CEFOPERAZONE SODIUM + SULBACTAM SODIUM

SULPERAZONE*
1.5 g Powder for Solution for Injection (IM/IV)

1.0 PHARMACOLOGIC CATEGORY

Anti-bacterial

2.0 DESCRIPTION

Sulbactam sodium/cefoperazone sodium combination is available as a dry

powder for reconstitution in both a 1:1 and 1:2 ratio in terms of free SBT/CPZ.

Sulbactam sodium is a derivative of the basic penicillin nucleus. It is an

irreversible beta-lactamase inhibitor for parenteral use only. Chemically it is
sodium penicillinate sulfone. It contains 92 mg sodium (4mEq) per gram.
Sulbactam is an off-white crystalline powder which is highly soluble in water.
The molecular weight is 255.22.

COONa
CH 3
O
N
CH 3

S
O O

Cefoperazone sodium is a semisynthetic broad-spectrum cephalosporin

antibiotic for parenteral use only. It contains 34 mg sodium (1.5 mEq) per
gram. Cefoperazone is a white crystalline powder which is freely soluble in
water. The molecular weight is 667.65.

OH

COONa CH3

O CH2S N
N N

H5C2 N N CONH C CONH ΠΠN N

H H S
H

O O
3.0 FORMULATION

Each vial contains cefoperazone sodium equivalent to 1000 mg of cefoperazone

and sulbactam sodium equivalent to 500 mg sulbactam.

4.0 CLINICAL PARTICULARS

4.1 Therapeutic Indications

Mono-therapy

Sulbactam/cefoperazone is indicated for the treatment of the following

infections when caused by susceptible organisms:

Respiratory Tract Infections (Upper and Lower)

Urinary Tract Infections (Upper and Lower)
Peritonitis, Cholecystitis, Cholangitis, and Other Intra-Abdominal
Infections
Septicemia
Meningitis
Skin and Soft Tissue Infections
Bone and Joint Infections
Pelvic Inflammatory Disease, Endometritis, Gonorrhea, and Other
Infections of the Genital Tract

Combination Therapy

Because of the broad spectrum of activity of sulbactam/cefoperazone,

most infections can be treated adequately with this antibiotic alone.
However, sulbactam/cefoperazone may be used concomitantly with other
antibiotics if such combinations are indicated. If an aminoglycoside is
used (see section 6.2 Incompatibilities Aminoglycosides), renal
function should be monitored during the course of therapy (see section
4.2 Dosage and Method of Administration Use in Renal Dysfunction).

4.2 Dosage and Method of Administration

Use in Adults

Daily dosage recommendations for sulbactam/cefoperazone in adults are

as follows:
 Sulbactam Cefoperazone
Ratio SBT/CPZ (g) Activity (g) Activity (g)
1:1 2.0 – 4.0 1.0 – 2.0 1.0 – 2.0
1:2 1.5 – 3.0 0.5 – 1.0 1.0 – 2.0

Doses should be administered every 12 hours in equally divided doses.

In severe or refractory infections the daily dosage of

sulbactam/cefoperazone may be increased up to 8 g of the 1:1 ratio (i.e.,
4 g cefoperazone activity) or 12 g of the 1:2 ratio (i.e., 8 g cefoperazone
activity). Patients receiving the 1:1 ratio may require additional
cefoperazone administered separately. Doses should be administered
every 12 hours in equally divided doses.

The recommended maximum daily dosage of sulbactam is 4 g.

Use in Hepatic Dysfunction

See section 4.4 Special Warnings and Special Precautions for Use

Use in Renal Dysfunction

Dosage regimens of sulbactam/cefoperazone should be adjusted in

patients with marked decrease in renal function (creatinine clearance of
less than 30 ml/min) to compensate for the reduced clearance of
sulbactam. Patients with creatinine clearances between 15 and 30 ml/min
should receive a maximum of 1 g of sulbactam administered every 12
hours (maximum daily dosage of 2 g sulbactam), while patients with
creatinine clearances of less than 15 ml/min should receive a maximum of
500 mg of sulbactam every 12 hours (maximum daily dosage of 1 g
sulbactam). In severe infections it may be necessary to administer
additional cefoperazone.

The pharmacokinetic profile of sulbactam is significantly altered by

hemodialysis. The serum half-life of cefoperazone is reduced slightly
during hemodialysis. Thus, dosing should be scheduled to follow a
dialysis period.

