IV in two divided
doses up to a maximum of 2 g, and patients 13 to 17 years of
age received INVANZ 1 g IV daily or ceftriaxone 50 mg/kg/day
IV in a single daily dose.

+ Includes Phase IIb Acute pelvic infections and Complicated
intra-abdominal infections studies in which patients 3
months to 12 years of age received INVANZ 15 mg/kg IV
twice daily up to a maximum of 1 g and patients 13 to 17
years of age received INVANZ 1 g IV daily or
ticarcillin/clavulanate 50 mg/kg for patients less than 60
kg or ticarcillin/clavulanate 3.0 g for patients greater
than 60 kg, 4 or 6 times a day.
---------------------------------------------------------------

Additional adverse experiences that were reported with INVANZ with
an incidence less than 1.0% and greater than 0.5% within each body
system are listed below: General Disorders and Administration Site
Condition: chest pain, infusion site pruritus; Infections and
Infestations: candidiasis, ear infection, oral candidiasis;

Metabolism and Nutrition Disorders: decreased appetite;

Musculoskeletal and Connective Tissue Disorders: arthralgia;

Nervous System Disorders: somnolence;

Psychiatric Disorders: insomnia;

Reproductive System and Breast Disorders: genital rash;

Respiratory, Thoracic and Mediastinal Disorders: pleural effusion,
rhinitis, rhinorrhea;
Skin and Subcutaneous Tissue Disorders: dermatitis atopic, rash
erythematous, skin lesion;

Vascular Disorders: phlebitis.

In a clinical trial for the treatment of diabetic foot infections
in which 289 adult diabetic patients were treated with ertapenem, the
adverse experience profile was generally similar to that seen in
previous clinical trials.

Post-Marketing Experience:

The following post-marketing adverse experiences have been
reported:

Immune System: anaphylaxis including anaphylactoid reactions

Nervous System & Psychiatric: hallucinations

Adverse Laboratory Changes

Adults

Laboratory adverse experiences that were reported during therapy
in (greater than or equal to )1.0% of adult patients treated with
INVANZ in clinical studies are presented in Table 8. Drug-related
laboratory adverse experiences that were reported during therapy in
(greater than or equal to )1.0% of adult patients treated with INVANZ,
including those who were switched to therapy with an oral
antimicrobial, in clinical studies were ALT increased (6.0%), AST
increased (5.2%), serum alkaline phosphatase increased (3.4%),
platelet count increased (2.8%), and eosinophils increased (1.1%).
Ertapenem was discontinued due to laboratory adverse experiences in
0.3% of patients.

Table 8
Incidence* (%) of Specific Laboratory Adverse Experiences Reported
During Study Therapy Plus 14-Day Follow-Up
in (greater than =)1.0% of Adult Patients Treated With INVANZ in
Clinical Studies
----------------------------------------------------------------------
Piperacillin/
INVANZ++ Tazobactam++ INVANZss. Ceftriaxone ss.
1 g daily 3.375 g q6h 1 g daily1 or 2 g daily
Adverse laboratory (n+=766) (n+=755) (n+=1122) (n+=920)
experiences
----------------------------------------------------------------------
ALT increased 8.8 7.3 8.3 6.9
AST increased 8.4 8.3 7.1 6.5
Serum albumin decreased 1.7 1.5 0.9 1.6
Serum alkaline
phosphatase increased 6.6 7.2 4.3 2.8
Serum creatinine
increased 1.1 2.7 0.9 1.2
Serum glucose increased 1.2 2.3 1.7 2.0
Serum potassium
decreased 1.7 2.8 1.8 2.4
Serum potassium
increased 1.3 0.5 0.5 0.7
Total serum bilirubin
increased 1.7 1.4 0.6 1.1
Eosinophils increased 1.1 1.1 2.1 1.8
Hematocrit decreased 3.0 2.9 3.4 2.4
Hemoglobin decreased 4.9 4.7 4.5 3.5
Platelet count
decreased 1.1 1.2 1.1 1.0
Platelet count
increased 6.5 6.3 4.3 3.5
Segmented neutrophils
decreased 1.0 0.3 1.5 0.8
Prothrombin time
increased 1.2 2.0 0.3 0.9
WBC decreased 0.8 0.7 1.5 1.4
Urine RBCs increased 2.5 2.9 1.1 1.0
Urine WBCs increased 2.5 3.2 1.6 1.1
----------------------------------------------------------------------
* Number of patients with laboratory adverse experiences/Number of
patients with the laboratory test
+ Number of patients with one or more laboratory tests
++ Includes Phase IIb/III Complicated intra-abdominal infections,
Complicated skin and skin structure infections and Acute pelvic
infections studies
ss. Includes Phase IIb/III Community acquired pneumonia and
Complicated urinary tract infections, and Phase IIa studies
----------------------------------------------------------------------

