A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Ceptaz Indications, Dosage, Storage, Stability - Ceftazidime
Ceptaz Indications, Dosage, Storage, Stability - Ceftazidime
INDICATIONS
CEPTAZ is indicated for the treatment
of patients with infections caused by susceptible
strains of the designated organisms in the following diseases:
- Lower Respiratory Tract Infections, including pneumonia,
caused by Pseudomonas aeruginosa and other Pseudomonas
spp., Haemophilus influenzae, including ampicillin-resistant
strains; Klebsiella spp.; Enterobacter spp.; Proteus
mirabilis; Escherichia
coli; Serratia spp.; Citrobacter spp.; Streptococcus
pneumoniae; and Staphylococcus aureus (methicillin
susceptible strains).
- Skin and Skin Structure Infections caused by Pseudomonas
aeruginosa; Klebsiella
spp.; Escherichia coli; Proteus
spp., including Proteus mirabilis and indole-positive
Proteus Enterobacter spp.; Serratia spp.; Staphylococcus
aureus (methicillin susceptible strains); and Streptococcus
pyogenes (group A beta-hemolytic streptococci).
- Urinary Tract Infections, both complicated and uncomplicated,
caused by Pseudomonas aeruginosa; Enterobacter
spp.; Proteus spp., including Proteus mirabilis
and indole-positive Proteus, Klebsiella spp.; and Escherichia
coli.
- Bacterial Septicemia caused by Pseudomonas aeruginosa,
Klebsiella spp., Haemophilus influenzae, Escherichia
coli, Serratia spp.,
Streptococcus pneumoniae, and Staphylococcus aureus
(methicillin susceptible strains).
- Bone and Joint Infections caused by Pseudomonas aeruginosa,
Klebsiella spp., Enterobacter spp., and Staphylococcus
aureus (methicillin susceptible
strains).
- Gynecologic Infections, including endometritis, pelvic
cellulitis, and other infections of the female
genital tract
caused by Escherichia coli.
- Intra abdominal
Infections, including peritonitis
caused by Escherichia coli, Klebsiella
spp., and Staphylococcus aureus (methicillin susceptible
strains) and polymicrobial
infections caused by aerobic
and anaerobic organisms
and Bacteroides spp. (many strains of Bacteroides fragilis
are resistant).
- Central Nervous System Infections, including meningitis,
caused by Haemophilus influenzae and Neisseria meningitidis.
Ceftazidime has also been used successfully in a limited number
of cases of meningitis due to Pseudomonas aeruginosa and
Streptococcus pneumoniae.
Specimens for bacterial cultures should be obtained before therapy
in order to isolate
and identify causative organisms and to determine their susceptibility
to ceftazidime. Therapy may be instituted before results of susceptibility
studies are known; however, once these results become available
the antibiotic treatment
should be adjusted accordingly.
CEPTAZ may be used alone in cases of confirmed or suspected sepsis.
Ceftazidime has been used successfully in clinical
trials as empiric therapy
in cases where various concomitant
therapies with other antibiotics have been used.
CEPTAZ may also be used concomitantly with other antibiotics, such
as aminoglycosides, vancomycin, and clindamycin; in severe and life-threatening
infections; and in the immunocompromised
patient (see DOSAGE
AND ADMINISTRATION: COMPATIBILITY AND STABILITY below). When
such concomitant
treatment is appropriate, prescribing information in the labeling
for the other antibiotics should be followed. The dosage
depends on the severity of the infection and the patient's condition.
DOSAGE AND ADMINISTRATION
Dosage
The usual adult dosage
is 1 gram administered
intravenously or intramuscularly every 8 to 12 hours. The dosage
and route should be determined by the susceptibility of the causative
organisms, the severity of infection
and the condition, and renal
function of the patient.
The guidelines for dosage
of C.P.A. are listed
in Table 3. The following dosage schedule
is recommended.