Use in Elderly

See section 5.2 Pharmacokinetic Properties

Use in Children
Daily dosage recommendations for sulbactam/cefoperazone in children
are as follows:

Sulbactam Activity Cefoperazone

Ratio SBT/CPZ mg/kg/day Activity mg/kg/day
mg/kg/day
1:1 40 – 80 20 – 40 20 – 40
1:2 30 – 60 10 – 20 20 – 40

Doses should be administered every 6 to 12 hours in equally divided

doses.

In serious or refractory infections, these dosages may be increased up to

160 mg/kg/day of the 1:1 ratio or 240 mg/kg/day of the 1:2 ratio (160
mg/kg/day cefoperazone activity). Doses should be administered in two to
four equally divided doses (see section 4.4 Special Warnings and
Special Precautions for Use Use in Infancy and section 5.3 Preclinical
Safety Data Use in Pediatrics).

Use in Neonates

For neonates in the first week of life, the drug should be given every 12
hours. The maximum daily dosage of sulbactam in pediatrics should not
exceed 80 mg/kg/day. For doses of sulbactam/cefoperazone requiring
more than 80 mg/kg/day cefoperazone activity, the 1:2 ratio product must
be used (see section 4.4 Special Warnings and Special Precautions
for Use Use in Infancy).

Intravenous Administration

For intermittent infusion, each vial of sulbactam/cefoperazone should be

reconstituted with the appropriate amount (see section 6.4 Instruction for
Use/Handling Reconstitution) of 5% dextrose in Water, 0.9% Sodium
Chloride Injection or Sterile Water for Injection and then diluted to 20 ml
with the same solution followed by administration over 15 to 60 minutes.

Lactated Ringer’s Solution is a suitable vehicle for intravenous infusion,

however, not for initial reconstitution (see section 6.3 Incompatibilities
Lactated Ringer’s Solution and section 6.4 Instructions for
Use/Handling Lactated Ringer’s Solution).

For intravenous injection, each vial should be reconstituted as above and

administered over a minimum of 3 minutes.
 Intramuscular Administration

Lidocaine HCl 2% is a suitable vehicle for intramuscular administration,

however, not for initial reconstitution (see section 6.2 Incompatibilities
Lidocaine and section 6.6 Instructions for Use/Handling Lidocaine).

4.3 CONTRAINDICATIONS

Sulbactam/cefoperazone is contraindicated in patients with known allergy

to penicillins, sulbactam, cefoperazone or any of the cephalosporins.

4.4 Special Warnings and Precautions for Use

Hypersensitivity

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions

have been reported in patients receiving beta-lactam or cephalosporin
therapy. These reactions are more apt to occur in individuals with a
history of hypersensitivity reactions to multiple allergens. If an allergic
reaction occurs, the drug should be discontinued and the appropriate
therapy instituted.

Serious anaphylactic reactions require immediate emergency treatment

with epinephrine. Oxygen, intravenous steroids, and airway management,
including intubation, should be administered as indicated.

Use in Hepatic Dysfunction

Cefoperazone is extensively excreted in bile. The serum half-life of

cefoperazone is usually prolonged and urinary excretion of the drug
increased in patients with hepatic diseases and/or biliary obstruction.
Even with severe hepatic dysfunction, therapeutic concentrations of
cefoperazone are obtained in bile and only a 2- to 4-fold increase in
half-life is seen.

Dose modification may be necessary in cases of severe biliary

obstruction, severe hepatic disease or in cases of renal dysfunction
coexistent with either of those conditions.

In patients with hepatic dysfunction and concomitant renal impairment,

cefoperazone serum concentrations should be monitored and dosage
adjusted as necessary. In these cases dosage should not exceed 2 g/day
of cefoperazone without close monitoring of serum concentrations.
General

As with other antibiotics, Vitamin K deficiency has occurred in a few

patients treated with cefoperazone. The mechanism is most probably
related to the suppression of gut flora which normally synthesize this
vitamin. Those at risk include patients with poor diet, malabsorption
states (e.g., cystic fibrosis) and patients on prolonged intravenous
alimentation regimens. Prothrombin time should be monitored in these
patients, and patients receiving anticoagulant therapy, and exogenous
vitamin K administered as indicated.

As with other antibiotics, overgrowth of nonsusceptible organisms may

occur during prolonged use of sulbactam/cefoperazone. Patients should
be observed carefully during treatment. As with any potent systemic
agent, it is advisable to check periodically for organ system dysfunction
during extended therapy; this includes renal, hepatic, and hematopoietic
systems. This is particularly important in neonates, especially when
premature, and other infants.