Additional laboratory adverse experiences that were reported
during therapy in greater than 0.1% but less than 1.0% of patients
treated with INVANZ in clinical studies include: increases in BUN,
direct and indirect serum bilirubin, serum sodium, monocytes, PTT,
urine epithelial cells; decreases in serum bicarbonate.

Pediatric Patients

Laboratory adverse experiences that were reported during therapy
in (greater than or equal to )1.0% of pediatric patients treated with
INVANZ in clinical studies are presented in Table 9. Drug-related
laboratory adverse experiences that were reported during therapy in
(greater than or equal to )2.0% of pediatric patients treated with
INVANZ, including those who were switched to therapy with an oral
antimicrobial, in clinical studies were neutrophil count decreased
(3.0%), ALT increased (2.2%), and AST increased (2.1%).

Table 9
Incidence* (%) of Specific Laboratory Adverse
Experiences Reported During Study Therapy Plus 14-
Day Follow-Up in (greater than =)1.0% of Pediatric
Patients Treated With INVANZ in Clinical Studies
----------------------------------------------------
Ticarcillin/
INVANZ CeftriaxoneClavulanate
Adverse (n+=379) (n+=97) (n+=24)
laboratory
experiences
----------------------------------------------------
ALT Increased 3.8 1.1 4.3
Alkaline
Phosphatase
Increased 1.1 0.0 0.0
AST Increased 3.8 1.1 4.3
Eosinophil Count
Increased 1.1 2.1 0.0
Neutrophil Count
Decreased 5.8 3.1 0.0
Platelet Count
Increased 1.3 0.0 8.7
----------------------------------------------------
* Number of patients with laboratory adverse
experiences/Number of patients with the
laboratory test; where at least 300 patients had the
test
+ Number of patients with one or more laboratory
tests
----------------------------------------------------

Additional laboratory adverse experiences that were reported
during therapy in greater than 0.5% but less than 1.0% of patients
treated with INVANZ in clinical studies include: white blood cell
count decreased and protein urine present.

In a clinical trial for the treatment of diabetic foot infections
in which 289 adult diabetic patients were treated with ertapenem, the
laboratory adverse experience profile was generally similar to that
seen in previous clinical trials.

OVERDOSAGE

No specific information is available on the treatment of
overdosage with INVANZ. Intentional overdosing of INVANZ is unlikely.
Intravenous administration of INVANZ at a dose of 2 g over 30 min or 3
g over 1-2h in healthy adult volunteers resulted in an increased
incidence of nausea. In clinical studies in adults, inadvertent
administration of three 1 g doses of INVANZ in a 24 hour period
resulted in diarrhea and transient dizziness in one patient. In
pediatric clinical studies, a single IV dose of 40 mg/kg up to a
maximum of 2 g did not result in toxicity.
In the event of an overdose, INVANZ should be discontinued and
general supportive treatment given until renal elimination takes
place.
INVANZ can be removed by hemodialysis; the plasma clearance of the
total fraction of ertapenem was increased 30% in subjects with
end-stage renal insufficiency when hemodialysis (4 hour session) was
performed immediately following administration. However, no
information is available on the use of hemodialysis to treat
overdosage.

DOSAGE AND ADMINISTRATION

The dose of INVANZ in patients 13 years of age and older is 1 gram
(g) given once a day. The dose of INVANZ in patients 3 months to 12
years of age is 15 mg/kg twice daily (not to exceed 1 g/day). INVANZ
may be administered by intravenous infusion for up to 14 days or
intramuscular injection for up to 7 days. When administered
intravenously, INVANZ should be infused over a period of 30 minutes.
Intramuscular administration of INVANZ may be used as an
alternative to intravenous administration in the treatment of those
infections for which intramuscular therapy is appropriate.
DO NOT MIX OR CO-INFUSE INVANZ WITH OTHER MEDICATIONS. DO NOT USE
DILUENTS CONTAINING DEXTROSE ((alpha)-D-GLUCOSE).