Table 3
Recommended Dosage Schedule
|
|
Dose
|
Frequency
|
|
Patients 12 years and older*
Usual recommended dosage
|
1 gram
IV or IM
|
Q8-12h
|
|
Uncomplicated urinary
tract infections
|
250 mg
IV or IM
|
Q12h
|
|
Bone and joint
infections
|
2 grams IV
|
Q12h
|
|
Complicated urinary
tract infections
|
500 mg
IV or IM
|
Q8-12h
|
|
Uncomplicated pneumonia; mild skin
and skin structure
infections
|
500 mg
-1 gram IV
or IM
|
Q8h
|
|
Serious gynecologic
and intra-abdominal
infections
|
2 grams IV
|
Q8h
|
|
Meningitis
|
2 grams IV
|
Q8h
|
|
Very Severe life
threatening infections, especially in immunocompromised
patients
|
2 grams IV
|
Q8h
|
|
Lung infections caused by Pseudomonas
spp. In patients
with cystic fibrosis
with normal renal
function**
|
30-50 mg/kg IV
to a maximum
of 6 grams per
day
|
Q8h
|
*This product
is for use in patients 12 years and older. If treatment
with ceftazidime is indicated for patients less than 12 years
old, a sodium carbonate
formulation should be used.
**Although clinical
improvement has been shown, bacteriologic cures cannot be expected
in patients with chronic
respiratory disease and cystic
fibrosis
Impaired Hepatic Function: No adjustment
in dosage is required
for patients with hepatic
dysfunction.
Impaired Renal Function: Ceftazidime is excreted
by the kidneys, almost exclusively by glomerular
filtration. Therefore, in patients with impaired renal
function (glomerular
filtration rate
[GFR]<50 mL/min) it is recommended that the dosage
of ceftazidime be reduced to compensate for its slower excretion.
In patients with suspected
renal insufficiency, an
initial loading
dose of 1 gram
of C.P.A. may be given.
An estimate of GFR should
be made to determine the appropriate
maintenance dosage. The recommended dosage
is presented in Table 4.
Table 4
Recommended Maintenance Dosages of C.P.A.
in Renal Insufficiency
NOTE: IF THE DOSE RECOMMENDED IN TABLE 3 ABOVE
IS LOWER THAN THAT RECOMMENDED
FOR PATIENTS WITH RENAL INSUFFICIENCY AS OUTLINED IN TABLE 4,
THE LOWER DOSE SHOULD BE USED
|
Creatinine clearance
mL/min
|
Recommended Unit dose
of CEPTAZ
|
Frequency of dosing
|
|
50-31
|
1 gram
|
Q12h
|
|
30-16
|
1 gram
|
Q24h
|
|
15-6
|
500 mg
|
Q24h
|
|
<5
|
500 mg
|
Q48h
|
When only serum creatinine
is available, the following formula
(Cockcroft's equation)4 may be used to estimate creatinine
clearance. The serum creatinine
should represent a steady state
of renal function:
|
|
Weight (kg) x (140-age)
72 x serum creatinine
(mg/dL)
|
In patients with severe infections who would normally receive 6
grams of C.P.A. daily
were it not for renal
insufficiency, the unit
dose given in the table
above may be increased by 50% or the dosing frequency
may be increased appropriately. Further dosing should be determined
by therapeutic monitoring, severity of the infection,
and susceptibility
of the causative organism.
In patients undergoing hemodialysis,
a loading dose
of 1 gram is recommended,
followed by 1 gram after
each hemodialysis
period.
CEPTAZ can also be used in patients undergoing intraperitoneal
dialysis and continuous ambulatory peritoneal
dialysis. In such
patients, a loading dose of 1 gram
of C.P.A. may be given,
followed by 500 mg every
24 hours. It is not known whether or not C.P.A.
can be safely incorporated into dialysis fluid.
Note: Generally C.P.A.
should be continued for 2 days after the signs and symptoms of infection
have disappeared, but in complicated infections longer therapy
may be required.