Use In Infancy

Sulbactam/cefoperazone has been effectively used in infants. It has not

been extensively studied in premature infants or neonates. Therefore, in
treating premature infants and neonates potential benefits and possible
risks involved should be considered before instituting therapy (see section
5.3 Preclinical Safety Data “Use in Pediatrics”).

Clostridium difficile associated diarrhea (CDAD) has been reported with

use of nearly all antibacterial agents, including sulbactam
sodium/cefoperazone sodium, and may range in severity from mild
diarrhea to fatal colitis. Treatment with antibacterial agents alters the
1-14
normal flora of the colon leading to overgrowth of C difficile.

C. difficile produces toxins A and B which contribute to the development of

CDAD. Hypertoxin producing strains of C. difficile cause increased
morbidity and mortality, as these infections can be refractory to
antimicrobial therapy and may require colectomy. CDAD must be
considered in all patients who present with diarrhea following antibiotic
use. Careful medical history is necessary since CDAD has been reported
to occur over two months after the administration of antibacterial agents.1-
14
 Cefoperazone does not displace bilirubin from plasma protein binding
sites.

4.5 Interaction with Other Medicaments and Other Forms of Interaction

Alcohol

A reaction characterized by flushing, sweating, headache, and tachycardia

has been reported when alcohol was ingested during and as late as the
fifth day after cefoperazone administration. A similar reaction has been
reported with certain other cephalosporins and patients should be
cautioned concerning ingestion of alcoholic beverages in conjunction with
administration of sulbactam/cefoperazone. For patients requiring artificial
feeding orally or parenterally, solutions containing ethanol should be
avoided.

Drug Laboratory Test Interactions

A false-positive reaction for glucose in the urine may occur with Benedict's
or Fehling's solution.

4.6 Pregnancy and Lactation

Usage During Pregnancy

Reproduction studies have been performed in rats at doses up to 10 times

the human dose and have revealed no evidence of impaired fertility and
no teratological findings. Sulbactam and cefoperazone cross the
placental barrier. 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.

Usage in Nursing Mothers

Only small quantities of sulbactam and cefoperazone are excreted in

human milk. Although both drugs pass poorly into breast milk of nursing
mothers, caution should be exercised when sulbactam/cefoperazone is
administered to a nursing mother.

4.7 Effects on Ability to Drive and Use Machines

 Clinical experience with sulbactam/cefoperazone indicates that it is
unlikely to impair a patient’s ability to drive or use machinery.

4.8 Undesirable Effects

Sulbactam/cefoperazone is generally well tolerated. The majority of

adverse events are of mild or moderate severity and are tolerated with
continued treatment. In pooled clinical trial data from comparative and
non-comparative studies in approximately 2,500 patients the following was
observed.

Gastrointestinal: As with other antibiotics, the most frequent side effects

observed with sulbactam/cefoperazone have been gastrointestinal.
Diarrhea/loose stools 3.9% have been reported most frequently followed
by nausea and vomiting 0.6%..

Dermatologic Reactions: As with all penicillins and cephalosporins,

hypersensitivity manifested by maculopapular 0.6% and urticaria 0.08%
has been reported. These reactions are more likely to occur in patients
with a history of allergies, particularly to penicillin.

Hematology: Slight decreases in neutrophils 0.4% (5/1131) have been

reported. As with other beta-lactam antibiotics, reversible neutropenia
0.5% (9/1696) may occur with prolonged administration. Some individuals
have developed a positive direct Coombs test 5.5% (15/269) during
treatment. Decreased hemoglobin 0.9% (13/1416) or hematocrit 0.9%
(13/1409) have been reported, which is consistent with published
literature on cephalosporins. Transient eosinophilia 3.5% (40/1130) and
thrombocytopenia 0.8% (11/1414) have occurred, and
hypo-prothrombinemia 3.8% (10/262) has been reported.

Miscellaneous: Headache 0.04%, fever 0.5%, injection pain 0.08% and

chills .04%.

Laboratory Abnormalities: Transient elevations of liver function tests,

SGOT 5.7% (94/1638), SGPT 6.2% (95/1529), alkaline phosphatase
2.4% (37/1518) and bilirubin 1.2% (12/1040) levels, have been noted.

Local Reactions: Sulbactam/cefoperazone is well tolerated following

intramuscular administration. Occasionally, transient pain may follow
administration by this route. As with other cephalosporins and penicillins,
when sulbactam/cefoperazone is administered by an intravenous catheter
some patients may develop phlebitis 0.1% at the infusion site.