Table 10 presents dosage guidelines for INVANZ.

Table 10
Dosage Guidelines for Adults and Pediatric Patients With Normal Renal
Function* and Body Weight
----------------------------------------------------------------------
Infection+ Daily Dose Daily Dose Recommended
(IV or IM) (IV or IM) Duration of Total
Adults and Pediatric Antimicrobial
Pediatric Patients 3 Treatment
Patients 13 months to
years of 12 years of
age and age
older
----------------------------------------------------------------------
Complicated intra-abdominal 1 g 15 mg/kg 5 to 14 days
infections twice
dailyss.
Complicated skin and skin 1 g 15 mg/kg 7 to 14 days|
structure infections, twice
including diabetic foot dailyss.
infections @
Community acquired 1 g 15 mg/kg 10 to 14 days++
pneumonia twice
dailyss.
Complicated urinary tract 1 g 15 mg/kg 10 to 14 days++
infections, including twice
pyelonephritis dailyss.
Acute pelvic infections 1 g 15 mg/kg 3 to 10 days
including postpartum twice
endomyometritis, septic dailyss.
abortion and post surgical
gynecologic infections
-----------------
* defined as creatinine clearance greater than 90 mL/min/1.73 m2

+ due to the designated pathogens (see INDICATIONS AND USAGE)

@ INVANZ has not been studied in diabetic foot infections with
concomitant osteomyelitis (see CLINICAL STUDIES).

|adult patients with diabetic foot infections received up to 28 days
of treatment (parenteral or parenteral plus oral switch therapy)

++ duration includes a possible switch to an appropriate oral therapy,
after at least 3 days of parenteral therapy, once clinical improvement
has been demonstrated.

ss. not to exceed 1 g/day
----------------------------------------------------------------------

Patients with Renal Insufficiency: INVANZ may be used for the
treatment of infections in adult patients with renal insufficiency. In
patients whose creatinine clearance is greater than 30 mL/min/1.73 m2,
no dosage adjustment is necessary. Adult patients with advanced renal
insufficiency (creatinine clearance (less than or equal to)30
mL/min/1.73 m2) and end-stage renal insufficiency (creatinine
clearance (less than or equal to)10 mL/min/1.73 m2) should receive 500
mg daily. There are no data in pediatric patients with renal
insufficiency. Patients on Hemodialysis: When adult patients on
hemodialysis are given the recommended daily dose of 500 mg of INVANZ
within 6 hours prior to hemodialysis, a supplementary dose of 150 mg
is recommended following the hemodialysis session. If INVANZ is given
at least 6 hours prior to hemodialysis, no supplementary dose is
needed. There are no data in patients undergoing peritoneal dialysis
or hemofiltration. There are no data in pediatric patients on
hemodialysis. When only the serum creatinine is available, the
following formula** may be used to estimate creatinine clearance.
The serum creatinine should represent a steady state of renal
function.


Males: (weight in kg) x (140-age in
years)
(72) x serum creatinine
(mg/100 mL)
------------------------------
Females: (0.85) x (value calculated for
males)

Patients with Hepatic Insufficiency: No dose adjustment
recommendations can be made in patients with impaired hepatic
function. (See CLINICAL PHARMACOLOGY, Special Populations, Hepatic
Insufficiency and PRECAUTIONS.)
No dosage adjustment is recommended based on age (13 years of age
and older) or gender. (See CLINICAL PHARMACOLOGY, Special
Populations.)

** Cockcroft and Gault equation: Cockcroft DW, Gault MH. Prediction
of creatinine clearance from serum creatinine. Nephron. 1976

PREPARATION OF SOLUTION

Adults and pediatric patients 13 years of age and older

Preparation for intravenous administration:

DO NOT MIX OR CO-INFUSE INVANZ WITH OTHER MEDICATIONS. DO NOT USE
DILUENTS CONTAINING DEXTROSE ((alpha)-D-GLUCOSE).
INVANZ MUST BE RECONSTITUTED AND THEN DILUTED PRIOR TO
ADMINISTRATION.
1. Reconstitute the contents of a 1 g vial of INVANZ with 10 mL of
one of the following: Water for Injection, 0.9% Sodium Chloride
Injection or Bacteriostatic Water for Injection.
2. Shake well to dissolve and immediately transfer contents of the
reconstituted vial to 50 mL of 0.9% Sodium Chloride Injection.