Administration
CEPTAZ may be given intravenously or by deep
IM injection into
a large muscle mass such
as the upper outer quadrant
of the gluteus maximus or lateral proof
of the thigh. Intra-arterial administration
should be avoided (see PRECAUTIONS).
Intramuscular Administration: For IM administration,
CEPTAZ should be constituted with one of the following diluents:
Sterile Water for Injection, Bacteriostatic Water for Injection,
or 0.5% or 1% Lidocaine Hydrochloride Injection. Refer to Table
5.
Intravenous Administration: The IV
route is preferable for patients with bacterial septicemia,
bacterial meningitis,
peritonitis, or other severe or life-threatening infections, or
for patients who may be p.o.
risks because of lowered resistance
resulting from such debilitating
conditions as malnutrition, trauma, surgery,
diabetes, heart
failure, or malignancy, particularly if shock
is present or pending.
For direct intermittent
IV administration, constitute
CEPTAZ as directed in Table 5 with Sterile Water for Injection,
5% Dextrose Injection, or 0.9 % Sodium Chloride Injection. Slowly
inject directly into
the vein over a period
of 3 to 5 minutes or give through the tubing of an administration
set while the patient
is also receiving one of the compatible IV fluids (see COMPATIBILITY
AND STABILITY below).
For IV infusion,
constitute the 1- or 2-gram infusion pack with 100 mL of
Sterile Water for Injection or one of the compatible IV fluids listed
under the COMPATIBILITY AND STABILITY subsection below. Alternatively
constitute the 1- or 2-gram vial
and add an appropriate quantity
of the resulting solution
to an IV container
with one of the compatible IV fluids.
Intermittent IV infusion
with a Y-type administration
set can be accomplished
with compatible solutions.
However, during infusion
of a solution containing
ceftazidime, it is desirable to discontinue the other solution.
Table 5
Preparation of Solutions of C.P.A.
|
Size
|
Amount of diluent
to be added (mL)
|
Volume to Be
Withdrawn (mL)
|
Approximate Ceftazidime Concentration
(mg/mL)
|
|
Intramuscular
|
|
1-gram vial
|
3.0
|
Total
|
250
|
|
Intravenous
|
|
1-gram vial
|
10.0
|
Total
|
90
|
|
2-gram vial
|
10.0
|
Total
|
170
|
|
Infusion pack
|
|
1-gram vial
|
100
|
-
|
10
|
|
2-gram vial
|
100
|
-
|
20
|
|
Pharmacy bulk
package
|
|
10-gram vial
|
40
|
Amount needed
|
200
|
Solutions of CEPTAZ, like those of most beta-lactam antibiotics,
should not be added to solutions of aminoglycoside
antibiotics because of potential interaction.
However, if concurrent therapy
with C.P.A. and an aminoglycoside
is indicated, each of these antibiotics can be administered separately
to the same patient.
Instructions for Constitution
Vials of C.P.A. as supplied
are under a slightly reduced pressure. This may assist entry of
the diluent. No gas-relief
needle is required when
adding the diluent, except for the infusion
pack where it is required
during the latter stages of addition
(in order to preserve
product sterility, a
gas relief
needle should not be
inserted until an overpressure
is produced in the vial). No
evolution of gas
occurs on constitution. When the vial contents are dissolved, vials
other than infusion
packs may still be under a reduced pressure. This reduced pressure
is particularly noticeable for the 10-gram pharmacy
bulk package.
COMPATIBILITY AND STABILITY
Intramuscular
CEPTAZ, when constituted as directed with Sterile Water for Injection,
Bacteriostatic Water for Injection, or 0.5% or 1% Lidocaine Hydrochloride
Injection, maintains satisfactory potency
for 18-hours at room temperature
or for 7 days under refrigeration. Solutions in Sterile Water for
Injection that are frozen immediately after constitution
in the original container are stable
for 6 months when stored at -20°C. Components of the solution
may precipitate
in the frozen state and
will dissolve
on reaching room temperature with little or no
agitation. Potency is not affected. Frozen solutions should only
be thawed at room temperature.