In post-marketing experience the following additional undesirable effects

have been reported: General: anaphylactoid reaction (including shock).
 Cardiovascular: hypotension, Gastrointestinal: pseudomembranous colitis,
Hematopoietic: leucopenia, Skin/Appendages: pruritus, Stevens Johnson
Syndrome, Urinary: hematuria, and Vascular: vasculitis.

4.9 Overdose

Limited information is available on the acute toxicity of cefoperazone

sodium and sulbactam sodium in humans. Overdosage of the drug would
be expected to produce manifestations that are principally extensions of
the adverse reactions reported with the drug. The fact that high CSF
concentrations of β-lactam antibiotics may cause neurologic effects,
including seizures, should be considered. Because cefoperazone and
sulbactam are both removed from the circulation by hemodialysis, these
procedures may enhance elimination of the drug from the body if
overdosage occurs in patients with impaired renal function.

5.0 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic Properties

The anti-bacterial component of sulbactam/cefoperazone is

cefoperazone, a third generation cephalosporin, which acts against
sensitive organisms during the stage of active multiplication by inhibiting
biosynthesis of cell wall mucopeptide. Sulbactam does not possess any
useful antibacterial activity, except against Neisseriaceae and
Acinetobacter. However, biochemical studies with cell-free bacterial
systems have shown it to be an irreversible inhibitor of most important
beta-lactamases produced by beta-lactam antibiotic-resistant organisms.

The potential for sulbactam's preventing the destruction of penicillins and

cephalosporins by resistant organisms was confirmed in whole-organism
studies using resistant strains in which sulbactam exhibited marked
synergy with penicillins and cephalosporins. As sulbactam also binds with
some penicillin binding proteins, sensitive strains are also often rendered
more susceptible to sulbactam/cefoperazone than to cefoperazone alone.

The combination of sulbactam and cefoperazone is active against all

organisms sensitive to cefoperazone. In addition it demonstrates
synergistic activity (up to fourfold reduction in minimum inhibitory
concentrations for the combination versus those for each component) in a
variety of organisms, most markedly the following:

Haemophilus influenzae
Bacteroides species
Staphylococcus species
Acinetobacter calcoaceticus
Enterobacter aerogenes
Escherichia coli
Proteus mirabilis
Klebsiella pneumoniae
Morganella morganii
Citrobacter freundii
Enterobacter cloacae
Citrobacter diversus

Sulbactam/cefoperazone is active in vitro against a wide variety of

clinically significant organisms:

Gram-Positive Organisms:

Staphylococcus aureus, penicillinase and non-penicillinase-producing

strains
Staphylococcus epidermidis
Streptococcus pneumoniae (formerly Diplococcus pneumoniae)
Streptococcus pyogenes (Group A beta-hemolytic streptococci)
Streptococcus agalactiae (Group B beta-hemolytic streptococci)
Most other strains of beta-hemolytic streptococci
Many strains of Streptococcus faecalis (enterococcus)

Gram-Negative Organisms:

Escherichia coli
Klebsiella species
Enterobacter species
Citrobacter species
Haemophilus influenzae
Proteus mirabilis
Proteus vulgaris
Morganella morganii (formerly Proteus morganii)
Providencia rettgeri (formerly Proteus rettgeri)
Providencia species
Serratia species (including S. marcescens)
Salmonella and Shigella species
Pseudomonas aeruginosa and some other Pseudomonas species
Acinetobacter calcoaceticus
Neisseria gonorrhoeae
Neisseria meningitidis
Bordetella pertussis
Yersinia enterocolitica

Anaerobic Organisms:
Gram-negative bacilli (including Bacteroides fragilis, other Bacteroides
species, and Fusobacterium species)

Gram-positive and gram-negative cocci (including Peptococcus,

Peptostreptococcus and Veillonella species)

Gram-positive bacilli (including Clostridium, Eubacterium and

Lactobacillus species)

The following susceptibility ranges have been established for

sulbactam/cefoperazone:

Minimal inhibitory concentration (MIC),

(mcg/mL-expressed as cefoperazone concentration)
Susceptible < 16
Intermediate 17 – 63
Resistant > 64

Susceptibility Disc Zone Size,

mm (Kirby – Bauer)
Susceptible > 21
Intermediate 16 – 20
Resistant < 15

For MIC determinations, serial dilutions of sulbactam/cefoperazone in a

1:1 or 1:2 sulbactam/cefoperazone ratio may be used with a broth or agar
dilution method. Use of a susceptibility test disc containing 30 mcg of
sulbactam and 75 mcg of cefoperazone is recommended. A report from
the laboratory of "susceptible" indicates that the infecting organism is
likely to respond to sulbactam/cefoperazone therapy, and a report of
"Resistant" indicates that the organism is not likely to respond. A report of
"Intermediate" suggests that the organism would be susceptible to
sulbactam/cefoperazone if a higher dosage is used or if the infection is
confined to tissues or fluids where high antibiotic levels are attained.