3. Complete the infusion within 6 hours of reconstitution.

Preparation for intramuscular administration:

INVANZ MUST BE RECONSTITUTED PRIOR TO ADMINISTRATION.

1. Reconstitute the contents of a 1 g vial of INVANZ with 3.2 mL
of 1.0% lidocaine HCl injection*** (without epinephrine). Shake
vial thoroughly to form solution.
2. Immediately withdraw the contents of the vial and administer by
deep intramuscular injection into a large muscle mass (such as the
gluteal muscles or lateral part of the thigh).
3. The reconstituted IM solution should be used within 1 hour
after preparation. NOTE: THE RECONSTITUTED SOLUTION SHOULD NOT BE
ADMINISTERED INTRAVENOUSLY.

Pediatric patients 3 months to 12 years of age:

Preparation for intravenous administration:

DO NOT MIX OR CO-INFUSE INVANZ WITH OTHER MEDICATIONS. DO NOT USE
DILUENTS CONTAINING DEXTROSE ((alpha)-D-GLUCOSE).
INVANZ MUST BE RECONSTITUTED AND THEN DILUTED PRIOR TO
ADMINISTRATION.
1. Reconstitute the contents of a 1 g vial of INVANZ with 10 mL of
one of the following: Water for Injection, 0.9% Sodium Chloride
Injection or Bacteriostatic Water for Injection.
2. Shake well to dissolve and immediately withdraw a volume equal
to 15 mg/kg of body weight (not to exceed 1 g/day) and dilute in 0.9%
Sodium Chloride Injection to a final concentration of 20 mg/mL or
less.

3. Complete the infusion within 6 hours of reconstitution.

Preparation for intramuscular administration:

INVANZ MUST BE RECONSTITUTED PRIOR TO ADMINISTRATION.

1. Reconstitute the contents of a 1 g vial of INVANZ with 3.2 mL
of 1.0% lidocaine HCl injection*** (without epinephrine). Shake vial
thoroughly to form solution.
2. Immediately withdraw a volume equal to 15 mg/kg of body weight
(not to exceed 1 g/day) and administer by deep intramuscular injection
into a large muscle mass (such as the gluteal muscles or lateral part
of the thigh).
3. The reconstituted IM solution should be used within 1 hour
after preparation. NOTE: THE RECONSTITUTED SOLUTION SHOULD NOT BE
ADMINISTERED INTRAVENOUSLY.
Parenteral drug products should be inspected visually for
particulate matter and discoloration prior to use, whenever solution
and container permit. Solutions of INVANZ range from colorless to pale
yellow. Variations of color within this range do not affect the
potency of the product.

STORAGE AND STABILITY

Before reconstitution

Do not store lyophilized powder above 25(degree)C (77(degree)F).

*** Refer to the prescribing information for lidocaine HCl.

Reconstituted and infusion solutions

The reconstituted solution, immediately diluted in 0.9% Sodium
Chloride Injection (see DOSAGE AND ADMINISTRATION, PREPARATION OF
SOLUTION), may be stored at room temperature (25(degree)C) and used
within 6 hours or stored for 24 hours under refrigeration (5(degree)C)
and used within 4 hours after removal from refrigeration. Solutions of
INVANZ should not be frozen.

HOW SUPPLIED

INVANZ is supplied as a sterile lyophilized powder in single dose
vials containing ertapenem for intravenous infusion or for
intramuscular injection as follows:

No. 3843--1 g ertapenem equivalent

NDC 0006-3843-71 in trays of 10 vials

No. 3843--1 g ertapenem equivalent

NDC 0006-3843-45 in trays of 25 vials.

CLINICAL STUDIES

Adults

Complicated Intra-Abdominal Infections

Ertapenem was evaluated in adults for the treatment of complicated
intra-abdominal infections in a clinical trial. This study compared
ertapenem (1 g intravenously once a day) with piperacillin/tazobactam
(3.375 g intravenously every 6 hours) for 5 to 14 days and enrolled
665 patients with localized complicated appendicitis, and any other
complicated intra-abdominal infection including colonic, small
intestinal, and biliary infections and generalized peritonitis. The
combined clinical and microbiologic success rates in the
microbiologically evaluable population at 4 to 6 weeks posttherapy
(test of cure) were 83.6% (163/195) for ertapenem and 80.4% (152/189)
for piperacillin/tazobactam.