Do not force thaw by immersion
in water baths or by microwave
irradiation. Once thawed, solutions should not be refrozen. Thawed
solutions may be stored for up to 12 hours at room
temperature or for
7 days in a refrigerator.
Intravenous
Ceftazidime concentration
greater than 100 mg/mL (2-g vial
or 10-g pharmacy bulk
package): CEPTAZ, when constituted as directed with Sterile
Water for Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose
Injection, maintains, satisfactory potency
for 18 hours at room temperature or for 7 days under refrigeration.
Solutions of a similar concentration in Sterile Water for Injection
that are frozen immediately after constitution in the original container
are stable for 6 months
when stored at 20° C. Components of the solution
may precipitate
in the frozen state and
will dissolve upon reaching room
temperature with
little or no agitation. Potency
is not affected. Frozen solutions should only be thawed at room
temperature. Do not force
thaw by immersion
in water baths or by microwave
irradiation.
Once thawed solutions should not be refrozen. Thawed solutions
may be stored for up to 12 hours at room
temperature or for
7 days in a refrigerator.
Ceftazidime concentration
of 100 mg/mL or less (1-g vial
or infusion packs): CEPTAZ, when constituted as directed
with Sterile Water for Injection, 0.9% Sodium Chloride Injection,
or 5% Dextrose Injection, maintains satisfactory potency
for 24 hours at room temperature
or for 7 days under refrigeration. Solutions, prepared by a pharmacist,
of the approved arginine
formulation of ceftazidime of a similar concentration in Sterile
Water for Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose
Injection in the original container
or in 0.9% Sodium Chloride Injection in VIAFLEX®
(PL 146® Plastic) small-volume
containers that are frozen immediately after constitution by the
pharmacist are stable
for 6 months when stored at -20° C. Solutions in the PL 146
Plastic small-volume containers are in contact
with the polyvinyl chloride layer
of this container
and can leach out certain chemical
components of the plastic
in very small amounts within the expiration
period. The suitability of the plastic
has been confirmed in tests in animals according to USP biological
tests for plastic containers
as well as by tissue
culture toxicity studies. Stability of the frozen solution
in other containers has not been confirmed. Frozen solutions should
only be thawed at room temperature. Do not force
thaw by immersion
in water baths or by microwave
irradiation. For the larger volumes of IV
infusion solutions
where it may be necessary to warm the frozen product, care should
be taken to avoid heating after thawing is complete. Once thawed
solutions should not be refrozen. Thawed solutions may be stored
for up to 18 hours at room
temperature or for 7 days in a refrigerator.
Components of the solution
may precipitate
in the frozen state and
will dissolve on reaching room
temperature with
little or no agitation. Potency
is not affected. Check for minute leaks in plastic
containers by squeezing bag firmly. Discard bag
if leaks are found as sterility
may be impaired. Do not add
supplementary medication
to bags. Do not use unless solution is clear and seal
is intact.
Use sterile equipment.
Caution: Do not use plastic
containers in series
connections. Such use could result in air
embolism due to residual
air being drawn from the
primary container
before administration
of the fluid from the
secondary container is complete.
Preparation for Administration:
- Suspend container
from eyelet support.
- Remove protector from outlet
proof at bottom of container.
- Attach administration
set. Refer to complete directions accompanying set.
CEPTAZ is compatible
with the more commonly used IV
infusion fluids. Solutions
at concentrations between 1 and 40 mg/mL in 0.9% Sodium Chloride
Injection; 1/6 M Sodium Lactate Injection; 5% Dextrose Injection;
5% Dextrose and 0.225% Sodium Chloride Injection; 5% Dextrose and
0.45% Sodium Chloride Injection; 5% Dextrose and 0.9% Sodium Chloride
Injection; 10% Dextrose Injection; Ringer's Injection, USP; Lactated
Ringer's Injection, USP; 10% Invert Sugar in Sterile Water for Injection;
and Normosol ®-M in 5% Dextrose
Injection may be stored for up to 24 hours at room
temperature or for
7 days if refrigerated.