The following quality control limits are recommended for 30 mcg/75 mcg
sulbactam/cefoperazone susceptibility discs.

CONTROL STRAIN ZONE SIZE mm

 Acinetobacter spp.,
ATCC 43498 26 - 32
Pseudomonas aeruginosa,
ATCC 27853 22 - 28
Escherichia coli,
ATCC 25922 27 - 33
Staphylococcus aureus,
ATCC 25923 23 - 30

5.2 Pharmacokinetic Properties

Approximately 84% of the sulbactam dose and 25% of the cefoperazone

dose administered with sulbactam/cefoperazone is excreted by the
kidney. Most of the remaining dose of cefoperazone is excreted in the
bile. After sulbactam/cefoperazone administration the mean half-life for
sulbactam is about 1 hour while that for cefoperazone is 1.7 hours.
Serum concentrations have been shown to be proportional to the dose
administered. These values are consistent with previously published
values for the agents when given alone.

Mean peak sulbactam and cefoperazone concentrations after the

administration of 2 grams of SULPERAZONE (1 g sulbactam, 1 g of
cefoperazone) intravenously over 5 minutes were 130.2 and 236.8 mcg/ml
respectively. This reflects the larger volume of distribution for sulbactam
(Vd = 18.0-27.6 L) compared to cefoperazone (Vd = 10.2-11.3 L).

After intramuscular administration of 1.5 g SULPERAZONE (0.5 g

sulbactam, 1 g cefoperazone) peak serum concentrations of sulbactam
and cefoperazone are seen from 15 minutes to 2 hours after
administration. Mean peak serum concentrations were 19.0 and 64.2
mcg/ml for sulbactam and cefoperazone, respectively.

Both sulbactam and cefoperazone distribute well into a variety of tissues

and fluids including bile, gall bladder, skin, appendix, fallopian tubes,
ovary, uterus, and others.

There is no evidence of any pharmacokinetic drug interaction between

sulbactam and cefoperazone when administered together in the form of
sulbactam/cefoperazone.

After multiple dosing no significant changes in the pharmacokinetics of

either component of sulbactam/cefoperazone have been reported and no
accumulation has been observed when administered every 8 to 12 hours.

Use in Hepatic Dysfunction

 See section 4.4 Special Warnings and Special Precautions for Use

Use in Renal Dysfunction

In patients with different degrees of renal function administered

sulbactam/cefoperazone, the total body clearance of sulbactam was
highly correlated with estimated creatinine clearance. Patients who are
functionally anephric showed a significantly longer half-life of sulbactam
(mean 6.9 and 9.7 hours in separate studies). Hemodialysis significantly
altered the half-life, total body clearance, and volume of distribution of
sulbactam. No significant differences have been observed in the
pharmacokinetics of cefoperazone in renal failure patients.

Use in Elderly

The pharmacokinetics of sulbactam/cefoperazone have been studied in

elderly individuals with renal insufficiency and compromised hepatic
function. Both sulbactam and cefoperazone exhibited longer half-life,
lower clearance, and larger volumes of distribution when compared to
data from normal volunteers. The pharmacokinetics of sulbactam
correlated well with the degree of renal dysfunction while for cefoperazone
there was a good correlation with the degree of hepatic dysfunction.

Use in Children

Studies conducted in pediatrics have shown no significant changes in the

pharmacokinetics of the components of sulbactam/cefoperazone
compared to adult values. The mean half-life in children has ranged from
0.91 to 1.42 hours for sulbactam and from 1.44 to 1.88 hours for
cefoperazone.

5.3 Preclinical Safety Data

Use in Pediatrics

Cefoperazone had adverse effects on the testes of prepubertal rats at all

doses tested. Subcutaneous administration of 1,000 mg/kg per day
(approximately 16 times the average adult human dose) resulted in
reduced testicular weight, arrested spermatogenesis, reduced germinal
cell population and vacuolation of Sertoli cell cytoplasm. The severity of
lesions was dose dependent in the 100 to 1,000 mg/kg per day range; the
low dose caused a minor decrease in spermatocytes. This effect has not
been observed in adult rats. Histologically the lesions were reversible at
all but the highest dosage levels. However, these studies did not evaluate
 subsequent development of reproductive function in the rats. The
relationship of these findings to humans is unknown.