Complicated Skin and Skin Structure Infections

Ertapenem was evaluated in adults for the treatment of complicated
skin and skin structure infections in a clinical trial. This study
compared ertapenem (1 g intravenously once a day) with
piperacillin/tazobactam (3.375 g intravenously every 6 hours) for 7 to
14 days and enrolled 540 patients including patients with deep soft
tissue abscess, posttraumatic wound infection and cellulitis with
purulent drainage. The clinical success rates at 10 to 21 days
posttherapy (test of cure) were 83.9% (141/168) for ertapenem and
85.3% (145/170) for piperacillin/tazobactam.

Diabetic Foot Infections

Ertapenem was evaluated in adults for the treatment of diabetic
foot infections without concomitant osteomyelitis in a multicenter,
randomized, double-blind clinical trial. This study compared ertapenem
(1 g intravenously once a day) with piperacillin/tazobactam (3.375 g
intravenously every 6 hours). Test-of-cure was defined as clinical
response between treatment groups in the clinically evaluable
population at the 10-day posttherapy follow-up visit. The study
included 295 patients randomized to ertapenem and 291 patients to
piperacillin/tazobactam. Both regimens allowed the option to switch to
oral amoxicillin/clavulanate for a total of 5 to 28 days of treatment
(parenteral and oral). All patients were eligible to receive
appropriate adjunctive treatment methods, such as debridement, as is
typically required in the treatment of diabetic foot infections, and
most patients received these treatments. Patients with suspected
osteomyelitis could be enrolled if all the infected bone was removed
within 2 days of initiation of study therapy, and preferably within
the prestudy period. Investigators had the option to add open-label
vancomycin if enterococci or methicillin-resistant Staphylococcus
aureus (MRSA) were among the pathogens isolated or if patients had a
history of MRSA infection and additional therapy was indicated in the
opinion of the investigator. Two hundred and four (204) patients
randomized to ertapenem and 202 patients randomized to
piperacillin/tazobactam were clinically evaluable. The clinical
success rates at 10 days posttherapy were 75.0% (153/204) for
ertapenem and 70.8% (143/202) for piperacillin/tazobactam.

Community Acquired Pneumonia

Ertapenem was evaluated in adults for the treatment of community
acquired pneumonia in two clinical trials. Both studies compared
ertapenem (1 g parenterally once a day) with ceftriaxone (1 g
parenterally once a day) and enrolled a total of 866 patients. Both
regimens allowed the option to switch to oral amoxicillin/clavulanate
for a total of 10 to 14 days of treatment (parenteral and oral). In
the first study the primary efficacy parameter was the clinical
success rate in the clinically evaluable population and success rates
were 92.3% (168/182) for ertapenem and 91.0% (183/201) for ceftriaxone
at 7 to 14 days posttherapy (test of cure). In the second study the
primary efficacy parameter was the clinical success rate in the
microbiologically evaluable population and success rates were 91%
(91/100) for ertapenem and 91.8% (45/49) for ceftriaxone at 7 to 14
days posttherapy (test of cure).

Complicated Urinary Tract Infections Including Pyelonephritis

Ertapenem was evaluated in adults for the treatment of complicated
urinary tract infections including pyelonephritis in two clinical
trials. Both studies compared ertapenem (1 g parenterally once a day)
with ceftriaxone (1 g parenterally once a day) and enrolled a total of
850 patients. Both regimens allowed the option to switch to oral
ciprofloxacin (500 mg twice daily) for a total of 10 to 14 days of
treatment (parenteral and oral). The microbiological success rates
(combined studies) at 5 to 9 days posttherapy (test of cure) were
89.5% (229/256) for ertapenem and 91.1% (204/224) for ceftriaxone.
Acute Pelvic Infections Including Endomyometritis, Septic Abortion
And Post-Surgical Gynecological Infections
Ertapenem was evaluated in adults for the treatment of acute
pelvic infections in a clinical trial. This study compared ertapenem
(1 g intravenously once a day) with piperacillin/tazobactam (3.375 g
intravenously every 6 hours) for 3 to 10 days and enrolled 412
patients including 350 patients with obstetric/postpartum infections
and 45 patients with septic abortion. The clinical success rates in
the clinically evaluable population at 2 to 4 weeks posttherapy (test
of cure) were 93.9% (153/163) for ertapenem and 91.5% (140/153) for
piperacillin/tazobactam.