CEPTAZ is less stable
in Sodium Bicarbonate Injection than in other IV fluids It is not
recommended as a diluent. Solutions of C.P.A.
in 5% Dextrose Injection and 0.9 % Sodium Chloride Injection are
stable for at least 6
hours at room temperature
in plastic tubing, drip
chambers, and volume control
devices of common IV infusion
sets.
Ceftazidime at a concentration
of 4 mg/mL has been found compatible for 24 hours at room
temperature or for
7 days under refrigeration
in 0.9% Sodium Chloride Injection or 5% Dextrose Injection when
admixed with: cefuroxime sodium (ZINACEF®)
3 mg/mL; heparin sodium in concentrations up to 50 U/mL; or potassium
chloride in concentrations
up to 40 mEq/L. Ceftazidime may be constituted at a concentration
of 20 mg/mL with metronidazole
injection 5 mg/mL,
and the resultant solution may be stored for 24 hours at room
temperature or for
7 days under refrigeration. Ceftazidime at a concentration
of 20 mg/mL has been found compatible
for 24 hours at room temperature
or for 7 days under refrigeration
in 0.9% Sodium Chloride Injection or 5% Dextrose Injection when
admixed with 6 mg/mL clindamycin (as clindamycin phosphate).
Vancomycin solution
exhibits a physical
incompatibility
when mixed with a number
of drugs, including ceftazidime. The likelihood of precipitation
with ceftazidime is dependent on the concentrations of vancomycin
and ceftazidime present. It is therefore recommended, when both
drugs are to be administered by intermittent
IV infusion,
that they be given separately, flushing the IV lines (with one of
the compatible IV
fluids) between the administration of these two agents.
Note: Parenteral drug
products should be inspected visually for particulate matter
before administration
whenever solution and
container permit.
As with other cephalosporins, C.P.A.
powder as well as solutions
tend to darken, depending on storage conditions; within the stated
recommendations, however, product
potency is not adversely
affected.
Directions for Dispensing
Pharmacy Bulk Package-Not for Direct Infusion: The
pharmacy bulk package is for use in a pharmacy
admixture service only under a laminar flow hood. Entry into the
vial must be made with
a sterile transfer
set or other sterile
dispensing device and
the contents dispensed in aliquots using aseptic technique. The
use of syringe and needle
is not recommended as it may cause
leakage (see DOSAGE AND ADMINISTRATION
). GOOD PHARMACY PRACTICE DICTATES THAT
THE CLOSURE BE PENETRATED ONLY ONE TIME AFTER CONSTITUTION AFTER
INITIAL PENETRATION OF THE CLOSURE, USE ENTIRE CONTENTS OF VIAL
PROMPTLY ANY UNUSED PORTION MUST
BE DISCARDED WITHIN 18 HOURS OF CONSTITUTION.
HOW SUPPLIED
CEPTAZ in the dry state
should be stored between 15° and 30° C (59° and 86°
F) and protected from light. C.P.A.
is a dry, white to off-white powder
supplied in vials and infusion
packs as follows:
REFERENCES
- Bauer AW, Kirby WMM Sherris JC, Turck M. Antibiotic
susceptibility testing by a standardized single disk
method. Am J Clin Pathol. 1966;45:493-496.
- National Committee for Clinical Laboratory Standards.
Approved Standard: Performance Standards for Antimicrobial
Disc Susceptibility Tests. (M2-A3) December 1984.
- Certification procedure
for antibiotic
sensitivity discs
(21 CFR 460).1). Federal Register May 30 1974;39:19182-19184.
- Cockcroft DW, Gault MH. Prediction of creatinine
clearance from serum
creatinine. Nephron 1976;16:31-41.
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