When sulbactam/cefoperazone (1:1) was given subcutaneously to

neonatal rats for 1 month reduced testicular weights and immature tubules
were seen in groups given 300 + 300 mg/kg/day. Because there is a
great individual variation in the degree of testicular maturation in rat pups
and because immature testes were found in controls any relation to study
drug is uncertain. No such findings were seen in infant dogs at doses
over 10 times the average adult dose.

6.0 PHARMACEUTICAL PARTICULARS

6.1 Shelf Life

See outer package for the expiry date.

6.2 Storage
0
Store at temperatures not exceeding 25 C. Protect from light.

Reconstituted solutions are stable for 24 hours at room temperature. All

unused solutions must be discarded after that time period.

6.3 Incompatibilities

Aminoglycosides

Solutions of sulbactam/cefoperazone and aminoglycosides should not be

directly mixed, since there is a physical incompatibility between them. If
combination therapy with sulbactam/cefoperazone and an aminoglycoside
is contemplated (see section 4.1 Therapeutic Indications Combination
Therapy) this can be accomplished by sequential intermittent intravenous
infusion provided that separate secondary intravenous tubing is used, and
that the primary intravenous tubing is adequately irrigated with an
approved diluent between doses. It is also suggested that doses of
sulbactam/cefoperazone be administered throughout the day at times as
far removed from administration of the aminoglycoside as possible.

Lactated Ringer’s Solution

Initial reconstitution with Lactated Ringer's Solution should be avoided

since this mixture has been shown to be incompatible. However, a two
step dilution process involving initial reconstitution in water for injection will
result in a compatible mixture when further diluted with Lactated Ringer's
 Solution (see section 6.4 Instructions for Use/Handling Lactated
Ringer’s Solution).

Lidocaine

Initial reconstitution with 2% lidocaine HCl solution should be avoided

since this mixture has been shown to be incompatible. However, a two
step dilution process involving initial reconstitution in water for injection will
result in a compatible mixture when further diluted with 2% lidocaine HCl
solution (see section 6.4 Instructions for Use/Handling Lidocaine)

6.4 Instruction for Use/Handling

Reconstitution

Sulbactam/cefoperazone is available in 1.5 g strength vial.

Total Equivalent Dosage of Volume of Maximum Final

Dosage sulb. + cefoperazone Diluent Conc. (mg/mL)
(g) (g)
1.5 0.5 + 1.0 3.2 125 + 250

Sulbactam/cefoperazone has been shown to be compatible with water for

injection, 5% dextrose, normal saline, 5% dextrose in 0.225% saline, and
5% dextrose in normal saline at concentrations of 10 mg cefoperazone
and 5 mg sulbactam per ml and up to 250 mg cefoperazone and 125 mg
sulbactam per mL.

Lactated Ringer’s Solution

Sterile Water for Injection should be used for reconstitution (see section
6.3 Incompatibilities Lactated Ringer’s Solution). A two step dilution is
required using Sterile Water for Injection (shown in table above) further
diluted with Lactated Ringer’s Solution to a sulbactam concentration of 5
mg/mL (use 2 mL initial dilution in 50 mL or 4 mL initial dilution in 100 mL
Lactated Ringer’s Solution).

Lidocaine

Sterile Water for Injection should be used for reconstitution (see section
6.3 Incompatibilities Lidocaine). For a concentration of cefoperazone of
250 mg/mL or larger, a two step dilution is required using Sterile Water for
Injection (shown in table above) further diluted with 2% lidocaine to yield
solutions containing up to 250 mg cefoperazone and 125 mg sulbactam
per mL in approximately 0.5% lidocaine HCl solution.
 6.5 Availability

Sulbactam/cefoperazone is available in 1.5 g vial.

CAUTION: Foods, Drugs, Devices and Cosmetics Act prohibits

dispensing without prescription.

Manufactured by: Haupt Pharma Latina S.r.l.

Strada Statale 156, Km 47,600
04010 Borgo San Michele, Latina, Italy

Imported by: Pfizer, Inc.

23/F Ayala Life-FGU Center
6811 Ayala Avenue, Makati City
Philippines
Under authority of Pfizer, Inc.
New York, N.Y., U.S.A.

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Revision No.: 2.1

Revision Date: 17 September 2009
Reference No.: 179
Reference Date: 18 October, 2007