Pediatric Patients

Ertapenem was evaluated in pediatric patients 3 months to 17 years
of age in two randomized, multicenter clinical trials. The first study
enrolled 404 patients and compared ertapenem (15 mg/kg IV every 12
hours in patients 3 months to 12 years of age, and 1 g IV once a day
in patients 13 to 17 years of age) to ceftriaxone (50 mg/kg/day IV in
two divided doses in patients 3 months to 12 years of age and 50
mg/kg/day IV as a single daily dose in patients 13 to 17 years of age)
for the treatment of complicated urinary tract infection (UTI), skin
and soft tissue infection (SSTI), or community-acquired pneumonia
(CAP). Both regimens allowed the option to switch to oral
amoxicillin/clavulanate for a total of up to 14 days of treatment
(parenteral and oral). The microbiological success rates in the
evaluable per protocol (EPP) analysis in patients treated for UTI were
87.0% (40/46) for ertapenem and 90.0% (18/20) for ceftriaxone. The
clinical success rates in the EPP analysis in patients treated for
SSTI were 95.5% (64/67) for ertapenem and 100% (26/26) for
ceftriaxone, and in patients treated for CAP were 96.1% (74/77) for
ertapenem and 96.4% (27/28) for ceftriaxone. The second study enrolled
112 patients and compared ertapenem (15 mg/kg IV every 12 hours in
patients 3 months to 12 years of age, and 1 g IV once a day in
patients 13 to 17 years of age) to ticarcillin/clavulanate (50 mg/kg
for patients less than 60 kg or 3.0 g for patients greater than 60 kg,
4 or 6 times a day) up to 14 days for the treatment of complicated
intra-abdominal infections (IAI) and acute pelvic infections (API). In
patients treated for IAI (primarily patients with perforated or
complicated appendicitis) the clinical success rates were 83.7%
(36/43) for ertapenem and 63.6% (7/11) for ticarcillin/clavulanate in
the EPP analysis. In patients treated for API (post-operative or
spontaneous obstetrical endomyometritis, or septic abortion) the
clinical success rates were 100% (23/23) for ertapenem and 100% (4/4)
for ticarcillin/clavulanate in the EPP analysis.

REFERENCES

1. National Committee for Clinical Laboratory Standards (NCCLS)
(Now Clinical and Laboratory Standards Institute (CLSI)). Methods for
Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow
Aerobically. Sixth Edition; Approved Standard, CLSI Document M7-A6,
Vol. 23, No. 2. Clinical and Laboratory Standards Institute, Wayne,
PA, January 2003.
2. Clinical And Laboratory Standards Institute (formerly NCCLS).
Performance Standards for Antimicrobial Susceptibility Testing -
Fifteenth Informational Supplement. Approved Standard, Clinical and
Laboratory Standards Institute (Formerly NCCLS) Document M100-S15,
Vol. 25, No. 1. Clinical and Laboratory Standards Institute, Wayne,
PA, January 2005.
3. National Committee for Clinical Laboratory Standards (NCCLS)
(Now Clinical and Laboratory Standards Institute (CLSI)). Performance
Standards for Antimicrobial Disk Susceptibility Tests. Seventh
Edition; Approved Standard, CLSI Document M2-A8, Vol. 23, No. 1.
Clinical and Laboratory Standards Institute, Wayne, PA, January 2003.
4. National Committee for Clinical Laboratory Standards (NCCLS)
(Now Clinical and Laboratory Standards Institute (CLSI)). Methods for
Antimicrobial Susceptibility Testing of Anaerobic Bacteria - Sixth
Edition; Approved Standard, CLSI Document M11-A6, Vol. 24, No. 2.
Clinical and Laboratory Standards Institute, Wayne, PA, January 2004.

MERCK & CO., Inc., 2001
Whitehouse Station, NJ 08889, USA

Issued October 2005
Printed in USA